Category Archives: Physiology

Physiology

A Nobel Prize with a connection to UB research – UB Now: News and views for UB faculty and staff – University at Buffalo Reporter

On Oct. 4, the Nobel Prize for Physiology or Medicine was awarded to two researchers for their work in identifying the proteins responsible for providing our ability to sense heat and touch.

These were milestones to commemorate, and well-deserved by the researchers who made the discoveries: Dr. David Julius at the University of California, San Francisco, and Dr. Ardem Patapoutian at Scripps Research in La Jolla, California.

With regard to sensing touch, Dr. Patapoutian won the prize for identifying Piezo proteins, which are a type of ion channel on the surface of cells that respond to pressure and stretching.

This can be the pressure or stretching felt as we slide our finger across the surface of a table, or the pressure in our arteries that occurs with each heartbeat. It can be the stretch felt in our lungs when we take a deep breath, or the pain felt by the inflammation caused by a mosquito bite.

The touch sensitivity award is significant to the UB community because the category of ion channels that provide this sensitivity were first observed right here in Buffalo.

Forty years ago, Dr. Frederick Sachs, SUNY Distinguished Professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB, used miniature glass pipettes to suck on the surface of skeletal muscle cells. And in so doing he recorded for the first time the tiny electrical currents that were produced by mechanosensitive ion channels that were most likely Piezo channels.

This seminal publication (Journal of Physiology, London, 1984, 352, 685-701) opened the door to the field of touch-pressure sensitivity. And this first paper was followed by many publications by Dr. Sachs and others over the next 25 years, using his technique to investigate how mechanosensitive ion channels provide many different cell types with the ability to feel their surroundings.

Additional publications by Dr. Sachs and colleagues showed the role of these ion channels in pathology for diseases like vascular disease, cardiac arrhythmias, muscular dystrophy, sickle cell anemia and cancer. Scientists soon realized that disease in any form can change the way tissues and cells respond to stretch and pressure in a variety of ways through pressure from a growing tumor pressing on the surrounding healthy tissue; through a heart arrhythmia that causes the heart muscle to contract with unsynchronized force; or through long-term stiffening of arteries that are under prolonged increased blood pressure from stress.

For many years these channels were being studied in normal physiology and disease using Dr. Sachs technique, but without knowing the identity of the protein that actually provided the ability to respond to stretch and pressure.

It wasnt until Dr. Patapoutian discovered the amino acid sequence of these channels that we knew their identity. And this discovery allowed researchers to investigate how expression of the channels in different tissues changes during normal development and their abnormal function contributes to disease. It also allowed more detailed studies of how the channels respond to stretch forces in different environments.

The role of these channels in disease led Dr. Sachs to search for blockers as a way to ameliorate negative effects of the overactivity of these channels.

Dr. Sachs teamed with me and Dr. Philip Gottlieb, also researchers in the Department of Physiology and Biophysics, to search for compounds that could block the channels. We hunted for compounds in spider and scorpion venom, and discovered an effective blocker of Piezo channels in the venom of the Chilean Rose tarantula and called it GsMTx4.

We then discovered the compounds unusual method of blocking, which so far has proven difficult to duplicate. To improve the lives of patients suffering from disease, we launched a biomedical company called Tonus Therapeutics to develop this blocker, which is now made as a synthetic version of the original tarantula venom compound.

The Sachs/Suchyna/Gottlieb lab continues to study pressure/touch sensitivity here at UB. We use a variety of novel techniques to provide new insights into the role of Piezo channels in living systems and into the development of therapeutic strategies to treat disease. The recognition of the Nobel award committee to pressure/touch sensitivity as a milestone in biology and medicine will bring welcomed exposure to the field for funding and help to attract young scientists into this important area of research.

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A Nobel Prize with a connection to UB research - UB Now: News and views for UB faculty and staff - University at Buffalo Reporter

Physiology

Penn study illuminates the biology of common heart disorder – EurekAlert

Researchers at Penn Medicine have made a major advance in understanding the biology of a common, puzzling, and often fatal heart disorder, dilated cardiomyopathy (DCM), which features the enlargement of the heart and a progressive decrease in its function, for reasons other than cardiovascular disease. DCM is estimated to affect at least hundreds of thousands of people in the United States. The largest single known cause, accounting for an estimated 10 to 20 percent of cases, involves the mutation of the gene that encodes a key heart-muscle protein called titin.

Titin (pronounced titan) is a giant among proteins, and unfortunately its enormity has made it hard to study. How titin mutations lead to DCM has therefore been largely a mystery. But the Penn Medicine researchers, who report their findings today in Science Translational Medicine[LB1], used an array of sophisticated methods to overcome the usual technical hurdles. They found that titin mutations in DCM patients lead to two key abnormalities in heart muscle cells: a shortage of normal-length titin, and the accumulation of mutant, truncated titin fragmentspointing to the possibility that both of these abnormalities drive heart dysfunction in DCM.

These findings change how we look at this genetic form of DCM and give us new directions to pursue for possible future therapies, said study co-senior author Zoltan Arany, MD, PhD, Samuel Bellet Professor of Cardiology at the Perelman School of Medicine at the University of Pennsylvania. Aranys co-senior author is Benjamin L. Prosser, PhD, an associate professor of Physiology.

There is a strong need for a disease-specific treatment for DCM, since the disorder is both common and lethal. It often leads, within a few years, to heart failure, and only about half of DCM patients live five years after their diagnosis. Many who survive do so by receiving heart transplants.

Developing an effective therapy has been a real challenge, however, given the lack of understanding of DCMs underlying biology. Pregnancy, the use of alcohol and other recreational drugs, certain types of infection, and gene mutations, have all been linked to DCMand there are hints that in many cases a combination of factors triggers this diseasebut the precise causes in most individual cases are obscure. Even the mechanism by which titin gene mutations cause DCM has been unclear.

In principle, these causative mutations offer researchers an opportunity to discover the details of how DCM arises. In practice, the size of the affected protein, titin, the largest known protein in biologyhundreds of times larger than many other common proteinshas made it uniquely hard to study. In particular, prior research has been unable to determine whether titin mutations in DCM patients cause heart disease through some direct toxic effect of mutant titin protein, or due to a shortage of normal titin protein.

In the new study, Arany and his colleagues tackled this question, and found evidence supporting both of these mechanisms.

A pathbreaking study

The titin mutations that are often linked to DCM are in the titin-encoding gene TTN, and are called truncatingshortenedvariants in TTN, or TTNtvs. Most genes in our genomes are inherited as a pair, one copy from the mother and one from the father, and DCM patients with TTNtvs typically have one normal copy of TTN to go with the abnormal copy.

Arany and his colleagues examined 184 failing hearts taken out of DCM patients during transplants by co-author Kenneth Margulies, MD, research director of Heart Failure/Transplantation and a professor of Medicine and Physiology at Penn. The researchers found TTNtvs in 22 of the hearts and, with an innovative set of techniques, detected abundant truncated titin fragments, even though prior studies of TTNtv hearts did not find them. That discovery reopens the possibility that these fragments are contributing to DCM by harming heart muscle cells.

In another novel finding, the researchers determined that levels of normal titin were about 30 percent lower in TTNtv-containing heart muscle, suggesting that a shortage of normal titin may also be a contributor to disease.

The study yielded many other findings, such as the observation that the severity of DCM doesnt seem to depend on the parts of titin affected by TTNtv mutations. Altogether, the study represents a leap forward in this fieldone that sends researchers along many new lines of investigation, which could ultimately yield the first DCM-specific treatments.

If it turns out that these chopped titin proteins are the chief cause of trouble, for example, wed want to design therapies to get rid of those proteins, Arany said. With these findings, were aiming in a different direction.

The research was supported by grants from the National Institutes of Health (R01-HL133080, R01-HL126797, AR 53461-12, R01 AG17022, R01 HL089847, R01 HL105993, R01 HL13308), the Gund Family Fund, and the Department of Defense (W81XWH18-1-0503).

Science Translational Medicine

Observational study

Human tissue samples

Truncated titin proteins in dilated cardiomyopathy

3-Nov-2021

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Penn study illuminates the biology of common heart disorder - EurekAlert

Physiology

The trouble of being tall – Vet Candy

The giraffe is a truly puzzling animal. With its exceptional anatomy and suite of evolutionary adaptations, the giraffe is an outstanding case of animal evolution and physiology. Now, an international team of researchers from the University of Copenhagen and Northwestern Polytechnical University in China have produced a high-quality genome from the giraffe and investigated which genes are likely to be responsible for its unique biological features.

The extraordinary stature of the giraffe has led to a long list of physiological co-adaptations. The blood pressure of the giraffe, for instance, is twice as high as in humans and most other mammals to allow a steady blood supply to the lofty head. How does the giraffe avoid the usual side effects of high blood pressure, such as severe damage to the cardiovascular system or strokes?

The team discovered a particular gene - known as FGFRL1 - that has undergone many changes in the giraffe compared to all other animals. Using sophisticated gene editing techniques they introduced giraffe-specific FGFRL1 mutations into lab mice. Interestingly, the giraffe-type mice differed from normal mice in two important aspects: they suffered less cardiovascular and organ damage when treated with a blood pressure increasing drug, and they grew more compact and denser bones.

- "Both of these changes are directly related to the unique physiological features of the giraffe - coping with high blood pressure and maintaining compact and strong bones, despite growing them faster than any other mammal, to form the elongated neck and legs.", says Rasmus Heller from the Department of Biology, University of Copenhagen, one of the lead authors on the study.

Giraffe's can't get no sleep

While jumping out of bed for (some) humans might be an effortless and elegant affair, this is definitely not the case for the giraffe. Merely standing up is an a lengthy and awkward procedure, let alone getting up and running away from a ferocious predator. Therefore, giraffes have evolved into spending much less time sleeping than most other mammals.

- Rasmus Heller elaborates: "We found that key genes regulating the circadian rhythm and sleep were under strong selection in giraffes, possibly allowing the giraffe a more interrupted sleep-wake cycle than other mammals".

In line with research in other animals an evolutionary trade-off also seem to be determining their sensory perception, Rasmus continues:

- "Giraffes are in general very alert and exploit their height advantage to scan the horizon using their excellent eyesight. Conversely, they have lost many genes related to olfaction, which is probably related to a radically diluted presence of scents at 5m compared to ground level".

A model of evolutionary mechanisms--and perhaps even human medicine?

These findings provide insights into basic modes of evolution. The dual effects of the strongly selected FGFRL1 gene are compatible with the phenomenon that one gene can affect several different aspects of the phenotype, so called evolutionary pleiotropy. Pleiotropy is particularly relevant for explaining unusually large phenotypic changes, because such changes often require that a suite of traits are changed within a short evolutionary time. Therefore, pleiotropy could provide one solution to the riddle of how evolution could achieve the many co-dependent changes needed to form an animal as extreme as a giraffe. Furthermore, the findings even identifies FGFRL1 as a possible target of research in human cardiovascular disease.

- "These results showcase that animals are interesting models, not only to understand the basic principles of evolution, but also to help us understand which genes influence some of the phenotypes we are really interested in - such as those related to disease. However, it's worth pointing out that genetic variants do not necessarily have the same phenotypic effect in different species, and that phenotypes are affected by many other things than variation in coding regions.", says Qiang Qiu from Northwestern Polytechnical University, another lead author on the study.

The results have just been published in the prestigious scientific journal,Science Advances.

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The trouble of being tall - Vet Candy

Physiology

Protein in the brain uses energy status to influence maturation, body size, new research shows – University of Michigan News

Scientists have identified how a protein in the brain uses information about the bodys energy balance to regulate growth rate and the onset of puberty in children.

The research, published Nov. 3 in the journal Nature, centered on the melanocortin 3 receptor (MC3R), a member of a family of proteins that have long been known to play central roles in metabolism and energy balance.

University of Michian physiologist Roger Cone and colleagues discovered the MC3R gene more than 20 years ago and demonstrated that mice lacking this protein exhibit reduced linear growth, reduced lean mass and increased obesity. Subsequent studies published by Cones group also demonstrated a role for the receptor in regulating the interaction between reproduction and energy state, including the increased feeding and weight gain during pregnancy.

Now, an international team of scientists led by Sir Stephen ORahilly at the Wellcome-MRC Institute of Metabolic Science, University of Cambridge, has revealed for the first time how defects in the MC3R translate to humanswith results strikingly similar to the findings in mice.

The ORahilly team reports identification of the first individual with mutations in both copies of the MC3R gene, leaving the person with no functioning MC3R. Such cases are extremely rare, perhaps occurring in as little as one in a billion people. This individual showed phenotypes, or physical traits, that were nearly identical to mice with no MC3R.

Using data from UK Biobank and the Avon Longitudinal Study of Parents and Children, the team analyzed the phenotypes in volunteers with mutations in one copy of the gene that encodes the MC3R. These individuals displayed shorter body height and reduced lean mass compared with those who had no MC3R mutations.

In terms of melanocortins, every phenotype that we have observed in the mouse has ultimately been found to be replicated in humans, said Cone, director of the U-M Life Sciences Institute and an author of the new study. This direct correlation between animal models and humans is not always the case; but this research shows that mice are a near-perfect model for studying human syndromes related to melanocortin receptors.

Additionally, ORahilly discovered one new phenotype in people with MC3R mutations: a long delay in the onset of puberty in the patient lacking MC3R, and subtle but significant delays in volunteers from the UK Biobank with mutations in only one copy of the gene. Due to the discovery of only a single patient with loss of both copies of the MC3R gene, the researchers also used mouse gene knockout models to confirm and further understand the findings.

New data generated by the Cone lab and collaborator Richard Simerly at the Vanderbilt School of Medicine, and published in this latest study, verify this effect and also argue that MC3R plays a role in communicating nutritional deprivation to the reproductive axis.

When mice are fasted for 24 hours, the MC3R detects the lack of energy stores in the body and relays that information to the part of the brain that regulates reproductive cycles. In normal mice, the reproductive cycles halt until energy stores return to normal, post-fasting. In mice with no MC3R, however, there is no change to the reproductive axis following fasting, indicating that communication about the energy balance has stopped.

These types of experiments give us important new understanding of the bodys metabolic and reproductive pathways, but they obviously cannot be done in humans, said Cone, who is also a professor of molecular and integrative physiology at the U-M Medical School. This research illustrates the critical role of animal models for studying the fundamentals of physiology, which can then be translated to human health and disease.

The research was supported by the National Institutes of Health (United States), the UK Medical Research Council, Wellcome and the National institute for Health Research (United Kingdom).

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Protein in the brain uses energy status to influence maturation, body size, new research shows - University of Michigan News

Physiology

Study paves the way for a better understanding of muscle injury – News-Medical.Net

Researchers from the INCLIVA Health Research Institute, the Clinical Hospital of Valencia, and the University of Valencia (UV) have participated in a study, the results of which have just been published in Science, which paves the way for a better understanding of muscle injury. The work will enable, in the future, the application of interventions that accelerate its repair both in the physiological field, in sports performance, and probably also in the clinical field, in the frail or sarcopenic patient (loss of muscle mass and strength in older adults).

The main finding of this study is the discovery that muscle cells are capable of regenerating rapidly and autonomously and not only through the intervention of stem cells, as was believed until now. The objective of the work in which Mari Carmen Gmez-Cabrera, professor of the Department of Physiology of the UV and researcher of this project for the INCLIVA, and the researcher Esther Garca have participated was to clarify the mechanisms by which the muscle fibre regenerates after moderate damage such as that induced by physical exercise.

The mechanisms by which muscle is repaired in the event of very serious muscle injury are well described and involve a type of cell called a muscle satellite cell. In less severe and much more common muscle injuries, such as those that occur after exercise and, probably also, in those associated with the muscle aging process itself, the repair mechanism was not well established.

According to Gmez-Cabrera, "contrary to what happens in other cells in our body, our muscles are made up of cells that have multiple nuclei. The muscle cell is damaged when, for example, we suffer a trauma (a blow) but also when we do physical exercise. Exercises with an important eccentric component (a type of contraction in which the muscle generates tension while increasing its length), such as walking down stairs, can cause muscle damage". In addition, the professor at the University of Valencia specifies: "muscle damage is very common in athletes and repair mechanisms are very important in the fields of sports medicine, traumatology and rehabilitation".

The expert highlights the importance of this study, "which has made it possible to find that the repair mechanism for non-severe muscle injuries does not involve, as was originally thought, muscle stem cells or satellite cells".

What happens in a damaged fibre is that the cores of the fibre itself are attracted to the place of damage, which accelerates their repair."

Mari Carmen Gmez-Cabrera, Professor, Department of Physiology, UV

The study is the result of a collaboration between the Pompeu Fabra University (UPF), the National Centre for Cardiovascular Research (CNIC) and CIBERNED, in Spain; and the Joo Lobo Antunes Institute of Molecular Medicine (iMM), in Portugal.

The nuclei near the damage area use the release of messenger RNA as a repair mechanism, which is translated into proteins, that act as building blocks to resolve the muscle injury and return the fibre to its functionality.

Three types of experimental models have been used in this work. They have included athletes who have performed an exercise protocol they knew to induce muscle damage, mice, and various cell models: myotubes and muscle myofibres. The repair mechanism they have described is preserved in the three models studied and represents a very efficient and highly relevant protection mechanism for minor muscle injuries.

In addition, the study has been fundamental in the housing units, as well as the equipment acquired by INCLIVA through the ERDF funds derived from the Valencian Community strategy for research on aging and frailty.

INCLIVA's work for this study has been developed thanks to funding received from the Carlos III Health Institute CB16 / 10/00435 (CIBERFES), from the Ministry of Science and Innovation (PID2019-110906RB-I00 / AEI / 10.13039 / 501100011033); 109_RESIFIT, CSIC General Foundation; PROMETEO / 2019/097 of the Ministry of Health of the Valencian Government and FEDER Funds.

M Carmen Gmez-Cabrera is coordinator of the Research Group on Exercise, Nutrition and Healthy Lifestyle and co-coordinator of the Transversal Program on Aging and Associated Diseases of INCLIVA. She is also part of CIBERFES (Centre for Biomedical Research on Frailty and Healthy Aging Network). Predoctoral researcher Esther Garca has also intervened in the work, through the design and development of in vivo studies with exercise, both in humans and in mice, over the last 18 months.

Source:

Journal reference:

Roman, W., et al. (2021) Muscle repair after physiological damage relies on nuclear migration for cellular reconstruction. Science. doi.org/10.1126/science.abe5620.

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Study paves the way for a better understanding of muscle injury - News-Medical.Net

Physiology

Guest Blog: Virtually Possible (How the Pandemic Forced Us to Rethink Data Collection) – Michigan Tech News

The pandemics impacts on our campus research ecosystem are many and varied. In his guest blog, Kevin Trewartha shares how the halt in face-to-face interactions compelled his team to find alternatives with applications far beyond current challenges.

In the Aging, Cognition, and Action Lab, we investigate the relationship between age-related changes in cognitive and motor function and the neurophysiological basis for those changes. Like so many others who study human behavior and physiology, our research relies on volunteers to perform tasks in the laboratory while we record their performance.

The pandemic caused a sudden and unexpected end to all face-to-face data collection, and an astounding pause in the research methods I have relied on for almost two decades. Yet, as is often opined, great challenges bring great opportunities.

Our understanding of human cognitive, motor, social, and physiological function is dependent on our ability to gather data from participants who volunteer their time in the spirit of scientific inquiry. For many scholars, collecting data means bringing participants into the laboratory to perform a variety of tasks in close contact with the experimenters.

In my lab, we study age-related changes in neurophysiological, cognitive, and motor function by testing individuals 65 and older. Collecting data with human participants means working closely with the Institutional Review Board (IRB) to ensure that our protocols do not present any significant physical or psychological risk to our participants. As researchers, we have a moral and ethical responsibility to ensure their safety. Any risks to the participant must be minimized and reasonable in relation to the expected benefits and importance of the knowledge to be obtained by the research.

The COVID-19 pandemic suddenly elevated the risk of recruiting participants for face-to-face data collection. Prior to widespread availability of a vaccine, the risk of developing serious illness after contracting the virus meant that it was no longer safe to bring participants into the lab. Data collection initiatives like ours were suspended in labs all over the world as we learned more about the virus.

As the weeks passed, a clear picture emerged about the relative risk of severe illness and death due to COVID-19. Older individuals and those with underlying medical conditions were at disproportionate risk for adverse outcomes. With careful planning and review, the IRB worked closely with researchers to mitigate the risks involved and allow human subjects research to eventually resume. However, work with individuals over 65 years old was deemed too risky for the participant.

On a personal level, too, I was unwilling to run the risk of a participant getting severely sick or dying just because they chose to volunteer for research in my lab. Although we expected the shutdown to be temporary, it ended up being more than 15 months before we could prepare to resume data collection with our most vulnerable participant populations.

One of our current National Institutes of Health-funded research projects involves working with older adults with mild cognitive impairment (MCI) or early stages of Alzheimers disease. We are investigating whether subtle changes in motor learning behavior could be a sign of early cognitive impairment. The very same week in March 2020 that Michigan Tech and the State of Michigan recognized the need to change our day-to-day operations, we were collecting data with this high-risk population. Immediately, we recognized the need to pause our data collection an incredibly frustrating albeit necessary decision, given that we were about halfway through our three-year project at the time.

Having to halt most progress on our funded project for almost as much time as we had been working on it provided an opportunity to refocus on one of the biggest challenges we face in behavioral and physiology labs: How do we collect data from human participants if we cannot meet with them face-to-face?

In fact, this was a problem we recognized. There were already well-known, existing disparities between the types of individuals who participate in research and those who do not. Much of the human performance literature is based on data collected from more urban centers, from people who have the physical and financial means to travel to our labs. Fewer studies tend to recruit rural populations, especially those living in more isolated communities and those who have physical and financial barriers to traveling. We once wrote a grant that included a request for funds to develop and test a mobile (tablet-based) platform for motor learning and cognitive testing. Unfortunately, it was not funded, and the idea was set aside.

Although the pandemic levied a devastating blow to our research program, it also provided an important opportunity for us to revisit the mobile testing idea and develop a method to collect data remotely. The development of such technology was beyond my expertise, so we reached out to a colleague in the College of Computing: Robert Pastel, who agreed to collaborate with us on this new project.

At the time, travel was ill advised, so we had some time to work through the development of a web-based app for administering the same motor learning experiments we typically run on our sophisticated equipment in the lab. One of my graduate students was then able to shift the focus of her masters thesis to testing the validity of this new app with healthy younger and older adults by administering the experiment remotely over Zoom.

There were several added challenges to shifting this focus that we did not anticipate at the time. We grow comfortable with our standard methodologies, and shifting to something completely different takes time. Anticipating hiccups along the way is difficult when you enter personally uncharted waters.

The pandemic imposed great challenges outside of work as well. Sudden losses of child care; sharing remote workspaces with family or roommates; trying to help care for family members who live elsewhere; figuring out how to stay physically active; and managing stress, isolation, fear and ever-shifting public health guidance were struggles we all shared. Trying to manage those challenges while trying to launch a new line of research was daunting, especially while working to stay as productive as we could with our existing projects. Despite all those challenges, we made steady progress and expect to finish our initial remote data collection project during the fall 2021 semester.

We are excited about this new line of research and fully expect to continue exploring remote data collection after the pandemic is over. This new approach is a silver lining to a year fraught with barriers to our research productivity. We also consider ourselves fortunate that it was feasible to shift some of our work to an online platform. Many methods of measuring human behavior and physiology, including some of our own, are simply not possible through remote data collection, at least with existing technology. But as is the case with many aspects of our daily lives, the pandemic taught us to adapt, think outside the box and be resilient.

Additional challenges will arise, even as the spread of SARS-CoV-2 wanes. For human subjects research, it will take time to ramp up data collection initiatives to normal levels. Testing sessions may also be slowed down by the need to practice careful mitigation strategies to further limit the risk of spreading the virus. It also remains unclear what lingering impact the pandemic may have on participant recruitment. Some individuals may be more hesitant to volunteer, especially high-risk populations. Regardless, I am so proud of my students, colleagues, collaborators and clinical consultants for their agility, patience and hard work this past year, and I am confident we will meet any new challenges that arise.

The new directions in our labs research program this past year are a testament to the importance of interdisciplinary and multidisciplinary collaborations. Without the expertise and efforts of Pastel, our new line of remote testing research wouldnt have happened. Our interactions during the development process also taught me a lot about considerations programmers need to make when developing apps like this. Collaborations of this sort really start with an informal conversation among colleagues. We have plenty of work to do in this area in the future, but I am excited for a new and somewhat unexpected direction for my research program.

The resilience and adaptability of human subjects researchers will continue to be put to the test for the foreseeable future. This pandemic is not over. We all look forward to a day when we can resume normal life again. That day can happen soon, but it requires that we acknowledge the pandemic for what it is a worldwide public health crisis that does not care about our politics.

Thanks to scientists who have dedicated their lives to developing health technologies, we have access to several safe and effective vaccines that not only prevent people from getting sick and dying, but will prevent the virus from mutating to a point that it evades our immune system defenses and puts us back to square one. When it comes to vaccination, we need to ignore the media, social media, armchair researchers and politicians in favor of seeking advice from our trusted medical professionals. As we collectively band together to end this pandemic, we are coming out the other side with new innovations that will make society better.

Michigan Technological University is a public research university founded in 1885 in Houghton, Michigan, and is home to more than 7,000 students from 55 countries around the world. Consistently ranked among the best universities in the country for return on investment, the University offers more than 125 undergraduate and graduate degree programs in science and technology, engineering, computing, forestry, business and economics, health professions, humanities, mathematics, social sciences, and the arts. The rural campus is situated just miles from Lake Superior in Michigan's Upper Peninsula, offering year-round opportunities for outdoor adventure.

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Physiology

Leslie A. Leinwand, Ph.D., of the University of Colorado, to receive the American Heart Association’s 2021 Eugene Braunwald Academic Mentorship Award…

Embargoed until 7 a.m. CT / 8 a.m. ET Wednesday, Nov. 3, 2021

DALLAS, Nov. 3, 2021 The American Heart Association, a global force for longer, healthier lives, will present its 2021 Eugene Braunwald Academic Mentorship Award to Leslie A. Leinwand, Ph.D., of the University of Colorado Boulder. She will receive the award during the Presidential Session on Sunday, Nov. 14 at the AssociationsScientific Sessions 2021. The meeting will be fully virtual, Saturday, Nov. 13 through Monday, Nov. 15, 2021, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide.

Dr. Leinwand is chief scientific officer of the BioFrontiers Institute, and a Distinguished Professor of Molecular, Cellular and Developmental Biology at the University of Colorado Boulder, Professor of Cardiology at the University of Colorado School of Medicine and Howard Hughes Medical Institute Professor. Her contributions have revolutionized our understanding of heart failure by using molecular techniques in heart and muscle biology. She was selected as this years recipient of the Eugene Braunwald Academic Mentorship Award because of her instrumental role in mentoring young cardiovascular scientists and physician scientists.

Dr. Leslie Leinwand has an impressive career history of shaping young scientists into outstanding leaders in health care and cardiovascular medicine, while continuing to advance our knowledge and understanding of the roles that gender and diet play in heart health, said Association President Donald M. Lloyd-Jones, M.D., Sc.M., FAHA. Her longstanding commitment to supporting the future of cardiovascular science is exemplary, and she has been an outstanding role model and inspiration for generations of scientists.

Throughout her career, she has been passionate about science education and advancement, she encourages pure scientific discovery, and she fosters career development, which she emphasizes through mentorships. She has provided invaluable support and guidance to scientists and researchers including her active mentees, as well as her previous students, many of whom remain in contact with her as their career-long mentor.

It is such an honor to receive this award in the name of Eugene Braunwald and to follow all of the previous outstanding awardees, said Dr. Leinwand. Mentoring is one of the most important things that we do as scientists, and I am tremendously proud of all of my trainees who have gone onto such distinguished careers and become great mentors themselves.

Dr. Leinwand earned her doctorate in biology from Yale University. She has mentored nearly 200 cardiovascular and physician scientists during the past 40 years. Many of her protgs are current cardiovascular leaders who hold the title of chief of cardiology, some have been internationally recognized for leading-edge research. In 2017, she was recognized with the Associations Distinguished Scientist Award for outstanding contributions to the field of heart health. Dr. Leinwand holds four U.S. patents for the solubilization of protein after bacterial expression using sarkosyl, transgenic model for heart failure, diagnosis and treatment of myocardial failure, and methods and compositions for inducing physiological hypertrophy, with another three patents pending. She has published more than 320 scientific papers in peer-reviewed journals.

The Leinwand Lab at the University of Colorados College of Arts and Sciences, founded and led by Dr. Leinwand, is focused on genetics and molecular physiology of inherited diseases of the heart, as well as how biological sex and diet affect the heart. The scientists utilize multidisciplinary approaches, including molecular biology, analysis of human tissues and mouse genetics and cardiac physiology. They study cardiac and skeletal muscle with particular focus on the genetic diseases that affect them. They also are exploring extreme biology exhibited by the Burmese python after consuming infrequent and massive meals.

Additional Resources:

The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Associations overall financial information are availablehere.

The American Heart AssociationsScientific Sessions 2021is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care professionals worldwide. The three-day meeting will feature more than 500 sessions focused on breakthrough cardiovascular basic, clinical and population science updates in a fully virtual experience Saturday, Nov. 13 through Monday, Nov. 15, 2021. Thousands of leading physicians, scientists, cardiologists, advanced practice nurses and allied health care professionals from around the world will convene virtually to participate in basic, clinical and population science presentations, discussions and curricula that can shape the future of cardiovascular science and medicine, including prevention and quality improvement. During the three-day meeting, attendees receive exclusive access to more than 4,000 original research presentations and can earn Continuing Medical Education (CME), Continuing Education (CE) or Maintenance of Certification (MOC) credits for educational sessions. Engage in Scientific Sessions 2021 on social media via#AHA21.

About the American Heart Association

The American Heart Association is a leading force for a world of longer, healthier lives. With nearly a century of lifesaving work, the Dallas-based association is dedicated to ensuring equitable health for all. We are a trustworthy source empowering people to improve their heart health, brain health and well-being. We collaborate with numerous organizations and millions of volunteers to fund innovative research, advocate for stronger public health policies, and share lifesaving resources and information. Connect with us onheart.org,Facebook,Twitteror by calling 1-800-AHA-USA1.

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Leslie A. Leinwand, Ph.D., of the University of Colorado, to receive the American Heart Association's 2021 Eugene Braunwald Academic Mentorship Award...

Physiology

What’s Behind The Strange Drop in American Body Temperatures Over The Past 200 Years? – ScienceAlert

The human body is often said to rest at a healthy internal temperature of 37 degrees Celsius, or 98.6 degrees Fahrenheit.

This average was established two centuries ago in France, and yet in the meantime, it seems our 'normal' physiology has changed ever so slightly.

Early last year, researchers in the United Statescombed Civil War veteran records and national health surveys and found temperatures among men born at the turn of this century were 0.59 degrees Celsius cooler than those men born around two hundred years earlier.

Women, on the other hand, had seen a 0.32 degrees Celsius decline since the 1890s.

At the time, the authors suggested it might have something to do with inflammation due to disease, which is closely tied to body temperature. With the rise of modern medicine, we've seen a decline in chronic infections, and maybe, the authors suggested, this has chilled us out, so to speak.

Later in 2020, another group of researchers found an eerily similar reduction in body temperature among a relatively remote indigenous tribe in Bolivia, where infections have remained widespread and medical care minimal, despite some modern changes.

The reasons for the recent decline in body temperature clearly had to go beyond improved hygiene, cleaner water, or improved medical care, and some researchers at Harvard are now investigating another explanation: a decline in physical activity.

When a person exercises regularly, it often coincides with an increase in their metabolism. This, in turn, can raise their body's resting temperature for hours or even up to a day, which means falling body temperature measurements might indicate falling physical activity.

Unfortunately, the methods we have for measuring physical activity today weren't around 200 years ago, so we can't really compare how we move now to how we moved then.

What could be possible, however, is to use historical body temperature data asa "thermometer" to gauge physical activity before we started keeping track of these things.

If we can model the relationships between physical activity, metabolism, and body temperature we could theoretically work backward.

The idea started as a "back-of-the-envelope" calculation among Harvard researchers, and while their "first pass estimate" is a good start, it's still based on a bunch of assumptions. That said, it is an intriguing hypothesis.

The model the researchers ultimately created found every 1C increase in historical body temperature is linked to an approximate 10 percent change in resting metabolic rate.

Given how much male body temperatures seem to have decreased since the 1820s, their metabolic rate must have therefore declined by 6 percent in the same time.

That's equivalent to about half an hour of physical activity a day, according to the authors' calculations. More precisely, a 27-minute fast walk or slow run for a 75-kilogram (165-pound) male.

"This is a first pass estimate of taking physiological data and trying to quantify declines in activity," explains skeletal biologist Andrew Yegian from Harvard University.

"The next step would be to try to apply this as a tool to other populations."

Because these initial estimates use body temperature as a proxy for metabolic activity and then metabolic activity as a proxy for physical activity, it's very unlikely these results are a perfect representation of the reality.

The rate at which a population metabolizes calories can be pinned down to more than just physical activity, although it is undoubtedly true the average American today exercises less than they did 50 years ago, thanks to automobiles, televisions, and the dawn of the desk job.

It's just less clear what that's doing to our metabolisms and the temperature of our bodies. And it might not be the same for men and women.

"Fat also acts as an insulator, affecting heat dissipation from the body, while also increasing the cost of PA, and our estimation methods did not correct for changes in fat mass over time," the authors write.

A reduced need to thermoregulate in modern environments could also be impacting our metabolic rates, as could improved health and nutrition.

The authors admit their calculations need further refinement, but they hope their approximation will serve "as an anchor for understanding how the decline in physical activity affected health and morbidity during the industrial era."

The study was published in Current Biology.

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What's Behind The Strange Drop in American Body Temperatures Over The Past 200 Years? - ScienceAlert

Physiology

Uncovering How Injury to the Pancreas Impacts Cancer Formation – Laboratory Equipment

Pioneering research from scientists at the Vanderbilt University School of Medicine Basic Sciences and the Salk Institute for Biological Studies shows that acinar cells in the pancreas form new cell types to mitigate injury but are then susceptible to cancerous mutations.

This research, led byKathy DelGiorno, assistant professor of cell and developmental biology at the School of Medicine Basic Sciences,Geoffrey Wahl, professor in the Gene Expression Laboratory and first authorZhibo Ma, postdoctoral fellow in the Wahl lab, was published inGastroenterology.

The findings establish a better understanding of the mechanisms of healing in the pancreas and when these processes go awry, DelGiorno said.

The team used a multidisciplinary approach that combined single-cell RNA sequencing, ultrastructural microscopy, genetically engineered models, and patient samples to identify the cell types that form in response to pancreatic injury. Vanderbilt contributions included computational analysis byKen Lau, associate professor of cell and developmental biology, and various microscopy approaches byDylan Burnette, associate professor of cell and developmental biology, andRafael Arrojo e Drigo, assistant professor of molecular physiology and biophysics.

From this approach, we compared our dataset to published datasets of gastric injury, oncogene-induced pancreatic neoplasia, and human pancreatitis to identify conserved processes across species and organ systems, said DelGiorno.

According to Wahl, the findings of this paper support our long-held thesis that tissue inflammation causes cells to reprogram to a more primitive, developmentally plastic state that under normal circumstances contributes to tissue repair. When subverted by oncogenes like RAS in pancreas cancer, it causes one of the most incalcitrant cancers known to medical science.

Pancreatic cancer is a major public health burden and is slated to become the second-leading cause of cancer-related deaths in the U.S. by the year 2030. Currently, the average five-year survival rate for pancreatic cancer is only 10 percent, one of the worst of any cancer type. New and innovative treatments are greatly needed to change these outcomes for pancreatic cancer patients.

Our work captured how these acinar cells change in response to injury with incredible resolution. Weve been able to identify multiple diverse cells generated by the acinar cells and uncover where they came from. Our findings provide a valuable resource to the field of pancreatic cancer research for understanding the processes that happen early in pancreas injury and tumorigenesis, Ma said.

We hope to co-opt and/or target these processes for the benefit of patients needing treatment for pancreatitis and cancer, DelGiorno said.

The Vanderbilt team has received a National Institute of General Medical Sciences Maximizing Investigators' Research Award to follow up on this work.

We will be using genetically engineered models to study the lineage trajectories and functional role of the cell types identified in this study, DelGiorno said. We will identify the physiological role of these cell types in pancreatic injury, regeneration, and tumorigenesis.

Republished courtesy of Vanderbilt University.Photo: Pancreatic acinar cells form a heterogeneous population of new cell types in response to injury with the potential to limit or drive disease. Acinar-derived clones labeled in red and green. Credit: DelGiorno, et. al.

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Uncovering How Injury to the Pancreas Impacts Cancer Formation - Laboratory Equipment

Physiology

What to know from the Educational Policy and Institutional Resources Committee meeting – Vermont Cynic

The board of trustees voted to terminate several majors, minors, graduate degrees and doctorates today in their meeting on Educational Policy & Institutional Resources.

The Educational Policy & Institutional Resources Committee unanimously voted to terminate molecular physiology masters and doctorate degrees, molecular biology and pharmacology doctorates, the Italian minor and the Italian studies major.

The committee terminated speech and debate and Vermont studies minors with one objecting vote.

Carolyn Dwyer, chair of the Educational Policy & Institutional Resources Committee, introduced resolutions for terminations without a summary because the meeting ran long.

Legislative Trustee John Bartholomew said some of these programs are necessary.

For these suggestions based on lack of enrollment[], a couple of [programs] seem pretty important, Bartholomew said. Like microbiology, molecular genetics and pharmacology.

However, Patricia Prelock, vice provost and senior vice president, said the new CME program in the College of Medicine now includes molecular physiology and molecular biology, rendering those masters and doctorates redundant.

These resolutions came through six points of contact before arriving at the board of trustees for a decision, Prelock said. A total of 11 minors were requested for termination and the rest are coming forward, she said.

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What to know from the Educational Policy and Institutional Resources Committee meeting - Vermont Cynic