RxPG News : Physiology

ACSM: Yoga helped older stroke victims improve balance, endurance

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) An Indiana University study that exposed older veterans with stroke to yoga produced exciting results as researchers explore whether this popular mind-body practice can help stroke victims cope with their increased risk for painful and even deadly falls.

The pilot study involved 19 men and one woman, average age of 66. For eight weeks, they participated in a twice weekly hour-long group yoga class taught by a yoga therapist who dramatically modified the poses to meet the veterans' needs.

A range of balance items measured by the Berg Balance Scale and Fullerton Advance Balance Scale improved by 17 percent and 34 percent respectively by the end of the program. But equally exciting to lead researcher Arlene A. Schmid, rehabilitation research scientist at the Richard L. Roudebush VA Medical Center in Indianapolis, was the measurable gain in confidence the study participants had in their balance.

It also was interesting to see how much the men liked it, said Schmid, assistant professor of occupational therapy in the School of Health and Rehabilitation Sciences at Indiana University-Purdue University Indianapolis. Many of the veterans wanted the study to continue or asked for a take-home exercise plan so they could continue the practice. They enjoyed it so much partly because they weren't getting any other treatment. They had already completed their rehabilitation but felt there still was room for improvement.

Schmid will discuss her findings on Saturday during the American College of Sports Medicine meeting in Denver. Her poster presentation, Preliminary Evidence of Yoga on Balance and Endurance Outcomes for Veterans with Stroke will be from 7:30 a.m.-11 a.m. in Hall B in the session for Fitness and Performance Testing for Posture, Stability and Balance.

Statistics concerning strokes and falls are grim, with studies showing that strokes can quadruple the risk of falling and greatly increase the risk of breaking a hip after a fall. An estimated 80 percent of people who have strokes will also have some degree of impaired balance.

The study participants performed poses initially while seated in chairs and then progressed to seated and standing poses. Eventually, they all performed poses on the floor, something Schmid considers significant because of a reluctance many older adults have to working on the floor.

Everything was modified because we wanted them to be successful on day one, Schmid said. Everyone could be successful at some level.

A score of less than 46 on the Berg Balance Scale indicates a fall risk. Schmid said the study participants on average began the study with a score of 40 and then improved to 47, moving them past the fall risk threshold. The study participants also showed significant improvements in endurance based on a seated two-minute step test and a six-minute walk test.

Schmid said research into therapeutic uses for yoga is really taking off, particularly in mental health fields. Clinically, she has been watching a small trend of occupational therapists and physical therapists also becoming yoga therapists. The yoga performed in the study was modified to the extent that Schmid said it would be very difficult to find a comparable class offered publicly. Such a class should be taught by a yoga therapist who has had additional training in anatomy and physiology and how to work with people with disabilities. Schmid hopes to expand the study so she and her colleagues can explore whether such classes are effective on a larger scale.

Heart drugs could cut blood pressure risks in pregnancy

Wed, 20 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Pregnant women could benefit from a pioneering trial that will test whether heart disease drugs can be used to treat pre-eclampsia.

Researchers are investigating if a class of drugs - known as statins - can prevent the potentially fatal condition, which affects up to eight per cent of pregnant women in the UK.

The world's first trial on statins in pregnancy follows on from research showing that statins, which are prescribed to lower heart disease, could also help to decrease amounts of two proteins linked to inducing pre-eclampsia.

Statins act on an enzyme that suppresses the production of these proteins - soluble FLt-1 and soluble endoglin.

The trial, funded by the Medical Research Council and led by the University of Edinburgh, will involve pregnant women in the UK diagnosed with very early-onset pre-eclampsia, which occurs in women who are less than 32 weeks pregnant.

It will also involve researchers from the University of Birmingham, University College London Hospital and Queen Mary, University of London.

The study follows on from previous research that shows the enzyme involved - heme oxygenase 1 - produces carbon monoxide within cells. This could explain why female smokers, who have higher levels of carbon monoxide in their blood, have a lower risk of pre-eclampsia.

The condition, which is responsible for around four million premature births worldwide each year, causes high blood pressure, inflammation of the lining of blood vessels and can also cause kidney and liver damage. In extreme cases, when unmanaged, it can also lead to convulsions and death.

Early onset pre-eclampsia affects one in 100 expectant mothers in Britain. The condition carries greater risk than pre-eclampsia occurring later in the pregnancy because the only treatment for the condition is to deliver babies prematurely.

Professor Asif Ahmed, who is leading the study, stressed that until the results were available, pregnant women who think they may be susceptible to pre-eclampsia should not ask their doctor to prescribe statins.

Professor Asif Ahmed, of the University of Edinburgh's Centre for Cardiovascular Science, said: This is the first stage, but we are confident that taking a scientific approach to find a way to alleviate pre-eclampsia would enable us to prolong affected pregnancies, improving the outcome for both the baby and the expectant mother. If successful this could help provide cheap, widely available therapy against pre-eclampsia which could help reduce maternal and infant deaths across the world.

The study is known as StAmP - statins to ameliorate early onset pre-eclampsia.

Professor Max Parmar, Director of the Medical Research Council's Clinical Trials Unit, said: The MRC supports trials which drive the translation of discoveries made in the lab into real benefits for public health. The design of the StAmP study means that it should provide important evidence on whether statins, which are already widely used in other conditions, could be exploited even further. Pre-eclampsia is a major problem area in women's health, so it would be a key step forward if this trial provides a positive outcome.

Higher CCSVI prevalence confirmed in MS, but meaning of findings remains unclear

Wed, 13 Apr 2011 04:00:00 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- A just released study on the relationship between multiple sclerosis (MS) and chronic cerebral venous insufficiency (CCSVI), a narrowing of the extracranial veins that restricts the normal outflow of blood from the brain, found that CCSVI may be a result of MS, not a cause.

The study, conducted by University at Buffalo researchers, appears in the current issue of Neurology, the journal of the American Academy of Neurology.

Robert Zivadinov, MD, PhD, associate professor of neurology in the UB School of Medicine and Biomedical Sciences and president of the International Society for Neurovascular Disease, is first author on the paper.

Zivadinov says of the findings: Given the intense interest in the hypothesis that CCSVI is a possible cause of MS, independent evaluation of CCSVI was identified as an urgent need.

Our results indicate that only 56.1 percent of MS patients and 38.1 percent of patients with a condition known as clinically isolated syndrome (CIS), an individual's first neurological episode, had CCSVI.

While this may suggest an association between the MS and CCSVI, association does not imply causality. In fact, 42.3 percent of participants classified as having other neurological diseases (OND), as well as 22.7 percent of healthy controls involved in the study, also presented with CCSVI.

These findings indicate that CCSVI does not have a primary role in causing MS, says Zivadinov. Our findings are consistent with increased prevalence of CCSVI in MS, but substantially lower than the sensitivity and specificity rates in MS reported originally by the Italian investigators.

CCSVI is a complex vascular condition discovered and described by Paolo Zamboni, MD, from Italy's University of Ferrara. It is characterized by narrowing of vessels draining blood from the cranium. Zamboni hypothesized that this narrowing restricts the normal outflow of blood from the brain, resulting in alterations in the blood flow patterns within the brain that eventually cause injury to brain tissue and degeneration of neurons, leading to MS.

Zamboni's original investigation in a group of 65 patients and 235 controls showed that CCSVI appeared to be strongly associated with MS, increasing the risk of having MS by 43 fold.

The results of the UB study are based on 499 participants in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) study, which began at the university in April 2009.

The study group consisted of 289 persons with MS, 163 healthy controls, 26 with OND and 21 with CIS.

MS patients also were defined by disease type: relapsing-remitting (RR), secondary progressive (SP), primary-progressive (PP), progressive-relapsing (PR) and MS with neuromyelitis optical (NMO) -- a type of MS that affects the optic nerves and spinal cord exclusively.

All patients underwent transcranial and extracranial echo-Doppler scans of the head and neck. Persons were considered CCSVI-positive if they met two or more of five venous hemodynamic (VH) criteria.

Prevalence rates were calculated in three groupings: only subjects with positive and negative CCSVI diagnoses; only borderline cases included in the negative group; and subjects who fulfilled any of the five criteria.

When only positive and negative CCSVI cases were considered, results showed a CCSVI prevalence of 62.5 percent in MS patients, 45.8 percent in those with OND, 42.1 percent in CIS, and 25.5 percent in healthy controls.

When borderline cases were included as negative for CCSVI, prevalence figures were 56.1 percent in MS patients, 42.3 percent in those with OND, 38.1 percent with CIS and 22.7 percent in healthy controls.

When all cases that met at least one of the five VH criteria were included in the analysis, CCSVI prevalence was 81.3 percent in MS cases, 76.2 percent in CIS patients, 65.4 percent in OND cases and 55.2 percent in healthy controls.

The highest prevalence was seen in relapsing primary-progressive MS (89.4 percent), followed by non-relapsing secondary-progressive MS (67.2 percent), NMO (66.6 percent), primary-progressive MS (54.5 percent) and relapsing-remitting MS (49.2 percent). CCSVI prevalence was substantially higher in progressive MS than in non-progressive MS patients. In addition, patients with a progressive MS disease subtype had higher CCSVI prevalence than those with non-progressive MS.

The higher prevalence of CCSVI in progressive MS patients suggests that CCSVI may be a consequence, rather than a cause, of MS, says Bianca Weinstock-Guttman, MD, co-principal investigator of the study and UB professor of neurology. Therefore, the possibility that CCSVI may be a consequence of MS progression cannot be excluded and should be further investigated.

Several studies have reported that patients with progressive MS show decreased blood flow through the brain's neuronal tissue, indicating that CCSVI may be secondary to reduced perfusion, says Weinstock-Guttman. In addition, we recently showed an association between the severity of CCSVI and reduced cerebral blood flow in brain parenchyma of MS patients in an published pilot study.

E. Ann Yeh, MD, UB assistant professor of neurology and a major collaborator on the study, noted that of the 10 pediatric MS patients who participated in the study, five presented with CCSVI (50 percent), yielding prevalence similar to that in adult MS patients.

Although the sample size was too small to draw any firm conclusions, these results suggest that CCSVI is also present in children and is not the result of aging, she says.

Concludes Zivadinov: The differences between our study, the original Italian CCSVI study and other recently published studies also emphasize the need for a multimodal approach for the assessment of CCSVI. In addition to Doppler sonography, use of selective venography, magnetic resonance venography and intraluminal Doppler methods can provide more evidence for the true prevalence of CCSVI in MS.

New insight into 'aha' memories

Thu, 31 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) When we suddenly get the answer to a riddle or understand the solution to a problem, we can practically feel the light bulb click on in our head. But what happens after the 'Aha!' moment? Why do the things we learn through sudden insight tend to stick in our memory?

'Much of memory research involves repetitive, rote learning,' says Kelly Ludmer, a research student in the group of Prof. Yadin Dudai of the Institute's Neurobiology Department, 'but in fact, we regularly absorb large blocks of information in the blink of an eye and remember things quite well from single events. Insight is an example of a one-time event that is often well-preserved in memory.'

To investigate how lessons we gain from insight get embedded in our long-term memory, Ludmer, Dudai and Prof. Nava Rubin of New York University designed a test with 'camouflage images' - photographs that had been systematically degraded until they resembled inkblots. When volunteers first viewed the images, they were hard pressed to identify them. But after the camouflage was switched with the original, undoctored picture for a second, the subjects experienced an 'Aha!' moment - the image now popped out clearly even in the degraded image. Their perceptions, says Ludmer, underwent a sudden change - just as a flash of insight instantly shifts our world view. To tax their memory of the insightful moment, participants were asked to repeat the exercise with dozens of different images and, in a later repeat session, they were given only the camouflaged images (together with some they hadn't seen before) to identify.

The team found that some of the memories disappeared over time, but the ones that made it past a week were likely to remain. All in all, about half of all the learned 'insights' seemed to be consolidated in the subjects' memories.

To reveal what occurs in the brain at the moment of insight, the initial viewing session was conducted in a functional MRI (fMRI) scanner. When the scientists looked at the fMRI results, they were surprised to find that among the areas that lit up in the scans - those known to be involved in object recognition, for instance - was the amygdala. The amygdala is more famously known as the seat of emotion in the brain. Though it has recently been found to play a role in the consolidation of certain memories, studies have implied that it does so by attaching special weight to emotion-laden events. But the images used in the experiment - hot-air balloons, dogs, people looking through binoculars, etc. - were hardly the sort to elicit an emotional response. Yet, not only was the amygdala lighting up in the fMRI, the team found that its activity was actually predictive of the subject's ability to identify the degraded image long after that moment of induced insight in which it was first recognized.

'Our results demonstrate, for the first time, that the amygdala is important for creating long-term memories - not only when the information learned is explicitly emotional, but also when there is a sudden reorganization of information in our brain, for example, involving a sudden shift in perception,' says Ludmer. 'It might somehow evaluate the event, 'deciding' whether it is significant and therefore worthy of preservation.'

Monash scientists uncover a new understanding of male puberty

Mon, 14 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists from Monash University have uncovered a new understanding of how male puberty begins.

The key to their findings lies with a protein known as SMAD3 and the rate at which it is produced.Researchers, Associate Professor Kate Loveland and Dr Catherine Itman from the Faculty of Medicine, Nursing and Health Sciences have discovered through laboratory testing that half as much SMAD3 protein results in faster maturation than the norm, and an inability to create SMAD3 results in abnormal responses to testosterone.

SMAD3 is a protein that translates signals from the environment outside the cell to the nucleus, where it switches genes on or off, Dr Itman said. We have been investigating how SMAD3 influences the growth of testis cells and their ability to respond to testosterone.

Puberty begins when the body starts to produce large amounts of the hormone testosterone. Early, or precocious, puberty involves the onset of puberty before eight years of age and affects around 1 in 10,000 boys. On the other hand, puberty is delayed when testis cells cannot respond normally to testosterone. Altered timing of puberty has implications in adulthood, with precocious puberty linked to reduced adult height and delayed puberty associated with reduced bone density.

Testosterone acts through specialized cells in the testis called Sertoli cells. Before puberty, Sertoli cells multiply, allowing the testis to grow. At puberty, Sertoli cells must stop growing so they can support sperm precursor cells to develop into sperm.

Professor Loveland, Dr Itman and their colleagues have been investigating how Sertoli cells switch from a multiplying state, making the testis big enough to make sperm, to a mature state that sustains sperm production.

We have discovered that this is not an on-off switch. Rather, it is the amount of the SMAD3 protein in the Sertoli cell that is different in the immature, multiplying Sertoli cell compared to the mature, adult cell. The research identified that it is the amount of SMAD3 present that controls Sertoli cell activity prior to, or after, puberty. When SMAD3 levels are reduced, sperm develop earlier. When SMAD3 is absent, Sertoli cells take longer to respond to testosterone.

Previous research on puberty suggests that pubertal development is delayed in boys exposed to endocrine disrupting compounds, chemicals which impair cell responses to hormones. These chemicals are widely used in industry and in the manufacture of everyday items, such as plastics, cosmetics, paints and detergents.

Dr Itman is supported by a National Health and Medical Research Council (NHMRC) Early Career Project Grant to investigate how these hormone-disrupting chemicals in the environment affect the growth and maturation of Sertoli cells around puberty, including changes to SMAD3 levels and activity.

We hope that through our research, we will inform decisions about the influence of chemicals in our environment on the timing of puberty in boys and on the fertility of adult men Dr Itman said.

Genes of the immune system are associated with increased risk of mental illness

Mon, 07 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Genes linked to the immune system can affect healthy people's personality traits as well as the risk of developing mental illness and suicidal behaviour, reveals a thesis from the University of Gothenburg, Sweden.

Inflammation is part of the immune system and is responsible for defending humans against infection as well as fascilitating the healing of injuries, and is therefore vital for our survival. Research has demonstrated that inflammatory processes also have other roles to play as inflammatory substances produced by the body influence mechanisms in the brain involving learning and memory.

Inflammatory substances produced in moderate quantities in the brain can be beneficial during the formation of new brain cells, for example. However, an increase in the levels of these substances as is the case during illness, can result in damage to the brain.

Previous studies have shown that individuals suffering from various mental illnesses have an increased peripheral inflammation, but the reason behind this increase is not known, says Petra Suchankova Karlsson, who wrote the thesis. It has been suggested that the stress that goes with mental illness activates the body's immune system, but it is also possible that inflammation in the body affects the brain, which in turn results in mental illness.

Previous studies have focused on how environmental and psychological factors affect the immune system's impact on the brain. Suchankova's thesis presents, for the first time, results that suggest that several different genes linked to the immune system are associated with healthy people's personality traits. It also demonstrates that some of these genes are associated with an increased risk of developing schizophrenia or suicidal behaviour.

One of the things we studied was a gene variant that increases impulsiveness in people who carry it, says Suchankova. We already knew that the risk of attempting suicide is higher in impulsive people and therefore analysed this gene variant in a group of patients who had attempted to take their life. We found that these patients more often carried the particular gene variant when compared to the general population which meant that this variant was not only associated with increased impulsiveness in healthy individuals but also with increased risk of suicidal behaviour.

The change in the levels of inflammatory substances in the blood of patients suffering from a mental illness as previously noted may have been caused by inflammation-related genes affecting the risk of mental illness, rather than the illness itself leading to a change in levels, as is traditionally believed.

It could well be that some variants of the genes play a role in the development of mental illness by controlling how the brain is formed, perhaps during the embryonic stage, or by affecting the transfer of signal substances, says Suchankova.

The results of this thesis support the proposed role of the immune system in mental illness, and could be used as a basis for further studies that, it is hoped, will lead to the development of new treatment methods.

The thesis has been successfully defended.

Learn more quickly by transcranial magnetic brain stimulation

Fri, 28 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) What sounds like science fiction is actually possible: thanks to magnetic stimulation, the activity of certain brain nerve cells can be deliberately influenced. What happens in the brain in this context has been unclear up to now. Medical experts from Bochum under the leadership of Prof. Dr. Klaus Funke (Department of Neurophysiology) have now shown that various stimulus patterns changed the activity of distinct neuronal cell types. In addition, certain stimulus patterns led to rats learning more easily. The knowledge obtained could contribute to cerebral stimulation being used more purposefully in future to treat functional disorders of the brain. The researchers have published their studies in the Journal of Neuroscience and in the European Journal of Neuroscience.

Magnetic pulses stimulate the brain

Transcranial magnetic stimulation (TMS) is a relatively new method of pain-free stimulation of cerebral nerve cells. The method, which was presented by Anthony Barker for the first time in 1985, is based on the fact that the cortex, the rind of the brain located directly underneath the skull bone, can be stimulated by means of a magnetic field. TMS is applied in diagnostics, in fundamental research and also as a potential therapeutic instrument. Used in diagnostics, one single magnetic pulse serves to test the activability of nerve cells in an area of the cortex, in order to assess changes in diseases or after consumption of medications or also following a prior artificial stimulation of the brain. One single magnetic pulse can also serve to test the involvement of a certain area of the cortex in a sensorial, motoric or cognitive task, as it disturbs its natural activity for a short period, i.e. switches off the area on a temporary basis.

Repeated stimuli change cerebral activity

Since the mid-1990's, repetitive TMS has been used to make purposeful changes to the activability of nerve cells in the human cortex: In general, the activity of the cells drops as a result of a low-frequency stimulation, i.e. with one magnetic pulse per second. At higher frequencies from five to 50 pulses per second, the activity of the cells increases, explained Prof. Funke. Above all, the researchers are specifically addressing with the effects of specific stimulus patterns like the so-called theta burst stimulation (TBS), in which 50 Hz bursts are repeated with 5 Hz. This rhythm is based on the natural theta rhythm of four to seven Hertz which can be observed in an EEG, says Funke. The effect is above all dependent on whether such stimulus patterns are provided continuously (cTBS, attenuating effect) or with interruptions (intermittent, iTBS, strengthening effect).

Contact points between cells are strengthened or weakened

It is unknown to a great extent how precisely the activity of nerve cells is changed by repeated stimulation. It is assumed that the contact points (synapses) between the cells are strengthened (synaptic potentation) or weakened (synaptic depression) as a result of the repeated stimulation, a process which also plays an important role in learning. Some time ago, it was also shown that the effects of TMS and learning interact in humans.

Inhibitory cortical cells react particularly sensitive to stimulation

The researchers in Bochum have now shown for the first time that an artificial cortex stimulation specifically changes the activity of certain inhibitory nerve cells as a function of the stimulus protocol used. The balanced interaction of excitatory and inhibitory nerve cells is the absolute prerequisite for healthy functioning of the brain. Nerve cells specialised in inhibition of other nerve cells show a much greater variety in terms of cell shape and activity structure than their excitatory counterparts. Amongst other things, they produce various functional proteins in their cell body. In his studies, Prof. Funke has concentrated on the examination of the proteins Parvalbumin (PV), Calbindin-D28k (CB) and Calretinin (CR). They are formed by various inhibitory cells as a function of activity, with the result that their quantity gives information about the activity of the nerve cells in question.

Stimulus patterns act specifically on certain cells

For example, the examinations showed that activating stimulation protocol (iTBS) almost only reduces the PV content of the cells, whereas continuous stimulation attenuating activity (cTBS protocol), or a likewise attenuating 1 Hz stimulation, mainly reduces the CB production. CR formation was not changed by any of the tested stimulus protocols. Registration of the electrical activity of nerve cells confirmed a change in inhibition of the cortical activity.

Learning more quickly after stimulation

In a second study, recently published in the European Journal of Neuroscience, Prof. Funke's group was able to show that rats also learned more quickly if they were treated with the activating stimulus protocol (iTBS) before each training, but not if the inhibiting cTBS protocol has been used. It was seen that the initially reduced formation of the protein Parvalbumin (PV) was increased again by the learning procedure, but only in the areas of the brain involved in the learning process. For animals not involved in the specific learning task, production of PV remained reduced following iTBS. The iTBS treatment therefore initially reduces the activity of certain inhibiting nerve cells more generally, with the result that the following learning activities can be stored more easily, concludes Prof. Funke. This process is termed gating. In a second step, the learning activity restores the normal inhibition and PV production.

More purposeful treatment in future

Repetitive TMS is already being used in clinical trials with limited success for therapy of functional disorders of the brain, above all in severe depressions. In addition, it was shown that especially disorders of the inhibitory nerve cells play an important role in neuropsychiatric diseases such as schizophrenia. It is doubtless too early to derive new forms of treatment of functional disorders of the brain from the results of our study, but the knowledge obtained provides an important contribution for a possibly more specific application of TMS in future, is Prof. Funke's hope.

Literature

Benali, A., Trippe, J., Weiler, E., Mix, A., Petrasch-Parwez, E., Girzalsky, W., Eysel, U.T., Erdmann, R. and Funke, K. (2011) Theta-burst transcranial magnetic stimulation alters cortical inhibition. J. Neurosci., in press.

Mix, A., Benali, A., Eysel, U.T., Funke, K. (2010) Continuous and intermittent transcranial magnetic theta burst stimulation modify tactile learning performance and cortical protein expression in the rat differently. In: Eur. J. Neurosci. 32(9):1575-86. doi: 10.1111/j.1460-9568.2010.07425.x. Epub 2010 Oct 18.

Further information

Prof. Dr. Klaus Funke, Dept. of Neurophysiology, Faculty of Medicine of the Ruhr University, 44780 Bochum, Tel. 0234/32-23944, E-Mail: funke@neurop.rub.de

Breakthrough on cystic fibrosis 1 step closer as new research alliance formed

Thu, 27 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) McGill University and GlaxoSmithKline plc (GSK) have signed a collaboration agreement to develop a potential breakthrough approach to treat cystic fibrosis, a fatal genetic disease. The trans-Atlantic effort between researchers from McGill's Faculty of Medicine and their GSK collaborators in the UK, will focus on developing molecules that could treat the disease by correcting the dysfunction caused by the mutated gene. This revolutionary approach will be a departure from current treatments, which only manage the symptoms or complications of the disorder. The collaborative research is co-sponsored by the Canadian Institutes of Health Research (CIHR).

Cystic fibrosis (CF) is one of the most common fatal genetic diseases. It is a multi-organ disease but primarily affects the lungs and digestive system, causing mucous to thicken and leaving patients at higher risk of infections. CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). About 90 per cent of those living with cystic fibrosis have a particular mutant form of this gene, which makes a protein that could still work but has a defect that prevents it getting to the right place in the cell to function correctly.

Dr. David Thomas, Chair of McGill's Department of Biochemistry and Canada Research Chair in Molecular Genetics, is an expert in protein quality control. Dr. John Hanrahan is Professor in McGill's Department of Physiology and an expert in chloride transport and epithelial biology. They are uniquely qualified as lead investigators on McGill's side, having conducted extensive research on the CFTR protein and have identified a number of molecules that look to restore normal CFTR function.

If we can restore normal function to the mutant cystic fibrosis protein, we can radically transform the lives of millions of children. It will move us from treatment of symptoms to prevention of the disease and would ultimately save lives, said Dr. Thomas. We will now be looking at enhancing these small molecules to improve their ability to rescue or correct the mutant protein, allowing it to reach its proper location and be more active, added Dr. Hanrahan.

GSK is excited to be applying our expertise in areas including medicinal chemistry to this innovative area of research, said Dr. Roberto Solari, head of respiratory biology at GSK. We hope at the end of this two year collaboration we will have a compound that is be ready to be investigated as a potential new medicine. Collaborations such as these - where we share knowledge, expertise and resource - provide a highly effective way of progressing cutting edge research.

This strong collaboration between an industry partner, government granting agencies and the University is a superb example of partners building on mutual strengths and collaborating where our research interests converge, said Dr. Rose Goldstein, Vice-Principal (Research and International Relations). We are grateful for the support provided by GSK and CIHR, facilitating our work together to give people with cystic fibrosis a healthy and full life expectancy.

Health research successes in the 21st century will be very much dependent on the ability of organizations from the public, academic and private sector to combine efforts and pool resources, said Dr. Marc Ouellette, Scientific Director for The Canadian Institutes of Health Research's Institute of Infection and Immunity. In particular, this grant will increase our understanding of the cellular mechanisms causing cystic fibrosis and provide novel ways of targeting genetic based diseases. Research done through the support of this partnership will add to groundbreaking work done by Canada's strong Cystic Fibrosis research community, including those funded under the Canadian led Human Microbiome Initiative.

Hormonal therapy for older, pregnant horses?

Mon, 24 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Most miscarriages in horses results at very early stages of pregnancy (within about three weeks) and it is generally believed that the primary cause is that the foetus grows or develops too slowly: smaller than normal embryos have a higher chance of being lost then normally sized ones. It is not clear whether low concentrations of progesterone lead to slower embryonic development but nevertheless the progestin altrenogest is routinely used to treat mares that frequently suffer miscarriages. Aurich's group has now found that altrenogest treatment has no effect on the levels of luteinizing hormone (LH) or progesterone, hormones that are known to be important in maintaining pregnancy. Furthermore, treatment does not influence the ease with which the mares became pregnant, nor does it affect the size of the vesicles housing the embryos, at least for the first 22 days after conception. However, the researchers did notice that at 20 days after conception the embryonic vesicles are smaller if the mares are older. They also found that the foetuses of older mares grow significantly more slowly after this period, although if the mares are treated with altrenogest their foetuses grow at the normal rate.

The smaller size of the foetuses in older mares provides a nice explanation for the higher rate of pregnancy losses as horses grow older. Smaller foetuses in these animals may result from a reduced quality of the eggs as the horses age, making the mares more susceptible to miscarriage. Encouragingly, treatment with altrenogest appeared to enable the smaller foetuses to recover and to grow at a normal rate during the second crucial period in the animals' development, when the embryonic organs are formed and the mare's placenta is generated (from 35 to 45 days after conception). It seems conceivable that altrenogest encourages the formation of the placenta.

The results show that altrenogest treatment does have an effect in reducing the risk of miscarriage in horses, although not the one that might have been expected. It does not seem able to prevent miscarriages in early pregnancy but instead to compensate for later problems in foetal development that are more frequently encountered as mares grow older. As Aurich says, We are now well used to the idea of a hormonal therapy in humans to prevent osteoporosis. Perhaps horses cold also benefit from the same type of treatment to help them avoid miscarriages.

The high price of sleep disorders

Fri, 17 Dec 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Danish sleep researchers at the University of Copenhagen and the Danish Institute for Health Services Research have examined the socio-economic consequences of the sleep disorder hypersomnia in one of the largest studies of its kind. The sleep disorder has far-reaching consequences for both the individual and society as a whole.

Hypersomnia is characterised by excessive tiredness during the day. Patients who suffer from the disorder are extremely sleepy and need to take a nap several times a day. This can occur both at work, during a meal, in the middle of a conversation or behind the steering wheel.

- Hypersomnia is often a symptom of sleep disorders such as narcolepsy, sleep apnoea, restless leg syndrome, violent snoring and/or obesity-related breathing difficulties, explains Professor of Clinical Neurophysiology Poul Jennum from the Center for Healthy Aging at the University of Copenhagen. The professor also leads the Danish Center for Sleep Medicine at Glostrup Hospital, which each year treats patients from across the country.

- Previous studies have indicated that these sleep disturbances affect people's quality of life to a considerable degree both socially and economically. Our studies show that people who e.g. snore violently but especially those who suffer from sleep apnoea, narcolepsy and obesity-related breathing difficulties use the health services more frequently, take more medicine, and are more frequently unemployed. The more serious the sleep disorder the higher the socio-economic cost.

Each person who snores violently, suffers from narcolepsy or hypersomnia is calculated to cost Danish society an annual figure of EURO 10,223 and EURO 2190 respectively. The figures refer to the direct cost of frequent doctor's visits, hospital admissions or medicine expenses and indirect costs in the form of lost working hours. In addition to this, costs are also incurred in the form of state benefits. The researchers demonstrated that hypersomnia patients received state benefits more often than healthy subjects and took state subsidised medicine more frequently. The study has highlighted the high costs that have arisen, especially those born by society and which is largely due to frequent absence from the work force and lower incomes among the sick.

Our study is the first to show the actual socio-economic consequences of untreated hypersomnia, explains Poul Jennum and refers to the fact that last year he and his colleagues carried out a similar study on the socio-economic consequences of the sleep disorder, narcolepsy. Here they also found an increase in the intake of medication, a higher rate of hospital admissions, and 30% more unemployment when the disease went undiagnosed and untreated. There is, however, significant potential for better diagnosis and treatment.

We have gotten better in the last few years at diagnosing and treating hypersomnia and the underlying diseases, explains Poul Jennum. This can be a help to patients because we know that there are a lot of people who go around incredibly tired during the day who do suffer from hypersomnia, but have never been diagnosed or discovered the reason for their tiredness. The question is whether their tiredness is owing to narcolepsy or is the fact that they sleep badly at night owing to some other reason?

It's clear to us that those who suffer from hypersomnia are more often ill and where hypersomnia is chronic, the economic costs to society can be quite considerable. That's why it is essential that people with the disorder have access to a system of treatment - otherwise the illness can affect their education, ability to work and thus their economic circumstances and health.

In the lab, engineer's novel liquid provides a solid fix for broken bones

Tue, 07 Dec 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Here's the vision: an elderly woman comes into the emergency room after a fall. She has broken her hip. The orthopaedic surgeon doesn't come with metal plates or screws or shiny titanium ball joints. Instead, she pulls out a syringe filled with a new kind of liquid that will solidify in seconds and injects into the break. Over time, new bone tissue will take its place, encouraged by natural growth factors embedded in the synthetic molecules of the material.

Although still early in its development, the liquid is real. In the Brown engineering lab of professor Thomas Webster it's called TBL, for the novel DNA-like twin-base linker molecules that give it seemingly ideal properties. The biotech company Audax Medical Inc., based in Littleton, Mass., announced on Dec. 7 an exclusive license of the technology from Brown. It brands the technology as Arxis and sees similar potential for repairing broken vertebrae.

The reason we're excited about this material is because it gets us away from metals, Webster said. Metals are not in us naturally and they can have a lot of problems with surrounding tissues.

In some of his work, Webster employs nanotechnology to try to bridge metals to bone better than traditional bone cement. But TBL is an entirely new material, co-developed with longtime colleague and chemist Hicham Fenniri at the University of Alberta. Fenniri synthesized the molecules, while Webster's research has focused on ensuring that TBL becomes viable material for medical use.

The molecules are artificial, but made from elements that are no strangers to the body: carbon, nitrogen, and oxygen. At room temperature their aggregate form is a liquid, but the material they form solidifies at body temperature. The molecules look like nanoscale tubes (billionths of a meter wide), and when they come together, it is in a spiraling ladder-shaped arrangement reminiscent of DNA or collagen. That natural structure makes it easy to integrate with bone tissue.

In the space within the nanotubes, the team, which includes graduate student Linlin Sun, has managed to stuff in various drugs including antibiotics, anti-inflammatory agents, and bone growth factors, which the tubes release over the course of months. Even better, different recipes of TBL, or Arxis, can be chemically tuned to become as hard as bone or as soft as cartilage, and can solidify in seconds or minutes, as needed. Once it is injected, nothing else is needed.

We really like the fact that it doesn't need anything other than temperature to solidify, Webster said. Other compounds that people have developed require exposure to ultraviolet light and cannot therefore be injected through a tiny syringe hole. They require larger openings to be created.

For all of TBL's apparent benefits, they have only been demonstrated in cow bone fragments in incubators on the lab bench top, Webster said. TBL still needs to be proven in vivo and, ultimately, in human trials. Part of the agreement with Audax will include support to continue the material's clinical development. Audax research and development director Whitney Sharp, a Brown alumna (Sc.B., 2008; Sc.M., 2009), is now working with Webster's group.

They see the future where hopefully we will get to the point where we won't be implanting these huge pieces of metal into people, Webster said. Instead we'll be implanting things through a needle that could be used to heal a hip that's more natural.

Falling in love 'more scientific than you think,' according to Syracuse University professor

Fri, 22 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A new meta-analysis study, The Neuroimaging of Love, conducted by Syracuse University Professor Stephanie Ortigue, reveals that falling in love can elicit not only the same euphoric feeling as using cocaine, but also affects intellectual areas of the brain. Researchers also found falling in love only takes about a fifth of a second.

Ortigue is an assistant professor of psychology and an adjunct assistant professor of neurology, both in The College of Arts and Sciences at Syracuse University.

Results from Ortigue's team revealed when a person falls in love, 12 areas of the brain work in tandem to release euphoria-inducing chemicals such as dopamine, oxytocin, adrenaline and vasopression. The love feeling also affects sophisticated cognitive functions, such as mental representation, metaphors and body image.

The findings beg the question, Does the heart fall in love, or the brain?

That's a tricky question always, says Ortigue. I would say the brain, but the heart is also related because the complex concept of love is formed by both bottom-up and top-down processes from the brain to the heart and vice versa. For instance, activation in some parts of the brain can generate stimulations to the heart, butterflies in the stomach. Some symptoms we sometimes feel as a manifestation of the heart may sometimes be coming from the brain.

Other researchers also found blood levels of nerve growth factor, or NGF, also increased. Those levels were significantly higher in couples who had just fallen in love. This molecule involved plays an important role in the social chemistry of humans, or the phenomenon 'love at first sight.' These results confirm love has a scientific basis, says Ortigue.

The findings have major implications for neuroscience and mental health research because when love doesn't work out, it can be a significant cause of emotional stress and depression. It's another probe into the brain and into the mind of a patient, says Ortigue. By understanding why they fall in love and why they are so heartbroken, they can use new therapies. By identifying the parts of the brain stimulated by love, doctors and therapists can better understand the pains of love-sick patients.

The study also shows different parts of the brain fall for love. For example, unconditional love, such as that between a mother and a child, is sparked by the common and different brain areas, including the middle of the brain. Passionate love is sparked by the reward part of the brain, and also associative cognitive brain areas that have higher-order cognitive functions, such as body image.

Ortigue and her team worked with a team from West Virginia University and a university hospital in Switzerland. The results of the study are published in the

New discovery may help to identify the healthiest embryos in IVF treatment

Mon, 11 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Australian scientists have developed a potentially groundbreaking new measure of the health of an embryo and the likelihood of a successful pregnancy in IVF treatment.

The research could lead to significantly improved birth rates in IVF to help the one in six Australian couples experiencing infertility to achieve their dream of parenthood.

It also has the potential to predict the gender of an embryo prior to implantation.

The research by the University of Melbourne and Repromed was presented this week at the Fertility Society of Australia annual scientific meeting at the Adelaide Convention Centre.

Professor David Gardner, Head of the Department of Zoology at the University of Melbourne, said the study related specifically to the glucose intake of embryos from the solution in which they grow in the laboratory.

IVF units use this solution, or media as it is known, to provide a bed of nutrients for embryos fertilised in the laboratory from the eggs and sperm of couples who cannot naturally conceive. The glucose in embryo solution closely matches that which occurs naturally in the uterus.

Professor Gardner said fertility specialists knew the precise amount of glucose in the solution before inserting an embryo.

By measuring the level of glucose on day four or five after fertilisation, we can determine how much has been consumed by a growing embryo, he explained. There is clear cut evidence that the greater the glucose intake the healthier the embryo.

On average, IVF units generate between eight and ten embryos per cycle, of which about half will progress through cell division to what is known as the blastocyst stage after four to five days.

By measuring the glucose consumption of an embryo, we can better determine which is the healthiest embryo for transfer back to the patient.

The research involved 50 patients undergoing IVF. Thirty-two of the women had a positive pregnancy test after embryo transfer and 28 babies were born.

The 28 babies resulted from the embryos which had the highest glucose uptake, Professor Gardner said.

Previous studies with animals have shown that the healthiest blastocysts are those with the greatest glucose consumption indicating the likelihood of a successful pregnancy.

It is exciting to find that this process appears to be the same in people knowing that the glucose in embryo culture media is a major energy source for cell division and is required for biosynthesis to enable cell replication.

Professor Gardner said another potentially exciting aspect of the research was that female embryos appeared to take up more glucose than male embryos.

This is a very early observation, but it may have the potential to help identify gender at early embryo stage, he said.

Northwestern first site open for spinal cord stem cell trial

Wed, 22 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO --- Northwestern Medicine is the first site open for enrollment in a national clinical research trial of a human embryonic stem cell-based therapy for participants with a subacute thoracic spinal cord injury. Following the procedure, participants will receive rehabilitation treatment at The Rehabilitation Institute of Chicago (RIC).

Northwestern also is the lead site of the trial, sponsored by Geron Corporation (Nasdaq: GERN). The trial eventually will include up to six other sites and enroll up to 10 participants nationally.

We are very pleased to be the first participating center in the world's first human embryonic stem cell clinical trial for spinal cord injury, said lead national investigator Richard Fessler, M.D., professor of neurological surgery at Northwestern University Feinberg School of Medicine and a surgeon at Northwestern Memorial Hospital.

Injection of oligodendrocyte progenitor cells directly into the spinal cord lesion is a rational way to attempt to arrest or reverse the structural damage in the spinal cord caused by severe trauma, Fessler said. We are eager to begin evaluating the effects of these cells in subjects with severe spinal cord injuries.

RIC is a vital member of the research team for this novel stem cell clinical trial, said David Chen, M.D., medical director of the RIC Spinal Cord Injury Rehabilitation Program. RIC's team of spinal cord injury rehabilitation specialists is responsible for customizing the rehabilitation care plan and therapeutic intervention for each participant, which may include robotic walking therapy and other procedures to facilitate the participant's neurologic repair and recovery. At RIC, restoring the participant's ability is our objective and the scientific application of embryonic stem cells offers new hope for recovery.

The primary objective of the phase I trial is to assess the safety and tolerability of special cells called human embryonic stem cell-derived oligodendrocyte progenitor cells when they are injected into the spinal cord injury of paralyzed subjects. The injuries have to have occurred within two weeks for someone to be eligible for the procedure.

In addition to evaluating safety, the secondary aim of the trial is to see if the stem cells improve neuromuscular control or sensation in the trunk or lower extremities.

In previous animal studies, these stem cells have demonstrated the ability to remyelinate or recoat damaged nerve cells that have lost their ability to conduct electrical impulses down the axon. The stem cells also have shown nerve-growth stimulating properties leading to restoration of function in animal models of acute spinal cord injury.

The trial is supported by positive animal research, Fessler said. He noted the trial is using the lowest dose possible for a human based on the animal studies.

Subjects eligible for the Phase I trial will have documented evidence of functionally complete (ASIA Impairment Scale grade A) spinal cord injury with a neurological level of T3 to T10 spinal segments and agree to have GRNOPC1 injected into the lesion sites between 7 and 14 days after injury.

Brain cells determine obesity -- not lack of willpower: Study

Wed, 08 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) An international study has discovered the reason why some people who eat a high-fat diet remain slim, yet others pile on the weight.

The study, led in Australia by the Monash Obesity and Diabetes Institute (MODI) at Monash University, found a high-fat diet causes brain cells to become insulated from the body preventing vital signals, which tell the body to stop eating and to burn energy, from reaching the brain efficiently.

MODI director and Australian Life Scientist of the Year Professor Michael Cowley said there were two clear outcomes from the findings.

'We discovered that a high-fat diet caused brain cells to become insulated from the body, rendering the cells unable to detect signals of fullness to stop eating, Professor Cowley said.

Secondly, the insulation also created a further complication in that the body was unable to detect signals to increase energy use and burn off calories/kilojoules.

The research showed that support cells in the brain developed overgrowth in a high-fat diet. This prevented the regular brain cells (the melanocortin system or POMC neurons) from connecting with other neural mechanisms, which determine appetite and energy expenditure.

Professor Cowley said the study findings provide a critical link in addressing the obesity epidemic.

These neuronal circuits regulate eating behaviours and energy expenditure and are a naturally occurring process in the brain. The circuits begin to form early in life so that people may have a tendency towards obesity even before they eat their first meal, Professor Cowley said.

Eating a high fat diet causes more insulation in the nerve cells, and makes it even harder for the brain to help a person lose weight.

Obese people are not necessarily lacking willpower. Their brains do not know how full or how much fat they have stored, so the brain does not tell the body to stop refuelling. Subsequently, their body's ability to lose weight is significantly reduced.

Professor Cowley and fellow MODI researcher Dr Pablo Enriori collaborated with Research Chair and Professor of Comparative Medicine and Professor of Neurobiology Tamas Horvath and his team at the Yale School of Medicine in the United States, together with teams of scientists in Cincinnati, New Jersey, Mexico and Spain.

For a period of four months, the researchers monitored the eating and body composition of groups of mice and rats and found that those with a neural predisposition to obesity gained 30 per cent more weight compared to six per cent of the group with obesity-resistant cells.

K-state researchers explore physiological effects of space travel with NASA grant

Mon, 23 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) MANHATTAN, KAN. -- The final frontier may be no further than Manhattan, Kan., as a team of Kansas State University researchers launches a project funded by a $1.2 million grant from the National Aeronautics and Space Administration.

The team -- composed of Thomas Barstow, professor of kinesiology; Steven Warren, associate professor of electrical and computer engineering; Russell Taylor, an engineer in the Electronics Design Laboratory; and Carl Ade, a doctoral student in anatomy and physiology, Salina -- will research what physical characteristics are necessary for an astronaut to perform lunar tasks. The team also will study ways to assess whether a person has enough physical capacity to perform the tasks.

Space travel is inherently dangerous, Barstow said. The absence of gravity, which we call microgravity or zero gravity, causes our bodies to deteriorate in a variety of ways.

A microgravity environment causes the weakening of muscles and the immune system, and it deteriorates the cardiovascular system's ability to regulate blood pressure. Barstow said this can affect an astronaut's ability to perform necessary tasks, such as climbing ladders, walking or opening doors. For the safety of the astronauts, NASA wants to make sure they are physically fit enough to perform those tasks during future missions to the moon and even Mars.

What seems like simple tasks as part of their life on the moon or other destinations could be life threatening if the astronauts aren't strong enough to do those tasks, Barstow said.

The goal of the research, Barstow said, is to develop a simple test or a series of tests that astronauts can use in space to identify their physical conditioning and to determine if they have the capacity to perform lunar tasks.

Each year of the three-year project will focus on a different aspect of space travel. In the first year the researchers will recruit 100 people to undergo an obstacle course of tasks that NASA has identified as simulating lunar activities -- including dragging a dummy, climbing up and down ladders, pushing a wheelbarrow of rocks, and walking for 10 km. The participants also will perform physical fitness tests, such as running on a treadmill and arm exercises. Warren is developing sensors that the participants can wear to measure muscle activity and the oxygen circulating to them while performing the tasks.

We're hoping to get a fairly complete description of each person's muscle strength, muscle endurance and cardiovascular endurance, so that with the results of those tests, we then can predict their performances during the simulated lunar tasks, Barstow said.

For the second year Warren and Taylor plan to develop a support system that can simulate different levels of gravity. The systems works by suspending the participant like a marionette -- with cables that are attached to a platform and can be adjusted to simulate the moon's gravity or gravity on mars. The system is hung from a forklift, or telehandler, so that it can move across a terrain while the subject traverses a simulated moonscape.

The third year researchers plan to observe participants performing the lunar tasks in space suits. Since the moon's gravity is one-sixth that of earth and Mars' gravity is three-eighths of the earth's, it will make some of the tasks easier than performing them on earth. But, Barstow said, the pressurized space suits that astronauts wear could make the tasks more difficult, especially tasks that require using hands to grip objects. The researchers also plan to develop special physical tests just for the arms and forearms.

At the end of the three years the researchers hope to continue working with NASA to develop countermeasures, or ways the astronauts can maintain strength and endurance in space.

Barstow said the project also creates research opportunities for kinesiology students, and he is looking for 15 to 20 students to help with research. The researchers are also looking for 100 people to participate in the study and for a building to perform the tests sheltered from the weather.

Proof that a gut-wrenching complaint -- irritable bowel syndrome -- is not in your head

Thu, 19 Aug 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Irritable bowel syndrome makes life miserable for those affected -- an estimated ten percent or more of the population. And what irritates many of them even more is that they often are labeled as hypochondriacs, since physical causes for irritable bowel syndrome have never been identified. Now, biologists at the Technische Universitaet Muenchen (TUM) have shed new light on the matter: They have discovered mini-inflammations in the mucosa of the gut, which upset the sensitive balance of the bowel and are accompanied by sensitization of the enteric nervous system.

Flatulence, constipation and diarrhea, nausea and stomach cramps: Irritable bowel syndrome (IBS) can turn digestion into a nightmare. Frequent visits to the bathroom are often accompanied by sleep disturbances, headaches, and backaches. In Germany alone, some seven million people are affected by the disorder -- and by the fact that their irritable bowel syndrome is often deemed psychosomatic. This is because the organic trigger of the disease has never been discovered, and consequently the various therapeutic interventions are disappointing for both the patients and their doctors. That may soon change, however, because now, for the first time, biologists in Munich have nailed down hidden physical causes of this bowel disorder.

Professor Michael Schemann's research team at the TUM Department for Human Biology has managed to demonstrate that micro-inflammations of the mucosa cause sensitization of the enteric nervous system, thereby causing irritable bowel syndrome. Using ultrafast optical measuring methods, the researchers were able to demonstrate that mediators from mast cells and enterochromaffin cells directly activate the nerve cells in the bowel. This hypersensitivity of the enteric nervous system upsets communication between the gut's mucosa and its nervous system, as project leader Prof. Schemann explains: The irritated mucosa releases increased amounts of neuroactive substances such as serotonin, histamine and protease. This cocktail produced by the body could be the real cause of the unpleasant IBS complaints.

The TUM researchers in human biology are blazing a trail as they follow this lead. Their current focus is to what extent nerve sensitization correlates with the severity of symptoms. Working with colleagues from Amsterdam, they have already substantiated the clinical relevance of their results: Irritable bowel symptoms improved after treatment with an antihistamine known for its immune-stabilizing effect in the treatment of allergic reactions such as hay fever. Thanks to funding from the German Research Foundation (DFG), the scientists are now investigating whether the improved symptoms are accompanied by a normalization of nerve activity.

Successful identification of the active components could enable the development of effective drugs to treat irritable bowel syndrome. Even now, though, the TUM team have made life easier for many IBS patients, in that they have shown that the chronic disorder does have physical causes and is not merely in their heads.

Tibetan adaptation to high altitude occurred in less than 3,000 years

Thu, 01 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A comparison of the genomes of 50 Tibetans and 40 Han Chinese shows that ethnic Tibetans split off from the Han less than 3,000 years ago and since then rapidly evolved a unique ability to thrive at high altitudes and low oxygen levels.

The genome-wide comparison, performed by evolutionary biologists at the University of California, Berkeley, uncovered more than 30 genes with DNA mutations that have become more prevalent in Tibetans than Han Chinese, nearly half of which are related to how the body uses oxygen. One mutation in particular spread from fewer than 10 percent of the Han Chinese to nearly 90 percent of all Tibetans.

This is the fastest genetic change ever observed in humans, said Rasmus Nielsen, UC Berkeley professor of integrative biology, who led the statistical analysis. For such a very strong change, a lot of people would have had to die simply due to the fact that they had the wrong version of a gene.

The widespread mutation in Tibetans is near a gene called EPAS1, a so-called super athlete gene identified several years ago and named because some variants of the gene are associated with improved athletic performance, Nielsen said. The gene codes for a protein involved in sensing oxygen levels and perhaps balancing aerobic and anaerobic metabolism.

The new findings could steer scientists to till-now unknown genes that play a role in how the body deals with decreased oxygen, and perhaps explain some diseases, including schizophrenia and epilepsy, associated with oxygen deprivation in the womb, he said.

Nielsen and his colleagues in China and Europe report their findings in the July 2 issue of the journal Science.

Nielsen, a computational evolutionary biologist, mines genomic information to discover genetic changes driven by natural selection as humans and animals have adapted to new environments. Changes in the frequency of DNA mutations are one clue.

You look for rapid evolution in genes because there must be something important about that gene forcing it to change so fast, he said. The new finding is really the first time evolutionary information alone has helped us pinpoint an important function of a gene in humans.

Adaptation to low oxygen levels has allowed many peoples, from Andeans to Tibetans, to live at high altitude. When people from lower elevations move above about 13,000 feet, where oxygen levels are about 40 percent lower than at sea level, they typically tire easily, develop headaches, produce babies with lower birth weights and have a higher infant mortality rate. Tibetans have none of these problems, despite lower oxygen saturation in the blood and lower hemoglobin levels. Hemoglobin, which gives blood its red color, binds and transports oxygen to the body's tissues.

Nielsen used genome data produced by the Beijing Genomics Institute (BGI) in Shenzhen, China's flagship genome center, to tease out the genetic changes associated with these physiological changes.

We're looking for footprints of past selection to find something functional in our genome, Nielsen said

BGI researchers obtained DNA from 50 Tibetans living in the Tibet Autonomous Region of China and 40 Han Chinese from Beijing. The Tibetans lived in two villages located at elevations of 4,300 meters (14,100 feet) and 4,600 meters (15,100 feet). All reported at least three generations of ancestors had lived at the same site. After obtaining informed consent, the Chinese researchers took blood samples from the participants and measured oxygen saturation, red blood cell concentration and hemoglobin content in their blood.

Back in the lab, the BGI team isolated only the active genes, or exons, from each individual, then used next-generation sequencing technology to sequence these so-called exomes. This involved cutting the DNA into many short pieces, sequencing each about 18 times with state-of-the-art Illumina sequencing machines, and then using overlaps to help reassemble the complete genome of each person. That work was directed by Jun Wang of BGI and the University of Copenhagen in Denmark.

Nielsen and post-doctoral fellows John E. Pool, Emilia-Huerta Sanchez and Nicolas Vinckenbosch conducted the analysis at UC Berkeley, locating all point mutations, called single-nucleotide polymorphisms (SNPs), in the 90 genomes and then comparing Tibetan and Han separately to a control group of 100 Europeans (Danes).

The analysis revealed that the common ancestors of Tibetans and Han Chinese split into two populations about 2,750 years ago, with the larger group moving to the Tibetan plateau. That group eventually shrank, while the low-elevation Han population expanded dramatically. Today, the Han Chinese are the dominant ethnic group in mainland China. The Tibetan branch either merged with the people's already occupying the Tibetan plateau, or replaced them.

We can't distinguish intermixing and replacement, Nielsen said. The Han Chinese and Tibetans are as different from one another as if the Han completely replaced the Tibetans about 3,000 years ago.

The Tibetan and Han Chinese genomes are essentially identical in terms of the frequency of polymorphisms in the roughly 20,000 genes, though some 30 genes stood out because of dramatic differences between the Tibetans and the Han.

We made a list of the genes that changed the most, Nielsen said, and what was fascinating was that, bing!, at the top of that list was a gene that had changed very strongly, and it was related to the response to oxygen.

The SNP with the most dramatic change in frequency, from 9 percent in Han Chinese to 87 percent in Tibetans, was associated with lower red blood cell count and lower hemoglobin levels in Tibetans. That variation occurred near a gene called EPAS1, which earlier studies suggest is involved in regulating hemoglobin in the blood as a response to oxygen levels. The mutation may be in a transcription factor that regulates the activity of EPAS1.

Tibetans carrying only one allele with this mutation had about the same hemoglobin concentration as Han Chinese, but those with two mutated alleles had significantly lower hemoglobin concentration. However, they all have about the same oxygen concentration in the blood. For some reason, individuals with two copies of the mutation function well in high altitude with relatively low hemoglobin concentration in their blood. The mutation seems to provide an alternative inborn mechanism for dealing with the low oxygen levels, Nielsen said.

Other strongly selected variants were near the genes for the fetal and adult versions of the globin genes, which produce the structural proteins of hemoglobin.

Two other genes showing a dramatic shift in frequency have been linked to anemia, while several other genes have been linked to diseases, including schizophrenia and epilepsy, possibly caused by low oxygen levels in the womb.

A*STAR scientist receives international award for innovation in healthcare technology

Mon, 21 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Physicist David William Townsend will be honoured with the prestigious 2010 IEEE Medal for Innovations in Healthcare Technology for the design, commercial development and clinical implementation of the PET/CT scanner. Prof Townsend will receive the medal jointly with his co-inventor, engineer Ronald Nutt, on 26 June 2010 at the IEEE Honors Ceremony in Montreal, Quebec, Canada. IEEE is the world's largest professional association advancing technology for humanity.

Heralded as Medical Invention of the Year in 2000 by TIME magazine, the PET/CT scanner revolutionised diagnostic medical imaging by enabling cancer tumours to be detected faster and more accurately, for diagnosis as well as staging and during treatment. The hybrid PET/CT scanner works by ingeniously combining the anatomical information offered by CT imaging with the high contrast of PET tumour imaging in a single examination. This enables the two sets of images to be more precisely registered as there is no changing of the patient's position between the two types of scans. Previously, patients had to take two separate PET and CT examinations, preventing accurate alignment of the images and limiting the quality of disease assessment. Since its commercial introduction in 2001, the PET/CT technology has been widely adopted by the medical profession. Over 95% of all PET scanners sold in 2004 were PET/CT scanners. By 2006, practically all stand-alone PET scanner purchases were replaced by PET/CT scanners.

Prof Townsend is currently head of PET and SPECT development at the Singapore Bioimaging Consortium (SBIC) under the Agency for Science, Technology and Research (A*STAR), and a Professor of Radiology at the Yong Loo Lin School of Medicine, National University of Singapore. He is leading his team to develop both single photon and positron-emitting radiotracers for pre-clinical imaging of disease.

Highly regarded as the world's leading authority on hybrid imaging systems, Prof Townsend conducted research on imaging systems at hospitals and institutes across the US and Europe for some 30 years before joining A*STAR in 2009. More information on Prof Townsend can be found at the Annex.

Said A*STAR Chairman, Mr Lim Chuan Poh, The IEEE medal gives due recognition to David's significant achievements and outstanding contributions to biomedical research and healthcare delivery. A*STAR is honoured to have him among our scientists. His multidisciplinary expertise and extensive experience make him a great asset in Singapore's push to develop itself into a translational and clinical research hub.

Added Chairman of SBIC, Prof Sir George Radda, David has contributed greatly to SBIC's plans to create an integrated platform for multidisciplinary research, and to become a focal point of interaction with the pharmaceutical and biotechnology industries. His winning of the IEEE medal is a nod to the widespread benefit his invention has brought, as well as an inspiration to our younger scientists. We are proud of him for his achievements.

Said Prof John Wong, Deputy Chief Executive of the National University Health System and Dean of the NUS Yong Loo Lin School of Medicine, David is one of the rare people who has changed the practice of medicine in his lifetime. The development of CT-PET scanning has revolutionised the practice of medicine, starting with the management of cancer and drug development. We are honoured to have someone of his stature on our faculty who is testimony to the power of bringing engineers, scientists, and clinicians together to develop better ways to diagnose and manage major diseases.

Hip exercises found effective at reducing, eliminating common knee pain in runners

Fri, 04 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A twice weekly hip strengthening regimen performed for six weeks proved surprisingly effective at reducing -- and in some cases eliminating -- knee pain referred to as patellofemoral pain (PFP) in female runners.

The study by Tracy Dierks, assistant professor in the Department of Physical Therapy at Indiana University-Purdue University Indianapolis, was based on the theory that stronger hips would correct running form errors that contribute to PFP, even though study participants were given no instruction in gait training. The study used a pain scale of 0 to 10, with 3 representing the onset of pain and 7 representing very strong pain -- the point at which the runners normally stop running because the pain is too great. The injured runners began the six-week trial registering pain of 7 when they ran on a treadmill and finished the study period registering pain levels of 2 or lower; i.e. no onset of pain.

I wasn't expecting such huge reductions, to be honest, Dierks said. We've had a couple of runners who have been at level 2, but the overwhelming majority have been a 2 or below.

PFP, one of the most common running injuries, is caused when the thigh bone rubs against the back of the knee cap. Runners with PFP typically do not feel pain when they begin running, but once the pain begins, it gets increasingly worse. Once they stop running, the pain goes away almost immediately. Dierks said studies indicate PFP essentially wears away cartilage and can have the same effect as osteoarthritis. His study participants showed many of the classic signs of PFP, the most prominent being their knees collapsing inward when running or doing a squat exercise move.

The pilot study thus far involved five runners and a control group that comprised another four runners. Hip strength measurements were taken before and after the runners in the control group maintained their normal running schedule for six weeks. Hip strength measurements were taken for all of the runners before and after the next six-week period in which they all performed the hip-strengthening exercises. The exercises, performed twice a week for around 30 to 45 minutes, involved single-leg squats and exercises with a resistance band, all exercises that can be performed at home. This study is part of an ongoing study involving hip exercises and PFP pain, with 11 runners successfully using the intervention. Dierks said he plans to seek funding to test the exercises on a larger group of runners.

Earlier research had focused on the feet as a possible root of PFP, with studies only recently looking more closely at the hips. Dierks said studies have found an association between PFP in women and weak hips, but his study is the first to test a possible treatment. He noted that PFP is considered multi-factorial, so his study is examining one of several possible causes of the pain.

Predicting risk for high blood pressure

Mon, 26 Apr 2010 04:00:00 PST

( from http://www.rxpgnews.com ) High blood pressure also called hypertension is a major health problem that when left untreated can lead to heart disease, stroke and kidney failure. African Americans are more likely to develop high blood pressure and develop it earlier in life than Caucasians. But the reasons for the heightened risk in African Americans still remained largely unknown, although new evidence may provide some insight.

Dr. TanYa Gwathmey from the Hypertension and Vascular Research Center of Wake Forest University Baptist Medical Center studies the factors that contribute to having high blood pressure, particularly in African Americans. Her group found that there are racial differences in the activity of enzymes that make or breakdown a major regulator of blood pressure. And her results correlate with the bias of African Americans being more at risk.

At the annual 2010 Experimental Biology conference in Anaheim, CA held April 24-28 (http://experimentalbiology.org/content/default.aspx), Gwathmey will be discussing these findings in her presentation titled Sex and Racial Background Influence Angiotensin Peptide Metabolism in Young Adults. The team of researchers that also contributed to this study includes Hossam Shaltout and Mark Chappell of the Hypertension and Vascular Research Center; James Rose of the Center for Perinatal Research; Lisa Washburn of the Department of Pediatrics from the Wake Forest University Baptist Medical Center; and Patricia Nixon of the Department of Health and Exercise Science of Wake Forest University, Winston-Salem, NC.

Two Peptides With Opposing FunctionBlood pressure is regulated by peptides (short strings of amino acids) called angiotensins. Specific forms of angiotensin affect blood pressure differently. Angiotensin II causes the body to retain salt and water and causes blood vessels to constrict; all characteristics that promote high blood pressure. On the other hand, angiotensin (1-7) has protective effects against high blood pressure by causing blood vessels to open up and allowing the body to release salt and water.

The enzyme ACE (angiotensin converting enzyme) makes the riskier angiotensin II. But angiotensin II can be converted to the protective angiotensin (1-7) by the enzyme ACE2. So someone with high ACE activity would make more angiotensin II and would be more at risk for high blood pressure. Alternatively, someone with higher ACE2 activity would make more angiotensin (1-7) and would not be as likely to develop high blood pressure.

High Risk Individuals Have Differences In Angiotensin Hormone MetabolismDuring adolescence, most individuals haven't developed high blood pressure yet. Gwathmey chose to study participants at age 15 to identify predicting factors of high blood pressure that may be present before the disease has set in. Gwathmey's study specifically examined African American boys and girls and Caucasian girls. All participants tested had normal blood pressure. Urine samples were collected from the participants and analyzed for levels of ACE and ACE2 enzymes as a read-out for the predominant form of angiotensin.

African American boys had higher ACE levels than both African American and Caucasian girls, meaning the African American boys may have higher levels of angiotensin II. Researchers also observed that African American girls had less ACE2 than Caucasian girls, meaning they may make less of the protective angiotensin (1-7) hormone. To put it more simply, African American boys have more of the enzyme that makes the hormone that contributes to high blood pressure and African American girls have less of the enzyme that makes the hormone that protects against high blood pressure or hypertension.

What is really interesting to me is that we are seeing changes in angiotensin metabolism before blood pressure changes, Gwathmey said. This could become a useful tool for predicting high pressure and potential therapeutic treatment before hypertension actually sets in.

Researchers are recruiting more participants to make this study more comprehensive. In the future studies, Gwathmey hopes to look at other contributors like obesity and certain dietary factors that may put African Americans at greater risk for high blood pressure than Caucasians.

We can't group all people into one category to assess the blood pressure system, said Gwathmey. If we look at a study without consideration of racial and/or gender influences, then we may be missing out on key information that may better help us to address this epidemic.

SSRIs and cardiovascular health

Mon, 26 Apr 2010 04:00:00 PST

( from http://www.rxpgnews.com ) A class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) may provide a boost to cardiovascular health by affecting the way platelets, small cells in the blood involved in clotting, clump together, say researchers at the Loyola University Medical Center in Maywood, Ill.

In a study of 50 adults, the researchers found that platelets were slower to clump together, or aggregate, in participants who were taking an SSRI to treat depression. As depression is associated with an increased risk of cardiovascular disease, this finding could indicate a beneficial side effect for people who take SSRIs to treat depression, said Evangelos Litinas, MD, Research Associate in the Center's Pathology Department. Dr. Litinas will present the team's research at the American Physiological Society's annual Experimental Biology 2010 conference being held in Anaheim, CA from April 24-28.

SSRIs and Platelet FunctionSSRIs function to modulate the effect of serotonin in the brain. Neurotransmitters, like serotonin, are messages sent across the gap called the synapse between nerve cells in the brain. The cell sending the message, called the pre-synaptic cell, releases serotonin into the synapse. The serotonin is taken in by the receiving, post-synaptic cell, or be taken back by the pre-synaptic cell.

In a depressed patient, the post-synaptic cell doesn't take in enough serotonin and the message gets lost. To treat the depression, SSRIs decrease the ability of the pre-synaptic cell to reuptake the serotonin, leaving the message in the synapse longer and giving the post-synaptic cell a better chance of receiving the serotonin.

However, this blocking activity of SSRIs may have an effect on other cells in the body that require serotonin uptake. Small cells called platelets, which are involved in blood clotting, absorb serotonin only once and use it for their activation in response to injury.

When a blood vessel is injured in a healthy patient, their platelets are exposed to proteins that normally reside beneath the endothelium, the thin layer of cells lining blood vessel walls. These proteins activate the platelets and prompt them to send out finger-like projections that grab onto each other. This also activates the clotting system so that a clot will form at the wound site. This kind of platelet activation also occurs when blood vessel walls become inflamed in atherosclerosis (hardening of the arteries).

Once activated, the platelets release the contents of small packages that they carry called delta granules. These packages contain calcium, various energy-containing molecules, and serotonin. When the delta granules are released by activated platelets, the serotonin and other molecules work in the injured area to amplify the coagulation response.

However, Dr. Litinas and his team believe that in depressed patients who have an associated risk of cardiovascular problems, the blocking activity of SSRIs may have a side-effect of preventing the serotonin uptake by platelets, making them less responsive to aggregation and may thereby improving the patients' cardiovascular health.

To test their hypothesis, the researchers recruited 50 volunteers, 25 who were healthy and were not taking antidepressant medications and 25 who were being treated for depression with an SSRI. The team collected blood samples from each volunteer at the beginning of the protocol and again at the study's fourth week and eighth week. After each round of blood-drawing, the team separated the blood into its components to obtain the platelet-rich plasma for study.

The researchers then treated all of the samples with platelet-activating substances and with saline, which does not activate platelets. They observed platelet activity and quantified the amount of aggregation in each sample by using an aggregometer, a machine that aims light into liquid samples. Cells that do not aggregate tend to prevent light from getting all the way through a sample to the other side, whereas cells that aggregate form large clusters that sink down out of the way, allowing the light to shine through.

When the platelets from healthy volunteers were treated with platelet-activating substances at the 4-week time point, 95% of the cells aggregated. In contrast, the platelets of participants taking an SSRI showed only 37% aggregation, indicating that the SSRI had somehow inhibited or changed the platelets' ability to clump together.

As the study progressed, the researchers noticed something peculiar: The platelets taken from SSRI-treated patients at the 8-week mark aggregated more than those drawn at the 4-week mark. This suggested that SSRIs have the greatest impact on preventing platelet activation early on in treatment. Dr. Litinas and his team believe this may be because the body takes several weeks to start modulating SSRIs in the body. The team has extended the study to include samples drawn at the 12-week mark. They will also conduct a study using another brand of SSRI.

The reason we're doing this is to better the lives of depressed patients, said Dr. Litinas. There is clear evidence that depressed patients have a higher risk of cardiovascular disease, and we want to eliminate that. Since depression can be treated with an SSRI, maybe the cardiovascular disease risk can also be decreased. We want our patients to live longer and happier lives, without depression or the risk of heart problems.

Dr. Litinas' colleagues for this study are Dr. Jawed Fareed and Dr. Omer Iqbal, both of whom are affiliated with the Department of Pathology, Loyola University Medical Center, Maywood, IL; and Erin Tobin, Dr. John Piletz, Dr. Edwin Meresh, and Dr. Angelos Halaris, all of the Department of Psychiatry, Loyola University Medical Center.

NYU dental professor Dr. Timothy Bromage selected to receive the 2010 Max Planck Research Award

Mon, 08 Mar 2010 05:00:00 PST

( from http://www.rxpgnews.com ) New York University College of Dentistry's Dr. Timothy Bromage has been selected to receive the 2010 Max Planck Research Award. Dr. Bromage will collaborate with Dr. Friedemann Schrenk of Frankfurt's Senckenberg Research Institute to research the microanatomical structure of bones and teeth, and the links between metabolic states, growth rates, life spans, and biological features such as sex and body size.

The award, given by the Max Planck Society and Alexander von Humboldt Foundation, includes a stipend of 750,000 Euros ($1.02 million USD). The 2010 award, given annually to two researchers, will be presented during the Annual Meeting of the Max Planck Society on June 17th in Hanover, Germany. This year's other recipient is psychologist Michael Tomasello, director of the Max Planck Institute for Evolutionary Anthropology in Leipzig.

In citing Dr. Bromage's qualifications for receiving the award, the selection committee noted that his research on the microanatomical structure of ancestral human teeth and bones has established the modern fields of human evolution growth, development, and life history -- the pace by which an organism grows. Moreover, noted the committee, his research has shown a relationship between bone and tooth microstructure and body size, metabolic rate, age, and other biological features.

Dr. Bromage, a professor of basic science and craniofacial biology and of biomaterials and biomimetics, was the first researcher to use biologically based principles of craniofacial development to reconstruct early hominid skulls. His computer-generated reconstruction of a 1.9 million-year-old skull originally discovered in Kenya in 1972 by renowned paleontologist and archeologist Richard Leakey showed that Homo rudolfensis, modern man's earliest-known close ancestor, looked more apelike than previously believed. Dr. Bromage's reconstruction had a surprisingly smaller brain and more distinctly protruding jaw than the reconstruction that Dr. Leakey assembled by hand, suggesting that early humans had features approaching those commonly associated with more apelike members of the hominid family living as long as four million years ago.

In human evolution fieldwork, Dr. Bromage's 1992 discovery of a 2.4-million-year-old jaw in Malawi unearthed the oldest known remains of the genus, Homo. The discovery, made in collaboration with Dr. Schrenk, director of Paleoanthropology at the Senckenberg Research Institute, marked the first time that scientists discovered an early human fossil outside of established early human sites in eastern and southern Africa.

In experimental biology approaches to human evolution research, Dr. Bromage discovered a new biological clock, or long-term rhythm, which controls many metabolic functions. Dr. Bromage discovered the new rhythm while observing incremental growth lines in tooth enamel, which appear much like the annual rings on a tree. He also observed a related pattern of incremental growth in skeletal bone tissue -- the first time such an incremental rhythm has ever been observed in bone. The findings suggest that the same biological rhythm that controls incremental tooth and bone growth also affects bone and body size and many metabolic processes, including heart and respiration rates.

In fact, Dr. Bromage said, the rhythm affects an organism's overall pace of life, and its life span. So, a rat that grows teeth and bone in one-eighth the time of a human also lives faster and dies younger.

Dr. Bromage has fundamentally altered the field of human evolution by prompting paradigm shifts in morphology, fieldwork, and experimental biology, thereby establishing the modern field of growth, development, and life history in paleoanthropology, said Dr. Charles N. Bertolami, dean of the NYU College of Dentistry.

A portion of the award will be dedicated to training junior scientists in the United States and Germany to assist on this research. Dr. Bromage has been honored for his academic achievements by the National Science Foundation (2009, 2007), the National Geographic Society (2008), and the National Institute of Health.

Babies and sleep: Another reason to love naps

Sun, 21 Feb 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Anyone who grew up in a large family likely remembers hearing Don't wake the baby. While it reinforces the message to older kids to keep it down, research shows that sleep also is an important part of how infants learn more about their new world.

Rebecca Gomez, Richard Bootzin and Lynn Nadel in the psychology department at the University of Arizona in Tucson found that babies who are able to get in a little daytime nap are more likely to exhibit an advanced level of learning known as abstraction.

Nadel, a Regents' Professor at the UA, will describe the group's work (Early Learning in Infants May Depend on Sleep) in a session at the American Association for the Advancement of Science annual meeting in San Diego on Sunday, Feb. 21, starting at 8:30 a.m., Pacific time.

In their research, Nadel and his colleagues played recordings of phrases created from an artificial language to four dozen 15-month-old infants during a learning session. Their methodology included repeatedly playing phrases like pel-wadim-jic until the babies became familiar with them.

These phrases contained three units, with the first and last unit forming a relationship. In this example, the first word, pel, predicts the last, jic. Even though these are nonsensical sounds, the language created for the test shares some similarity with structure commonly found in subject-verb agreement in English sentences.

Prior to being tested, some infants learning this faux language took their normally scheduled naps. Others were scheduled at a time when they would not nap following the session. When the infants returned to the lab, they again heard the recordings - along with a set of different phrases in which the predictive relationship between the first and last words were new.

By carefully watching the babies' facial expressions as they listened to both old and new phrases, the researchers were able to rate their level of attention. They found that babies' longer gazes at a flashing light that coincided with the phrases signaled attention, which indicated that they had learned a particular phrase or relationship.

Differences arose between the infants who had napped and those who had not. The infants who did not sleep after the sessions still recognized the phrases they had learned earlier. But those babies who had slept in between sessions were able to generalize their knowledge of sentence structure to draw predictive relationships to the new phrases. This suggests that napping supports abstract learning - that is, the ability to detect a general pattern contained in new information.

In follow-up work, the UA researchers have shown that infants must have their naps within four hours of listening to the artificial language in order for them to demonstrate this beneficial abstraction effect. Those who failed to nap within that time, but slept normally that evening, failed to show the abstraction effect the next day.

It's a fairly nuanced story, Nadel said. What we know is that infants have mostly REM sleep, given the type of sleep they have, given how their brains are developed at that point. And they have to get some of that sleep within a reasonable amount of time after inputting information in order to be able to do abstracting work on it. If they don't sleep within four to eight hours, they probably just lose the entire thing, he said.

What this should reinforce for parents, he said, is that while it obviously is important to give infants and young children the kind of stimulation that comes from reading, talking and exposing them to lots of words, thise stimuli need to happen within the context of a reasonably well-regulated daily cycle that includes adequate sleep.

Neuroscientist: Think twice about cutting music in schools

Sat, 20 Feb 2010 05:00:00 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- At an 11 a.m. press briefing, Saturday, Feb. 20, at the American Association for the Advancement of Science annual meeting, a Northwestern University neuroscientist will argue that music training has profound effects that shape the sensory system and should be a mainstay of K-12 education.

Playing an instrument may help youngsters better process speech in noisy classrooms and more accurately interpret the nuances of language that are conveyed by subtle changes in the human voice, says Nina Kraus, Hugh Knowles Professor of Neurobiology, Physiology and Communication Sciences at Northwestern University.

Cash-strapped school districts are making a mistake when they cut music from the K-12 curriculum, says Kraus, director of the Auditory Neuroscience Laboratory in Northwestern's School of Communication.

Kraus will present her own research and the research of other neuroscientists suggesting music education can be an effective strategy in helping typically developing children as well as children with developmental dyslexia or autism more accurately encode speech.

People's hearing systems are fine-tuned by the experiences they've had with sound throughout their lives, says Kraus. Music training is not only beneficial for processing music stimuli. We've found that years of music training may also improve how sounds are processed for language and emotion.

Researchers in the Kraus lab provided the first concrete evidence that playing a musical instrument significantly enhances the brainstem's sensitivity to speech sounds. The findings are consistent with other studies they have conducted revealing that anomalies in brainstem sound encoding in some learning disabled children can be improved with auditory training.

The Kraus lab has a unique approach for demonstrating how the nervous system responds to the acoustic properties of speech and music sounds with sub-millisecond precision. The fidelity with which they can access the transformation of the sound waves into brain waves in individual people is a powerful new development.

The neural enhancements seen in individuals with musical training is not just an amplifying or volume knob effect, says Kraus. Individuals with music training show a selective fine-tuning of relevant aspects of auditory signals.

By comparing brain responses to predictable versus variable sound sequences, Kraus and her colleagues found that an effective or well-tuned sensory system takes advantage of stimulus regularities, such as the sound patterns that distinguish a teacher's voice from competing sounds in a noisy classroom.

They previously found that the ability of the nervous system to utilize acoustic patterns correlates with reading ability and the ability to hear speech in noise. Now they have discovered that the effectiveness of the nervous system to utilize sound patterns is linked to musical ability.

Playing music engages the ability to extract relevant patterns, such as the sound of one's own instrument, harmonies and rhythms, from the 'soundscape,' Kraus says. Not surprisingly, musicians' nervous systems are more effective at utilizing the patterns in music and speech alike.

Studies in Kraus' laboratory indicate that music -- a high-order cognitive process -- affects automatic processing that occurs early in the processing stream. The brainstem, an evolutionarily ancient part of the brain, is modified by our experience with sound, says Kraus. Now we know that music can fundamentally shape our subcortical sensory circuitry in ways that may enhance everyday tasks, including reading and listening in noise.

At 3:30 p.m., Saturday, Feb. 20, Kraus will present Cognitive-Sensory Interaction in the Neural Encoding of Music and Speech as part of a panel on music-language interactions in the brain at the annual meeting of the American Association for the Advancement of Science.

Antioxidants aren't always good for you and can impair muscle function, study shows

Tue, 26 Jan 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Antioxidants increasingly have been praised for their benefits against disease and aging, but recent studies at Kansas State University show that they also can cause harm.

Researchers in K-State's Cardiorespiratory Exercise Laboratory have been studying how to improve oxygen delivery to the skeletal muscle during physical activity by using antioxidants, which are nutrients in foods that can prevent or slow the oxidative damage to the body. Their findings show that sometimes antioxidants can impair muscle function.

Antioxidant is one of those buzz words right now, said Steven Copp, a doctoral student in anatomy and physiology from Manhattan and a researcher in the lab. Walking around grocery stores you see things advertised that are loaded with antioxidants. I think what a lot of people don't realize is that the antioxidant and pro-oxidant balance is really delicate. One of the things we've seen in our research is that you can't just give a larger dose of antioxidants and presume that there will be some sort of beneficial effect. In fact, you can actually make a problem worse.

David C. Poole and Timothy I. Musch, K-State professors from both the departments of kinesiology and anatomy and physiology, direct the Cardiorespiratory Exercise Laboratory, located in the College of Veterinary Medicine complex. Researchers in the lab study the physiology of physical activity in health and disease through animal models. Copp and Daniel Hirai, an anatomy and physiology doctoral student from Manhattan working in the lab, have conducted various studies associated with how muscles control blood flow and the effects of different doses and types of antioxidants.

Abnormalities in the circulatory system, such as those that result from aging or a disease like chronic heart failure, can impair oxygen delivery to the skeletal muscle and increase fatigability during physical activity, Copp said. The researchers are studying the effects antioxidants could have in the process.

If you have a person trying to recover from a heart attack and you put them in cardiac rehab, when they walk ona treadmill they might say it's difficult, Poole said. Their muscles get sore and stiff. We try to understand why the blood cells aren't flowing properly and why they can't get oxygen to the muscles, as happens in healthy individuals.

Copp said there is a potential for antioxidants to reverse or partially reverse some of those changes that result from aging or disease. However, K-State's studies have shown that some of the oxidants in our body, such as hydrogen peroxide, are helpful to increase blood flow.

New genetic variants for COPD discovered in a groundbreaking study by SpiroMeta Consortium

Tue, 15 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Scientists have discovered five genetic variants that are associated with the health of the human lung. The research by an international consortium of 96 scientists from 63 centres in Europe and Australia sheds new light on the molecular basis of lung diseases.

The research, part-funded by the Medical Research Council (MRC) and Asthma UK, is published today in Nature Genetics. It represents a significant advance because it is the first time that these five common genetic variations have been definitely linked with lung function.

The new findings provide hope for better treatment for lung diseases like Chronic Obstructive Pulmonary Disease (COPD) and asthma. In the past it has been difficult to develop new treatments because the molecular pathways that affect the health of the lung are not completely understood. It's hoped the new pathways discovered could in the future be targeted by drugs.

The ground-breaking research involved a genetic study of 2.5 million sites across the human genome involving samples from 20,000 people across the world. The consortium was led by Dr Martin Tobin from the University of Leicester and Professor Ian Hall from The University of Nottingham.

Lung function is commonly expressed using two measures recorded using a simple device called a spirometer. These measures are termed the FEV1 (or forced expiratory volume in 1 second) which is the volume of air that can be breathed out in 1 second, and the FVC (forced vital capacity) which is the total volume of air that can be breathed out. In chronic obstructive pulmonary disease (COPD), which encompasses chronic bronchitis and emphysema, narrowing of the airways causes a disproportionate reduction in FEV1. Cough, phlegm and shortness of breath are common symptoms of COPD. The simplest way to diagnose COPD is through spirometry, which is usually available in general practitioners' surgeries. Although there is no cure for COPD, stopping smoking and treatments can improve symptoms and reduce the impact of COPD on exercise and daily activities. Drug treatments include bronchodilators and, for exacerbations, may include short-term steroids. Patients with COPD are more susceptible to serious lung infections, so flu vaccination each winter is important.

The genetic determinants of COPD can be studied by investigating the genetic variants that affect the risk of developing COPD itself or by studying lung function itself, on which the diagnosis of COPD is based. Reduced lung function may also occur in patients with other airway diseases such as asthma.

Further research will be needed to study in detail the molecular alterations in the lung that result from the genetic variants identified, and to investigate whether these might be targeted by drugs. At this time there is no case for testing for common genetic variants that might predispose to COPD.

The scientists said: "This work is important because until now we have known very little about the genetic factors that determine an individual's lung function. By identifying the genes important in determining lung function, we can start to unravel the underlying mechanisms which control both lung development and lung damage. This will lead to a better understanding of diseases such as chronic obstructive pulmonary disease (COPD) and asthma. Crucially, it could open up new opportunities to manage and treat patients with lung conditions".

The authors added: "A large reduction in lung function occurs in chronic obstructive pulmonary disease (COPD), which affects around 1 in 10 adults above the age of 40 and is thought to be the fourth most common cause of death worldwide. Smoking is the major risk factor for development of COPD. Lung function and COPD cluster within families, indicating that variations in genes also predispose individuals to reduced lung function.

"The scientists of the SpiroMeta consortium compared genetic variants at each of 2.5 million sites across the human genome in over 20,000 individuals of European ancestry with their lung function measures. In five different locations in the human genome, genetic variants resulted in alterations in lung function. The scientists showed that these were real findings by checking the effects of the same variants in over 33,000 additional individuals. They also compared their results to those of a second consortium, CHARGE, which has published a paper in the same issue of the journal.

The scientists emphasise that they do not expect these findings to lead to immediately to genetic tests to predict who will develop lung disease. What is more important, they say, is that the findings will help understand the underlying causes of lung diseases and thus may indicate new ways of treating the condition.

"The research would not have been possible without the generous support of the participants of the contributing studies from the UK, Europe and Australia, to whom we offer our thanks."

Sticks and stones break bones, but this UH study may prevent it

Wed, 09 Dec 2009 05:00:00 PST

( from http://www.rxpgnews.com ) The best way to prevent a fracture is to stop bones from reaching the point where they are prone to breaking, but understanding the process of how bones form and mature has been challenging. Now researchers at the University of Houston department of health and human performance have created a process that grows real human bone in tissue culture, which can be used to investigate how bones form and grow.

We have manufactured a structure that has no synthetic components, said Mark Clarke, associate professor and principal investigator. It's all made by the two cell types bones start with inside the body. What you end up with is a piece of material that is identical to newly-formed, human, trabecular bone, including its mineral components, its histology and its growth factor content.

Being in a microgravity environment causes astronauts' bodies to lose more bone mineral than they can replace, which makes them vulnerable to fractures and breaks. Even when they return to Earth, the bone loss continues as their bodies slowly begin the process of replacing the bone mineral content.

The NASA-funded study, which included Clarke's collaborators at NASA-Johnson Space Center, Dr. Neal Pellis and Dr. Alamelu Sundaresan, used human osteoblasts and osteoclasts, the two major cell types involved in the formation of and breaking down of bone. The 3-dimensional bone constructs allowed for ideal conditions to investigate how bone forms and, more importantly, how bone is lost in environments such as space flight and conditions present in post-menopausal women and spinal cord patients.

Clarke has worked with NASA on other bone loss studies. He served as a principal investigator in a NASA study of micro-fabricated skin patches that collect sweat for analysis of biomarkers of bone loss, like calcium.

His research on bone formation also is proving to be market-ready, as a newly formed start-up company, OsteoSphere Inc., examines ways the breakthrough research can be used in a clinical setting for applications such as spinal fusions, facial reconstructions following bomb blasts or the re-growing of an individual bone outside of the patient,.

UH has now licensed the technology to OsteoSphere Inc. which is looking at ways to commercialize the technology in a clinical setting, including culturing an individual's own bone for subsequent transplantation back into the patient, developing other products for use in orthopedic reconstruction or using the technology as a screening tool for development of pharmaceuticals for combating bone loss or stimulating bone regeneration, Clarke said.

Think again about keeping little ones so squeaky clean

Tue, 08 Dec 2009 05:00:00 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- A new Northwestern University study suggests that American parents should ease up on antibacterial soap and perhaps allow their little ones a romp or two in the mud --- or at least a much better acquaintance with everyday germs.

The study is the first to look at how microbial exposures early in life affect inflammatory processes related to diseases associated with aging in adulthood.

Most provocatively, the Northwestern study suggests that exposure to infectious microbes early in life may actually protect individuals from cardiovascular diseases that can lead to death as an adult.

Contrary to assumptions related to earlier studies, our research suggests that ultra-clean, ultra-hygienic environments early in life may contribute to higher levels of inflammation as an adult, which in turn increases risks for a wide range of diseases, said Thomas McDade, lead author of the study, associate professor of anthropology in Northwestern's Weinberg College of Arts and Sciences and a faculty fellow at the Institute for Policy Research.

Relatively speaking, humans only recently have lived in such hyper-hygienic environments, he stressed.

The research suggests that inflammatory systems may need a higher level of exposure to common everyday bacteria and microbes to guide their development. In other words, inflammatory networks may need the same type of microbial exposures early in life that have been part of the human environment for all of our evolutionary history to function optimally in adulthood, said McDade, also a member of Northwestern's Cells to Society (C2S).

The Northwestern study is the first research on microbial effects on inflammatory systems in infancy that relate in later life to diseases associated with aging. Advancing the scientific literature on the developmental origins of disease, the study arguably is the most significant research on long-term effects of early environments on human physiological function and health in adulthood.

The research took advantage of a longitudinal study of Filipinos, following participants in utero through 22 years of age, to get a better understanding of how environments early in life affect production of C-reactive protein (CRP) production in adulthood.

Levels of the protein rise in the blood due to inflammation, an integral part of the immune system's fight against infection. CRP research mostly has centered on the protein as a predictor of heart disease, independent of lipids, cholesterol and blood pressure, though researchers still dispute that association. Researchers have been looking at excess body fat as a primary source of pro-inflammatory cytokines that produce CRP and behavioral factors related to diet, exercise and smoking. And the CRP research largely has been conducted in relatively affluent settings, such as in the United States, with low levels of infectious diseases.

The Northwestern researchers were interested in what CRP production looks like in the Philippines, a population with a high level of infectious diseases in early childhood compared to Western countries. Relative to Western countries, the Philippines also has relatively low rates of obesity and cardiovascular diseases, consistent with the Northwestern research findings.

Blood tests showed that C-reactive protein was at least 80 percent lower for study participants in the Philippines when they reached young adulthood, relative to their American counterparts, though the Filipinos suffered from many more infectious diseases as infants and toddlers. Filipino participants in their early 20s had average CRP concentrations of .2 milligrams per liter -- five to seven times lower than average CRP levels for Americans. CRP concentrations for Americans in their early 20s were on average around 1 to 1.5 milligram per liter.

Early Origins of Inflammation: Microbial Exposures in Infancy Predict Lower Levels of C-reactive Protein in Adulthood, will be published online December 9 in the journal

Women's soccer -- get fit while having fun

Fri, 02 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com )

Over a period of two years, 30 scientist lead by Associate Professor Peter Krustrup, University of Copenhagen, have investigated physiological, sociological and psychological aspects of women's soccer in comparison to running. 100 untrained adult premenopausal women have participated in the study.

The women (65 participated in the physiological study) were randomly divided into three groups: One soccer group, one running group and one control group. The soccer players and runners trained twice a week for one hour. After four and sixteen weeks, all the subjects went through extensive physiological tests. The same 65 subjects + another 35 women playing in soccer clubs were continually observed and interviewed to study the sociological and psychological effects of their training.

Many women find it difficult to fit in sport and exercise in their busy daily lives, and many state family and especially small children as the main reason for not finding the time.

The study reveals that contrary to common assumption, the flexibility of running as exercise form actually makes running harder to stick to for most women than soccer, which requires a fixed time and place.

What is really interesting is that the soccer players differed from the runners in their motivation. The runners were motivated by the idea of getting in shape and improving health. But the soccer players focused on the game itself and were motivated by the social interaction and by having fun with others. As it turns out, the soccer players got in better shape than the runners, and that combined with the social benefits makes soccer a great alternative to running, says Associate Professor Laila Ottesen and continues:

The women who played soccer have continued their soccer training as a group whereas few of the women in the running group continued running after the study. Actually, some of the women from the running group joined teams with the soccer group after the project finished.

When choosing a sport, women tend to favour cardiovascular training to strength training although the build-up of muscles and bone strength are vital to preserve health into old age.

While playing soccer, the women have high heart rates and perform many sprints, turns, kicks and tackles, making soccer an effective integration of both cardio and strength training, says project leader Peter Krustrup.

Our study shows that the 16 weeks of recreational women's soccer causes marked improvement in maximal oxygen uptake, muscle mass and physical performance, including the endurance, intermittent exercise and sprinting ability, explains Peter Krustrup, and continues

This makes soccer a very favourable choice of exercise training for women.

In the recent decade, we have seen a significant rise in women and girls playing soccer. It seems as though women are really beginning to take in soccer and make it a popular sport for women on their own terms. This is a very positive step forward, not only because of the improved physical fitness and health profile but also for the enjoyment of sports, Krustrup concludes.

The present results will be submitted online in the high-level international journal Scandinavian Journal of Medicine and Science in Sports next week (Bangsbo, Nielsen, Mohr, Randers, Krustrup, Brito, Nybo and Krustrup. Performance enhancements and muscular adaptations of a 16-week recreational football intervention for untrained women. Scand J Med Sci Sports, 2009).

In January 2010, the same journal will publish a supplementum describing multiple health effects of recreational football for various subject groups, including men, women, young and elderly. The supplementum includes one review and 13 original scientific papers.

The data will also be presented at the Scandinavian Congress of Medicine and Science in Sports 2010, Copenhagen, Denmark, 4-6 February 2010, and at the 3rd International Football Medicine Conference in Sun City, South Africa, 19-21 February 2010.

The project group currently includes collaborators from Switzerland, Norway and Italy, and major applications are currently being processed to include collaborators from England, Portugal, Belgium, Australia and Kenya.

Early identification of dementia increasingly difficult

Wed, 20 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) If grandma seems to forget things, will she end up demented? These days, memory loss is one of the very few symptoms that may signal which 70-year-olds risk developing dementia. This is shown in a doctoral thesis at the Sahlgrenska Academy at the University of Gothenburg, Sweden.

Several of the tests previously used to predict which elderly individuals risk developing dementia do not seem to work any longer. The thesis shows that memory loss is the only factor that can still be used to indicate who is at risk, although not among the very old.

The study compared nondemented 70-year-olds examined in the early 1970s with nondemented 70-year-olds examined in the year 2000. The results show that those who were examined in 2000 scored much higher on psychological tests than those examined 30 years earlier. This finding clearly indicates that such tests can no longer be used to predict future dementia.

'In the early 1970s, several different tests could be used to predict people's risks of developing dementia, but today it seems like psychiatric evaluation of the memory is the only useful test. In addition, it is more difficult to predict dementia the higher the person's level of education', says physician PhD Simona Sacuiu, the author of the thesis.

The follow-up of the 70-year-olds five years later showed that 5% had developed dementia. Those with memory problems showed an increased risk of developing dementia, although not everybody with poor memory developed dementia. Consequently, the link between forgetfulness and future dementia is more complex than commonly thought. Memory loss among elderly individuals may, but doesn't have to be, an early sign.

'In order to effectively detect dementia at an early stage, we need a useful tool that includes several types of tests, but the tests need continuous adjustments since the elderly of today perform much better at standardised psychological tests than previous generations', says PhD Sacuiu.

Examinations of a group of nondemented 85-year-olds show that the link between memory problems and dementia is not as clear in this age group. The 85-year-olds' ability to find words, to copy a geometric figure and to take quick decisions were some qualities that were evaluated in a psychiatric assessment. More than 300 individuals participated in the study, of which 17% had developed dementia three years later.

'We can't say that memory loss is the only meaningful sign of future dementia among 85-year-olds, since other symptoms, such as difficulties finding words or drawing a geometric figure, were needed for their risk of developing dementia to increase', says Sacuiu.

Navy grant to fund probe of squid and octopus camouflage

Wed, 20 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. -- Octopuses and squid are big brained species that use much of their mental powers to adjust their own appearances. This remarkable ability to camouflage on the fly has inspired the Office of Naval Research to award $7.5 million to Duke University and two collaborating institutions to learn more about how the animals do it.

Participating researchers plan to build an underwater version of the fictional Star Trek virtual reality holodeck. They will also go out on expeditions both to collect animals for study and to document their surroundings in unprecedented detail. They will even take their investigations down to the molecular level where the skin can change its own optical properties.

We need to know how the different animals we're going to look at actually see the world, said Sonke Johnsen, the Duke associate professor of biology who is principal investigator for this five-year Multidisciplinary University Research Initiative (MURI) study. What is the nature of their vision? How sharp is it, how quick does it respond to changes, and can they see colors?

Especially at the surface, where waves are moving and water quality is changing and the sun's positions are shifting, we need to measure how light fields around them change. We also want to see how they behave and change in different environments. That's where the holodeck will come in.

The cubical holodeck will be built by engineer and research oceanographer Jules Jaffe, one of two participating researchers at the University of California at San Diego's Scripps Institution of Oceanography. The aquarium-like chamber will be big enough to enclose the largest animals studied. Its walls will enable Duke and Scripps researchers to duplicate the changeable hues, lighting and optical conditions of the open ocean.

Cephalopods, the hundreds of different species classified as either octopuses or squids, are known to self-adjust skin colors and patterns in their effort to remain unnoticeable to predators or prey. Some can respond to the kinds of polarizing effects that humans need special sunglasses to discern. Some bioluminescent species even emit their own light, which they use to eliminate shadows that would give away their silhouettes.

We will be able to change the colors, resolution, speed and everything else so that we can step inside their visual world under laboratory conditions, Johnsen said. We will be able to show them natural scenes, but then also scenes that have been altered in different ways. The holodeck will be like a virtual reality machine for the ocean. In the world of marine biology we know of no other like it.

The other collaborator at Scripps will be Dariusz Stramski, a professor of oceanography who is a world expert on measuring rapidly changing light fields.

At the University of California at Santa Barbara, post-doctoral fellow Alison Sweeney, a former graduate student of Johnsen, will work with Daniel Morse, a professor of molecular genetics and biochemistry, to study proteins that can alter the animals' coloration. These pigments can self-assemble and disassemble, more or less under the control of their nervous systems, Johnsen said. And then those control how the animals look.

Meanwhile, a separate MURI led by the University of Texas at Austin will work toward goals so similar that some participants will be going on each other's research trips. In the case of the Duke-led group, that involves expeditions to islands off California and work on the Pacific island of Palau. The Texas group will head to the Florida Keys and the Gulf of Mexico. Collectively, the two efforts will receive about $15 million, Johnsen added.

So why is the military interested? Obviously, you can think that camouflage is a good thing to have, Johnsen said. You would like to be able to hide. But the work we do is at a basic, fundamental level. We won't do it with a particular application in mind. The military for ages has funded fairly basic research.

A second MURI award announced May 8 also has a Duke scientist as its principal investigator. Electrical and computer engineering professor David R. Smith is leading a study on transformation optical metamaterials funded by the U.S, Army Research Office. Smith's group works on metamaterials that can bend light to make an object appear invisible.

K-State professor awarded $1.48 million to study LASIK complictions

Fri, 01 May 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Gary Conrad, a university distinguished professor at Kansas State University's Division of Biology, has received a four-year grant renewal of $1.48 million from The National Eye Institute of the National Institutes of Health to study the cornea.

The NIH renewal will make Conrad's grant the longest continuously funded R01 grant in the state of Kansas at 41 years, said Jim Guikema, K-State associate vice president for research.

From the beginning, Conrad has been fascinated by the unique structure of the cornea.

Among all body tissues, the cornea is unique in being transparent, very highly innervated, free of blood vessels and yet composed of three layers of living cells, he said.

Conrad's research on embryonic development of the eye has led to knowledge that could possibly improve LASIK surgery. He and his research associates have identified a difference in the connective tissue of normal corneas compared to those that have been cut during LASIK.

LASIK, which stands for laser-assisted in situ keratomileusis, is a surgery using a laser to reshape the cornea as an alternative to wearing glasses or contact lens. During the procedure a thin-hinged flap is cut in the front of the cornea and peeled back out of the way to allow the laser to reshape the corneal connective tissue underneath the flap. When the laser is finished the flap is pulled back to its original position.

It was once believed that the flap would re-adhere permanently. However, the unique connective tissue of the cornea and a lack of blood vessels limit its ability to fully heal even years after the procedure, Conrad said. A trauma to the face, such as impact from an automobile air bag provides enough force to dislodge the flap, reopening the cornea, infecting it with dirt and debris, and causing instant loss of visual acuity.

After LASIK, differences in the structure of sugar molecules made the cornea prevent cut nerve ends from regenerating, as well as preventing the flap from re-adhering. However, the National Institutes of Health grant renewal will enable the lab group to test a possible solution that would strengthen the stromal flap and allow it to permanently bind back to the cornea after LASIK, Conrad said. It uses a combination of riboflavin and UVA light to permanently cross-link the connective tissue of the flap to the underlying corneal connective tissue. The treatment is currently in clinical trials in the U.S. for another eye dysfunction known as keratoconus.

The density of sensory nerve fibers that normally develop in our cornea is higher than anywhere else on the surface of our entire body, Conrad said. However, they regenerate extremely slowly if they are cut, so if we could get those nerves to regenerate, it would be a major medical advance.

Since the grant began in 1971, Conrad's lab group has discovered many properties of embryonic and adult corneas. He credits these accomplishments to the research professors, postdoctoral research associates, graduate students, research assistants and undergraduates in his lab who co-author many research publications that have made continuing grant funding possible.

His closest colleagues include his wife, Abigail Conrad, a K-State molecular, cellular, and developmental biologist; Yuntao Zhang, a K-State structural carbohydrate chemist; Peter Lwigale, a 2001 K-State doctoral graduate in biology and now an assistant professor at Rice University; Scott McCall, a K-State senior in biology and biochemistry and a 2008 Goldwater Scholar from Parker, Colo.; and Conrad's first doctoral student Gerald Hart, director of the department of biological chemistry at the Johns Hopkins University School of Medicine, Baltimore, Md.

Conrad is known for mentoring and encouraging undergraduates in his lab. As a result, Conrad has recommended McCall for a summer position in Hart's lab, researching structural chemistry.

Our molecular biology research is only as good as our K-State freshmen dishwashers and autoclavers, so we try to train them carefully, listen to their questions, and counsel them as our closest research colleagues, Conrad said. They teach us many things.

Risk of vibration-induced vascular injuries linked to vibration frequency differences

Sun, 19 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Speaking on April 19 at the Experimental Biology 2009 meeting in New Orleans, Dr. Kristine Krajnak, a team leader in the Engineering and Control Technologies Branch of the Health Effects Laboratory Division of NIOSH in Morgantown, West Virginia, describes results from the first study to directly link the different physical responses of tissue that occur with exposure to different vibration frequencies with biological mechanisms underlying the development of vascular dysfunction. Her presentation is part of the scientific program of The American Physiological Society.

The study, along with results of other studies conducted by NIOSH, supports the importance of reducing job-related exposure to vibration. Ongoing research is evaluating the effectiveness of anti-vibration devices, such as anti-vibration gloves and tools.

Higher frequency vibrations produced by an electric sander (greater than 100 Hz) are smoother than the slower vibrations of an electric hand drill (approximately 63 Hz) and therefore are less likely to cause users discomfort.

Don't let that fool you into not using protective devices that can reduce your exposure to vibration, she says. The new research study conducted at the National Institute for Occupational Safety and Health (NIOSH) suggests that exposure to high and low frequencies cause different physiological responses, but both may affect the risk of developing vibration-induced peripheral vascular dysfunction.

Of the 1.1 to 1.5 million U.S. workers exposed to hand transmitted vibration on a fairly regular basis, approximately half eventually develop some disorder such as Vibration White Finger, in which a single finger or sometimes the entire hand turns white and numb when exposed to the cold, due to restricted blood flow.

Workers also may experience reductions in tactile sensitivity, grip strength, and/or manual dexterity. Earlier studies have shown that risk goes up with frequency and duration of exposure, although NIOSH studies are underway to determine why certain people appear more susceptible to shorter exposure durations.

Dr. Krajnak's team looked at two aspects of vibration injury about which very little is known: the mechanisms of injury and the differences in response to frequency of vibration. The researchers used rats, since the tissues, nerves and arteries of rat-tails are similar to those in human fingers and the tails are known to respond to vibration in a way similar to that seen in fingers.

For four hours a day (the longest time a human can be exposed to workplace vibration according to U.S. and international standards) for 10 days, 15 rats (five in each group) were placed in a container where their tails were vibrated at either 63, 125 or 250 Hz. One control group of five rats accompanied them to the experimental area, to make sure any results seen were not related to noise or change of locale. A second control group stayed in their home cages, uninvolved in the activity.

After the last exposure, the scientists examined the tail arteries for changes. Neither control group had changes, suggesting the changes seen were directly related to the effects of vibration. The rats that experienced high frequency (125 and 250 Hz) vibration had higher levels of measures of oxidative stress, while rats that experienced the lower frequency (65 Hz) vibration showed higher levels of pro-inflammatory factors.

The changes seen following higher frequency vibration are associated with more immediate changes in the peripheral vascular system, such as those seen in workers with vibration injury, says Dr. Krajnak, but the changes following lower frequency vibration also can lead to vascular problems.

Jet lag disturbs sleep by upsetting internal clocks in 2 neural centers

Thu, 16 Apr 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Jet lag is the bane of many travelers, and similar fatigue can plague people who work in rotating shifts. Scientists know the problem results from disruption to the body's normal rhythms and are getting closer to a better understanding that might lead to more effective treatment.

New University of Washington research shows the disruption occurs in two separate but linked groups of neurons in a structure called the suprachiasmatic nucleus, below the hypothalamus at the base of the brain. One group is synchronized with deep sleep that results from physical fatigue and the other controls the dream state of rapid eye movement, or REM, sleep.

The ventral, or bottom, neurons receive light information directly from the eyes and govern rhythms in tune with periods of light and dark. The dorsal, or top, neurons do not receive direct light information and so govern rhythms as a more independent internal, or circadian, biological clock.

It turns out that some of the body's rhythms are more loyal to the ventral neurons and others are much more in tune with the dorsal neurons, said Horacio de la Iglesia, a UW associate professor of biology.

Normally the two neuron groups are synchronized with each other, but disruptions such as jet travel across time zones or shift work can throw the cycles out of kilter. Deep sleep is most closely tied to light-dark cycles and typically adjusts to a new schedule in a couple of days, but REM sleep is more tied to the light-insensitive dorsal neurons and can be out of sync for a week or more.

When we impose a 22-hour light-dark cycle on animals, the ventral center can catch up but the dorsal doesn't adapt and defaults to its own inner cycle, de la Iglesia said.

In the laboratory rats he uses for his research, that normal cycle is 25 hours. When the artificial 22-hour light-dark schedule was imposed, he found that the rats' deep sleep, largely governed by light but also a response to fatigue, quickly adapted to the 22-hour cycle, while their REM sleep continued to follow a 25-hour cycle. As a result, REM sleep did not occur in a normal progression following deep sleep.

We found that after exposing rats to a shift of the light-dark timing that simulates a trip from Paris to New York, REM sleep needed 6 to 8 days to catch up with non-REM, or deep, sleep, the sleep you usually experience in the first part of the night, de la Iglesia said.

The two types of sleep overlap immediately after the simulated jet lag occurs, he noted, and there is a greater likelihood of the animals entering REM sleep earlier than they should. That likely explains why it can take several days for travelers and shift workers to adapt to their new schedules, he said.

It also could explain why jet lag is associated with lower learning performance. We think the disruption of the normal circadian sequence of sleep states is very detrimental to learning, he said.

One of the problems is that you are doing things at times that your body isn't prepared to do them. One group of neurons tells your body it is Paris time and another says that it is New York time. You are internally desynchronized, said de la Iglesia.

He is lead author of a paper describing the work published online April 16 by

Two NYU Scientists Named Howard Hughes Medical Institute's early career scientists

Thu, 26 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Two researchers from NYU School of Medicine have been named Early Career Scientists by the Howard Hughes Medical Institute (HHMI). The honorees, Iannis Aifantis, Ph.D. associate professor of pathology, co-director of the Cancer Stem Cell Program at the NYU Cancer Institute and Jeremy S. Dasen Ph.D., assistant professor of physiology and neuroscience at NYU School of Medicine are among 50 of the nation's top scientists being honored by HHMI under this new initiative to establish, develop and grow unique research programs.

Dr. Aifantis, a cancer biologist investigating T-cell acute lymphocytic leukemia, a common form of leukemia in children and Dr. Dasen, a neuroscientist investigating the molecular code that helps developing motor neurons in the spinal cord connect with the muscles they control, will both receive a six-year appointment to the HHMI and funding to further explore their areas of research. HHMI will provide each NYU researcher with his full salary, benefits, and a research budget of $1.5 million over six-years.

The entire NYU Langone Medical Center community is proud of the groundbreaking work being conducted by Dr. Aifantis and Dr. Dasen and we congratulate them on their selection as HHMI Early Career Scientists, said Robert I. Grossman, M.D., Dean and CEO of NYU Langone Medical Center. These awards are recognition of the immense talent of these two scientists and the importance of the work that they are pursuing.

Dr. Aifantis has made majors strides towards understanding and developing new treatments for T-cell acute lymphocytic leukemia. He recently discovered a molecular door by which T cells, the soldiers of the immune system, slip into spinal fluid and the brain after they become malignant. Blocking this process could save thousands of lives each year. Aifantis is now testing hundreds of potential drugs that might prevent malignant T cells from reaching the nervous system. At the same time, he is learning what goes awry in blood stem cells that transform into leukemic T cells. Such insights may provide even more ways to combat deadly blood cancers.

Dr. Dasen's research focuses on deciphering the molecular code that helps developing motor neurons in the spinal cord connect with the muscles they control. Understanding this code, which relies on a large family of genes that produce proteins called Hox factors, may help scientists restore motor neuron function in people whose spinal cords have been damaged by trauma or disease. Dasen, has found that Hox proteins are not just present in motor neurons; they are pervasive throughout the nervous system. He plans to explore whether Hox proteins in interneurons and sensory neurons, which control motor neuron firing patterns and transmit feedback about muscle action, help assemble the complete circuits that control walking and running.

Children who are dissatisfied with their appearance often have problems with their peer group

Wed, 18 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Being satisfied with one's appearance is one of the most important prerequisites for a positive self image. However, in today's appearance culture it is the rule rather than the exception that children and young people are dissatisfied with their appearance.

Those children who are teased or subject to bullying are particularly critical of their appearance - and they tend to be this way over a long period. This is revealed in a new thesis in psychology from the University of Gothenburg, Sweden.

In her thesis Carolina Lunde has followed almost 1,000 children between the ages of 10 and 14. The aim has been to investigate the link between body image and peer group relationships.

An important conclusion is that both boys and girls become more dissatisfied with their body and their appearance during this age bracket - even though the girls were consistently more dissatisfied with their appearance than the boys.

The early teens can therefore be regarded as a high risk period for acquiring a negative body image. The children who weighed the most at 10 years old were particularly dissatisfied with their appearance. Furthermore, overweight children, primarily girls, were bullied and teased about their appearance considerably more often than the other children in the study.

Overweight children who are bullied can therefore be said to bear a double burden, which means that they are in the risk zone in terms of developing a negative body image.

As negative attitudes towards overweight people are formed when children are young, Carolina Lunde feels that it is important to try to counteract these prejudices at an early stage.

The fact that children and young people have a negative body image can have a number of serious psychological consequences. It increases the risk of developing eating disorders and depression. Exercising too much is also related to a negative body image. Being dissatisfied with one's appearance can also limit children and young people in their everyday lives.

They might focus to such an extent on their dissatisfaction with their appearance that they find it difficult to think of anything else. Avoiding situations that make them feel self-conscious and uncomfortable, getting changed for sports activities at school for example, is also common.

Carolina Lunde says that the title of the thesis What people tell you gets to you is a direct quotation from one of the young people who took part in one of the studies. The most dissatisfied young people indicated that their parents and their peer group frequently commented negatively about their appearance.

It might be the case that being bullied and teased about one's appearance during the early teens when the body is changing so much has a particularly negative impact on body image, observes Carolina Lunde.

Unexplained chest pain can be due to stress

Mon, 09 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) Each year, many people seek emergency treatment for unexplained chest pains. A thesis from the Sahlgrenska Academy, University of Gothenburg, Sweden, indicates several common factors among those affected, including stress at work, anxiety, depression and a sedentary lifestyle.

Chest pain is a common reason for patients to seek emergency treatment. A considerable number of patients are diagnosed with unexplained chest pain, which means that the pain cannot be linked to biomedical factors such as heart disease, or some other illness. The patient group is significant in size, with just over 20,000 patients seeking hospital treatment in 2006, and so far researchers have been unable to identify specific causes for unexplained chest pain.

Many suffer from recurring bouts of pain over several years, while the healthcare services are unable to find out what's causing it, says Registered nurse Annika Janson Fagring, the author of the thesis.

In her thesis, Annika Janson Fagring describes and analyses symptoms among patients with unexplained chest pain. The results show that most of them are middle-aged, and that over a third of those affected were born outside Sweden. The chest pain had a negative impact on the patients' daily life in the form of tiredness, anxiety and fear of death.

The main difference between women and men with unexplained chest pain is that men were more likely to perceive their lives and jobs as being stressful, while women tended more to suffer from symptoms of depressions and anxiety, says Annika Janson Fagring.

The patients, both men and women, experienced more symptoms of depression and anxiety, and work-related stress when compared with a reference group of people who were not suffering from heart disease. The male patients were more physically active in their spare time than the female patients, but compared with the reference group, both the men and the women with unexplained chest pain led a more sedentary lifestyle.

The thesis also looks at the development of symptoms and the prognosis for patients with unexplained chest pain over a period of time, compared with patients suffering from angina and patients who had suffered a heart attack. A register study revealed that from 1987 up until 2000, the number of patients with diagnosed unexplained chest pain increased, and then levelled out. The number of patients with angina increased up until 1994 and has since fallen, while the number of patients who have suffered heart attacks has fallen throughout the whole period examined.

There were fewer deaths among patients with unexplained chest pain a year after they became ill, compared with patients that became ill with angina or suffered heart attacks. Deaths among men a year after falling ill with unexplained chest pain were a third higher compared with men in the rest of the population, while women did not display any increased risk of death.

Annika Janson Fagring says that the thesis shows that it is important to improve knowledge and understanding of the symptoms experienced by patients with unexplained chest pain, in order to be able to offer more individualised care.

New study raises concerns about screen time among urban children with asthma

Wed, 04 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) Urban children with asthma engage in an average of an hour more of screen time daily than the maximum amount American Academy of Pediatrics (AAP) recommends. This is the first study to examine screen time among children with asthma.

We know that both asthma and excessive screen time can be associated with other difficulties, including behavior problems, difficulty with attention, poor school performance and obesity, said Kelly M. Conn, M.P.H., of General Pediatrics at Golisano Children's Hospital at Strong and lead author of the study, which was published recently in Academic Pediatrics. (Academic Pediatrics changed its name from Ambulatory Pediatrics this year.) The study was conducted out of the University of Rochester Medical Center.

As a part of a larger study on how to more effectively treat asthma, Conn and her colleagues surveyed parents of urban children with asthma in Rochester, NY, to better understand their screen time viewing habits. Screen time includes TV watching and video tapes, playing video and computer games and using the Internet. The study found that 74 percent of the 226 children whose parents were surveyed exceeded more than two hours of screen time per day. On average, these children with asthma watched 3.4 hours daily.

Even though these findings are preliminary, a message for parents would be to remain aware of the amount of time your child is spending in front of screens and try to encourage your child to participate in a range of activities, Conn said. The types of programs children watch are also important; young children should watch shows meant for their age group, rather than watching PG-13 or R-rated movies, or playing Teen-rated games.

More than half of the parents interviewed knew that the AAP recommends a maximum of two hours of screen time per day and most parents who reported that their child had too much screen time were worried that this was the case. Though the AAP recommends that no child have a television in their bedroom, 77 percent of the children had a TV in their room and nearly half the children owned a hand-held video game system. The widespread presence and popularity of screen time activities in children's lives makes monitoring and setting limits for screen use very difficult. In addition, in an urban setting, safety concerns often limit a child's ability to engage in activities outside of the home.

Even though the goals of asthma therapy are to quell asthmatic symptoms and prevent limitations with activities, about 63 percent of children used screen time when their asthma symptoms physically limited their activities. Those children who used screens when they were having physically limiting symptoms used an average of 3.67 hours daily, which is more than half an hour extra daily than children who engaged in other non-physical activities such as resting, reading or coloring. Researchers suspect that some parents could have underestimated their child's screen time, which would demonstrate an even larger problem of excessive screen time and lack of other physical and mental activities than the study found.

The study did not have a control group of children without asthma. Children with asthma most likely watch a similar amount of screen time to all children, but children with asthma are more at risk for the health problems associated with too much screen time. In the study, children included were between 3- and 10-years-old. According to the Kaiser Family Foundation, on average children in this age range watch between two and four hours of screen time daily. So, while they may not spend more time on screens than children without asthma, the lost opportunities for physical and mental engagement may be even more detrimental to these vulnerable children.

It is not unreasonable or uncommon for children to watch TV or play a video game when they are not feeling well or when they need to slow down their activity. For all children, it is important for parents to be aware of how much screen time their children have and the types of programs they are watching, Conn said.

Conn suggests that parents of children with asthma can encourage a variety of alternate activities for their child, including reading, drawing and arts and crafts, or playing board games or puzzles. In addition, if a child is experiencing limitation of activity due to their asthma, parents should speak with their child's medical provider about ways to improve their asthma control. Many areas have organizations that were created to provide resources and support for families of children with asthma.

UT faculty members win American Heart Association awards for advancing research

Tue, 23 Dec 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Faculty members at The University of Texas Health Science Center at Houston (UTHSC-Houston) were honored for their work in the fight against heart disease at the 2008 American Heart Association's Scientific Sessions in New Orleans. Heart disease is the nation's No. 1 killer.

UT faculty members recognized were: Nobel Laureate Ferid Murad, M.D., Ph.D., director emeritus of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of the UTHSC-Houston; John Holcomb, M.D., director of the Center for Translational Injury Research at the UTHSC-Houston; and Raffaella Lombardi, M.D., Ph.D., IMM postdoctoral fellow. The AHA scientific sessions were Nov. 8 -12.

Murad was named one of 13 Distinguished Scientists for 2008 by the American Heart Association. The prestigious award was created to honor researchers whose work has advanced the understanding of cardiovascular disease and stroke.

Murad found that nitroglycerin and several related heart drugs induce the formation of nitric oxide and that this gas acts to increase the diameter of blood vessels in the body, according to the American Heart Association. He shared the 1998 Nobel Prize in Physiology or Medicine with Robert Furchgott and Louis Ignarro for their major discoveries involving nitric oxide as a unique signaling molecule in the cardiovascular system.

Nitric oxide is one of the most important signaling molecules produced within our body. Dr. Murad's contributions to the field have revolutionized the concept of cell signaling by a gaseous molecule. Potential applications are far-reaching across multiple organ systems. Discovery of this pathway has allowed new therapeutic strategies to control blood pressure, correct conditions of endothelial dysfunction and even treat erectile dysfunction, said Nathan Bryan, Ph.D., assistant professor of molecular medicine at the IMM.

Murad completed his undergraduate work at DePauw University and received his M.D. and Ph.D. from Case Western Reserve University. He completed a medical residency at Massachusetts General Hospital and a fellowship at NIH in the Heart Institute.

Holcomb received the 2008 Lifetime Achievement Award in Trauma Resuscitation Science, which was established in 2003 to recognize leaders in this field. Holcomb's contributions to trauma medicine include increased hemorrhage control through dressings, tourniquets and intravenous methods, as well as trauma informatics and systems.

Each year the American Heart Association selects one surgeon to receive a Lifetime Achievement award for their contributions to the resuscitation of critically ill or injured patients. Dr. Holcomb, while serving in the U.S. Army (now retired) made significant contributions to the understanding and treatment of injured patients in war zones as well as civilian trauma. His contributions have led to a new paradigm in transfusion of patients sustaining blood loss. He well deserves this recognition, said Richard Andrassy, M.D., professor and chairman, the Denton A. Cooley, M.D., Chair in Surgery and the Jack H. Mayfield, M.D. Distinguished University Chair at The University of Texas Medical School at Houston.

Holcomb is past commander of the United States Army Institute of Surgical Research at the Brooke Army Medical Center in San Antonio. He finished his undergraduate work at Centenary College and received his degree of medicine at the University of Arkansas Medical School in Little Rock. He completed an internship and residency in general surgery at the William Beaumont Army Medical Center in El Paso.

Lombardi won the 2008 Louis N. and Arnold M. Katz Basic Science Research Award Prize for Young Investigators, which is given to the best scientific presentation at the annual scientific sessions of the American Heart Association.

Lombardi presented a manuscript describing the origin of the fat cells in the heart in a disease condition referred to as arrhythmogenic right ventricular cardiomyopathy, which is an important cause of sudden cardiac death in the young, especially athletes. In this disease, which is a genetic disorder, excessive fat cells replace cardiac myocytes in the heart, particularly the right side of the heart. She and her colleagues showed that fat cells originate from the stem cells in the heart that through a unique mechanism convert to fat cells in the presence of genetic mutations.

The Katz Award is the most prestigious award given to young investigators in basic cardiovascular research by the American Heart Association, said Ali Marian, M.D., professor and director of the Center for Cardiovascular Genetic Research at the IMM. The work (of Lombardi) could lead to the development of new therapies aimed at preventing the cardiac stem cells from switching a muscle fate to a fat cell fate and therefore, prevention of this potentially deadly disease.

Lombardi received her medical degree and clinical training in internal medicine and cardiology at Federico II University of Naples, Italy. She joined Marian's research group in the IMM three years ago and earned a doctorate in clinical physiopathology and experimental medicine from Federico II University of Naples during this period.

Sweat it out: UH study examines ability of sweat patches to monitor bone loss

Wed, 01 Oct 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Some health assessments that are routinely carried out on Earth are not practical when the patients are free-floating astronauts on long space flights, such as missions to Mars or the Moon. A new, NASA-funded study from the University of Houston department of health and human performance will examine how well sweat patches the size of adhesive strips can detect levels of chemicals that may indicate bone loss.

Current assessments involve blood tests, urine analysis or bone density scans, all of which are time-consuming, inconvenient to the working astronauts or, in the case of bone density scans, require large equipment that's not practical on a space station, said Mark Clarke, associate professor and principal investigator. These patches are small, non-intrusive, and placed on the skin to collect a sweat sample. The sample is then analyzed for biomarkers of bone loss markers, such as calcium.

The three-year, $780,000 study will examine three types of sweat patches, each differing in the way the sweat is collected and extracted from the devices. One device collects the sweat between the skin and a plastic layer; another is a commercially used patch that absorbs the sweat and is then reconstituted with water. The third is called a Microfabricated Sweat Patch (MSP) built using micro-chip inspired-technology. Sweat is removed from the MSP using a mini-centrifuge. The technology was developed by Clarke and Daniel Feeback, a lead scientist with NASA's Life Science Directorate.

Our goal is to develop a micro-fabricated sweat patch that collects a sweat sample from the skin, performs a biomarker analysis and immediately provides a read-out to the user, said Clarke. The first phase of the study will determine if sweat can be used to monitor bone loss. Next, it will determine which patch technology most accurately measures the chemicals associated with bone loss.

The last phase of the study will look specifically at the MSP and will involve 60 people, from young college students to elderly men and women, to new Air Force recruits. Each will wear a series of patches during normal daily activities and then perform exercises at the UH Laboratory of Integrated Physiology. The patches then will be collected and the sweat analyzed. Changes in bone also will be monitored using bone mineral density scans performed in the department. Clarke expects this phase of the project to span at least eight months.

Being in a microgravity environment causes astronauts' bodies to lose more bone mineral than they can replace, which makes them vulnerable to fractures and breaks. Even when they return to Earth, the bone loss continues as their bodies slowly begin the process of replacing the bone mineral content. This is a critical concern, especially as the space program considers longer space missions to Mars or the Moon.

Clarke says the research has applications for those susceptible to bone loss, such as the elderly, post-menopausal women and adolescent girls

Typically, it takes up to six months to see if changes in your exercise and eating habits are helping to maintain or increase bone mineral density, Clarke said. Astronauts on long flights need this information quicker so that they can make adjustments to their exercise protocols, diet or drug treatments. Similarly, bone loss in women can be seen as early as the teen years, so this kind of fast and easy screening device can provide advance notice to fend off serious bone density issues later in their lives.

Better understanding of blood vessel constrictor needed to harness its power for patients

Thu, 18 Sep 2008 04:00:00 PST

( from http://www.rxpgnews.com ) To harness endothelin-1's power to constrict blood vessels and help patients manage high blood pressure or heart failure, scientists must learn more about how endothelin functions naturally and in disease states, says a Medical College of Georgia researcher.

Despite strong laboratory evidence that blocking endothelin-1 receptors would be an effective, targeted therapy for these two major health problems, the drugs failed patients, says Dr. Adviye Ergul, physiologist in the MCG Schools of Medicine and Graduate Studies.

These endothelin-1 receptors are logical targets for drugs to treat hypertension because of their key role in vasoconstriction, but the targets are moving and we don't know how one target plays off another, says Dr. Ergul, who discussed novel aspects of endothelin receptor interaction during the 62nd High Blood Pressure Research Conference and Workshop in Atlanta.

The current thinking in pharmacology is one hormone, one receptor equals boom: the effect. I think cells are much smarter, she says. This week, Dr. Ergul challenged colleagues across the country to consider emerging evidence that usual receptor communication is likely more complex than they thought and that disease may significantly alter communication.

Endothelin-1 receptors are known to interact: one way blood vessels keep a healthy tone, for example, is that a and b receptors on smooth muscle cells prompt constriction while b receptors on the lining of blood vessels work with nitric oxide to promote relaxation. Endothelin-1 receptors on the kidneys are a player as well, helping wring out excess water and salt. There is a delicate balance, says Dr. Ergul.

But there's apparently more to the relationships. She holds up a handful of recent journal articles which reflect mounting evidence that receptors actively work as teams of two or more. That teamwork could change their function. New technology enables scientists to literally watch receptors move closer together on a cell surface, clearly indicating that something is going on.

Numerous drugs have been developed that are antagonists that can block these receptors with the idea they can be used in hypertension and heart failure. In animal models, they worked well, she says. But in clinical trials they failed badly; a drug for heart failure actually worsened problems such as labored breathing and swelling in patients already having difficulty moving blood through their body.

The first antagonists blocked both known receptors: a and b; the next generation blocked one or the other but still didn't work. A notable exception is endothelin-1 antagonists that reduce excessive pressure and tissue buildup inside the blood vessels of patients with pulmonary hypertension. In addition to constricting blood vessels, endothelin-1 can help blood vessels grow bigger but too much can result in protein deposits that stiffen blood vessel walls.

Scientists have been scratching their heads over why blocking these receptors hasn't panned out; they've even looked for an atypical receptor that might explain it. But Dr. Ergul, an expert on endothelin-1's role in diabetes, believes the unexpected results are better explained by poorly understood relationships in normal and disease states. How receptors dimerize, how they get closer together on the cell surface, likely needs to affect our drug design, she says.

UGA researchers win $9.2 million stem cell grant from NIH

Mon, 04 Aug 2008 04:00:00 PST

( from http://www.rxpgnews.com ) A research group led by Stephen Dalton, professor and Georgia Research Alliance Eminent Scholar of Molecular Biology at the University of Georgia, has been awarded $9.2 million as part of a major new research grant by the National Institute of General Medical Sciences, part of the National Institutes of Health.

Dalton's group, headquartered in the department of biochemistry and molecular biology, will address the molecular underpinnings of the early steps that stem cells take in becoming specialized cell types. The scientists will also seek to identify the genetic and protein modification patterns that accompany this process of differentiation.

The new grant in UGA's Franklin College of Arts and Sciences is part of $27 million in funding awarded to the University of Wisconsin, UCLA and UGA that NIGMS has added to its ongoing effort to uncover the basic biology of human embryonic stem cells.

Our program will offer training for scientists seeking to gain expertise in the specialized techniques needed to work with embryonic stem cells and will serve as a source of reagents, technical support and methodology development, said Dalton, who is also a Georgia Cancer Coalition Distinguished Scholar and a member of UGA's developmental biology program.

The results of all three new programs are expected to deepen existing knowledge of the unique properties of stem cells and will be important to researchers trying to develop stem-cell-based therapies.

This program project grant is important for a number of reasons, said David Lee, UGA vice president for research. Certainly it highlights the expertise in stem cell biology and glycomics at the University of Georgia. But perhaps more important, it is cleverly designed to promote stem cell research throughout the Southeast. One of the core facilities funded by the grant is specifically tasked with developing new stem cell technologies that will be disseminated to researchers across the region via the new Southeast Stem Cell Consortium, which Professor Dalton chairs. We are extremely pleased by the leadership provided by Dr. Dalton in an area that offers so much promise for human health.

Dalton's position as a leader in stem-cell research has been solidified with the recent establishment of the Southeast Stem Cell Consortium. The consortium has strong interests in the basic biology of stem cells, their utility as a model for studying mammalian development and their potential as a cell source to develop therapies for degenerative disease and repair of chronic injury. Focus areas include diabetes, cardiovascular disease, spinal cord injury and neurodegenerative disease.

This is an innovative program that focuses on an understudied area of stem cell biology, said Marion Zatz, Ph.D., who oversees stem cell grants at the National Institute of General Medical Sciences of the National Institutes of Health. By looking at how proteins are modified by sugar molecules as stem cells differentiate, Dalton's team could help us understand how the many distinct cell types in our bodies are formed.

Dalton's research group at UGA focuses on the uses of stem cells in understanding diabetes and cardiovascular disease. One current project involves finding ways to use stem cells to repair the human heart.

The heart is an organ that doesn't repair itself, said Dalton. But we're studying a resident population of stem cells that have the capability of dividing and turning into cardiac cells. Theoretically, they could be used to help the heart repair itself after a heart attack.

The new programs join an NIGMS effort launched in 2003 to explore the basic molecular and genetic features of human embryonic stem cells. Prior to the latest awards, the initiative has included six exploratory centers, two multidisciplinary research programs and several independent research projects and supplements.

Special horseshoes measure acceleration in horses

Sun, 06 Jul 2008 04:00:00 PST

( from http://www.rxpgnews.com ) The most frequent injuries that horses suffer are derived from pressure exerted by riders, and knowing which forces are involved when horses move can prove highly informative when considering treatment for such injuries. A team of scientists from Wageningen University, led by Professor Johan van Leeuwen, has carried out studies both into the advantages of different rider techniques in reducing injury risk, and into the benefits of a method of equine rehabilitation. By using computer modelling and specialist horseshoes to measure acceleration, these investigations suggest that aqua-training rehabilitation is beneficial due to lower impact accelerations. However, rising trot may not be as advantageous as previously thought. Results will be presented on Monday 7th July at the Society for Experimental Biology's Annual Meeting in Marseille [Session A3].

Rehabilitation after equine joint and muscle injuries, including those of the back, shoulders and legs, now often involves 'aquatraining', whereby horses move in water-filled treadmills. Due to buoyancy, this treatment is currently thought to reduce weight-bearing forces, which can otherwise have detrimental effects on joints, but to date there has been a virtual absence of studies into the magnitude of these benefits. Professor van Leeuwen's team has used special horseshoes to measure accelerations of horses undergoing aquatraining, as well as walking normally, which provide a good indication of the impact forces involved. Our results, based on data from seven horses, show the accelerations are significantly lower during 'aquatic walking', he asserts. We will be carrying out further experiments to confirm these results, but at this stage, it appears that aquatraining may indeed be beneficial for rehabilitation after joint injury.

Professor van Leeuwen and his colleagues have also used specialised force gauges to measure the strain placed on the backs of horses through the saddle and stirrups. These measurements have been combined with the output of computer models to provide insight into the mechanisms that a rider can use to respond to the movements of a horse, and to prevent injury. We have given particular attention to the comparison of sitting and rising trot, as it is broadly accepted in the equestrian world that rising trot imposes less loading on the back of the horse, Professor van Leeuwen explains. However, our results have not been able to confirm the belief that rising trot is mechanically less demanding for the horse. Looking at back extension, which is most often related to back injuries, we found that the extension of the back is similar in rising and sitting trot.

Study identifies brain pathway that shuts down seizures

Sun, 08 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Iowa and the Veterans Affairs Iowa City Health Care System have uncovered a brain pathway that shuts down seizures.

The multidisciplinary team of scientists pieced together information from clinical observations made in the first half of the 20th century with knowledge from modern genetics and molecular biology to show that an acid-activated ion channel in the brain reacts to a drop in pH (increased acid) in a way that shuts down seizure activity.

The link between low pH in the brain and seizure termination was first hinted at nearly 80 years ago when clinical experiments showed that breathing carbon dioxide, which makes brain tissue more acidic, helps stop epileptic seizures. Subsequent studies in the 1950s found that seizures themselves reduce brain pH. However, it was the modern discovery of an acid-activated ion channel (ASIC1a) in the brain that provided the key to the UI discovery, which is reported in Nature Neuroscience Advance Online Publication on June 8.

We found that ASIC1a does not seem to play a role in how a seizure starts, but as the seizure continues and the pH is reduced, ASIC1a appears to play a role in stopping additional seizure activity, said Adam Ziemann, a student in the Medical Scientist Training Program at the UI and co-lead author of the study.

Specifically, the study shows that mice without the ASIC1a gene have more severe and longer seizures than mice with the gene. In addition, chemically blocking ASIC1a increases the severity and duration of seizures in mice with the gene. Conversely, increasing the expression of ASIC1a in mice protects the animals from severe seizures.

The team also showed that reducing the pH in slices of brain tissue expressing ASIC1a reduced seizure activity, but acid had no effect on seizures in tissue without the protein.

When the team measured pH in mouse brains, they showed that seizures lower the pH to levels that can activate ASIC1a channels. They also found that breathing carbon dioxide causes an additional rapid drop in brain pH, and that breathing 10 percent carbon dioxide was sufficient to protect mice with the ASIC1a protein from lethal seizures.

In seizures, ASIC1a appears to be activating inhibitory neurons, explained John Wemmie, M.D., Ph.D., senior study author and assistant professor of psychiatry in the UI Roy J. and Lucille A. Carver College of Medicine, and a staff physician and researcher at the VA Iowa City Health Care System. This is the first study to show that ASIC1a activation can have an inhibitory effect.

One of the most exciting aspects of the work is that it highlights the potent anti-epileptic effects of acid in the brain -- effects that have been recognized for nearly 100 years but until recently have been poorly understood -- and it identifies ASIC1a as a key player in mediating the anti-epileptic effect of low pH, Ziemann said.

We don't know yet, but presumably there might be examples where the seizures don't stop because of a deficit in this pathway, Wemmie added.

Seizures involve abnormal synchronous firing of groups of neurons, which can cause physical symptoms such as spasms or convulsions and, in the most serious cases, altered control of vital bodily functions, like breathing. Approximately 2 to 4 percent of people will have a seizure at some point in their lives. People who have epilepsy experience repeated seizure activity.

Although the vast majority of seizures are self-limiting and stop by themselves, seizures that don't stop can develop into a life-threatening condition called status epilepticus with a mortality rate of up to 20 percent.

The discovery helps explain why breathing carbon dioxide stops seizures, which might stimulate the use of carbon dioxide for stopping seizures, Wemmie said. However, although this work provides insight into how seizures normally stop and might help us learn more about how to terminate those seizures that don't stop, it will take more work to turn the finding into a new therapeutic approach. We will be working with colleagues in neurology and neurosurgery to try and translate the findings to treatments.

Ziemann noted that a particular strength of neuroscience research at the UI is the close interaction between faculty doing cutting-edge human studies and those pursuing basic science.

Toad research could leapfrog to new muscle model

Mon, 02 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) A toad sits at a pond's edge eyeing a cricket on a blade of grass. In the blink of an eye, the toad snares the insect with its tongue. This deceptively simple, remarkably fast feeding action offers a new look at how muscles work.

This fresh perspective could lead to designing more efficient electric motors, better prostheses and new medical treatments for neuromuscular diseases like Parkinson's.

Science has long held that muscles behave largely like motors. Northern Arizona University researcher Kiisa Nishikawa suggests that muscle acts more like a spring.

Existing theories don't explain how muscles shorten rapidly, Nishikawa said. Muscles can only shorten to do work; they can't do work by lengthening. A spring also can only do work by shortening.

By example, Nishikawa explains that the jaw muscles in toads and chameleons shorten in the lower jaw, and the opening of the jaws causes the tongue to stretch by its own momentum.

When a toad or chameleon captures prey with its tongue, it exerts force over a distance. Figuring out how they do it has immense application to any device that actually moves.

A toad's jaw muscles can produce forces greater than 700 times the animal's weight. The best electric motor achieves about one-third of that force-to-weight ratio, Nishikawa noted.

Muscles also function as self-stabilizing springs.

They have built-in self-correcting mechanisms. Before the brain can even react, muscles are changing their elasticity adaptively, she said. Think of walking down a flight of steps and missing a step. Leg muscles instantly become less stiff to afford better shock absorption. It's an intrinsic property of muscle, Nishikawa said.

Tom Sugar and his colleagues Arizona State University have been inspired by biology in designing a robotic tendon. After meeting with Nishikawa about her work, Sugar said, We were amazed at the speed, energy storage and power of muscle. We learned how a frog tongue will store energy and release it in a powerful burst.

At ASU's Human Machine Integration Laboratory, Sugar and his team are building SPARKy (Spring Ankle with Regenerative Kinetics) that mimics biology by storing and releasing energy during the ankle gait cycle.

Energy is stored as the leg and body rolls over the ankle, and then this energy is released in a powerful burst to propel the user forward. By mimicking biology, we are able to build a very lightweight and functional device, Sugar said.

Putting motors and springs together in a smart way is something nature hit on about 600 million years ago (with the earliest vertebrates), Nishikawa said.

It's a notion that captured the interest of Discovery Channel Canada, which spent a day at NAU and a day at ASU taping for a segment of its Daily Planet show that will air in the fall.

The NAU researcher wants to know more about how the brain controls movement. About decade ago Nishikawa realized that how the brain and body work together to produce coordinated movement means understanding what muscles contribute to the whole process.

Understanding what the neurological part is and what the muscular part is can help establish cause and effect, she said.

Identifying these mechanisms at the molecular level might aid medical research in developing better treatments for sufferers of Parkinson's, whose low force output results in stiff movements.

Nishikawa's studies of the neuromuscular basis for extremely rapid movements in animals, such as the toad snaring prey with its tongue, could leapfrog to a new model of muscle function, changing the standard representation of muscle as a motor.

Genetic mutation linked to walking on all 4s

Sun, 01 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: What are the genes implicated in upright walking of humans? The discovery of four families in which some members only walk on all fours (quadrupedality) may help us understand how humans, unlike other primates, are able to walk for long periods on only two legs, a scientist will tell the annual conference of the European Society of Human Genetics tomorrow (Monday 2 June).

The quadrupedal families in Turkey previously attracted attention in 2005, when they were discovered. Now the Turkish team reports that they have found the first gene implicated in quadrupedal locomotion in these families.

Professor Tayfun Ozcelik, of Bilkent University, Ankara, Turkey, and colleagues, studied four unrelated families where some members were affected by the rare quadrupedic condition, Unertan syndrome, which is also associated with imperfect articulation of speech, mental retardation, and defects in the cerebellum, a part of the brain involved in motor control. They found that the affected individuals in two families had mutations in the gene responsible for the expression of very low density lipoprotein receptor (VLDLR), a protein which is known to be critical to the proper functioning of the cerebellum during development.

Although the families lived in isolated villages 200-300 km apart and reported no ancestral relationships, the scientists expected to find a single genetic mutation implicated in the condition. They were surprised to find that this was not the case.

We carried out genome-wide screening on these families, said Professor Ozcelik, and found regions of DNA that were shared by all those family members who walk on all fours. However, we were surprised to find that genes on three different chromosomes are responsible for the condition in four different families.

In families A and D there were mutations in VLDLR on chromosome 9, and in family B the phenotype maps to chromosome 17 to a region that contains at least 157 genes, and we are still looking for the precise mutation. Neither region appears to be implicated for family C.

In all cases, the affected individuals were the offspring of consanguineous marriages, which suggests that if they had married outside the family they would not have had the condition. All of them had significant developmental delay in infancy. Whereas normal infants make the transition to walking on two legs in a relatively short period, said Professor Ozcelik, these individuals continued to move on their palms and feet and never walked upright. Although they can stand from a sitting position and maintain this upright position with flexed hips and knees, they virtually never initiate bipedal walking on their own.

It has been suggested in the past that lack of access to medical care exacerbated the effects of an under-developed cerebellum, and that this led to quadrupedality. Although it may be true that family B lacked proper medical care, families A and D had consistent access to good medical attention, and both families sought a correction of quadrupedality in their affected children, said Professor Ozcelik. Indeed, an unaffected member of family A is a physician, who has been actively involved in the medical interventions. In addition, the parents in family A also discouraged their affected children from walking on all fours, to no avail. We think that social factors are unlikely to be involved in the development of quadrupedal locomotion.

Mutations causing VLDLR deficiency are also found in Hutterites, a group of Anabaptists who live in colonies of North America. There, however, most of the affected individuals cannot walk at all. The neurological characteristics of the affected members of the Turkish families and the Hutterites seem similar, with the most striking difference being that the Turkish individuals are able to walk on all fours, said the scientists. They hypothesize that the Hutterites may be more profoundly affected due to the deficiency in VLDLR and a neighbouring gene, and therefore lack the motor skills even for quadrupedal locomotion.

Along with brain enlargement, speech, and the ability to make tools, upright walking has long been regarded as one of the key traits that have led to modern humans. Professor Ozcelik's team have opened a window on how mutations in VLDLR affect brain development and influence gait in humans.

It will be interesting to see if the VLDLR gene is involved in other types of cerebellar ataxias. In addition, we hope to identify the defective genes associated with quadrupedal locomotion in families B and C, he says.

How exercise changes structure and function of heart

Tue, 22 Apr 2008 04:00:00 PST

( from http://www.rxpgnews.com ) For the first time researchers are beginning to understand exactly how various forms of exercise impact the heart. Massachusetts General Hospital (MGH) investigators, in collaboration with the Harvard University Health Services, have found that 90 days of vigorous athletic training produces significant changes in cardiac structure and function and that the type of change varies with the type of exercise performed. Their study appears in the April Journal of Applied Physiology.

“Most of what we know about cardiac changes in athletes and other physically active people comes from ‘snapshots,’ taken at one specific point in time. What we did in this first-of-a-kind study was to follow athletes over several months to determine how the training process actually causes change to occur,” says Aaron Baggish, MD, a fellow in the MGH Cardiology Division and lead author of the study.

To investigate how exercise affects the heart over time, the MGH researchers enrolled two groups of Harvard University student athletes at the beginning of the fall 2006 semester. One group was comprised of endurance athletes – 20 male and 20 female rowers – and the other, strength athletes – 35 male football players. Student athletes were studied while participating their normal team training, with emphasis on how the heart adapts to a typical season of competitive athletics.

Echocardiography studies – ultrasound examination of the heart’s structure and function – were taken at the beginning and end of the 90-day study period. Participants followed the normal training regimens developed by their coaches and trainers, and weekly training activity was recorded. Endurance training included one- to three-hour sessions of on-water practice or use of indoor rowing equipment. The strength athletes took part in skill-focused drills, exercises designed to improve muscle strength and reaction time, and supervised weight training. Participants also were questioned confidentially about the use of steroids, and any who reported such use were excluded from the study.

At the end of the 90-day study period, both groups had significant overall increases in the size of their hearts. For endurance athletes, the left and right ventricles – the chambers that send blood into the aorta and to the lungs, respectively – expanded. In contrast, the heart muscle of the strength athletes tended to thicken, a phenomenon that appeared to be confined to the left ventricle. The most significant functional differences related to the relaxation of the heart muscle between beats – which increased in the endurance athletes but decreased in strength athletes, while still remaining within normal ranges.

“We were quite surprised by both the magnitude of changes over a relatively short period and by how great the differences were between the two groups of athletes,” Baggish says. “The functional differences raise questions about the potential impact of long-term training, which should be followed up in future studies.”

While this study looks at young athletes with healthy hearts, the information it provides may someday benefit heart disease patients. “The take-home message is that, just as not all heart disease is equal, not all exercise prescriptions are equal,” Baggish explains. “This should start us thinking about whether we should tailor the type of exercise patients should do to their specific type of heart disease. The concept will need to be studied in heart disease patients before we can make any definitive recommendations.”

Repeated methamphetamine use causes long-term adaptations in brains of mice, researchers find

Wed, 09 Apr 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Repeatedly stimulating the mouse brain with methamphetamine depresses important areas of the brain, and those changes can only be undone by re-introducing the drug, according to research at the University of Washington and other institutions. The study, which appears in the April 10 issue of the journal Neuron, provides one of the most in-depth views of the mechanisms of methamphetamine addiction, and suggests that withdrawal from the drug may not undo the changes the stimulant can cause in the brain.

The researchers set out to determine what sort of changes happen in the brain because of repeated use of the stimulant methamphetamine, and to better understand addiction-related behaviors like drug craving and relapse. Methamphetamine, also known as simply meth, is one of the most popular illegal drugs in the United States, and abuse of the drug can cause severe addiction.

Scientists have believed that abuse of drugs like meth can cause changes to the neurons in the brain and the synapses and terminals that control transmission of information in the brain. In this project, researchers focused on the mouse brain, and how it was affected by methamphetamine over 10 days, which is the mouse equivalent of chronic use in humans.

They found that the long administration and withdrawal of the drug depressed the neural terminals controlling the flow of signals between two areas of the brain, the cortex and striatum. Even a long period of withdrawal -- the equivalent of years in humans -- did not return the terminals to normal activity level. Re-introducing the drug, however, reversed the changes in the brain.

The areas affected by the drug are called pre-synaptic terminals, and are related to the flow of information from the cortex to the striatum. When a person sees something new in their environment, the scientists explained, she focuses attention on that item. At the neuron level, that process stimulates the release of dopamine, a chemical involved in transmitting signals in the brain. As the person sees the new item over and over again, the dopamine response drops, and synapses in the brain adapt to the no-longer-new item.

What happens with methamphetamine use is that the drug makes the nervous system release dopamine, which helps a user focus a lot of attention on a particular goal. Scientists believe that meth allows dopamine in the striatum to filter information coming from the cortex through the pre-synaptic terminals. The filtering of some of the terminals would help someone ignore other things and focus on that one goal or task.

After chronic use of methamphetamine, the filtering process eventually becomes a permanent depression in the activity of those terminals in the brain, the scientists found. And the only thing that can help the pre-synaptic terminals recover in mice, they found, was re-administering the drug.

What we found is that the repeated use of methamphetamine causes adaptations in the brain, and that only re-introducing the drug can reverse that, said Dr. Nigel Bamford, UW assistant professor of neurology and pediatrics and a physician at Seattle Children's Hospital. We think these changes in the brain may account for at least some of the physiological components of meth addiction.

If the mechanism turns out to be similar in people, Bamford said, this could have big effects on the treatment and management of methamphetamine addiction. One treatment for drug addiction is to give people smaller and smaller amounts of the drug to wean them from it and reduce the effects of withdrawal. Unfortunately, that method would not affect the adaptation of the neural terminals in the brain.

Now that we have some understanding of the mechanism through which meth addiction occurs, we may be able to develop other approaches to treating addiction, explained Bamford. We might be able to target some of the chemical receptors in the brain to reset the system and get rid of this depressed state in the pre-synaptic terminals.

Though scientists believe that other stimulants, like methylphenidate, may have similar effects on the brain, they caution against applying these findings to other situations. These synaptic changes may not occur in patients with underlying conditions that require treatment with stimulants, the scientists said.

U. Iowa study finds biological link between pain and fatigue

Mon, 07 Apr 2008 04:00:00 PST

( from http://www.rxpgnews.com ) A recent University of Iowa study reveals a biological link between pain and fatigue and may help explain why more women than men are diagnosed with chronic pain and fatigue conditions like fibromyalgia and chronic fatigue syndrome.

Working with mice, the researchers, led by Kathleen Sluka, Ph.D., professor in the Graduate Program in Physical Therapy and Rehabilitation Science in the UI Roy J. and Lucille A. Carver College of Medicine, found that a protein involved in muscle pain works in conjunction with the male hormone testosterone to protect against muscle fatigue.

Chronic pain and fatigue often occur together -- as many as three in four people with chronic, widespread musculoskeletal pain report having fatigue; and as many as 94 percent of people with chronic fatigue syndromes report muscle pain. Women make up the majority of patients with these conditions.

To probe the link between pain and fatigue, and the influence of sex, the UI team compared exercise-induced muscle fatigue in male and female mice with and without ASIC3 -- an acid-activated ion channel protein that the team has shown to be involved in musculoskeletal pain.

A task involving three one-hour runs produced different levels of fatigue in the different groups of mice as measured by the temporary loss of muscle strength caused by the exercise.

Male mice with ASIC3 were less fatigued by the task than female mice. However, male mice without the ASIC3 protein showed levels of fatigue that were similar to the female mice and were greater than for the normal males.

In addition, when female mice with ASIC3 were given testosterone, their muscles became as resistant to fatigue as the normal male mice. In contrast, the muscle strength of female mice without the protein was not boosted by testosterone.

The differences in fatigue between males and females depends on both the presence of testosterone and the activation of ASIC3 channels, which suggests that they are interacting somehow to protect against fatigue, Sluka said. These differences may help explain some of the underlying differences we see in chronic pain conditions that include fatigue with respect to the predominance of women over men.

The study, which was published in the Feb. 28 issue of the American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, indicates that muscle pain and fatigue are not independent conditions and may share a common pathway that is disrupted in chronic muscle pain conditions. The team plans to continue their studies and investigate whether pain enhances fatigue more in females than males.

Our long-term goal is to come up with better treatments for chronic musculoskeletal pain, Sluka said. But the fatigue that is typically associated with chronic widespread pain is also big clinical problem -- it leaves people unable to work or engage in social activities. If we could find a way to reduce fatigue, we could really improve quality of life for these patients.

Scientists identify new longevity genes

Wed, 12 Mar 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Scientists at the University of Washington and other institutions have identified 25 genes regulating lifespan in two organisms separated by about 1.5 billion years in evolutionary change. At least 15 of those genes have very similar versions in humans, suggesting that scientists may be able to target those genes to help slow down the aging process and treat age-related conditions. The study will be published online by the journal Genome Research on March 13.

The two organisms used in this study, the single-celled budding yeast and the roundworm C. elegans, are commonly used models for aging research. Finding genes that are conserved between the two organisms is significant, researchers say, because the two species are so far apart on the evolutionary scale -- even farther apart than the tiny worms and humans. That, combined with the presence of similar human genes, is an indication that these genes could regulate human longevity as well.

Now that we know what many of these genes actually are, we have potential targets to go after in humans, said Brian Kennedy, UW associate professor of biochemistry and one of the senior authors of the study. We hope that in the future we could affect those targets and improve not just lifespan, but also the 'health span' or the period of a person's life when they can be healthy and not suffer from age-related illnesses.

Several of the genes that the scientists identified as being involved in aging are also connected to a key nutrient response pathway known as known as the Target of Rapamycin, or TOR. That finding gives more evidence to the theory that calorie intake and nutrient response affect lifespan by altering TOR activity. Previous studies have found that drastically restricting the caloric intake of organisms, an approach known as dietary restriction, can prolong their lifespan and reduce the incidence of age-related diseases. TOR inhibitors are being tested clinically in people for anti-cancer properties, and this work suggests they may also be useful against a variety of age-associated diseases.

What we'd like to eventually do is be able to mimic the effects of dietary restriction with a drug, explained Matt Kaeberlein, another senior author on the paper and a UW assistant professor of pathology. Most people don't want to cut their diet that drastically, just so they may live a little longer. But someday in the future, we may be able to accomplish the same thing with a pill.

These findings also give new insight into the genetic basis of aging, the scientists said, and provide some of the first quantitative evidence that genes regulating aging have been conserved during the process of evolution. Earlier evolutionary theories suggested that aging was not genetically controlled, since an organism does not get any advantage in natural selection by having a very long lifespan that goes far past their reproductive age.

To find these lifespan-controlling genes, the scientists took a genomic approach to comprehensively examine genes that affect aging in yeast and worms. Based on published reports, they first identified 276 genes in C. elegans that affected aging, and then searched for similar genetic sequences in the yeast genome. Of the 25 aging-related genes they found in both worms and yeast, only three had been previously thought to be conserved across many organisms.

Oregon study raises questions on synthetic progestins

Sun, 09 Mar 2008 05:00:00 PST

( from http://www.rxpgnews.com ) The widely used synthetic progestin medroxyprogesterone acetate (MPA) decreased endothelial function in premenopausal women in a study done at the University of Oregon. The finding, researchers said, raises concerns about long-term effects of MPA and possibly other synthetic hormones on vascular health in young women.

The vascular endothelium lines the inside of blood vessels. In recent years, it has been found to be a dynamic organ that serves an important role in the prevention of atherosclerosis.

The logical conclusion of this study is that over a long period of time it would not be good to have exposure to an agent that is reducing blood vessel flexibility, because it could be associated with the development of heart disease or related problems, said co-author Dr. Paul F. Kaplan, a long-time Eugene gynecologist and senior researcher in the UO's human physiology department. He stressed, however, that a longer, larger study is needed.

MPA is the progestin that was used in the Women's Health Initiative (WHI), including a clinical study on hormone-replacement therapy halted because of health concerns in postmenopausal women. MPA is the active ingredient of Provera, which is used to treat abnormal uterine bleeding, induce menstrual cycles and relieve symptoms of the menopause.

It's also a component in Depo/Provera, an injectible long-lasting contraceptive used by many young women. Millions of women use various hormone therapies with a variety of progestin types for contraception. In the U.S. alone, 80 percent of women have used oral contraceptives.

The UO study, appearing online ahead of regular publication by the journal Heart and Circulatory Physiology, is among the first to focus on the impact of MPA in premenopausal women. Fourteen women, 19-27 years old, took part in the study after passing thorough medical exams to screen out numerous health conditions.

The five-member UO team -- led by Jessica R. Meendering, a former UO doctoral student now a professor of exercise science at the University of Nebraska in Omaha -- studied the effects of the sex hormone estradiol by itself and in combination with MPA on endothelial function of the brachial artery. The health of the endothelium in this artery has been shown to be a telling proxy for the coronary arteries and a good predictor of cardiovascular risk.

When researchers gave an oral version of MPA to determine its impact, they found that it wiped out the positive effects on endothelial function that estradiol had provided. MPA reduced the function by reducing the brachial artery's ability to dilate -- grow bigger in diameter -- in response to the stress of changing blood flow, Kaplan said.

UO researchers also found that MPA had an effect on concentrations of endothelin-1, a peptide that promotes cell division and serves as a mediator of inflammation. It also acts as a constricting factor for blood vessels. When peptide levels rise, endothelin-1 is suspected to play a key role in many diseases of the airways, pulmonary circulation, inflammatory lung diseases and vasoconstriction of blood vessels. UO researchers saw levels decline with estradiol alone, but increase substantially with the addition of MPA, negating the benefits of the estrogen.

There is an overwhelming amount of evidence to suggest that estrogen is beneficial to arterial vascular health of women, Meendering said. Since the WHI found either no benefit or a slight increase in adverse cardiovascular events in postmenopausal women taking combination hormone-replacement therapy containing estrogen and MPA, many have questioned the vascular effects MPA and its use in postmenopausal women. This led our group to question how MPA affects the vasculature in young women.

We need to be taking the time to find out if different synthetic hormones have different effects on vascular health in young women, she said. It's not a big health concern right now, because there are no obvious short-term effects raising health concerns. But we don't know how these synthetic hormones taken by young women affect their long-term cardiovascular health. Maybe effects aren't being noticed while women are young, but maybe they are adding to the fact that rates of cardiovascular disease are so high in women.

Kaplan stressed that this project was a starting point of major basic science research, so this study does not say women should change what they are doing.

We can say that we saw vascular changes in the arteries of the arm that have been shown in previous studies involving coronary arteries, he added. This study does let us say that whatever changes we are seeing are important not just for the arm but probably for most of the major arteries in the body, and this is important for cardiac disease.

Genetic tags reveal secrets of memories' staying power in mice

Thu, 21 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) A better understanding of how memory works is emerging from a newfound ability to link a learning experience in a mouse to consequent changes in the inner workings of its neurons. Researchers, supported in part by the National Institutes of Health's National Institute of Mental Health (NIMH), have developed a way to pinpoint the specific cellular components that sustain a specific memory in genetically-engineered mice.

Remarkably, this research demonstrates a way to untangle precisely which cells and connections are activated by a particular memory, said NIMH Director Thomas Insel, M.D. We are actually learning the molecular basis of learning and memory.

For a memory to last long-term, the neural connections holding it need to be strengthened by incorporating new proteins triggered by the learning. Yet, it's been a mystery how these new proteins -- born deep inside a neuron -- end up becoming part of the specific connections in far-off neuronal extensions that encode that memory.

By tracing the destinations of such migrating proteins, the researchers located the neural connections, called synapses, holding a specific fear memory. In the process, they discovered these synapses are distinguished by telltale molecular tags that enable them to capture the memory-sustaining proteins.

Mark Mayford, Ph.D., and Naoki Matsuo, Ph.D., of the Scripps Research Institute, report on their findings in the February 22, 2008, issue of the journal Science.

The Scripps researchers have been applying their new technique in a series of studies that focus on progressively finer details of the molecular machinery of memory.

Inside neurons involved in a specific memory, we're tracing molecules activated by that learning to see how it ultimately changes neural connections, explained Mayford.

In a study published in the August 31, 2007, Science, Mayford and colleagues showed the same neurons activated by a learning experience are also activated when that memory is retrieved. The more neurons involved in the learning, the stronger the memory.

The researchers determined this by genetically engineering a strain of mice with traceable neurons in the brain's fear center, called the amygdala. Inserted genes caused activated neurons to glow red when the animals learned to fear situations where they received shocks, in a process known as fear conditioning -- and to glow green when the memory was later retrieved. The researchers then chemically prevented further expression of those neurons, so that resulting neural and behavioral changes could be confidently attributed to that learning experience at a later time. The study revealed which circuits and neurons were involved in the specific learning experience.

In the new study, Mayford and Matsuo adapted this approach to discover how fear learning works at a deeper level -- inside neurons of the brain's memory hub, called the hippocampus.

Evidence suggested that proteins called AMPA receptors strengthen memories by becoming part of the synapses encoding them. To identify these synapses, the researchers genetically engineered a strain of mice to express AMPA receptors traceable by a green glow. After fear conditioning had triggered new AMPA receptors deep in the neuron's nucleus, they chemically suppressed any further expression of the proteins. This allowed time for the receptors to migrate to their appointed synapses. Hours later, green fluorescence revealed the fate of the specific AMPA receptors born in response to the learning.

As expected, the newly synthesized AMPA receptors had traveled and become part of only certain hippocampus synapses -- presumably the ones holding the memory. Synaptic connections are made onto small nubs on the neuron called spines. These spines come in three different shapes called thin, stubby and mushroom. While little was known about the function of these differently shaped spines, the fact that they are altered in various forms of mental retardation, like Fragile-X syndrome, suggests a critical importance in mental function.

The researchers discovered the synapses that received the AMPA receptors with memory were limited to the mushroom type. The mushroom spines also figured prominently in the same neurons when the fear conditioning was reversed by repeatedly exposing the animals to the feared situation without getting shocked -- a procedure called extinction learning. This indicated that the same neurons activated when a fear is learned are also activated when it is lost. The surge in mushroom spine capture of the receptors appeared within hours of learning and was gone after a few days, but appeared to be critical for cementing the memory.

Immune deficiency and balance disorder result from single gene defect

Thu, 21 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) A genetic defect that causes a severe immune deficiency in humans may also produce balance disorders, according to a new study by researchers at the University of Iowa, The Jackson Laboratory and East Carolina University.

The study, published online Feb. 21 in the Journal of Clinical Investigation, examined a specialized strain of Jackson Laboratory mice with a mutation that eliminates the production a protein called p22phox. Disruption of this protein causes a form of chronic granulomatous disease (CGD) -- a severe immune deficiency -- in humans.

The researchers found that mice without p22phox develop an immune deficiency that mimics human CGD. They also discovered that the gene defect produces a severe balance disorder in the mice caused by loss of gravity-sensing crystals in the inner ear.

The implication is that human patients with CGD caused by defects in this gene may also have balance disorders, said Botond Banfi, M.D., Ph.D., UI assistant professor of anatomy and cell biology and senior author of the study. If that is the case, this would be the first patient population where we could study the consequences of losing the sensation of gravity.

We hope that clinicians will test the balance capacity of those patients with this rare form of CGD Banfi added. Although it is hard to say what the consequences might be of not sensing gravity, these patients may be more prone to accidents like falling.

In addition to Banfi, the research team included Yoko Nakano, Ph.D., a UI postdoctoral fellow in Banfi's laboratory and lead author of the study; David Bergstrom, Ph.D., research scientist, and Chantal Longo-Guess, research assistant, both at The Jackson Laboratory; Sherri Jones, Ph.D., associate professor of communication sciences and disorders at East Carolina University; and William Nauseef, M.D., UI professor of internal medicine.

P22phox is emerging as a critical subunit of a family of enzymes that produce reactive oxygen species (ROS). For many years, ROS were simply thought of as destructive molecules that can kill infecting bacteria but also damage human cells. More recently, however, ROS have been shown to play an important role in many normal cell processes, including development and blood pressure regulation. The family of enzymes that produce ROS are called NADPH oxidases (Nox), and disruption of these enzymes has been implicated in a range of diseases, including cardiovascular and neurodegenerative diseases as well as immune deficiencies like CGD.

There are several forms of CGD caused by different genetic defects affecting the Nox complex of pathogen-fighting cells called phagocytes. CGD caused by lack of p22phox is one of the least common forms of the disease in humans. The mutant mouse, which was produced by The Jackson Laboratory's Neuromutagenesis Facility, represents the first animal model for this version of CGD and will be helpful in understanding the disease and developing potential treatments.

The study found that the mice without the p22phox protein were unable to produce ROS in phagocytes and were particularly susceptible to infection. For mice without the protein, infection with bacterial pneumonia was universally fatal. In contrast, normal mice had a 100 percent recovery rate from the same infection.

The mutant mice also had a severe balance disorder. Unlike normal mice that quickly learned how to walk on a rotating rod without falling off, the mutant mice always fell off within a few seconds. Additionally, the study showed that activity of nerve cells in the inner ear responsible for sending gravity signals to the brain was absent in the mutant mice.

Loss of p22phox affects two enzyme complexes: one in phagocytes that is responsible for the immune defect, and one in the inner ear, Banfi said. Since this is the first mouse model for defects in the p22phox subunit, this is the first time that its role in balance has been revealed.

Although inner ear cells looked normal in the mutant mice, the researchers discovered that otoconia -- tiny calcium carbonate crystals that are essential for sensing gravity -- do not form in the inner ears of these mice. Restoring the normal gene to the mutant mice rescued otoconial production and prevented the balance disorder. However, although the treatment did improve the mice's immune response, the partial restoration of gene expression was not sufficient to cure the immune deficiency completely.

This may mean that gene therapy, which would only partially restore expression of p22phox, would not completely cure CGD in humans, cautioned Banfi. We may have to look for alternatives and these mice will be ideal models to test new ideas for therapy.

The team was also able to track the location of the Nox complex during embryonic development of the inner ear by visualizing the location of p22phox. Interestingly, the complex does not reside in the same place that the otoconia form leading the researchers to propose a new mechanism by which the Nox complex controls production of the crystals.

Transparent fish to make human biology clearer

Wed, 06 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Zebrafish are genetically similar to humans and are good models for human biology and disease. Now, researchers at Children's Hospital Boston have created a zebrafish that is transparent throughout its life. The new fish allows scientists to directly view its internal organs, and observe processes like tumor metastasis and blood production after bone-marrow transplant in a living organism.

The fish, described in the February 7 issue of Cell Stem Cell, was created by Richard White, MD, PhD, a clinical fellow in the Stem Cell Program at Children's, with others in the laboratory of Leonard Zon, PhD.

The classic method for studying human diseases in animals is to allow the animal to get the disease, kill and dissect the animal, then ask, what happened? But in cancer and other fast-changing processes that traverse the body, this method is bound to miss something. It's like taking a photograph when you need a video, says White, also an instructor of medicine at the Dana-Farber Cancer Institute.

Zebrafish embryos have enabled researchers to study disease in live organisms, since they are transparent. But zebrafish adults are opaque. Everything after four weeks has been invisible to us, says White.

White's first experiment on the zebrafish examined how a cancer spreads. The process by which a tumor goes from being localized to widespread and ultimately fatal is the most vexing problem that oncologists face, says White. We don't know why cancer cells decide to move away from their primary site to other parts in the body.

White created a fluorescent melanoma tumor in the transparent fish's abdominal cavity. Viewing the fish under a microscope, White saw the cancer cells begin to spread within five days. He even saw individual cells metastasize, something that has not been observed, so readily and in real-time, in a living organism.

The spreading melanoma cells appeared to home to the skin after leaving the abdominal cavity. This told us that when tumor cells spread to other parts in the body, they don't do it randomly, says White. They know where to go.

White plans to study tumor cell homing, then look for ways to modify the tumor cells or cells of the host so that the spreading cells never find their new location.

The fish may also answer questions about stem cell transplants. While transplants of blood-forming stem cells help cancer patients rebuild healthy blood, some transplants don't take, for reasons that are unknown. Scientists have lacked a full understanding what steps blood stem cells must take to do their job, says White.

White showed the process is observable in the fish. He first irradiated a transparent fish's bone marrow, then transplanted fluorescent blood-forming stem cells from another zebrafish. By four weeks, the fluorescent stem cells had visibly migrated and grown in the fish's bone marrow, which is in the kidney. Even individual stem cells were visible, something researchers haven't easily observed in a living organism, White says.

By studying how the stem cells embed and build blood in the fish, scientists can look for ways to help patients rebuild their blood faster. Drugs and genes could be tested in the living fish, with direct observation of results, White says.

Anemia treatment may be a double-edged sword

Wed, 30 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Erythropoietin has so far been known to doctors as a hormone that boosts red-blood-cell production. Now, a mouse study led by Lois Smith, MD, PhD, an ophthalmologist at Children's Hospital Boston, shows it also keeps blood vessels alive and growing in the eye. The findings not only add a new function to the hormone, but also give doctors a reason to pause before prescribing it to patients with diseases affected by abnormal blood-vessel growth, such as retinopathy and cancer.

The study, published in the February issue of the Journal of Clinical Investigation (online January 24), also found that whether the hormone is a risk or benefit depends on the timing of administration.

Smith and first author Jing Chen, PhD, worked in mice with retinopathy, an eye disease that begins when healthy blood vessels nourishing the retina die. Numerous vessels then grow in, but they are deformed. Ultimately, the deformed vessels may pull the retina off the back of the eye, causing blindness.

The researchers measured erythropoietin produced in the retina as the disease progressed. Production was 3 to 10 times below normal during early-stage retinopathy, when healthy blood vessels died, and 12 to 33 times above normal during late-stage retinopathy, when deformed blood vessels grew into the retina. The researchers concluded that erythropoietin helps blood vessels survive and grow in the retina, with effects that may be healthy or harmful.

Next, the team examined whether giving erythropoietin could treat retinopathy. They injected erythropoietin into the bloodstream either early, as the mice lost healthy blood vessels, or later, when deformed blood vessels began to invade--then compared them with untreated mice.

Boosting erythropoietin early slowed the disease. The mice lost half as many healthy blood vessels, causing about 30 percent fewer deformed vessels to grow in. Raising erythropoietin levels later, when deformed blood vessels were present, appeared to accelerate the disease--slightly more deformed blood vessels grew in.

If similar effects are found in humans, and its use is properly timed, then giving erythropoietin early could slow loss of healthy blood vessels in retinopathy, says Smith. Right now, there is very little out there to treat blood vessel loss in patients with retinopathy. However, further studies on the restoration of normal levels of erythropoietin are needed to translate these results to patients.

In other diseases, like cancer, in which doctors need to slow blood vessel growth, the hormone could be blocked, although clinical trials would need to confirm this idea, she adds.

But given at the wrong time, erythropoietin may make blood vessels grow in an unhealthy way, says Smith. For example, because it boosts red blood cells, erythropoietin is often prescribed to premature babies and diabetic adults for anemia. Some of these patients also have retinopathy. Giving the hormone at the wrong time might help anemia, but worsen the eye disease.

We're not saying, 'don't do it.' We're saying, 'think about it,' says Smith. Physicians should look at the state of the eye before giving erythropoietin to patients with retinopathy. They should consider not giving it to patients with full-blown retinopathy, in which abnormal vessels are present, because our work suggests it may accelerate the disease. However, if a patient is early on in the disease, then our work suggests erythropoietin may be beneficial.

Cancer patients, who often take erythropoietin for anemia, face a similar potential risk, says Smith. Since erythropoietin has the potential to make blood vessels in tumors grow, it could make tumors worse, although a clinical trial is required to know if this is true in humans.

Overall, Smith says her mouse studies are a reason for doctors to think and researchers to investigate, not for patients to panic.

Breakdown of kidney's ability to clean its own filters likely causes disease

Tue, 29 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Jan. 29, 2008 -- The kidney actively cleans its most selective filter to keep it from clogging with blood proteins, scientists from Washington University School of Medicine in St. Louis reveal in a new study.

Researchers showed that breakdown of this self-cleaning feature can make kidneys more vulnerable to dysfunction and disease.

We speculate that defects of this clearance mechanism can leave things on the filter that can damage it, says senior author Andrey Shaw, M.D., Emil R. Unanue Professor of Immunobiology in Pathology and Immunology. This could include autoimmune antibodies that mistakenly target the body's own tissues like those that occur in the disease lupus.

The study appears in the Jan. 22 Proceedings of the National Academy of Sciences.

Despite extensive knowledge of the structure of the kidney, several scientific controversies linger over how the organ does its complicated and essential job of filtering wastes from the blood for disposal without simultaneously discarding too much water or key blood proteins in the urine. Understanding how these tricky tasks are accomplished is essential to developing new treatments for kidney disease and renal failure, which are among the top ten causes of death in the United States.

Like many mechanical filtering systems, the kidney passes the blood through a series of progressively finer screens. After passing through a structure known as the glomerular basement membrane (GBM), fluid and serum proteins must finally pass through the most selective filter of the kidney, which is comprised of specialized epithelial cells called podocytes. These cells form a web-like barrier to the passage of large serum proteins into the urine.

The kidney screens 150 to 200 liters of blood daily, and we were curious as to how the kidney keeps the filter from clogging up, says first author Shreeram Akilesh, an M.D./Ph.D. student. The two most common blood serum and plasma proteins are albumin, which helps regulate blood volume and convey a number of different substances around the body, and immunoglobin G (IgG), a type of immune system antibody. Because they're so common, we figured they would be among the most likely to get stuck on the filter, and set out to look for proteins that help clear them.

Researchers looked for proteins made in podocytes that could bind to albumin and IgG, reasoning that such proteins likely provide the handles the podocytes need to grab proteins and clear them from the filter.

A protein known as FcRn was high on the list of likely suspects. Akilesh had studied FcRn previously in the laboratory of coauthor Derry C. Roopenian, Ph.D., professor at the Jackson Laboratory in Bar Harbor, Maine. Prior research there and in other laboratories had revealed that FcRn binds to both IgG and albumin and is present in human podocytes.

After confirming that the FcRn protein also is made in mouse podocytes, scientists then asked if FcRn was responsible for clearing IgG antibody from the filter. To do this, they measured the retention of a radioactive tracer in the kidneys of normal mice and in mice where the gene for FcRn had been disabled. Mice lacking FcRn had difficulty clearing antibody from the kidney.

When researchers studied the mice lacking FcRn for longer periods of time, they saw evidence that antibodies were accumulating in the kidney.

In another experiment, researchers gave the mice injections of large quantities of protein to saturate the clearance system. They followed those injections with what would normally have been a harmlessly small dose of an antibody potentially toxic to the kidney. The mice developed kidney damage as a result. Researchers believe this was because they couldn't clear the toxic antibody from the GBM quickly enough.

This is the first clear demonstration that the filter system in the kidney isn't just a passive mechanical filter, it's actually involved in its own maintenance, says Akilesh. It also provides us with a nice mechanism for explaining how the normal function of this filter may be breaking down in ways that leads to kidney disease and damage.

To follow up, Shaw plans to look for other podocyte proteins involved in filter clearance.

Lungs' mast cells could provide new treatment target for asthma, other respiratory disease

Tue, 29 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Jan. 29, 2008) -- An enzyme released by mast cells in the lungs appears to play a key role in the tightening of airways that is a hallmark of asthma -- pointing to a potential new target for treatment against the illness.

Reporting in the online edition of Proceedings of the National Academy of Sciences, a team at Weill Cornell Medical College explains that during an immune response, mast cells release the enzyme -- called renin -- which in turn produces angiotensin, a potent constrictor of the smooth muscle that lines airways.

Mast cells are normally present in small numbers in all organs, and are best known for their role in allergy, shock, wound healing and defense against pathogens.

Back in 2005, our team was the first to discover that mast cells in the heart released renin locally, which elicited heart arrhythmias by triggering angiotensin production within the heart, explained co-senior author Dr. Roberto Levi, professor of pharmacology at Weill Cornell Medical College.

Now, we've expanded those findings to the lungs, where similar mechanisms appear to work locally to help trigger constriction in the airway, he says.

Renin is no stranger to medical research -- for decades, doctors have known that the enzyme is produced by the kidney in relatively large quantities for systemic use throughout the body. But the Weill Cornell team was the first to discover that mast cells also produced their own local supply of the enzyme, at a variety of body sites.

In the heart and now the lungs, this localized production of renin appears to have a profound effect on nearby tissues, says co-senior author Dr. Randi Silver, associate professor of physiology and biophysics at Weill Cornell.

More study is needed, of course, but our finding suggests that drugs that target renin might prove effective agents in dampening asthma or other respiratory diseases, she says. These types of 'renin inhibitors' are, in fact, currently being developed by the pharmaceutical industry right now.

The genesis of the new study came through the efforts of the study's lead author, Arul Veerappan, now a postdoctoral researcher in Dr. Silver's laboratory. He looked closely at rings of bronchial tissue from rodents, discovering that mast cells in these rings released renin along with other substances.

You ended up getting the same biochemical cascade that we had seen elsewhere -- newly produced renin bringing about a local rise in angiotensin in tissues, Veerappan says.

Research led by co-author Alicia Reid, also a postdoctoral associate in Dr. Silver's lab, led to another first. Using a technology Reid developed, the researchers confirmed for the first time that mast cells from human lung tissue release a form of renin that is nearly identical to renin found in human mast cells grown in culture or human kidney renin.

That's a big achievement, because it supports the notion that the mechanism we have discovered is not just a laboratory phenomenon -- it's actually occurring in the living human lung, Dr. Levi notes.

New research suggests that local renin production may also be crucial in diseases marked by tissue fibrosis (stiffening). In fact, Dr. Silver's lab is now looking at the role locally produced renin might play in a rare, deadly illness called idiopathic pulmonary fibrosis (IPF), where lung tissue becomes increasingly inflexible over time.

We're interested in any disease in which we can also detect local renin/angiotensin production because it appears to be linked to fibrosis, vasoconstriction, and now bronchoconstriction, Dr. Silver explains.

The goal of all this research: new treatment targets for a range of illnesses.

Of course, we already have antihypertensive medicines -- such as ACE inhibitors and angiotensin receptor blockers -- that focus on curbing angiotensin in a more systemic way, says Dr. Levi. But if we could find agents that dampen this renin-angiotensin cascade locally -- in the heart or the lung, for example -- that could prove to be a formidable new weapon against disease.

The pitter patter of little feet... climbing straight up a wall

Tue, 29 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Building upon several years of research into the gecko's uncanny ability to climb sheer walls, researchers at the University of California, Berkeley, have developed an adhesive that is the first to master the easy attach and easy release of the reptile's padded feet. The material could prove useful for a range of products, from climbing equipment to medical devices.

Unlike duct tape or glue, the new material is crafted from millions of tiny, hard, plastic fibers that establish grip; a mere square two centimeters on a side can support 400 grams (close to a pound). While tape sticks when it presses onto a surface, the new adhesive sticks as it slides on a surface and releases as it lifts -- this is the trick behind a gecko's speedy vertical escapes.

The new study appeared online Jan. 23, 2008, in the Journal of the Royal Society Interface.

There are other synthetic adhesives inspired by gecko feet and they adhere much like conventional tape. In contrast, the new adhesive brushes along a surface to develop traction. While ideal for hanging posters, the characteristic is even more important for any application that requires movement, such as climbing.

The gecko has a very sophisticated hierarchical structure of compliant toes, microfibers, nanofibers and nanoattachment plates that allows the foot to attach and release with very little effort, said co-author and Berkeley professor Ron Fearing, The gecko makes it look simple, but the animal needs to control the directions it is moving its toes--correct movement equates to little effort, he said.

The new material is also novel in that it gets stronger with use. In experiments, it tightened its hold as it was rubbed repeatedly against a glass plate. The extra strength is caused by the fibers bending over to make more contact, yet once released, the fibers returned to their original shape. The research team is exploring ways to permanently bend the fibers so that the grip strength is its strongest from the outset, no massaging required.

According to Fearing, the new material is the first to mimic the nature of the gecko's characteristic non-sticky by default feet. The Berkeley researchers, all engineers, have worked closely with biologists Robert Full, also at Berkeley, and Kellar Autumn of Lewis and Clark College in Portland, Ore., to uncover the key natural properties behind that unique foot, the secret to high mobility on sheer surfaces.

Fearing and his colleagues are part of an NSF-supported Nanoscale Interdisciplinary Research Team (NIRT) that was specifically tasked in 2003 with developing biologically-inspired synthetic gecko adhesives.

The results of this project are an impressive example of how teaming engineers with biologists results in a better understanding of the role of 'engineering' in nature, says Lynn Preston, the NSF officer who supported these NIRT researchers, and many other teams of engineers and biologists, through her leadership of NSF's Engineering Research Centers program. This is a perfect example of how to turn that understanding into products that are as sophisticated as those developed by 'Mother Nature'.

Researchers put the bite on mosquitoes

Wed, 16 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Few things sting like a mosquito's bite--especially if that bite carries a disease such as malaria, yellow fever, Dengue fever or West Nile virus. But if researchers from The University of Arizona in Tucson have their way, one day mosquito bites may prove deadly to the mosquitoes as well.

Our goal is to turn the female mosquito's blood meal into the last meal she ever eats, said project leader Roger L. Miesfeld, a professor of biochemistry and molecular biophysics in UA's College of Science and a member of BIO5 and the Arizona Cancer Center.

Other UA researchers involved with the project include Patricia Y. Scaraffia, Guanhong Tan, Jun Isoe, BIO5 member Vicki H. Wysocki, and the late Michael A. Wells.

These researchers have discovered that one particular mosquito species, Aedes aegypti, has a surprisingly complex metabolic pathway, one that requires its members to excrete toxic nitrogen after gorging on human blood. If the mosquitoes fail to do so, they'll also fail to lay eggs--and will likely sicken and die.

Scaraffia, a research assistant professor in UA's department of biochemistry and molecular biophysics, and the other members of the team published their findings in the January 15 issue of the Proceedings of the National Academy of Sciences. The research was funded by the National Institutes of Health.

Miesfeld and his colleagues are seeking a molecule that is harmless to humans, but will gum up the works of mosquito metabolism, forcing the mosquitoes to hang onto the nitrogen. Such a molecule would kill both the mosquitoes and their would-be progeny--thus slowing the spread of disease.

Once found, this molecule--and similar molecules aimed at other mosquito species--could be developed into an insecticide and sprayed in places where mosquitoes congregate, such as around water and on mosquito netting.

The researchers also envision developing an oral insecticide--a mosquito-slaying pill that members of a community with a high instance of, say, yellow fever or malaria might take to reduce the mosquito population. The pill wouldn't be a vaccine; if people who took it were later bitten by a disease-carrying mosquito, they would still become infected. However, the mosquito would ingest the insecticide along with the blood, causing her to bear fewer young and possibly die before she could bite anyone else.

The whole community would essentially become one big mosquito trap, Miesfeld said. Over time, mosquito populations and disease rates would both decline. It would be a group effort that in the long run could have a huge impact.

In a world where both mosquitoes and the diseases they carry are becoming increasingly resistant to known insecticides and medicines, finding new ways to fight them is crucial.

This would be one more weapon in our arsenal against diseases that kill millions of people a year, Miesfeld said.

UVa biomedical engineering study shows magnetic field can reduce swelling

Thu, 03 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) A recent study by University of Virginia researchers demonstrates that the use of an acute, localized static magnetic field of moderate strength can result in significant reduction of swelling when applied immediately after an inflammatory injury.

Thomas Skalak, professor and chair of biomedical engineering, and Cassandra Morris, a former Ph.D. student in biomedical engineering at U.Va., reported their findings in the November 2007 edition of the American Journal of Physiology.

In the study, the hind paws of anesthetized rats were treated with inflammatory agents in order to simulate tissue injury. Magnetic therapy was then applied to the paws. The research results indicate that magnets can significantly reduce swelling if applied immediately after tissue trauma.

Since muscle bruising and joint sprains are the most common injuries worldwide, this discovery has potentially significant implications. If an injury doesn't swell, it will heal faster - and the person will experience less pain and better mobility, says Skalak. This means that magnets might be used much the way ice packs and compression are now used for everyday sprains, bumps, and bruises, but with more beneficial results. The ready availability and low cost of this treatment could produce huge gains in worker productivity and quality of life.

Magnets have been touted for their healing properties since ancient Greece. Magnetic therapy is still widely used today as an alternative method for treating a number of conditions, from arthritis to depression, but there hasn't been scientific proof that magnets can heal.

Lack of regulation and widespread public acceptance have turned magnetic therapy into a $5 billion world market. Hopeful consumers buy bracelets, knee braces, shoe inserts, mattresses and other products that are embedded with magnets based on anecdotal evidence, hoping for a non-invasive and drug-free cure to what ails them.

The Federal Drug Administration regulates specific claims of medical efficacy, but in general static magnetic fields are viewed as safe, notes Skalak, who has been carefully studying magnets for a number of years in order to develop real scientific evidence about the effectiveness of magnetic therapy.

Skalak's lab leads the field in the area of microcirculation research - the study of blood flow through the body's tiniest blood vessels. With a five-year, $875,000 grant from the National Institutes of Health's National Center for Complementary and Alternative Medicine, Skalak and Morris set out to investigate the effect of magnetic therapy on microcirculation. Initially, they sought to examine a major claim made by companies that sell magnets: that magnets increase blood flow.

In their initial study, magnets of 70 milliTesla (mT) field strength - about 10 times the strength of the common refrigerator variety - were placed near the rats' blood vessels. Quantitative measurements of blood vessel diameter were taken both before and after exposure to the static magnetic fields - the force created by the magnets. Morris and Skalak found that the force had a significant effect: the vessels that had been dilated constricted, and the constricted vessels dilated, implying that the magnetic field could induce vessel relaxation in tissues with constrained blood supply, ultimately increasing blood flow.

Dilation of blood vessels is often a major cause of swelling at sites of trauma to soft tissues such as muscles or ligaments. The prior results on vessel constriction led Morris and Skalak to look closer at whether magnets, by limiting blood flow in such cases, would also reduce swelling.

Given the results of this latest study, Skalak envisions the magnets being particularly useful to high school, college and professional sports teams, as well as school nurses and retirement communities. He has plans to continue testing the effectiveness of magnets through clinical trials and testing in elite athletes. A key to the success of magnetic therapy for tissue swelling is careful engineering of the proper field strength at the tissue location, a challenge in which most currently available commercial magnet systems fall short. The new research should allow Skalak's biomedical engineering group to design field strengths that provide real benefit for specific injuries and parts of the body.

We now hope to implement a series of steps, including private investment partners and eventually a major corporate partner, to realize these very widespread applications that will make a positive difference for human health, says Skalak.

'Runner's high' may also strengthen hearts

Thu, 08 Nov 2007 05:00:00 PST

( from http://www.rxpgnews.com ) Endorphins and other morphine-like substances known as opioids, which are released during exercise, don't just make you feel good -- they may also protect you from heart attacks, according to University of Iowa researchers.

It has long been known that the so-called runner's high is caused by natural opioids that are released during exercise. However, a UI study, which is published in the online edition of the American Journal of Physiology's Heart and Circulatory Physiology, suggests that these opioids may also be responsible for some of exercise's cardiovascular benefits.

Working with rats, UI researchers showed that blocking the receptors that bind morphine, endorphins and other opioids eliminates the cardiovascular benefits of exercise. Moreover, the UI team showed that exercise was associated with increased expression of several genes involved in opioid pathways that appear to be critical in protecting the heart.

This is the first evidence linking the natural opioids produced during exercise to the cardio-protective effects of exercise, said Eric Dickson, M.D., UI associate professor and head of emergency medicine in the Roy J. and Lucille A. Carver College of Medicine and the study's lead investigator. We have known for a long time that exercise is great for the heart. This study helps us better understand why.

Studies have shown that regular vigorous exercise reduces the risk of having a heart attack and improves survival rates following heart attack, even in people with cardiovascular disease. In addition, exercise also decreases the risk of atherosclerosis, stroke, osteoporosis and even depression. However, despite these proven health benefits, much less is understood about how exercise produces these benefits.

The UI study investigated the idea that the opioids produced by exercise might have a direct role in cardio-protection. The researchers compared rats that exercised with rats that did not. As expected, exercised rats sustained significantly less heart damage from a heart attack than non-exercised rats. The researchers then showed that blocking opioid receptors completely eliminated these cardio-protective effects in exercising rats, suggesting that opioids are responsible for some of the cardiac benefits of exercise.

The UI team also showed that exercise was associated with transient increases in expression of several opioid system genes in heart muscle, and changes in expression of other genes that are involved in inflammation and cell death. The researchers plan to investigate whether these altered gene expression patterns reveal specific cardio-protective pathways.

A better understanding of how exercise protects the heart may eventually allow scientists to harness these protective effects for patients with decreased mobility.

Hopefully this study will move us closer to developing therapies that mimic the benefits of exercise, Dickson said. It also serves as a reminder of how important it is to get out and exercise every day.

University of Iowa team discovers first moisture-sensing genes

Wed, 07 Nov 2007 05:00:00 PST

( from http://www.rxpgnews.com ) Researchers in the University of Iowa Roy J. and Lucille A. Carver College of Medicine have discovered the first two genes involved in moisture sensing (hygrosensation). The discovery also reveals a two-sensor hygrosensing system in fruit flies that may allow the flies to detect subtle changes in humidity -- an ability that is critical for the flies' survival. The results appear in the Nov. 8 issue of Nature.

Subtle variations in humidity influence reproductive behavior and geographic distribution in many animals, including insects, reptiles and birds. Because of their small size, insects, in particular, require a finely tuned ability to detect moisture levels in their environment in order to survive. However, the mechanisms and molecules involved in moisture sensing have remained a mystery.

Moisture sensing is a sensory modality, which up to this point no one has understood. This is the first study to identify genes that are involved, said Lei Liu, Ph.D., UI postdoctoral fellow in internal medicine and lead author of the study.

Liu and colleagues made their discovery by testing the idea that moisture sensing is a special form of mechanosensation -- the ability to detect physical forces like touch or movement. The researchers used various genetic techniques to study over 20 genes assumed to be involved in touch in fruit flies. Screening each gene mutation for its effect on the flies' ability to detect moisture, the researchers identified two genes that are required for normal moisture sensing. Furthermore, they found that one of the genes, nanchung, is involved in detecting dry air, while the other gene, water witch, is required for detecting moist air.

Both genes are members of the transient receptor potential (TRP) family of genes that code for ion channels. Nanchung, which means can't hear in Korean, has previously been shown to be involved in hearing. Water witch has no other known function and was named by Liu and colleagues for its role in sensing moist air. Disruption of either gene impaired the flies' hygrosensing ability.

The researchers also examined where the two genes are expressed in the fruit flies and determined that not only are two separate genes involved in hygrosensation, but also two types of neurons.

This work provides the first evidence for a sensory system coded by two types of sensory neurons, one responsible for detecting increased moisture and the other responsible for detecting decreased moisture, Liu said.

The researchers speculate that this two-sensor system may allow the flies to detect relative humidity with great sensitivity. Liu added that the two-sensor system might also be a model for other sensory processes where the ability to detect subtle environmental changes is important, such as temperature sensing.

The UI findings open the way to a better understanding of hygrosensation, they provide important clues for learning how mechanosensation works, and they may offer new insights into how sensory systems work in living creatures.

Hearing changes how we perceive gender

Wed, 24 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- Think about the confused feelings that occur when you meet someone whose tone of voice doesn�t seem to quite fit with his or her gender.

A new study by neuroscientists from Northwestern University focuses on the brain�s processing of such sensory information about another�s gender to examine whether hearing fundamentally changes visual experience.

The study concludes that it does, weighing in with findings that contribute to provocative evidence about multi-sensory processing of our world that has been emerging in recent years.

�Auditory-Visual Cross-Modal Integration in Perception of Face Gender,� was published in a recent issue of Current Biology. The study�s co-authors are investigators at Northwestern�s Visual Perception, Cognition and Neuroscience Laboratory: lead author Eric Smith, graduate student, Marcia Grabowecky, research assistant professor of psychology, and Satoru Suzuki, associate professor of psychology.

�Researchers have long thought that one part of the brain does vision and another does auditory processing and that the two really don�t communicate with each other,� said Grabowecky.

�But emerging research suggests that rich information from different senses come together quickly and influence each other so that we don�t experience the world one sense at a time.�

The Northwestern study suggests that sensory interactions are happening at a very early level and tones of voices indeed fundamentally change visual processing.

�For our study, we used simple tones with no explicit gender information to get a window into how vision and audition work together to process gender information,� Grabowecky said. �Unlike stereotypical voices, the tones only hinted at male and female characteristics, and by coupling them with ambiguous faces, we were able to see how processing of various pitches affected vision very early in the sensory process.�

The study builds upon scarce scientific evidence supporting the idea that sounds can alter how masculine or feminine a person looks.

�Our vision can bias our experience of other senses, such as hearing,� said Smith. �We hear, for example, the ventriloquist�s voice coming from the dummy. In this study we wanted to see if hearing could change our visual experience.�

�We learn early on what auditory and visual characteristics accompany female and male voices, starting with our earliest experiences with our mothers and fathers,� said Grabowecky. �The question from the neuroscience perspective is when in the processing of perceptual information do auditory and visual senses interact with each other How does the brain do this�

To test whether a sound can influence perception of a face�s gender, the researchers digitally morphed male and female faces to create androgynous faces not easily categorized as male or female. Study participants were asked to look at the faces while listening to brief auditory tones, which fell within the fundamental speaking frequency range of either male or female voices.

In the initial stage of auditory processing, sounds are decomposed into basic frequency components, the lowest one called the fundamental frequency and higher ones called the harmonics. The fundamental frequency in the human voice typically falls between about 100 to 150 Hz for males and 160 to 300 Hz for females. Roughly speaking, the fundamental frequency determines the perceived pitch (lower for men and higher for women), and the harmonics add timbre (the quality of human voice).

In higher auditory brain areas, these frequencies are put back together to be coded as a human voice. The researchers took advantage of the fact that pure tones can be used to deliver individual frequency components that are registered in early auditory brain areas.

The findings showed that when an androgynous face was paired with a pure tone that fell within the female fundamental-frequency range, people were more likely to report that the ambiguous face was that of a female. But when the same face was paired with a pure tone in the male fundamental-frequency range, people were more likely to see a male face. (The bias did not occur when a face was paired with a pure tone that was too low or too high to be in the typical speaking range.)

�The strength of the study is that pure tones sound like beeps, and they primarily activate early stages of auditory processing,� Grabowecky said. �We think that the effect demonstrates a direct input from early auditory processing to visual perception.�

When people were forced to guess whether the tones were in the male range, the female range or outside of the typical speaking frequency range, their guesses were inaccurate and relative. In other words, when people heard a pair of pure tones, they tended to hear the higher tone to be feminine and the lower tone to be masculine regardless of the actual frequencies of the tones.

�Such relativity is not surprising, because our auditory experience depends on relative, rather than absolute, frequencies as most useful and entertaining auditory information, such as speech and music, is carried by how sound frequencies change over time,� Grabowecky said.

Absolute frequencies do not matter much, as we readily understand speech spoken by people with low and high voices and enjoy songs regardless of the keys in which they are played. In contrast, it is the �neglected� absolute-frequency information that influences visual perception of gender.

�A conscious impression of your voice is not what enhances your look of masculinity or femininity,� said Suzuki. �Sounds seem to influence visual gender in a much more fundamental way on the basis of their absolute frequencies processed in early auditory brain areas.�

The researchers focused on gender perception, because people have such a strong need to categorize people as male or female. �We all know the feeling of meeting a person who is very androgynous,� said Smith. �We simply need to know and will use any information at our disposal to identify a person�s gender. It is probably quite evolutionarily adaptive to be able to accurately tell males from females, as far as propagation of one�s genes is concerned.�

What is on the horizon?

�If sound can implicitly bias visual gender perception, then we need to consider whether other senses, such as smell, might yield similar effects,� said Smith. �Future studies might use masculine and feminine colognes, or even human pheromones to bias people to see androgynous faces as either male or female. With the possibility of other senses biasing the way that we see the world, our visual experience of gender might turn out to be much more than meets the eye.�

MSU researcher helps develop computer game for Ugandan children recovering from cerebral malaria

Tue, 23 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) EAST LANSING, Mich. �The computer program Captain�s Log � originally used with individuals diagnosed with attention deficit hyperactivity disorder, brain injuries or learning disabilities � is being adapted to rehabilitate Ugandan children who are survivors of cerebral malaria.

Michael Boivin, a Michigan State University associate professor of neurology and ophthalmology and of psychiatry, and Bruno Giordani, a University of Michigan associate professor of psychiatry, are leading the project.

�So far as we know, this will be the first attempt to implement a cognitive rehabilitation training program in Uganda with children in the aftermath of brain injury,� Boivin said. �Such programs for children with special needs are readily available in America, and in other parts of the developed world, but not in Africa.�

Every 30 seconds a child in Africa dies from malaria - around 1 million every year, he said. Cerebral malaria is a severe form of malaria that affects the brain and is fatal in about 15 percent to 30 percent of the cases for hospitalized children.

�Our most recent follow-up evaluation of our cerebral malaria children indicates that 26 percent of them have persisting mild to moderate cognitive impairment, mostly in the area of attention and to some extent in visual-spatial working memory,� Boivin said.

The computer game is a comprehensive set of computerized cognitive training programs consisting of five modules including developmental, visual motor skills, conceptual skills, numeric concepts with memory skills and attention skills.

The research team is hoping that this intervention can help cerebral malaria-affected school-age Ugandan children improve their cognitive skills, leading to improvements for both activities of daily living and school-related learning and skill development.

�The program attempts to do so with the use of 33 multilevel brain-training exercises designed to help develop and remediate attention, concentration, memory, eye-hand coordination, basic numeric concepts, problem solving-reasoning skills, self-esteem and self-control,� Boivin said.

Originally developed in 1985, the program is used with children 6 years and older and adults and has been used in a variety of therapeutic, school and home settings in all 50 states, U.S. territories and 23

foreign countries. Also, the program has been adapted for use in a wide range of non-English speaking settings.

Boivin and Giordani have trained a Ugandan study team to help implement and evaluate the program.

�We trained our study team at Mulago Hospital in Uganda, and they helped us in testing the program,� Boivin said. �The onsite project research manager, Paul Bangirana, can now program and set up Captain's Log on his own.�

Endobronchial valve significantly improves emphysema

Mon, 22 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO, Oct. 22 � Emphysema patients whose lungs are implanted with a pencil eraser-sized, one-way endobronchial valve experience significantly improved measures of lung function and report better quality of life, University of Pittsburgh School of Medicine researcher Frank C. Sciurba, M.D., reported today at CHEST 2007, the annual meeting of the American College of Chest Physicians. Scientific sessions continue through Thursday, Oct. 25, at the McCormick Place Lakeside Center in Chicago.

�Normally, lungs easily expand and contract with breathing. But with emphysema, air sacs in the lungs lose elasticity and become hyper-inflated, resulting in decreased function and a feeling of breathlessness,� said Dr. Sciurba, principal investigator of the multi-center trial, known as the Endobronchial Valve for Emphysema Palliation Trial (VENT) and director of the Emphysema Research Center at the University of Pittsburgh. �Endobronchial valves can allow these over-distended, diseased portions of lung to deflate, improving overall function.�

The 31-center, two-year study ended in April 2006 and involved 321 patients in the United States. In the trial, emphysema patients were randomly assigned to either a treatment or control group. Lung function was re-evaluated at six months using a common clinical measure of the volume of air forcibly exhaled in one second (FEV-1) and a six-minute walk test, said Dr. Sciurba. Of the 220 patients who received valve implants, there was a 6.4 percent greater improvement in FEV-1, and a 5.7 percent improvement in distance walked, compared to controls, he said. For some important subsets of treated patients, the results were even more dramatic, Dr. Sciurba added.

�For example, patients who had a fissure completely separating the lobes of the lung and whose endobronchial valves were placed to exclude the entire diseased lobe had changes in FEV-1 of greater than 20 percent,� he said. �This is akin to the results achieved in unilateral lung-volume reduction surgery, without the risks of major surgery. Lessons learned in this trial can lead us to more effective targeting of regions in the lung that could provide an even greater response.�

Most patients required implantation of three to five valves to isolate the most damaged sections of their lungs. Computed tomography (CT) scanning confirmed significant reduction in size of the lung region where valves were placed, particularly among the subsets of patients with the most favorable responses.

Emphysema is the most common cause of respiratory-related death and the fourth most common cause of death overall in the United States. There are an estimated 1.8 million people in the U.S. who have emphysema, a disease heavily related to smoking.

Treated patients had a slightly higher risk of pneumonia. Most complications resolved within eight days of the procedure, and included shortness of breath, chest pain and low oxygen concentration in the bloodstream. Some patients who received valve treatment later had the valves removed for reasons including lack of efficacy or shifting of position. In nearly all cases, valves were easily removed up to a year following insertion.

Endobronchial valve data must be presented to the Food and Drug Administration and the Center for Medicare and Medicaid Services before the treatment becomes widely available to emphysema patients. Currently, the treatment is limited to those who took part in the clinical trial.

Spinal cord injury expert to be honored by research foundation

Thu, 18 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) NEW BRUNSWICK/PISCATAWAY, N.J. � Dr. Wise Young, the Richard H. Shindell Professor of Neuroscience at Rutgers University and founding director of Rutgers� W.M. Keck Center for Collaborative Neuroscience, is receiving the Melvyn H. Motolinsky Research Foundation�s 2007 Distinguished Service Award.

The award will be presented at the foundation�s annual meeting Oct. 28 at 2 p.m. in the Conference Center of the Clinical Academic Building at University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School in New Brunswick.

Dr. Clifton R. Lacy, president of the Motolinsky Foundation, associate professor of medicine at UMDNJ-Robert Wood Johnson Medical School and adjunct professor at Rutgers University Ernest Mario School of Pharmacy, said that Dr. Young was selected to receive the award because of his groundbreaking research in the treatment of spinal cord injury as well as his passionate support of stem cell research. �We also recognize the compassion and caring he shows for individuals with spinal cord injury and their families,� Lacy said.

Young is a world leader in the area of spinal cord injury and treatment. He is an outspoken advocate for stem cell research, a potential source of nerve cell regeneration therapies for damaged spinal cord tissue and other devastating conditions, such as Parkinson�s and Alzheimer�s diseases. Young is taking a leadership position at home and abroad in gathering support for stem cell research and has carried his strong advocacy to patients and politicians in the state and into the halls of Congress.

Young practices what he calls compassionate science, focusing on the needs of patients. He personally involves himself with people who have sustained these injuries and their families, holding regular open-house evenings at the Keck Center, where they are updated on the latest research findings and newest therapies.

At the Keck Center, Young assembled a team of researchers who collaborate with more than 100 laboratories worldwide in the search for cures to spinal cord injuries and brain injuries and disorders. He recently embarked on an initiative to set up a clinical network of more than a dozen spinal trauma centers in China capable of performing state-of-the-art clinical trials.

�I am truly honored to be amongst such eminent recipients of the Distinguished Service Award as Mason Gross, Denton Cooley and Clifton Lacy,� Young said. �To me, this award is not just an honor but recognition that scientists do science not just for its own sake but for the people who will benefit from that science.�

Immune cells promote blood vessel formation in mouse endometriosis

Thu, 18 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A discovery in mice of immune cells that promote the formation of new blood vessels could lead to new treatments for endometriosis, a painful condition associated with infertility that affects up to 15 percent of women of reproductive age.

The formation of new blood vessels, or angiogenesis, is known to encourage the growth of tumors and endometriosis lesions. A team led by Ofer Fainaru, MD, PhD, a research associate in the Vascular Biology Program at Children's Hospital Boston and Harvard Medical School, found that dendritic cells�highly specialized immune cells�help trigger angiogenesis in a mouse model of endometriosis. Their findings were published online last month in the FASEB journal. Judah Folkman, MD, director of Children�s Vacular Biology Program, who helped found the field of angiogenesis, was the paper�s senior author.

Endometriosis occurs when endometrium, a tissue normally found in the inner lining of the uterus, grows elsewhere in the body�most commonly in the abdominal cavity. The misplaced endometrial tissue begins as small lesions, or masses, but once blood vessels are recruited, the lesions grow larger and respond to female hormones, resulting in inflammation, cyclic pelvic pain, and infertility.

In the mouse model, the researchers observed that dendritic cells infiltrate endometriosis lesions, and near the sites where they invade, new blood vessels form. Injecting mice with excess dendritic cells caused their lesions to gain more blood vessels and to grow larger.

The researchers also found that dendritic cells have a strikingly similar effect on intra-abdominal tumors.

When the researchers grew dendritic cells together with endothelial cells�the cells that line blood vessel walls�the endothelial cells migrated towards the dendritic cells. The team hypothesizes that dendritic cells, after embedding in a new lesion or tumor, act like foremen on a building team: they call in, direct and support endothelial cells that build the new blood vessels.

We believe that targeting dendritic cells may prove to be a promising strategy for treating conditions dependent on angiogenesis, such as endometriosis and cancer, says Fainaru. But first, the team must demonstrate that dendritic cells are essential�that without these cells in mice, new blood vessels do not form.

Our next step would be to look for specific dendritic cell inhibitors that could have the potential to block angiogenesis in these conditions, says Fainaru.

The team hopes to develop cell-specific therapy for angiogenesis-dependent diseases that will be more effective and less toxic than current treatments. Currently, the most effective treatment for endometriosis is surgically removing the lesions, but this does not prevent them from growing back�as large and symptomatic as before. If dendritic cells are indeed ringmasters and not sideliners in new blood vessel growth, locally knocking them out just after an initial surgery, or altering them in some way, could render the lesions tiny and harmless.

Similarly, potential dendritic-cell inhibitors, when added to other agents that stop new blood vessels from forming, could enhance doctors� ability to choke off growing tumors, Fainaru adds.

Massive microRNA scan uncovers leads to treating muscle degeneration

Wed, 17 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have discovered the first microRNAs � tiny bits of code that regulate gene activity � linked to each of 10 major degenerative muscular disorders, opening doors to new treatments and a better biological understanding of these debilitating, poorly understood, often untreatable diseases. The study, to be published online this week by the Proceedings of the National Academy of Sciences, was led by Iris Eisenberg, PhD, of the Program in Genomics at Children�s Hospital Boston. Louis Kunkel, PhD, director of the Program in Genomics and an investigator with the Howard Hughes Medical Institute, was senior investigator.

The disorders include the muscular dystrophies (Duchenne muscular dystrophy, Becker muscular dystrophy, limb girdle muscular dystrophies, Miyoshi myopathy, and fascioscapulohumeral muscular dystrophy); the congenital myopathies (nemaline myopathy); and the inflammatory myopathies (polymyositis, dermatomyositis, and inclusion body myositis). While past studies have linked them with an increasing number of genes, it's still largely unknown how these genes cause muscle weakness and wasting, and, more importantly, how to translate the discoveries into treatments.

For instance, most muscular dystrophies begin with a known mutation in a �master gene,� leading to damaged or absent proteins in muscle cells. In Duchenne and Becker muscular dystrophies, the absent protein is dystrophin, as Kunkel himself discovered in 1987. Its absence causes muscle tissue to weaken and rupture, and the tissue becomes progressively nonfunctional through inflammatory attacks and other damaging events that aren�t fully understood.

�The initial mutations do not explain why patients are losing their muscle so fast,� says Eisenberg. �There are still many unknown genes involved in these processes, as well as in the inflammatory processes taking place in the damaged muscle tissue.�

She and Kunkel believe microRNAs may help provide the missing genetic links. Their team analyzed muscle tissue from patients with each of the ten muscular disorders, discovering that 185 microRNAs are either too abundant or too scarce in wasting muscle, compared with healthy muscle.

Discovered in humans only in the past decade, microRNAs are already known to regulate major processes in the body. Therefore, Eisenberg believes microRNAs may be involved in orchestrating the tissue death, inflammatory response and other major degenerative processes in the affected muscle tissue. The researchers used bioinformatics to uncover a list of genes the microRNAs may act on, and now plan to find which microRNAs and genes actually underlie these processes.

The findings raise the possibility of slowing muscle loss by targeting the microRNAs that control these �cascades� of damaging events. This approach is more efficient than targeting individual genes.

The team also defined the abnormal microRNA �signatures� that correspond to each of the ten wasting diseases. They hope these will shed light on the genes and disease mechanisms involved in the most poorly understood and least treatable of the degenerative disorders, such as inclusion body myositis.

�At this point, it�s very theoretical, but it�s possible,� says Eisenberg.

Testosterone turns male juncos into blustery hunks -- and bad dads

Mon, 15 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) BLOOMINGTON, Ind. -- The ability to ramp up testosterone production appears to drive male dark-eyed juncos to find and win mates, but it comes with an evolutionary cost. Big fluctuations in testosterone may also cause males to lose interest in parenting their own young, scientists have learned.

In the December issue of The American Naturalist (now online), Indiana University Bloomington, University of Virginia and University of Southern Mississippi researchers report the results of the first study to examine, in the wild, the way in which natural changes in testosterone levels determine how a male spends his time.

It's a new take on the subject. IUB biologist Ellen Ketterson and other researchers had thought it might be the total amount of testosterone in a male bird that determines his tendency toward aggression and monogamy. The latest findings suggest it's a bit more complicated. It's how much and how quickly his testosterone levels can rise and fall that determines whether he's the kind to stick around and feed his young. Males whose testosterone levels were more stable were more likely to invest more time and energy in parenting.

This study is one of the first to show for a songbird living in the field under natural conditions that individual variation in the hormone testosterone maps onto variation in aggression and parental behavior, said Ketterson, senior author of the study. Our data also suggest that there is more than one way to be successful at reproduction. Some males may seek mates at the expense of parental behavior, but other males are doing the opposite. They are being more parental at the expense of aggression. And apparently both ways of being in the world work.

Ketterson, lead author Joel McGlothlin (University of Virginia) and Jodie Jawor (University of Southern Mississippi) see the male Junco's plight as a classic trade-off in evolutionary biology: males have a certain amount of energy and time they can invest in attracting mates and sticking around to parent offspring. Under certain circumstances it may be beneficial for male birds to love 'em and leave 'em, maximizing the number of female partners during a mating season. Under other circumstances, it may be in the male junco's best interests to mate with only one female and stick around until the chick is old enough to fend for itself.

The results are exciting because they show us how animals that make different choices might differ from each other on a physiological level. On an evolutionary level, they suggest that there may often be more than one right choice, depending on the circumstances, Virginia's McGlothlin said.

Is testosterone calling all the shots It is surely more complicated than that, Ketterson said. The link between testosterone and aggressive and sexual behavior is probably more direct than the link between testosterone and parental behavior. The latter needs much more study.

Diversity in the behavior of male dark-eyed junco is more of a continuum than a dichotomy of Don Juans and Mr. Moms.

One of the interesting things is that all males stick around and help, Ketterson said. If they have higher testosterone they help less. If they have lower testosterone they help more.

The situation presents an interesting evolutionary question. Why wouldn't one of the behaviors win out over the other

Variation in behavior may persist because the environment varies, Ketterson said. In cold, wet years, or years when lots of predators are attacking young in the nest, good fathers may be more successful at leaving offspring. When food is plentiful and predators are few, males that focus on mating may be more successful. The balance between the two is probably dynamic.

Another possibility, McGlothlin explained, is that male quality is why males divide up their time differently.

There are only so many eggs out there to fertilize, so every male can't be successful getting extra-pair fertilizations, McGlothlin said. High-quality males -- those who have more energy to invest -- ought to spend more of it on trying to attract mates. These males may be less likely to survive, but they are more likely to be successful at getting extra-pair fertilizations. The low-quality males don't have as much energy to invest, so they play it safe.

Ketterson, McGlothlin and Jawor studied a natural population of Carolina dark-eyed juncos (Junco hyemalis carolinensis). The birds' behavior is well known -- thanks to the work of IU Bloomington biologist (emeritus) Val Nolan, who is married to Ketterson. Male birds were observed extensively in and around nests, and were at times captured and catalogued. During the male birds' brief captivity, the scientists measured circulating testosterone levels, then injected the birds with gonadotropin-releasing hormone (GnRH) to determine the degree to which each male could produce testosterone in response.

Males that were capable of producing more testosterone in response to the injections not only demonstrated more aggressive behavior, but were also observed to spend less time parenting.

The next essential step is to relate variation in testosterone to actual measures of fitness, namely lifespan and offspring actually produced, Ketterson said. Is it true that individuals who resolve the trade-off in different ways have equal fitness Can a good parent be just as successful in an evolutionary sense as a good mater

Marines land at UO, leave with plans to wear Oregon-made training suits

Wed, 10 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) EUGENE, Ore. -- (Oct. 10, 2007) -- A few came. They ran. They left. As a result of their August visit the U.S. Marine Corp begins training in 2008 in new running suits chosen after tests of competing products in the University of Oregon's environmental chamber.

The experience was enough to make both the University of Oregon and Beaverton-based InSport Inc. proud. UO researchers were unaware that it was InSport's training clothes that they had recommended until the company announced Oct. 2 that it had won a $14 million contract to produce the suits for the Marine Corps, said John Halliwill, a professor of human physiology and co-director of the UO's Exercise and Environmental Physiology Laboratories.

The Marine Corps cold-called us and asked us to run tests for them and to report back to them, Halliwill said. We weren't supposed to know who the suits came from, and, to be honest if someone had mentioned InSport to me last summer I wouldn't have known who they were talking about. But I do now.

Halliwill and lab co-director Christopher Minson led the testing, in which 29 Marines (22 men and seven women) jogged on a treadmill for 30 minutes at 6 mph and at a 2 percent incline on four separate occasions. The climate in the lab was manipulated to mimic two common training periods: either cool and humid early mornings (45 degrees Fahrenheit and 70-80 percent relative humidity) or warm and humid late mornings (55 degrees and 40-65 percent relative humidity).

The UO's state-of-the-art environmental chamber is a 12-foot-square room capable of simulating altitude up to 18,000 feet, holding temperature constant at a set point between 14 degrees and 122 degrees Fahrenheit, and controlling humidity anywhere from 10 percent to 95 percent. The chamber was installed in 2005, built with a $250,000 grant from the U.S. Department of Defense and a $150,000 gift from Dave and Nancy Petrone of San Mateo, Calif. It can be switched from one extreme environment to another in 30 minutes, and the system allows researchers to monitor minute vascular and respiratory changes of subjects both at rest and when exercising.

The Marines had a specific need to see how the suits performed during typical winter conditions at U.S. Marine bases such as Quantico and Camp Pendelton, but testing had to be completed during the summer so that the suits could be deployed in time for winter, Halliwill said. We have the ability to create weather on demand, practically any climate or weather condition we want with the flip of a switch, so we were able to give them Base Quantico in winter even though it was August in Oregon.”

Each Marine was weighed immediately before and after each running session. Hearts were monitored throughout the sessions, and each subject was asked every five minutes about skin moisture, comfort and difficulty they perceived while in one of the jogging suits. Subjects each day took a two-hour break and then repeated the procedure a second time.

Researchers recorded heart rates, pre-exercise weight of the suits, changes in body weight in each run, moisture retained in suits and underwear and the moisture transferred into the environment.

Dealing with cooler temperatures is not difficult in terms of clothing, Minson said. What is difficult is moisture management. Even on relatively dry days, moisture from sweating can build up under a suit that does not ventilate well. This leads to less heat loss and less comfort. Most importantly, the excess moisture in clothes can lead to very rapid heat loss when exercise is stopped, which can be uncomfortable at best, but can be dangerous in certain circumstances. Moisture management is one of the areas where the material by InSport really stood out.

In the end, the Marines reported more comfort and a preference for Design 2, which turned out to be InSport's product, over Design 1, and, the researchers concluded in their report: In our view, and we believe supported by the data, Design 2 is superior to Design 1 and should be considered for adoption by the Marine Corps.

The recommended product, according to participating Marines, generated less friction. Researchers noted that neither design was tested for wind- or water-proofness, which usually are important to people during their exercise regimens. There were few significant differences between the suits in the tested environments, but Design 2 weighed less before exercise, retained less moisture and allowed for better moisture transfer to the environment than the other product.

Appendix isn't useless at all: It's a safe house for bacteria

Mon, 08 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. � Long denigrated as vestigial or useless, the appendix now appears to have a reason to be � as a �safe house� for the beneficial bacteria living in the human gut.

Drawing upon a series of observations and experiments, Duke University Medical Center investigators postulate that the beneficial bacteria in the appendix that aid digestion can ride out a bout of diarrhea that completely evacuates the intestines and emerge afterwards to repopulate the gut. Their theory appears online in the Journal of Theoretical Biology.

�While there is no smoking gun, the abundance of circumstantial evidence makes a strong case for the role of the appendix as a place where the good bacteria can live safe and undisturbed until they are needed,� said William Parker, Ph.D., assistant professor of experimental surgery, who conducted the analysis in collaboration with R. Randal Bollinger, M.D., Ph.D., Duke professor emeritus in general surgery.

The appendix is a slender two- to four-inch pouch located near the juncture of the large and small intestines. While its exact function in humans has been debated by physicians, it is known that there is immune system tissue in the appendix.

The gut is populated with different microbes that help the digestive system break down the foods we eat. In return, the gut provides nourishment and safety to the bacteria. Parker now believes that the immune system cells found in the appendix are there to protect, rather than harm, the good bacteria.

For the past ten years, Parker has been studying the interplay of these bacteria in the bowels, and in the process has documented the existence in the bowel of what is known as a biofilm. This thin and delicate layer is an amalgamation of microbes, mucous and immune system molecules living together atop of the lining the intestines.

�Our studies have indicated that the immune system protects and nourishes the colonies of microbes living in the biofilm,� Parkers explained. �By protecting these good microbes, the harmful microbes have no place to locate. We have also shown that biofilms are most pronounced in the appendix and their prevalence decreases moving away from it.�

This new function of the appendix might be envisioned if conditions in the absence of modern health care and sanitation are considered, Parker said.

�Diseases causing severe diarrhea are endemic in countries without modern health and sanitation practices, which often results in the entire contents of the bowels, including the biofilms, being flushed from the body,� Parker said. He added that the appendix�s location and position is such that it is expected to be relatively difficult for anything to enter it as the contents of the bowels are emptied.

�Once the bowel contents have left the body, the good bacteria hidden away in the appendix can emerge and repopulate the lining of the intestine before more harmful bacteria can take up residence,� Parker continued. �In industrialized societies with modern medical care and sanitation practices, the maintenance of a reserve of beneficial bacteria may not be necessary. This is consistent with the observation that removing the appendix in modern societies has no discernable negative effects.�

Several decades ago, scientists suggested that people in industrialized societies might have such a high rate of appendicitis because of the so-called �hygiene hypothesis,� Parker said. This hypothesis posits that people in hygienic societies have higher rates of allergy and perhaps autoimmune disease because they -- and hence their immune systems -- have not been as challenged during everyday life by the host of parasites or other disease-causing organisms commonly found in the environment. So when these immune systems are challenged, they can over-react.

�This over-reactive immune system may lead to the inflammation associated with appendicitis and could lead to the obstruction of the intestines that causes acute appendicitis,� Parker said. �Thus, our modern health care and sanitation practices may account not only for the lack of a need for an appendix in our society, but also for much of the problems caused by the appendix in our society.�

Parker conducted a deductive study because direct examination the appendix�s function would be difficult. Other than humans, the only mammals known to have appendices are rabbits, opossums and wombats, and their appendices are markedly different than the human appendix.

Parker�s overall research into the existence and function of biofilms is supported by the National Institutes of Health. Other Duke members of the team were Andrew Barbas, Errol Bush, and Shu Lin.

New thoracic imaging approach can pinpoint underlying venous problems

Mon, 08 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CINCINNATI� University of Cincinnati (UC) radiologists have developed a new technique for capturing images of chest veins that eases diagnosis of venous diseases.

Multi-detector computed tomography (CT) scanners are traditionally used to create three-dimensional images of arteries, the vessels which carry oxygen-rich blood away from the heart and distribute blood throughout the body. Veins, smaller vessels that return blood to the heart, are more difficult to accurately image.

Developed by Cristopher Meyer, MD and Achala Vagal, MD, the new protocol allows radiologists to compensate for the extra time it takes contrast solution to reach the veins so useful images can be produced using the CT scanner.

�We found that the rapid-imaging scanners were almost too fast for venous studies,� explains Vagal, a UC assistant professor and radiologist at University Hospital. �By the time the contrast reached the patient�s veins, there were too many artifacts to make any meaningful conclusions about possible disease�for example, blood clots.�

�Venous disease is rare and can be difficult to pinpoint,� she adds. �This new protocol uses the same imaging equipment in a novel way that allows us to acquire better venous images and make good clinical decisions.�

Vagal presented guidelines for this thoracic imaging protocol at the North American Society of Cardiovascular Imaging�s 35th Annual Meeting and Scientific Sessions in Washington, D.C., on Oct. 8.

For this new imaging technique, the CT technologist prepares two syringes of contrast: The first includes 140 cubic centimeters (CC) of undiluted contrast; the second contains a diluted mixture of 100 CC of contrast and 10 CC of saline solution.

�The key to getting accurate clinical images of the veins is in the timing,� Vagal says.

Both syringes are given consecutively at a rate of four CC per second, with a 60-second delay between the final injection and initiation of the CT scan.

�Previously, there was so much dense contrast in the veins that all you could see on the CT scan were streaks that didn�t tell you anything about possible venous disease,� explains Vagal. �Delaying the scan gave us enough time for both the arteries and the veins to be opacified, which resulted in the crisp images that allowed us to make better clinical determinations.�

Vagal is affiliated with the Neuroscience Institute at UC and University Hospital, a center of excellence that focuses on the main diseases of the brain and nerves such as stroke, brain tumors, brain trauma, Parkinson�s and Alzheimer�s disease, epilepsy, ALS and multiple sclerosis.

Evil genes made me do it

Mon, 08 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) While there have been numerous medical studies investigating the physiological and biochemical basis for behavioral disorders such as antisocial personality disorder and borderline personality disorder, there have been virtually no comprehensive studies aimed at providing a physiological explanation of malignant narcissism�a term that characterizes individuals who exhibit malevolent behavior but are still able to function effectively in society.

Inspired both by the dearth of scientific literature on the subject and by her sister�s Machiavellian personality, Barbara Oakley, Associate Professor of Bioengineering at Oakland University in Michigan, set out to conduct an investigation of the physiology of this particular disorder and the impact it has had on human society. The result is Evil Genes: Why Rome Fell, Hitler Rose, Enron Failed, and My Sister Stole My Mother�s Boyfriend (Prometheus Books $28.95), which Harvard professor Steven Pinker praises as �a fascinating scientific and personal exploration of the roots of evil, filled with human insight and telling detail.�

Evil Genes is the first book to tie together the cutting edge neuroscientific and genetic results that explain human evil, showing that some deceitful, manipulative, and even sadistic behavior appears to be programmed genetically. Unlike other popular books about human evil, Evil Genes goes far beyond �explaining� psychopathic behavior using old-fashioned psychological theories or religious dogma. Instead, it centers on what neuroscience and genetics are revealing about not only psychopathy, but also the more subtly devious behavior of seemingly ordinary people. Oakley follows clues from the diary of her late sister�who actually did steal her mother�s boyfriend�and takes the reader inside the heads of malevolent people you know, perhaps all too well, but could never understand�until now.

Starting with psychology as a frame of reference, Oakley uses cutting-edge images of the working brain to provide startling support for the idea that �evil� people act the way they do mainly as the result of certain dysfunctions, some of which have a genetic basis. But there are unexpected fringe benefits to Evil Genes. We may not like them�but we literally can�t live without them. The recent dramatic findings presented in Evil Genes illuminate not only the eerily similar behavior of dictators far afield, such as Hitler, Mao, and Milosevic, but aspects of politics at home, as well as business, religion, and everyday life. As Terrance Deacon, Professor of Biological Anthropology and Neuroscience at UC Berkeley, says, �shining this light on some of the most problematic figures of our era�challenges our assumptions about the roots of terrorism, genocide, crime, corruption�and even the sinister sides of politics, business, and religion.�

In fact, history has been shaped by the strange confluence of genes and environment that science is just now beginning to understand. Oakley links the latest findings of molecular research to a wide array of seemingly unrelated historical and current phenomena, from the harems of the Ottomans and the chummy jokes of �Uncle Joe� Stalin, to the remarkable memory of investor Warren Buffett.

William A. Wulf, President Emeritus, National Academy of Engineering, says, �Oakley deftly moves through psychology, functional brain imagery, and molecular biology to weave a compelling and provocative case for a genetic base for evil. 'Scientific non-fiction' and 'page turner' aren�t two phrases I�d expect in the same sentence, but for the remarkable Evil Genes, they fit.�

Evil Genes is a tour-de-force of popular science writing that brilliantly melds scientific research with intriguing family history and puts both a human and scientific face to evil.

Barbara Oakley, PhD, �a female Indiana Jones,� is one of the few women to hold a doctorate in systems engineering. She chronicled her adventures on Soviet fishing boats in the Bering Sea in Hair of the Dog: Tales From Aboard a Russian Trawler. She also served as a radio operator in Antarctica and rose from private to captain in the U.S. Army. Now an associate professor of engineering at Oakland University in Michigan, Oakley is a recent vice president of the IEEE Engineering in Medicine and Biology Society. Her work has appeared in numerous publications.

Study links chemical to inhibited milk synthesis, secretion in humans

Mon, 08 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CINCINNATI�University of Cincinnati (UC) researchers have identified the neurotransmitter serotonin as the chemical responsible for inhibiting milk production and secretion in human mammary glands.

As growing demand outstrips milk supplies in some parts of the world, the finding could aid development of therapeutics or technologies that would increase milk production and yields from other mammals.

Results of the human study, led by Nelson Horseman, PhD, UC professor of molecular and cellular physiology, appear in the Oct. 8�12, 2007, early edition of Proceedings of the National Academy of Sciences (PNAS).

�Knowing the chemical responsible for inhibiting milk production could help us to improve milk yields in other mammals,� Horseman says.

In lactating mammals, milk synthesis and secretion gradually slows to a stop when mammary glands become full. Once mammary glands are emptied, milk production begins again.

For decades, scientists have been trying to pinpoint the cause of inhibited milk production. In the 1970s, researchers in Scotland and New Zealand determined that a chemical had to regulate milk synthesis and secretion. A UC-led rodent study in 2004 identified the chemical as serotonin.

Serotonin is a naturally occurring neurotransmitter made in the brain and intestinal tract. When produced in the intestinal tract, the chemical is stored in blood platelets and released at wound sites to promote clotting and healing. Low levels of serotonin in the brain have been linked to depression and other mood disorders.

Horseman and his team now report that serotonin is also produced in human mammary glands�building up as the mammary gland fills with milk, inhibiting further milk synthesis and secretion.

�If we can understand how to stop or reduce serotonin production in the mammary gland, we can reverse its actions,� Horseman says.

The investigator was recently issued a patent for specific drugs known to inhibit serotonin production. Inhibiting this chemical in the mammary gland, he says, has been shown to increase milk yields by up to 15 percent.

Improved milk yields, says Horseman, could help ease milk shortages in some parts of the world caused by drought and increased demand.

�Demand for milk has increased in Asia and prices for milk have gone up across the world,� says Horseman.

A United States Department of Agriculture (USDA) 2001�2005 summary of 30 American cities showed that, over a five-year period, the average price of whole milk rose by 11 percent.

�Farmers currently use a growth hormone to improve milk yields,� says Horseman. �Use of that hormone has declined in recent years at the request of consumers, but milk shortages are getting worse. Finding ways to increase yield in a way that�s acceptable to consumers is important.�

In March 2007, the USDA awarded Horseman and colleagues a $350,000 grant to further study milk synthesis and secretion in cows.

The UC team is partnering with researchers in the University of Arizona�s animal science program to study cows and cow mammary tissue.

Although the rodent and human cells they have studied have many similarities, cow cells appear to have some unique differences. For example, Horseman�s team has identified one receptor for serotonin in the mammary gland of humans and rodents, and at least three in cows.

�We hope that by gaining a better understanding of how serotonin works in cows, we can find ways to inhibit its synthesis without the use of drugs or growth hormones,� says Horseman. �Our ultimate goal would be to increase milk yield in a way that�s effective without side effects.�

Treatment blocks pain without disrupting other functions

Wed, 03 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A combination of two drugs can selectively block pain-sensing neurons in rats without impairing movement or other sensations such as touch, according to a new study by National Institutes of Health (NIH)-supported investigators. The finding suggests an improved way to treat pain from childbirth and surgical procedures. It may also lead to new treatments to help the millions of Americans who suffer from chronic pain.

The study used a combination of capsaicin � the substance that makes chili peppers hot � and a drug called QX-314. This combination exploits a characteristic unique to pain-sensing neurons, also called nociceptors, in order to block their activity without impairing signals from other cells. In contrast, most pain relievers used for surgical procedures block activity in all types of neurons. This can cause numbness, paralysis and other nervous system disturbances.

The Holy Grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, coordination, or other vital functions of the nervous system. This finding shows that a specific combination of two molecules can block only pain-related neurons. It holds the promise of major future breakthroughs for the millions of persons who suffer with disabling pain, says Story C. Landis, Ph.D., director of the National Institute of Neurological Disorders and Stroke (NINDS) at the NIH, which funds the investigators' research along with the National Institute of Dental and Craniofacial Research (NIDCR) and the National Institute of General Medical Sciences (NIGMS). NINDS and NIDCR are co-chairs of the NIH Pain Consortium. The study appears in the October 4, 2007, issue of Nature.*

Lidocaine, the most commonly used local anesthetic, relieves pain by blocking electric currents in all nerve cells. Although it is a lidocaine derivative, QX-314 alone cannot get through cell membranes to block their electrical activity.

That's where capsaicin comes in. It opens large pores called TRPV1 channels � found only within the cell membrane of pain-sensing neurons. With these channels propped open by capsaicin, QX-314 can pass through and selectively block the cells� activity.

The research team, led by Clifford J. Woolf, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School and Bruce Bean, Ph.D., at Harvard Medical School, tested the combination of capsaicin and QX-314 in neurons isolated in Petri dishes and found that it blocked pain-sensing neurons without affecting other nerve cells. They then injected the drugs into the paws of rats and found that the treated animals could tolerate much more heat than usual. They also injected the two drugs near the sciatic nerve that runs down the hind leg. The treated rats did not show any signs of pain, and five of the six animals continued to move and behave normally. This showed that the drugs could block pain without impairing motor neurons that control movement.

The drug combination took half an hour to fully block pain in the rats. However, once it began, the pain relief lasted for several hours.

Current nerve blocks cause paralysis and total numbness, Dr. Woolf says. This new strategy could profoundly change pain treatment in the perioperative setting.

The treatment tested in this study is unique in that it uses a type of ion channel (TRPV1 channels) as an avenue to deliver medication. Ion channels are pores in the cell membrane that control the flow of electrically charged ions in and out of cells. I'm not aware of any other strategy that uses a channel within cells to deliver a drug to a select set of cells, Dr. Woolf says. The strategy builds on research done since the 1970's, largely supported by NIH, that shows how electrical signaling in the nervous system results from expression of dozens of different types of ion channels. Some of these ion channels are found only in specific types of neurons.

This project is a nice illustration of how research trying to understand very basic biological principles can have practical applications, says Dr. Bean.This type of treatment has great potential to improve pain treatment during childbirth, dental procedures, and surgery, the researchers say. Surgical pain is the obvious first application for this type of treatment, Dr. Woolf says. However, similar therapies might eventually be useful for treating chronic pain, he adds. Chronic pain continues for weeks, months, or even years and can cause severe problems, and is often resistant to standard medical treatments.

While the researchers focused on finding a treatment for pain, this strategy might also be useful for treating itch from eczema, poison ivy rashes, and other conditions, Dr. Woolf says. Like pain sensations, itch signals come from nociceptors. One problem with the combination treatment is that the capsaicin can cause unpleasant burning sensations until the QX-314 takes effect, Dr. Woolf says. Administering the QX-314 ten minutes before the capsaicin minimized this problem in rats. The investigators are now looking for ways to open the TRPV1 channels without the burning sensations, perhaps by finding an alternative to capsaicin. They also hope to find ways of prolonging the pain relief. Eventually, they might be able to develop pills that will stop pain signals without requiring injections, Dr. Woolf adds.

UAB wins $5.7M neurofibromatosis grant

Tue, 02 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) BIRMINGHAM, Ala. � A team of UAB geneticists, doctors and biostatisticians has received $5.7 million from the U.S. Department of Defense to study and test new treatments for neurofibromatosis, or NF.

UAB is the lead research center in a nine-institution group called the NF Consortium. The coalition formed more than two years ago to design and manage multiple clinical trials held across the nation looking at new and more effective therapeutic options for adults and children diagnosed with NF.

The $5.7 million award will be shared among the NF Consortium members, with UAB�s research team serving as the operations center and distribution point for the government funds.

Bruce Korf, M.D., Ph.D., chair of the UAB Department of Genetics and an internationally recognized expert in neurofibromatosis type 1, said the goal of the consortium is to streamline and improve the way clinical trials are performed for this disease, and to break down past barriers to discovering and testing cutting-edge NF treatments.

�We expect results from the NF Consortium studies to provide a wider range of therapeutic options for patients with the goal of reducing the rates of tumor growth, and improving quality of life,� Korf said.

�By monitoring not only the clinical outcomes, but the effects of therapies on molecular targets, it will be possible to better understand NF as a disease,� he said.

The other eight participating institutions are Children�s Hospital Boston, Children�s Hospital of Philadelphia, Children�s National Medical Center in Washington, D.C., Cincinnati Children�s Hospital Medical Center, Washington University in St. Louis, the University of Chicago, the University of Utah in Salt Lake City, and the National Cancer Institute in Bethesda, Md.

Often diagnosed in childhood, NF is a hereditary condition that causes tumors to grow on nerve tissue that affects many bodily systems. As the tumors grow, they can press on vital areas and lead to deformities, high blood pressure, scoliosis, speech impairment, early or delayed puberty, blindness and other medical problems. About 10 percent of NF type 1 cases lead to cancer.

The recent $5.7 million grant is in addition to $2.9 million awarded two years ago to start the NF Consortium. The recent award will be used to put the group�s scientific plans into action, said Jeannette Y. Lee, Ph.D., a biostatistician and professor in the UAB School of Medicine. Lee directs the NF Consortium operations center and serves as the grant�s overall principal investigator.

Lee said three clinical trials will be the focus of the consortium�s first studies. These include:

Scientists say sabercat bit like a pussycat

Mon, 01 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) In public imagination, the sabre-toothed cat Smilodon ranks alongside Tyrannosaurus rex as the ultimate killing machine. Powerfully built, with upper canines like knives, Smilodon was a fearsome predator of Ice-Age America's lost giants.

For more than 150 years, scientists have debated how this iconic predator used its ferocious fangs to kill its prey. Now a new Australian study, published today in the US Proceedings of the National Academy of Science, hopes to lay the arguments to rest. And the results will put in dent in Smilodon's reputation.

Scientists from the University of New South Wales and University of Newcastle have used a computer-based technique called Finite Element Analysis (FEA) to test the bite force and feeding mechanics of the fearsome predator.

FEA, normally used in the analysis of trains, planes and cars, allowed the team to reverse engineer designs to find out what sort of forces a structure like a sabrecat skull was able to handle.

Skulls are much more complex then most man-made structures, and to apply the technique to a fossil big cat required some tricks engineers usually have to handle, says the University of Newcastle's Colin McHenry, lead author on the paper.

Historically there have been a number of interpretations about how Smilodon killed, says UNSW palaeontologist Dr Steve Wroe. Early researchers thought it had a weak bite. More recently, people have suggested that the bite was strong.

Using the skull of a modern-day lion for comparison, the team determined that Smilodon had a relatively weak bite - about one third as powerful as a lion of similar size. For all its reputation, Smilodon had a wimpy bite says Dr Wroe. It bit like a moggy.

In a range of digital crash-tests, the team found that under most conditions, the sabre-tooth skull performed very poorly compared to that of the lion. This would have seriously limited the big toothed fossil cat cat to a very specific range of killing behaviours.

Although its bite was weak, this is not to imply Smilodon was not was a formidable predator. Anything but, says Dr Wroe. Smilodon was an awesome beast -- and what it lacked in bite force it more than made up for elsewhere.

The sabrecat had an immensely powerful body; perfect for wrestling large prey to the ground, and our models show that it needed to do this before trying a bite, explains Mr McHenry. Killing was more likely applied to the prey's throat, because it is easier to restrain the prey this way. Once the bite was done the prey would have died almost instantly.

Dr Wroe describes the lion as a better all rounder in the hunting stakes. Smilodon was massively over-engineered for the purposes of taking small prey, but a ruthlessly efficient hunter of big game.

The team is now applying their techniques to inform medical research involving dentists, surgeons and safety scientists.

Discovery supports theory of Alzheimer's disease as form of diabetes

Wed, 26 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer�s memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer�s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer�s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for �amyloid �-derived diffusible ligand.�)

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer�s disease, the Northwestern study sheds light on the emerging idea of Alzheimer�s being a �type 3� diabetes.

The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer�s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)

In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer�s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.

�We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,� said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. �Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer�s disease.�

ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer�s disease and block memory function by a process predicted to be reversible.

In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.

�We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer�s brains,� said Klein, a member of Northwestern�s Cognitive Neurology and Alzheimer's Disease Center. �We�re dealing with a fundamental new connection between two fields, diabetes and Alzheimer�s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.�

Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.

They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.

�In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,� said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein�s lab. �These factors suggest that insulin resistance in the brains of those with Alzheimer�s is a response to ADDLs.�

�With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer�s treatment,� said Klein. �I think such drugs could supercede currently available Alzheimer�s drugs.�

Pathway to cell death redefined in landmark study

Thu, 20 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Sept. 20 -- A new study led by investigators from the University of Pittsburgh School of Medicine demonstrates that the process of necrosis, long thought to be a chaotic, irreversible pathway to cell death, may actually be triggered as part of a regulated response to stress by a powerful protein, SRP-6, that can potentially halt necrosis in its path. Further, the research team realized that this protein might be harnessed to direct some cells -- those in cancerous tumors, for instance -- to die, while saving others, such as degenerating neural cells responsible for Alzheimer�s and Parkinson�s diseases. The work appears on the Sept. 21 cover of the journal Cell.

This remarkable molecular trigger, SRP-6, is a serine protease inhibitor or serpin, and targets the cell�s digestive center, the lysosome. The authors report that the family of intracellular serpins may help cells survive in the face of stressors by protecting against lysosomal injury and its cellular consequences.

�For years, we believed that cell death related to a catastrophic insult such as a stroke or heart attack that deprives tissue of oxygen couldn�t really be treated, so we focused on strategies to prevent further damage by restoring blood flow as quickly as possible with clot busters and surgery,� said Gary A. Silverman, M.D., Ph.D., chief of newborn medicine in the department of pediatrics at the Pitt School of Medicine and the study�s senior author. �But our research indicates that necrosis can be interrupted and possibly repaired, even after the injury process is well underway. This insight has exciting implications for the management of heart disease, stroke and neurological illnesses.�

Representing more than five years of study, the Cell publication is the result of a chance observation made by primary author Cliff J. Luke, Ph.D., assistant professor of pediatrics at Pitt and an investigator at the university-affiliated Magee-Womens Research Institute. Drs. Luke, Silverman and colleagues have been studying how a certain class of proteins called proteases, when uncontrolled, can kill cells. In the process, they discovered that another group of proteins, the serpins, might block, or inhibit, these destructive proteases and protect cells from injury. SRP-6 is among a vast family of pro-survival serpins, which are key regulatory molecules in many complex biologic processes, including blood cell coagulation, inflammation, tumor growth and cell death. Although previous research has shown that bloodstream serpins, including antithrombin and alpha-1 antitrypsin, control protein degradation, little is known about the role of serpins that function within cells, especially in a living organism.

Enter serendipity. When collecting specimens of a microscopic worm called Caenorhabditis elegans in water, rather than in a saline solution as is more common, Dr. Luke noticed that an extraordinarily large number of the animals were dying. �My worm yield was way down,� he said. When he examined the dying worms, he determined that they were genetic �knock-outs� that had been modified to be deficient in SRP-6. The normal worms were just fine.

A frequently studied animal model because of its 1,000-cell structure, transparency and easily visible development, C. elegans is a primitive organism whose complete genetic code has been sequenced and is well known to scientists. The worm typically lives in soil, flourishes in water and exists to eat bacteria and reproduce. The investigators were using a �reverse genetic� approach in which they hoped, by studying the relatively limited intracellular serpin repertoire of C. elegans, they could gain insights that might be applicable to serpin function in higher organisms, including humans.

�Serpin proteins are critical,� said Dr. Silverman, a neonatologist and a senior investigator at the Magee-Womens Research Institute. �For example, we know that in patients who have a certain type of skin cancer, those whose tumors express a lot of intracellular serpins don�t do as well. Now we know that SRP-6 is a crucial pro-survival mechanism that can protect cells from injury, initiate repair after injury, or, if absent, lead to a cascade of cell death.�

With further investigation, it may be possible to use this knowledge to deprive cancer cells of their serpin protectors and target them for death. Alternatively, physicians might be able to boost serpin activity to stop cells from dying � for example, intestinal cells affected by the bacterial infection necrotizing enterocolitis (NEC), a major cause of death and illness in fragile, premature infants.

�We still treat NEC the same way we did 30 years ago, with supportive care, antibiotics and surgery to remove dead portions of intestine,� said Dr. Silverman. �We can�t stop the mucosal lining from dying. But with these worms as models, we can do drug screens to search for compounds that can block necrosis.�

Drs. Silverman, Luke and colleagues have dramatically illustrated the devastating consequences of cellular stress in C. elegans when the crucial protector SRP-6 is missing. A cascade of cell necrosis begins in SRP-6-deficient animals exposed to a number of different stressors, including water, heat and lack of oxygen. In the case of water exposure, the SRP-6 knock-outs move a bit but soon become immobile. Finally, the worms� organs are violently expelled through their bodily openings, resulting in what the authors refer to as a �grim fate.�

�Animals with normal genetic sequences are fine in water, but the knock-out animals usually die rapidly,� said Dr. Luke, explaining that this observation led him to realize the importance of SRP-6 in protecting the lysosome, an internal cell structure enclosed in its own protective membrane that acts as the cell�s garbage disposal. Powerful enzymes within the lysosome digest old, worn out proteins, carbohydrates, lipids, DNA, RNA, other damaged cell structures and even invading bacteria and viruses. But if the lysosome becomes damaged and leaky, these enzymes can turn against the cell and possibly overcome the serpin defense � useful if the cell is part of a cancerous tumor.

The investigators determined that SRP-6 staves off necrosis by protecting the lysosome membrane from damage caused by the calpain family of cysteine proteases and by neutralizing other cysteine proteases released from injured cellular structures called organelles as they are being digested by the lysosome. As part of their study, Drs. Silverman, Luke and colleagues labeled enzymes within the lysosomes of SRP-6-deficient animals with a fluorescent biomarker to observe how these enzymes reacted after an injury to the critical structure.

�The lysosomes popped, released their contents into the cell and these digestive enzymes began to activate, making the whole animal fluoresce,� said Dr. Silverman. �Again, this experiment showed the importance of SRP-6 in management of the necrosis pathway.�

�There are a lot of diseases associated with cell necrosis, such as stroke, neurodegenerative diseases and NEC, and now we know that the pathway to necrosis is much more systematic than we once thought it was,� said Dr. Luke. �With further study, we may be able to identify targets of intervention to halt the necrotic progression in some of these diseases and possibly even prevent them.�

Velociraptor had feathers

Thu, 20 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A new look at some old bones have shown that velociraptor, the dinosaur made famous in the movie Jurassic Park, had feathers. A paper describing the discovery, made by paleontologists at the American Museum of Natural History and the Field Museum of Natural History, appears in the Sept. 21 issue of the journal Science.

Scientists have known for years that many dinosaurs had feathers. Now the presence of feathers has been documented in velociraptor, one of the most iconic of dinosaurs and a close relative of birds.

The fossil specimen that the group examined was a velociraptor forearm unearthed in Mongolia in 1998. They found on it clear indications of quill knobs�places where the quills of secondary feathers, the flight or wing feathers of modern birds, were anchored to the bone with ligaments. Quill knobs are also found in many living bird species and are most evident in birds that are strong flyers. Those that primarily soar or that have lost the ability to fly entirely, however, were shown in the study to typically lack signs of quill knobs.

�A lack of quill knobs does not necessarily mean that a dinosaur did not have feathers,� said Alan Turner, lead author on the study and a graduate student of paleontology at the American Museum of Natural History and at Columbia University in New York. �Finding quill knobs on velociraptor, though, means that it definitely had feathers. This is something we'd long suspected, but no one had been able to prove.�

Previous signs of feathers on dinosaurs had been restricted to fossils found in a particular kind of lake sediment that favored preservation of small-bodied animals.

The velociraptor in the current study stood about three feet tall, was about five feet long, and weighed about 30 pounds. Combined with its relatively short forelimbs compared to a modern bird, this indicated it lacked volant, or flight, abilities. The authors suggest that perhaps an ancestor of velociraptor lost the ability to fly, but retained its feathers. In velociraptor, the feathers may have been useful for display, to shield nests, for temperature control, or to help it maneuver while running.

�The more that we learn about these animals the more we find that there is basically no difference between birds and their closely related dinosaur ancestors like velociraptor,� said Mark Norell, a Curator in the Division of Paleontology at the American Museum of Natural History and co-author on the study. �Both have wishbones, brooded their nests, possess hollow bones, and were covered in feathers. If animals like velociraptor were alive today our first impression would be that they were just very unusual looking birds�.

Species still have more viable offspring if they can choose their best mate

Tue, 18 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Athens, Ga. -- When it comes to picking a mate, Crosby, Stills, Nash and Young had an answer: �If you can�t be with the one you love, love the one you�re with.� As it turns out, that may be a cardinal rule in the animal kingdom, too.

New research that crosses several species boundaries shows that when animals must choose less-than-preferred (to them) mates, females and males apparently have ways to compensate that increase the chance their offspring will survive. The study, just published in the Proceedings of the National Academy of Sciences, adds weight to the Compensation Hypothesis, a proposal that has given insight into how individuals can pass on their genes even under less than ideal circumstances.

�It�s always better for offspring if parents can mate with preferred partners, but it�s becoming clear that when parents can�t have that preferred partner, they have ways of making up for it,� said Patricia Adair Gowaty, a Distinguished Research Professor of Ecology and Genetics at the University of Georgia and lead author of the study. �When female �choosers� were in enforced pairs with males they did not prefer, they laid more eggs. Similarly, when males are paired with females they do not prefer, they ejaculate more sperm. This compensation seems to be a way of making the best of a bad job.�

Co-authors of the paper were Wyatt Anderson, Alumni Foundation Distinguished Professor of Genetics, and Yong-Kyu Kim, an assistant research scientist in Anderson�s lab, both at UGA; Cynthia K. Bluhm of the Delta Waterfowl and Wetlands Research Station in Canada; Lee C. Drickamer of Northern Arizona University; and Allen J. Moore of Centre for Ecology and Conservation at the University of Exeter in the United Kingdom.

One of the new study�s strongest arguments for the Compensation Hypothesis is that it includes experimental results in Tanzanian cockroaches, fruit flies, pipefish, wild mallards and feral house mice. When each species faced experimental constraints on free expression of their mate preferences, individuals found ways around the predicament that could improve the chances that offspring could survive and perhaps even flourish.

�Just how an individual finds its best mate isn�t really known,� said Gowaty, �though there�s some evidence that he or she may be somehow sensing the advantage of the potential mate�s immune system in relation to the chooser�s own.� She points out that many factors are probably at work, including behavioral cues and what potential resources a mate may bring.

While the strategies for dealing with nonpreferred mates can help offspring, advantages for the mating pairs themselves are less clear. In experimental situations, for example, females mated to non-preferred males didn�t live as long as females mated to their preferred choice.

One interesting aspect of the study is its implication that all individuals in a species have a flexible response to such problems as constraints on expression of their mating preferences. If that�s true, it hints that compensation may evolve�which could add an unexpected wrinkle to the story of natural selection.

�How compensation evolves is crucial,� Anderson said.

The issues at stake are, in fact, even broader.

�The study also has implications for conservation because it suggests that the best way to keep species alive may be, if possible, to let individuals choose their own mates,� said Gowaty.

The Compensation Hypothesis is Gowaty�s work and was first published only four years ago, though she has been working on it for more than a decade.

Just how�and if�the hypothesis works in humans remains unknown, since studying the subject remains practically (and ethically) improbable. Still, the idea remains a deep part of popular culture.

When Mick Jagger sings �You can�t always get what you want,� most of us nod. And then we start to plot a way around the problem.

New research seeks to enhance quality and security of wireless telemedicine

Mon, 17 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A team of researchers led by Fei Hu, assistant professor of computer engineering at Rochester Institute of Technology, is working to advance the integration of radio frequency identification technology, also known as RFID, into cardiac sensor networks, a new wireless technology for telemedicine delivery. The team will also work to enhance the security of the systems used in the process, thereby reducing the possibility of identity theft and cyber-terrorism. The effort is being supported by a $400,000 grant from the National Science Foundation�s Cyber Trust Program. Hu, the principal investigator, will collaborate with Yang Xiao, professor of computer science at the University of Alabama.

�Telemedicine technology can greatly increase the quality of medical care while also decreasing health care costs,� notes Hu. �Through this project we hope to increase the integration of RFID into existing cardiac sensor networks, ensure the overall security of the system and promote the implementation of the technology in nursing homes and adult care facilities across the country.�

�This research will advance an important technology development, while also enhancing RIT�s skills and capabilities in the area of computer engineering and design,� adds Andreas Savakis, chair of RIT�s Department of Computer Engineering.

The United States� growing nursing home and long-term care populations are putting a severe strain on the national health care system, in part due to the costs of medical care and doctor visits to these facilities. Cardiac sensor networks use wireless sensors to remotely monitor a patient�s heart beating pattern and blood pressure and transfer this information to doctors and hospitals off site. According to Hu, they are seen as a major avenue for increasing the quality of diagnosis and reducing the need for medical supervision.

Furthermore, the integration of RFID tags on medication bottles into this system will allow doctors to know immediately what medications a person is taking and reduce the chance of negative drug reactions or accidental over doses, adds Hu.

One of the major roadblocks in the further development of the system has been concern over the security of wireless networks used in telemedicine delivery. Hu and Xiao will research the use of anti-interference technology to reduce radio distortion of these networks and design and test new RFID security schemes that will decrease the chance of information being stolen. They will also look to assist the overall implementation and integration of RFID to further the development of this technology in telemedicine systems.

�There are well known security challenges associated with cardiac sensor networks and RFID,� Hu notes. �It is my hope this research will assist in better protecting these systems and allow greater numbers of doctors and patients to take advantage of the benefits of telemedicine.�

Women prescribed drugs linked to birth defects not often advised to use birth control

Mon, 17 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Sept. 17 � Although prescription medications that may increase the risk of birth defects are commonly used by women in their childbearing years, only about half receive contraceptive counseling from their health care providers, according to a large-scale study from the University of Pittsburgh School of Medicine reported in the Sept. 18 issue of the Annals of Internal Medicine.

�We found that over the course of a year, one in six women of reproductive age filled a prescription for a medication labeled by the Food and Drug Administration as increasing the risk of fetal abnormalities,� said Eleanor Bimla Schwarz, M.D., assistant professor in the departments of medicine and obstetrics, gynecology and reproductive medicine at the University of Pittsburgh School of Medicine and first study author. �Unfortunately, many women filling prescriptions that can increase risk of birth defects remain at risk of pregnancy.�

Half of pregnancies in the United States are unintended, according to national estimates. While regular use of contraception can prevent unplanned pregnancies, women filling prescriptions that can increase the risk of birth defects are no more likely to use contraception than other women, the study authors note.

For this investigation, Dr. Schwarz and colleagues studied patient data related to all prescriptions filled by 488,175 reproductive-aged women enrolled with a large managed health care plan during 2001. Prescriptions involved drugs considered safe for use in pregnancy and those labeled as posing a fetal risk.

The researchers examined use of contraception and results of pregnancy tests. When they compared medications labeled as increasing the risk of birth defects to safer medications, the researchers found little difference in rates of contraceptive counseling, use of contraception or subsequent pregnancy test results.

�Many women � and perhaps their physicians � may be unaware of the risks associated with the use of some medications, the chance that women may become pregnant, or both,� said Dr. Schwarz, who also is an assistant investigator at the Pitt-affiliated Magee-Womens Research Institute. �The scary thing is that we know women in other primary care health care settings are even less likely to get information about birth control.�

While about half of the women in this study had received contraceptive counseling, other studies have shown that nationwide, only about 20 percent of women are advised to use birth control when they receive potentially dangerous medications.

�While efforts are needed to ensure that women get information about birth control and the risk of medication-induced birth defects, it also is important to realize that different birth control methods are not equally effective,� she said. �Women who were using the most effective methods of contraception, such as the intrauterine device or IUD, were least likely to have a positive pregnancy test after filling a prescription for a potentially dangerous medication.�

The researchers found that internists and family practitioners prescribed the largest proportion (48 percent) of riskier medications to women of childbearing age. Psychiatrists prescribed 15 percent of these drugs; dermatologists, 12 percent; obstetrician/gynecologists, 6 percent; and pediatricians, 3 percent, according to the study.

�Women should not avoid using prescription medications, but clinicians need to remember that sometimes birth control is needed until a woman is ready to have a healthy pregnancy and a healthy baby,� Dr. Schwarz added.

Researchers discover correlation between GERD and obesity in females

Fri, 14 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A group of scientists recently discovered an association between being overweightand a disease called gastro-esophageal reflux disease (GERD) in women.

This discovery was published in the Sept. 14 issue of the World Journal of Gastroenterology by a research group led by Dr. Corazziari from the University La Sapienza of Rome. Dr. Corazziari has been a leader in the field of gastroenterology for a long time and published over 200 research articles and 20 professional books. He and his fellow researchers (with Dr. Piretta being the first author of this article) discovered that, in comparison to average population, overweight and obesity are risk factors for GERD in women and not so much in men.

GERD is a disease with chronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. Heartburn (burning discomfort behind the breastbone) is the major symptom of GERD because the gastric acid gets into esophagus.

It is known that fatty foods can produce a prolonged inhibitory effect on the lower esophageal sphincter (LES), thus increase the possibility of gastro-esophageal reflux (GER). Gastric distention following a copious meal also relaxes LER and increases the possibility of GER too.

Had these mechanisms play big roles in the patients studied by Dr Corazziari, then the overweight male patients (not just female) should also have a significant higher possibility of GERD than general population.

Since oestrogen can also inhibit the LES, Dr. Corazziari suggests that concentration of this hormone may be a possible explanation of increased GERD prevalence in obese females.

Nicotine may accelerate atherosclerosis, may be as dangerous as tar

Wed, 12 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Sept. 10, 2007) -- It's well known that smoking cigarettes increases risk for a host of serious health problems from cancer to heart disease. Now a new study from Weill Cornell Medical College in New York City looks at how they do their dirty work by contributing to atherosclerosis, or hardening of the arteries. The evidence points to nicotine, the addictive chemical in cigarettes.

By comparing reduced-nicotine cigarettes like Quest 3 and Eclipse with regular cigarettes, researchers discovered that the extent of cigarette-smoke induced atherosclerosis in mice correlated with the levels of nicotine -- the higher the nicotine, the more disease.

Right now, the general consensus is that the problem with cigarettes is tar and that nicotine is safe. That's why you can buy nicotine gum or patches to help you stop smoking. Our study presents new evidence that nicotine may not be safe at all, especially for your heart, says Dr. Daniel F. Catanzaro, principal investigator of the study, recently published in the journal Cardiovascular Toxicology. Dr. Catanzaro is associate research professor of physiology and biophysics in the Departments of Medicine and Cardiothoracic Surgery at Weill Cornell Medical College.

Previous studies have suggested that nicotine in cigarettes can hurt the heart by activating the sympathetic nervous system and increasing the heart rate -- potentially leading to fatal arrhythmias. (Nicotine also affects most organ systems -- including the gastrointestinal tract, the skin and the central nervous system.)

The new Weill Cornell study looked at two so-called potentially reduced exposure products (PREPs) -- Eclipse and Quest. Eclipse cigarettes work by heating inhaled air to activate its contents without burning the tobacco. Quest cigarettes are made with tobacco that is genetically-modified to have lower nicotine. Eclipse and Quest 3 have nicotine yields of 0.2 and 0.05 mg per cigarette, respectively. This compares to the two regular cigarettes studied -- 2R4F and Quest 1, with nicotine yields of 1 and 0.6 mg per cigarette, respectively. Eclipse and Quest cigarettes are marketed with the implication that they may be less harmful or addictive than conventional cigarettes. Quest cigarettes purportedly provide smokers the opportunity to taper their nicotine consumption by progressively moving to lower nicotine cigarettes. 2R4F is a research cigarette supplied by the University of Kentucky.

The study found that mice exposed to smoke from low-nicotine cigarettes had significantly smaller atherosclerotic lesions, compared to those exposed to regular cigarettes but still larger than lesions in control mice not exposed to cigarette smoke, which showed the least evidence of atherosclerosis. The accelerating effects of smoking on lesions was seen early, within weeks of smoke exposure.

While our study seems to suggest that low-nicotine cigarettes are safer, we also know that smokers adjust their smoking habits to maintain their level of nicotine. In other words, if you switch to a low-nicotine product, you will probably increase the number of cigarettes you smoke, or change the way you smoke to get more nicotine out of each cigarette. The best thing to do is quit, says Dr. Catanzaro.

Although Quest 1, Quest 3 and 2R4F cigarettes all have the same tar yield (10 mg/cigarette), mice exposed to smoke from the high-nicotine 2R4F and Quest 1 cigarettes developed larger lesions than did mice exposed to smoke from Quest 3, which has the lowest nicotine content of all the products tested. According to the Weill Cornell investigators, this finding points to the special role of nicotine in promoting arteriosclerosis.

Researchers also found that iPF2alphaV, a marker for oxidative stress that has been linked with atherosclerosis in humans, increased proportionately with the level of nicotine. This finding may indicate that nicotine promotes atherosclerosis, in part, by blocking production of nitric oxide, a chemical that mediates the protective functions of the lining of blood vessels.

These findings are preliminary. Going forward we will want to look at whether doping cigarettes with extra nicotine increases their atherogenic potential; whether blockers of nicotine reduce atherosclerosis; and if oral administration of nicotine has the same effects, says Dr. Catanzaro.

About 20 percent of Americans smoke. Cigarette smoke is linked to risk for cancer, chronic lung disease (emphysema and chronic bronchitis), cardiovascular disease (atherosclerosis, thrombosis and vascular dysfunction), stroke and cataracts as well as poor wound healing.

MIT: Leveraging learning for artificial respiration

Tue, 11 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CAMBRIDGE, MA- MIT researchers have found that the body's innate ability to adapt to recurring stimuli could be leveraged to design more effective and less costly artificial respirators. The new approach could minimize the need for the induced sedation or paralysis currently necessary for some patients on mechanical ventilation.

Nonassociative learning, or our innate ability to adapt to recurring stimuli, is the focus of work to be described in the September 12 issue of PLoS ONE, the online, open-access journal from the Public Library of Science.

Specifically, Chi-Sang Poon, a research scientist at the Harvard-MIT Division of Health Sciences and Technology (HST), and colleagues examined rats under mechanical ventilation to see how they applied different forms of nonassociative learning to adapt to the rhythm imposed by the respirator.

Existing respirators do not consider the adaptive nature of breathing in their design. Some ignore the patient's natural rhythm and pump air in and out of the lungs on set intervals. As a result, doctors often must sedate or paralyze patients to prevent them from fighting an unfamiliar rhythm. Other respirator designs rely entirely on the patient to trigger the airflow. These systems, however, are costly and tend to be unreliable for weak patients such as newborns or those in critical care.

The MIT research suggests, however, that if a doctor takes the patient's natural breathing rhythm into account and sets the ventilator's rhythm in that same range, the patient will adapt and synchronize with the ventilator. This new approach could minimize the need for induced sedation or paralysis.

�We have intrinsic nonassociative learning capabilities, called habituation and desensitization, that [can] make up for changes in the spontaneous rhythm due to artificial lung inflation,� says Poon.

In tests of rats under artificial respiration, Poon found that, if using a suitable rhythm, rats adapted to the mechanical ventilation. He also found that this learning capability enabled mice to adapt to an artificial rhythm even when the mechanical respirators applied constant air pressure. The rats effectively �tuned out� this extra pressure, filtering it out as background noise. When Poon disabled the neural pathways involved in nonassociative learning, the rats' ability to adapt was either eliminated or compromised.

Though nonassociative learning is familiar and commonly applied to smelling roses and adjusting to sunlight after emerging from a dark movie theater, it is not usually applied in a clinical environment. Because of their focus on stabilizing patients, clinicians often discount the power of learning. Many ventilators are designed as if the patient were never in the equation,� says Poon. �But it turns out, our vital functions can learn to adapt in order to survive.�

Low vitamin D during pregnancy linked to pre-eclampsia

Fri, 07 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Sept. 7 � Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia, according to a study from the University of Pittsburgh Schools of the Health Sciences reported this week in the Journal of Clinical Endocrinology and Metabolism.

A serious complication of pregnancy marked by soaring blood pressure and swelling of the hands and feet, preeclampsia is the leading cause of premature delivery and maternal and fetal illness and death worldwide, conservatively projected to contribute to 76,000 deaths each year. Preeclampsia, also known as toxemia, affects up to 7 percent of first pregnancies, and health care costs associated with preeclampsia are estimated at $7 billion a year in the United States alone, according to the Preeclampsia Foundation.

�Our results showed that maternal vitamin D deficiency early in pregnancy is a strong, independent risk factor for preeclampsia,� said Lisa M. Bodnar, Ph.D., M.P.H., R.D., assistant professor of epidemiology at the University of Pittsburgh Graduate School of Public Health (GSPH) and lead author of the study. �Women who developed preeclampsia had vitamin D concentrations that were significantly lower early in pregnancy compared to women whose pregnancies were normal. And even though vitamin D deficiency was common in both groups, the deficiency was more prevalent among those who went on to develop preeclampsia.�

For this investigation, Dr. Bodnar and her colleagues evaluated data and banked blood samples taken from women and newborns between 1997 and 2001 at Magee-Womens Hospital of the University of Pittsburgh Medical Center (UPMC) and affiliated private obstetrician practices. Data were analyzed for 1,198 women enrolled in the Pregnancy Exposures and Preeclampsia Prevention Study, a prospective survey designed to examine factors that may predispose women to preeclampsia. Out of this group, 55 cases of preeclampsia and 220 controls were selected for further study.

Samples of maternal blood were taken prior to 22 weeks pregnancy and again just before delivery. Samples of newborn umbilical cord blood also were tested for 25 hydroxyvitamin D, an indicator of vitamin D status.

�Low vitamin D early in pregnancy was associated with a five-fold increase in the odds of preeclampsia,� said Dr. Bodnar, who also is an assistant investigator at the university-affiliated Magee-Womens Research Institute (MWRI). �Data showed this increase risk persisted even after adjusting for other known risk factors such as race, ethnicity and pre-pregnancy body weight. Also troubling was the fact that many of the women reported taking prenatal vitamins, which typically contain 200 to 400 International Units of vitamin D,� she said.

�Even a small decline in vitamin D concentration more than doubled the risk of preeclampsia,� noted James M. Roberts, M.D., senior author of the study and MWRI founding director. �And since newborn�s vitamin D stores are completely reliant on vitamin D from the mother, low vitamin levels also were observed in the umbilical cord blood of newborns from mothers with preeclampsia.�

A vitamin closely associated with bone health, vitamin D deficiency early in life is associated with rickets � a disorder thought to have been eradicated in the United States more than 50 years ago � as well as increased risk for type 1 diabetes, asthma and schizophrenia.

In the developing world, preeclampsia accounts for up to 80 percent of maternal deaths. And while treatment is more available in developed countries, preeclampsia remains the leading cause of maternal death. Infants born to mothers with preeclampsia have a risk of mortality five times greater than those born to women with normal pregnancies. In the United States alone, nearly 15 percent of preterm deliveries are a result of preeclampsia.

Specific brain protein required for nerve cell connections to form and function

Wed, 05 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CHAPEL HILL � Neurons, or nerve cells, communicate with each other through contact points called synapses. When these connections are damaged, communication breaks down, causing the messages that would normally help our feet push our bike pedals or our mind locate our car keys to fall short.

Now scientists at the University of North Carolina at Chapel Hill School of Medicine have shown that a protein called neurexin is required for these nerve cell connections to form and function correctly.

The discovery, made in Drosophila fruit flies may lead to advances in understanding autism spectrum disorders, as recently, human neurexins have been identified as a genetic risk factor for autism.

This finding now gives us the opportunity to see what job neurexin performs within the cell, so that we can gain a better insight into what can go wrong in the nervous system when neurexin function is lost� said Dr. Manzoor Bhat, associate professor of cell and molecular physiology in the UNC School of Medicine and senior author of the study.

The study, published online September 6, 2007, in the journal Neuron, is the first to successfully demonstrate in a Drosophila model the consequences that mutating this important protein may have on synapses.

The research was supported in part by grants from the National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health and funds from the state of North Carolina.

During the last decade, scientists have learned that neurexins are integral to the transmission of chemical signals within the nervous system. Neurexins interact with binding partners called neuroligins to link neighboring nerve cells together so that signals can be sent and received correctly.

Previous attempts to study these proteins in animal models have been challenging. In vertebrates such as mice, three different genes code for the production of certain neurexin proteins. Deleting just one of these genes causes no adverse effects in mouse models, while removing all three is fatal. But fruit flies have only one gene for neurexin, and when Bhat and colleagues deleted the gene, the flies survived � barely.

Knocking out neurexin basically resulted in a fly with defective nervous system� said Bhat, also a member of the UNC Neuroscience Center and the UNC Neurodevelopmental Disorders Research Center.

First of all, the mutated fruit flies had trouble moving around. When the researchers examined the synapses in these flies, they found that half of them were gone. The synapses that remained were deformed, causing them to send out less chemical signals. The researchers, led by Jingjun Li, a graduate student in neurobiology in the UNC School of Medicine, concluded that neurexin is required for the growth of synapses, for the maintenance of their structure and for their function.

Currently, Bhat and other scientists are working to identify the proteins that neurexin binds to, how they interact, and what sequence of events ultimately results in the organization of synapses within nerve cells. The hope is that such studies in Drosophila will one day clarify the role neurexin plays in learning and memory, ultimately leading to a better understanding of how defects in this protein can lead to human disorders such as autism, Bhat said.

Mice stressed in simulated weightlessness show organ atrophy

Mon, 03 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) New Brunswick, N.J. � A ground-based, experimental model used to simulate astronaut weightlessness in space has provided Rutgers scientists an opportunity to study the effects of stress on immune organs.

Earlier collaborative research with Japanese scientists employing this model implicated the protein osteopontin (OPN) in bone mineral loss associated with simulated weightlessness in mice. This research was made possible by the creation at Rutgers of a mouse unable to make OPN (a �knock-out� mouse). Studies with this Rutgers mouse have demonstrated that OPN likely plays a role in a variety of human problems including cancer metastasis, multiple sclerosis and other autoimmune diseases, osteoporosis and certain inflammatory responses.

The new study, which also simulated weightlessness, demonstrated that OPN is required for the atrophy of immune organs brought on by the stress resulting from hindlimb unloading � a technique employed to simulate weightless conditions by lifting the animal�s body weight off its hind legs. Results are presented Sept. 3 online in the Proceedings of the National Academy of Sciences (PNAS) and in the Sept. 11 print issue.

�The bone loss seen in astronauts or bedridden patients is not a stress issue,� explained David Denhardt, a professor in the Department of Cell Biology and Neuroscience at Rutgers, The State University of New Jersey. �They are experiencing a loss of weight bearing on the bones, and the loss of bone mineral is a direct result of this load reduction.�

The presence of OPN, a feature common to both the bone loss and the organ atrophy, is produced by two different causes � weightlessness and stress � coincidentally related to the same laboratory conditions.

OPN is the continuing focus of Denhardt�s research interests. His long-term goal is to develop an OPN antibody � a monoclonal or target-specific antibody � that will inhibit OPN function in lab mice, and ultimately, in humans. This antibody could prove useful in treating the many destructive diseases associated with OPN.

Denhardt�s graduate student Kathryn Wang, a co-author on the PNAS paper, had previously conducted experiments in which the mouse was positioned in such a way as to produce hind limb unloading. This simulated weightless condition produced OPN-dependent bone loss in the hind limbs and provided a potential testing ground for possible OPN antibodies. The specialized equipment for that experiment was supplied by another co-author on the paper, Yufang Shi, a professor in the Department of Molecular Genetics, Microbiology and Immunology at Robert Wood Johnson Medical School�University of Medicine and Dentistry of New Jersey.

Shi, an authority on stress, suggested that along with the bone loss studies, the Rutgers researchers should look at the spleen and thymus � the organs responsible for most of the animal�s immune cells. If stress affects the spleen and thymus so that they atrophy, the immune system becomes impaired. People under severe stress often get sick.

The Rutgers scientists took their colleague�s advice and compared the OPN-deficient knock-out mice to normal mice, with some dramatic results.

�To our astonishment and surprise, the OPN-deficient animals responded differently to the stress than the normal controls,� Denhardt said. �We had no basis to expect this, but the spleen and thymus of the OPN-deficient animals remained normal whereas there was atrophy of the spleen and thymus in the normal controls. This was a novel and totally unexpected result for which we have no explanation at this time. The next phase of our research will ask what exactly is going on.�

The stressed normal mice also displayed elevated levels of corticosterone � a hormone known to induce apoptosis (programmed cell death), a process evident in the spleen and thymus of these mice and a possible mechanism underlying the atrophy.

Denhardt said that their results indicate that OPN needs to be present for these stress related symptoms to occur, pointing to a whole new physiological realm in which the culprit osteopontin is causing problems.

High and mighty: first common height gene identified by researchers behind 'obesity gene' finding

Sun, 02 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Whilst we all know that tall parents are more likely to have tall children, scientists have been unable to identify any common genes that make people taller than others. Now, however, scientists have identified the first gene, known as HMGA2, a common variant of which directly influences height.

The difference in height between a person carrying two copies of the variant and a person carrying no copies is just under 1cm in height, so does not on its own explain the range of heights across the population. However, the researchers believe the findings may prove important.

Previous studies have suggested that, unlike conditions such as obesity, which is caused by a mix of genetic and environmental factors � so called nature and nurture � 90% of normal variation in human height is due to genetic factors rather than, for example, diet. However, other than very rare gene variants that affect height in only a small number of people, no common gene variants have until now been identified.

The research was led by Dr Tim Frayling from the Peninsula Medical School, Exeter, Professor Mark McCarthy from the University of Oxford and Dr Joel Hirschhorn from the Broad Institute of Harvard and MIT in Cambridge, US. Dr Frayling and Professor McCarthy were also part of a Wellcome Trust-funded study team that discovered the first common gene linked to obesity in April this year.

Using data from the Wellcome Trust Case Control Consortium, the largest study ever undertaken into the genetics underlying common diseases, and the Diabetes Genetics Initiative, in the US, the researchers conducted a genome-wide study of DNA samples from 5,000 people. The findings � that variations in the gene HMGA2 make some people taller than others � are published online today in the journal Nature Genetics.

Each of us carries two copies of each gene, one from our mother and one from our father. However, each copy can be a variant, or allele � in the case of the HMGA2 gene, a tall version and a short version. The researchers found that as many as 25% of white Europeans carried two tall versions of this particular gene, making them approximately 1cm taller than the 25% of people who carry two short versions.

Height is a typical 'polygenic trait' � in other words, many genes contribute towards making us taller or shorter, explains Dr Frayling. Clearly, our results do not explain why one person will be 6'5 and another only 4'10. This is just the first of many that will be found � possibly as many as several hundred.

The exact role that HMGA2 has in growth is unclear, but the researchers believe it is most likely in increased cell production. This may have implications for the development of cancer as tumours occur due to unregulated cell growth. Previous studies have shown an association between height and certain cancers: taller people are statistically more likely to be at risk from cancers, including those found in the prostate, bladder and lung.

There appears to be a definite correlation between height and some diseases, explains Dr Mike Weedon, lead author on the study. For example, there are associations between shortness and slightly increased risks of conditions such as heart disease. Similarly, tall people are more at risk from certain cancers and possibly osteoporosis.

Dr Frayling believes that the study has major implications for helping scientists understand how common variations in DNA in the human the genome actually affect us, especially in relation to growth and development.

Even though improved nutrition means that each generation is getting successively taller, variation in height within a population is almost entirely influenced by our genes, says Dr Frayling. This fact, coupled with the ease of measuring height, means that height can act as a model trait, allowing us to explore in detail the influence that the genome actually has on our general make-up, not just disease risk.

In addition to being a textbook example of a complex trait, height is a common reason children are referred to specialists. Although short stature by itself typically does not signify cause for concern, delayed growth can sometimes reflect a more serious underlying medical condition.

�By defining the genes that normally affect stature, we might someday be able to better reassure parents that their child�s height is within the range predicted by their genes, rather than a consequence of disease,� said Dr Hirschhorn from the Broad Institute of Harvard and MIT.

Flies prefer fizzy drinks

Wed, 29 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) While you may not catch a fly sipping Perrier, the insect has specialized taste cells for carbonated water that probably encourage it to binge on food with growing microorganisms. Yeast and bacteria both produce carbon dioxide (CO2) when they feast, and CO2 dissolves readily in water to produce seltzer or soda water.

This is one of the first, if not the only taste sensation discovered in animals beyond the five that humans taste - sweet, sour, bitter, salty and umami, or savory.

This was unexpected, because fruit flies also smell CO2 and they avoid it, said neurobiologist Kristin Scott, assistant professor of molecular and cell biology at UC Berkeley. One way that we like to think of it is that flies seek the right amount of rottenness - if fruit is only half rotten, producing a little CO2, it's good; if too rotten, it gives off a lot of CO2 and is bad tasting. They seek a balance.

Scott and her UC Berkeley colleagues, graduate students Walter Fischler, technician Priscilla Kong and postdoctoral fellow Sunanda Marella - all in the Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute - report their discovery in the Aug. 30 issue of Nature.

Mammals have five known types of taste receptors, though there may be more to discover, Scott said. Flies may have five distinct receptors also, but not the same ones mammals have. While Scott has shown that fruit flies can detect sweet and bitter compounds, and now carbonation, she has discounted their ability to taste umami and said that their ability to taste sour compounds is questionable. She and her lab continue to investigate other unknown taste modalities in fruit flies, which could be any of a number of tastes, such as salt or alcohol.

The discovery came when Fischler, frustrated that he could not find a chemical that stimulated an unknown type of fruit fly taste cell he had isolated, tested the cells' reaction to a drop of Samuel Adams beer. Surprised by a positive response, he tried to narrow down the taste preference to one of the many chemicals in beer. Flat beer and dry yeast, for example, did not work. That's when he discovered the leftover bottle of Calistoga mineral water.

As he was searching for beer components to test, he said, I opened the refrigerator and looked in, when a light bulb went on. Calistoga would be a great way of testing CO2.

The rest is history. Dry ice - frozen CO2 - produced a strong response, while high levels of gaseous CO2 produced a weak response in the taste cells. Sodium bicarbonate in a basic solution that does not contain CO2 bubbles did not work; bicarbonate in a solution with CO2 bubbles did. The liquid in which yeast grow, though not the yeast themselves, also elicited a response from the taste cell. These and a few other genetic tests narrowed the taste trigger down to dissolved carbon dioxide.

The preference for carbonation is weak compared with that for sweetness, Scott noted, implying that seltzer enhances taste or makes other tastes more acceptable. This makes sense because CO2 has no nutritional value, but is a byproduct of organisms - yeast and bacteria - that do provide nutrients, she said.

The newly discovered taste sensors for carbonation reside on their own structures, called taste pegs, on the tongue of the fly. While a fruit fly's four other taste cells are perched on the tip of bristles that cover the entire body, the carbonated water taste cells are clustered around the margins of the sponge-like tip of the proboscis, at the base of taste bristles.

Scott investigates taste cells, which are a type of nerve cell, and is characterizing the cells and genes associated with different tastes. So far, she and her laboratory colleagues have identified the sweet and bitter cells and some of the gustatory receptor genes that detect sweet and bitter compounds in fruit flies.

Fischler now is trying to isolate the actual receptor in the CO2-sensing nerve cell that grabs the CO2 molecule and sends a signal to the fly brain that there is carbonation in the food. It will then be possible to see if others, including humans, also have carbonation receptors on taste cells.

There may be many more taste modalities in humans than the five known today, said Scott. Even if CO2 is a taste unique to fruit flies, it's discovery suggests that other animals may have taste receptors tuned to important chemicals in their environment, she said, either to avoid them, as is the case with bitter chemicals, or seek them out, as is the case with sugars and CO2.

Thus, taste modalities may differ according to nutritional needs, she and her colleagues wrote. Alternatively, CO2 may be an unappreciated taste modality in many organisms.

Gene triggers obsessive compulsive disorder-like syndrome in mice

Wed, 22 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Using genetic engineering, researchers have created an obsessive-compulsive disorder (OCD) - like set of behaviors in mice and reversed them with antidepressants and genetic targeting of a key brain circuit. The study, by National Institutes of Health (NIH) -funded researchers, suggests new strategies for treating the disorder.

Researchers bred mice without a specific gene, and found defects in a brain circuit previously implicated in OCD. Much like people with a form of OCD, the mice engaged in compulsive grooming, which led to bald patches with open sores on their heads. They also exhibited anxiety-like behaviors. When the missing gene was reinserted into the circuit, both the behaviors and the defects were largely prevented.

The gene, SAPAP3, makes a protein that helps brain cells communicate via the glutamate chemical messenger system.

�Since this is the first study to directly link OCD-like behaviors to abnormalities in the glutamate system in a specific brain circuit, it may lead to new targets for drug development,� explained Guoping Feng, Ph.D., Duke University, whose study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health, and the National Institute of Environmental Health Sciences (NIEHS). �An imbalance in SAPAP3 gene-related circuitry could help explain OCD.�

Feng, Jeffrey Welch, Ph.D., Jing Lu, Ph.D., William Wetsel, Ph.D., Nicole Calakos, M.D., Ph.D., and colleagues report on their discovery in the August 23, 2007, issue of Nature.

�This serendipitous discovery illustrates how pursuit of basic science questions can provide important insights with promising clinical implications into poorly understood diseases,� said NINDS director Story C. Landis, Ph.D.

�Ultimately, the challenge will be to translate what we learn from this stunning new genetic animal model into help for the 2.2 million American adults haunted by unwanted thoughts and repetitive behaviors,� added NIMH director Thomas R. Insel, M.D., who conducted clinical studies on OCD earlier in his career.

Previous studies of OCD had implicated a circuit in which the striatum, which straddles the middle of the brain, processes decisions by the cortex, the executive hub at the front of the brain. But exactly how circuit communications might go awry remained a mystery, and glutamate was not a prime suspect.

Nor were Feng and colleagues initially interested in OCD. Rather, they sought to understand the function of the protein made by the SAPAP3 gene, which is involved in glutamate-mediated communications in the cortex-striatum circuit. To find out how it worked, they used genetic engineering to generate SAPAP3 knockout mice.

The mice seemed normal at first, but after four to six months, all developed telltale bald patches of raw flesh on their faces, caused by compulsive scratching. Videotapes confirmed that the sores were self-inflicted � grooming behavior gone amok.

�We were surprised by the magnitude of this phenomenon,� recalled Feng. �The parallels with OCD were pretty striking.�

In a series of behavioral tests, his team determined that the SAPAP3 knockout mice also showed anxiety-like behaviors, often associated with OCD. They were slower to venture into � and quicker to exit � risky environments. And like their human counterparts, the animals responded to treatment with a serotonin selective reuptake inhibitor (fluoxetine), which reduced both the excessive grooming and anxiety-like behaviors.

SAPAP3 is the only member of a glutamate-regulating family of proteins that is present in large amounts in the striatum. It is part of the machinery at the receiving end of the connections between brain cells, where the neurotransmitter binds to receptors, triggering increased activity among the cells.

The researchers found that lack of SAPAP3 genes dampened the increased activity usually caused by glutamate and stunted the development and functioning of circuit connections.

When the researchers injected the striatum of seven-day-old knockout mice with a probe containing the SAPAP3 gene, it protected them from developing the OCD and anxiety-like behaviors 4 to 6 months later and corrected the circuit dysfunction. This confirmed that the absence of the SAPAP3 gene in the striatum was indeed responsible for the OCD-like effects.

The findings suggest that anxiety-related behavior may stem from the striatum, which serves as a pivotal link between the cortex and emotion hubs. The researchers note that recent genetic studies of OCD have hinted at involvement of glutamate-related mechanisms.

Feng�s team is also looking beyond the SAPAP3 gene to other related genes in the circuit that could lead to similar behavioral problems. They are exploring how the SAPAP3 gene affects neural communications and how it works at the molecular level � with an eye to possible applications in drug development. Collaborating clinical investigators are exploring whether specific variants of the SAPAP3 gene in humans may be related to OCD spectrum disorders, such as trichotillomania, or obsessive hair pulling � a human syndrome also characterized by bald patches on the head.

Elephantnose fish 'see' with their chin

Tue, 21 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Originating in Central Africa, Peters' elephantnose fish (Gnathonemus petersii), finds its bearings by means of weak electrical fields. Scientists from the University of Bonn have now been able to show how well this works. In complete darkness the animals can even distinguish the material of objects at a distance or dead organisms from living ones. The results have now been published in the Journal of Experimental Biology.

The fish, which is as long as a cigar, hovers with its head inclined, close to the gravel-covered bed. While it swims forward slowly, its trunk-like elongated chin sweeps steadily from right to left, always at a distance of a few millimetres from the bottom. This way the fish behaves like treasure hunters searching for buried gold coins on the beach with their metal detector. Basically, this is precisely what the fish is doing. Hidden in the sediment there are large numbers of dead nematocera larvae waiting for it, its favourite food.

Zoologists from the University of Bonn have hidden the larvae there. 'We wanted to see whether it can find them and if the answer is yes, then down to what depth,' Professor Gerhard von der Emde explains. 'It', that is the African Peters' elephantnose fish. Yet its characteristically shaped chin does not work like a particularly sensitive nose. Instead, it contains more than 500 electric sensors with which it senses its surroundings. With this sense the animal has conquered the night. During the day it hides, only under cover of darkness does it goes searching for food.

The chin of Peters' elephantnose fish is basically its eye. In its tail is the corresponding torch. Via mutated muscle cells it produces regular electrical pulses of a few volts with it. 80 times per second the fish switches this little battery on and off for the blink of an eye. 'At the same time it measures the electrical field which builds up around it via sensors in the skin,' explains Professor von der Emde. Nearby objects distort the field, so that the fish obtains an image of its surroundings, which is a surprisingly complex one.

Professor von der Emde and his team have tested what the animals can perceive with their electric sense. For this they set up a small cube and a pyramid in an aquarium, for example. Whenever the fish swam to the pyramid, they were rewarded with a nematocera larva. Their eyes were no use to these agile fish, because the experiments took place with infrared lighting, so that only the researchers could see anything, using their special cameras. They were flabbergasted themselves by their results. In nine out of ten cases the fish swam straight towards the pyramid through the pitch black darkness. Even when the researchers used wire models instead of solid objects, the fish could not be fooled. They were even able to handle discontinuous contours. 'For example, we removed the vertical edges of a cube, i.e. we embedded two wire squares on top of each other in a gel that was permeable for electrical fields,' Professor von der Emde says. 'The fish still perceived it as a cube, so they supplied the contours very much like humans would.' Furthermore, they seem to calculate the volume of objects in water. 'A cube has a larger volume than a pyramid of the same height,' Gerhard von der Emde explains. 'If we decreased the size of the cube so much that its volume became smaller than that of the pyramid, the fish often changed their minds and swam to the cube.' So, the Peters' elephantnose fish can also internalise abstract concepts: 'Always swim to the less voluminous of two objects, irrespective of their absolute size.'

As in Starship Enterprise

What Bones, the ship's doctor of the Enterprise does, the little fish from Africa has been doing for a long time, viz. distinguishing living from dying or dead organisms without touching them. 'With its electric sense, it measures their capacitative properties, i.e. their ability to store charges,' Prof. von der Emde explains. 'Dead plants or animals cannot do that.' The electrical field image even tells it what material the object in question is made of. The image of metal is very bright, by contrast non-conductors weaken the electrical field around the fish. And it can even measure distances to a precision of several millimetres. In order to do so, it uses the fact that the electrical image becomes increasingly 'blurred'. From the degree of fuzziness it thus calculates the distance.

There is a reason for this brain power. The cerebellum of Peters' elephantnose fish is hugely enlarged. In comparison with their body length the animals have a larger brain than humans. 'They are really intelligent,' the zoologist says fondly, 'that's why it is so much fun working with them.' At one point he tried to train electric fish from South America. 'That was a flop,' he reminisces, 'the fish are beautiful, but definitely too stupid for complex tasks.'

Scientists tackle mystery mountain illness

Tue, 21 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Experts at the University are studying an illness known as HAPE (high altitude pulmonary oedema), which causes fluid to build up in the lungs can and can occur from as low as 2,500 metres, affecting people of all age groups and fitness levels.

Little is known about the condition and there is no way of predicting who is likely to be affected although studies have suggested a genetic link. It is thought that around one in 50 people who travel to high altitudes suffer from HAPE.

The database, which is being run in collaboration with researchers from America, Austria, Bolivia, and Britain, aims to encourage registration from previous sufferers of HAPE. It will facilitate research that could potentially identify people susceptible to the condition. Genetic studies using the database may also provide greater understanding of what happens in HAPE sufferers' lungs.

Dr Kenneth Baillie, co-ordinator of the database and a researcher at the University of Edinburgh, said: �There is no way of predicting who is likely to suffer from HAPE, as it can affect anyone even if you are young, healthy and active. Because it occurs from 2,500 metres, it can affect skiers as well as mountaineers. Treatment options are very limited and sufferers need to descend from high altitude and see a doctor straight away.

�A major problem is that sufferers may not know that they have HAPE until it is too late. Once the symptoms start to appear � which may include breathlessness at rest and blueness of the lips � sufferers may not realise the severity of the illness and the urgency of reducing altitude and seeking medical treatment. It may also be that sufferers are not in a position to go down a mountain in time, whether this is due to how ill they are, weather conditions or how high up they are. This all reinforces how important it is to find out who may be susceptible in advance so that they can either try to prevent the onset of the illness or not put themselves in a potentially life-threatening situation.�

Use of the database will be open to researchers worldwide, although details of individual members will be not be given out without their consent.

HAPE is the most common form of altitude sickness and can kill within hours if untreated. As the illness progresses, it can cause drowsiness and lack of coordination, leading to a coma and death. As cases are not registered, nobody knows exactly how many people have died as a result of the condition.

The main treatment is descent, but this is often impossible as a sufferer may need to be carried for miles on a stretcher, only to descend a few hundred feet. Other treatments include breathing oxygen and two drugs, dexamethasone and nifepidine, which may not be available when somebody becomes ill.

Blood vessels inside the lungs constrict in response to low oxygen to such an extent that fluid is forced from the capillaries (narrow tubes through which blood cells pass), leading to flooding of the lung�s air sacs.

Risk factors include rapid ascent, physical exertion and a previous history of the condition. By understanding who is most at risk, potential sufferers could take precautions such as climbing much more slowly or taking drugs to prevent the onset of the condition.

Understanding hypertension in African Americans proves elusive

Thu, 16 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Exercise cannot reduce a sodium-retaining hormone in African Americans known to potentially cause hypertension, found Michael D. Brown, Ph.D., the senior author of a study in the September issue of Experimental Physiology. Brown is an associate professor of kinesiology at Temple Universityï¿½s College of Health Professions.

The hormone, aldosterone, influences the kidneyï¿½s regulation of blood pressure, but too much of it can contribute to the development of hypertension because it causes the kidney to retain salt. Aldosterone, released by the adrenal glands on top of the kidneys, plays a role in the complex system used by the body to regulate blood pressure.

ï¿½Although the results are discouraging for African Americans and hypertension, itï¿½ll point us in other directions that may have more potential and could be the key to reducing hypertension,ï¿½ said Brown, who has a background in exercise physiology.

Many African Americans develop the salt-sensitive form of hypertension. Approximately 40 percent of African Americans have hypertension ï¿½ the highest rate of any racial or ethnic group in the United States ï¿½ but there is little data about what makes them more susceptible to this condition, Brown said.

This study is based on the premise that the prevalence of blood pressure sensitivity to salt is extremely high is African Americans. Alterations in aldosterone regulation may play a role because aldosterone causes the kidney to retain salt. Brown said he wanted to find out if exercise could lower the levels.

In the study, he found that the level of aldosterone was related to how the two racial groups distributed body fat. Caucasians generally stored fat in the abdomen area, whereas African Americans had fat distributed throughout the body in a layer under the skin. The six-month study involving 35 Caucasians and African Americans with hypertension found that aerobic exercise training program reduced aldosterone levels in Caucasians by 32 percent, but levels for African Americans were reduced by only 8 percent. Total body fat was reduced only in Caucasians, which might be a clue to the drop in aldosterone.

ï¿½The kidneys help to regulate blood pressure by changing the levels of salt and water in our body. Sometimes the kidneys reset at a higher blood pressure level if it has retained too much salt,ï¿½ Brown said.

While the study showed exercise did not lower aldosterone in African Americans, exercise still has many other benefits for this population, Brown said.

ï¿½Exercise has the capacity to affect so many things. Itï¿½s a way for the body to correct itself,ï¿½ he added.

Brown will continue his research in this area with a $3.5 million National Institutes of Health grant awarded earlier this year. In September, Brown will recruit African Americans with hypertension for a study on how exercise can improve the blood vessel condition. The study will also take an in-depth look at how genes can contribute to hypertension.

ï¿½Solving the cause of hypertension is similar to solving a big puzzle. Each piece of the puzzle represents a contributing factor to hypertension. Each of these pieces, or possible causes of hypertension, needs to be studied in a systematic way,ï¿½ Brown said.

New Joslin research identifies sirtuin protein instrumental in fat production and metabolism

Wed, 15 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) BOSTON--August 15, 2007--A new Joslin Diabetes Center-led study has identified a protein found in fat cells that may play a major role in how fat is produced and stored, offering a new target for treatments to prevent obesity and reduce the risk for type 2 diabetes. This latest research appears in the August 2007 issue of Cell Metabolism.

The study examined the role of a protein called Sirt2, a member of the sirtuin family of seven cellular proteins. These proteins have recently been shown to be important in the control of aging and metabolism. Previous studies have focused on one member of this family, Sirt1, which is activated by high doses of resveratrol, a substance found in red grapes, which can prevent diabetes from developing and also prolong life. This finding generated tremendous attention, leading biotechnology and pharmaceutical companies to begin developing drugs and supplements to harness this effect. Joslin researchers have focused on other sirtuin proteins to find out what role they might play in fat and glucose metabolism and fat development.

This led to the discovery that Sirt2 is the most abundant of the sirtuins in fat cells, expressed in quantities five to ten times higher than other sirtuin proteins. We wanted to find out what would happen to the behavior of fat cells--in terms of metabolism or growth--if we changed the levels of Sirt2, said lead investigator C. Ronald Kahn, M.D., an internationally recognized researcher who is head of the Joslin section on Obesity and Hormone Action and the Mary K. Iacocca Professor of Medicine at Harvard Medical School.

When a person gains weight, cells in connective tissue known as pre-adipocytes differentiate and fill with fat and form adipocytes, which are able to store fat as a potential energy source when food is not available. However, too much fat storage leads to obesity and obesity-related diseases, including type 2 diabetes.

Using genetically altered cells from mice, the Joslin researchers were able to manipulate Sirt2 levels in adipocytes. They found that increasing Sirt2 levels in the cell would block the cell's ability to undergo differentiation and store fat, while reducing Sirt2 would promote adiopogenesis, or fat production. They then went on to pinpoint exactly how Sirt2 produced these effects by interacting with and modifying one of the key transcription factors, or molecular switches, regulating fat differentiation and function, a molecule called FoxO1. FoxO1 is also an important target of insulin action in fat where it helps control the aging process.

Thus, when Sirt2 levels in pre-adipocytes are low, more fat cells develop, while when Sirt2 levels are high, this process is blocked. So, to reduce the amount of fat in the body and help people stay thin, we need to find an activator of Sirt2, said Kahn.

The discovery of Sirt2's role in fat production gives researchers a new avenue to pursue in preventing and treating obesity. Since most of the diabetes epidemic is driven by obesity, Sirt2 may also play a role in preventing type 2 diabetes from developing and in treating people who have already developed the disease, said Kahn.

This is an important goal since more than 60 percent of Americans are now overweight or obese, and obesity is a major factor driving the current epidemic of type 2 diabetes, which now affects more than 20 million people in the U.S. alone.

The next step in the research process will be to create an animal model to validate the results. Once they are confirmed, biotechnology companies can try to develop drugs that would activate Sirt2 in fat cells and provide another tool for combating obesity and diabetes.

Older climbers face uphill battle on Mount Everest

Tue, 14 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) In this era of not surrendering to age, some claim that 60 is the new 40. But new research shows that 60 year olds cannot keep up with 40 year olds on Mount Everest and suffer a sharply higher chance of dying if they do reach the summit.

The study shows that among 2,211 climbers during the spring seasons from 1990 through 2005, the overall chances of reaching Everest's summit were nearly 31 percent, but they dropped to 13 percent for climbers in their 60s. The overall chances of dying on the mountain were 1.5 percent, but they more than tripled to 5 percent for climbers 60 and older.

The researchers did not find any gender differences.

Before we did this analysis, we didn't know whether age would be important. Younger climbers have a physical advantage but probably have less experience than older climbers, said Raymond Huey, a University of Washington biology professor. We used to refer to this advantage of age as the Kareem Abdul-Jabbar effect. As he got older, his physical skills declined but he was so smart and experienced that he was able to compensate and still play professional basketball at the highest levels.

Unfortunately for older climbers, that effect does not apply on the world's highest mountain, said Huey, lead author of a paper describing the research published online Aug. 15 in the Royal Society journal Biology Letters. The Royal Society is the United Kingdom's national science academy.

Other authors are Richard Salisbury, a database analyst and mountaineering historian in Ann Arbor, Mich., and statisticians Jane-Ling Wang and Meng Mao at the University of California, Davis.

The findings run counter to the notion published in a medical journal in 2000 that people in their 60s could safely climb peaks of about 26,300 feet. Mount Everest is about 29,030 feet.

I think they were overstating the safety factor. I think it's much more risky, Huey said.

Huey suspects there are two possible reasons why fewer climbers older than 40 reach the summit and successfully make it down again declining physical capacities and a higher degree of caution that causes them to stop short of their goal of reaching the summit.

By the time you are 50 or 60, you've probably been banged up once or twice. You know it hurts, and you've seen consequences of losing fingers or toes to frostbite, Huey said. So older climbers are probably more cautious, but I can't determine whether it's greater caution, reduced fitness or a combination of the two that explains the lower success rate for older climbers.

The research, funded by the National Science Foundation, consisted of a statistical analysis of climbers since 1990, looking at the influence of age and gender on success and death rates. Much of the data come from Elizabeth Hawley, who chronicled climbing expeditions in the Himalayas and for four decades conducted interviews that provided a large historical archive of mountaineering information.

The analysis found virtually no difference between men and women on Everest there are many fewer women climbers, but their rates of reaching the summit and of dying are very similar to those for men.

But age differences were stark. Those at least 60 years old who started up the mountain had a death rate at least three times higher than younger climbers. For those who actually reached the summit, 25 percent died before completing the descent, compared with 2.2 percent for younger climbers. However, because the sample of older climbers is relatively small, the actual difference could be exaggerated or understated, Huey said.

Many more people in general are trying to climb Everest than, say, 30 years ago there are reports that just this spring more than 600 people reached the summit. The first two climbers to scale Everest, Edmund Hillary and Tenzing Norgay, were 33 and 39 when they succeeded in 1953. For many years, only about 20 percent of the climbers were older than 40, and those older than 60 were very rare. But the scientists found that in recent years nearly half of all climbers are at least 40, and one of every 30 is at least 60 years old. Until now, these older climbers had no way of knowing about how age correlates with their chances of success and death.

Huey believes it is likely more older climbers are now attempting to climb Everest because guided expeditions are readily available and because many older climbers have sufficient disposable income to pay for those guided trips.

Older people are usually healthier now than they were 50 years ago, he said. Many fewer people smoke and health care is better, so increasingly older people are participating in a variety of sports.

But, as the researchers concluded in their paper, On Everest, youth and vigor trump age and experience.

Risk of common vaginal infection linked to preterm birth appears higher for blacks

Sat, 11 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) BOSTON, Aug. 11 Risk of a common vaginal infection linked to preterm birth appears to escalate when even one partner is African-American, according to a University of Pittsburgh School of Medicine study presented today at the 34th annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology in Boston.

When a pregnant woman has bacterial vaginosis, her risk of preterm birth goes up, said Hyagriv Simhan, M.D., M.S.C.R., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine. And now we can say that gauging risk for bacterial vaginosis is not as simple as just looking at the woman. We also should consider her partner.

Bacterial vaginosis (BV) is a common gynecological infection that affects up to 50 percent of women in some populations. BV is characterized by an increase in vaginal alkalinity and an overgrowth of abnormal bacteria. Among the infections more prominent symptoms is a milky, foul-smelling discharge.

For years, clinicians have thought of BV infection as a minor problem, but in addition to increasing the risk for preterm birth, other studies have shown that women who have BV also are more likely to get herpes and other sexually transmitted diseases, including HIV, said Dr. Simhan, a maternal-fetal medicine specialist at the Magee-Womens Hospital of the University of Pittsburgh Medical Center.

For this observational study, Dr. Simhan and his colleagues considered 325 women who were in their first trimester of pregnancy. Among these women, 129 (39.7 percent) were white female/white male partnerships, 35 (10.8 percent) were white female/black male couples, 12 (3.7 percent) were black female/white male couples, and 149 (45.9 percent) were black female/black male partnerships.

Generally, BV was less common among white women compared to black women in the group. But notably, partner race also showed an influence on BV risk, Dr. Simhan said. Our results showed that when one partner is black whether male or female risk of BV goes up two-fold.

BV infection is commonly treated with a range of antibiotics. However, in some cases treatment fails and infections become resistant. Even women whose infection clears frequently can become re-infected later.

We found that paternal race is an independent risk factor for BV during pregnancy, and that this is at least as important a risk factor as maternal race, continued Dr. Simhan. Studies on the contribution of BV to adverse pregnancy outcomes should consider paternal race as an important factor.

A recent study from the U.S. Centers for Disease Control and Prevention found that preterm birth contributed to more than a third of infant deaths twice as many as previously thought, making it the leading cause of infant deaths yet the underlying causes of premature birth are not well understood.

Reasons for the observed variance in BV rates among racial groups also are not well understood, Dr. Simhan said.

There could be genetic differences that relate to why infection rates are different, and maybe some differences in nutritional status that could play a part. But we dont even know the differences in normal vaginal flora among racial groups, he said. More study is definitely needed. What we can say now is that its just not as simple as treating the woman.

Gene predicts better outcome as cortex normalizes in teens with ADHD

Mon, 06 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Brain areas that control attention were thinnest in children with attention deficit hyperactivity disorder (ADHD) who carried a particular version of a gene in a study by the National Institutes of Healths (NIH) National Institute of Mental Health (NIMH). However, the areas, on the right side of the brains outer mantle, or cortex, normalized in thickness during the teen years in these children, coinciding with clinical improvement. Although this particular gene version increased risk for ADHD, it also predicted better clinical outcomes and higher IQ than two other common versions of the same gene in youth with ADHD.

Since this gene version had similar structural effects in healthy children as in children with the disorder, our findings suggest that ADHD is at the far end of a continuum of normal traits, said Philip Shaw, M.D., NIMH Child Psychiatry Branch, who led the research. ADHD likely stems from interactions between several such genes and non-genetic factors.

Shaw, Judith Rapoport M.D., and colleagues report on their magnetic resonance imaging (MRI) study in the August 2007 Archives of General Psychiatry.

This study provides us with a first glimpse of how variation in a specific gene influences both brain development and clinical prognosis in ADHD, said NIMH Director Thomas R. Insel, M.D.

When the NIMH researchers first reported last year that normalization of right cortex thickening was associated with better clinical outcomes in ADHD, there were few hints of a genetic connection. Yet evidence from several previous studies led them to suspect involvement of an ADHD-implicated version of a gene that codes for a receptor protein that binds to the brain chemical messenger dopamine.

This version of the dopamine D4 receptor gene, called the 7-repeat variant, accounts for about 30 percent of the genetic risk for ADHD, making it by far the strongest candidate gene implicated in the disorder. Its called the 7-repeat because it contains the same repeating sequence in its genetic code seven times. Everyone inherits two copies of the D4 receptor gene, one from each parent, so some people have two copies of the same version while others may carry two different versions.

For the current study, the researchers scanned and determined the D4 gene types of 105 children with ADHD and 103 healthy controls and re-scanned them through their teen years.

They found that nearly one-fourth of youth with ADHD and in about one-sixth of the healthy controls had at least one copy of the 7-repeat version. Nearly two thirds of the ADHD youth and three-fourths of the healthy controls had the most common 4-repeat version; fewer than one-tenth in each group had a 2-repeat version.

While the 7-repeat version was linked to thinner attention-controlling cortex in both ADHD and healthy subjects, it appeared to confer advantage only among youth with ADHD. For example, participants with ADHD who lacked at least one copy of this 7-repeat variant had significantly lower IQs, and more than half of them still had pronounced ADHD symptoms when followed-up about six years later, compared to only 21 percent of those with at least one copy of the 7-repeat variant. There was also a trend toward better overall functioning among those with at least one copy of the 7-repeat variant at follow-up.

The MRI scans revealed that 7-repeat carriers with ADHD started out with the thinnest cortex areas important for controlling attention (right orbitofrontal and posterior parieto-occipital). The next thinnest were children with ADHD who did not have the 7-repeat version, followed by healthy children with the 7-repeat. Healthy children lacking the 7-repeat had the thickest cortex, but this did not appear to affect their IQ. However, the researchers note that other studies have found correlations between cortex thickness and certain measures of memory and intelligence.

In 7-repeat carriers with ADHD, the attention-controlling areas thickened to normal by age 16 (see time-lapse image below). Gene variants of two other dopamine system components showed few such anatomic correlates, confirming that the findings were specific to the D4 receptor gene.

Some genes have a good side, even though theyre linked to disorder, said Shaw, who noted that other traits linked to the 7-repeat version, such as novelty seeking and impulsiveness, might confer advantage in some settings. Evidence suggests that the 7-repeat may be a relatively new variant that may have been favored through evolution because such traits proved adaptive for survival.

The researchers are following up with studies on the relationship between cortex thickness and cognitive features of ADHD, such as working memory and the ability to inhibit responses.