Category Archives: Physiology

Physiology

Explained | The 2021 Nobel Prize in Physiology or Medicine – The Hindu

Does the knowledge of nerve impulses which can perceive temperature and pressure when initiated help to treat pain?

The story so far: The 2021 Nobel Prize in Physiology or Medicine was jointly awarded to David Julius, 66, at the University of California, San Francisco, and Ardem Patapoutian, 54, at Scripps Research, La Jolla, California, for their discoveries of receptors for temperature and touch.

Editorial | Sensing heat: On 2021 Nobel Prize in Physiology or Medicine

What is the significance of their work?

The two researchers discovered the molecular mechanism by which our body senses temperature and touch. Being able to do this opens the field for a lot of practical chemistry whereby individual cells and pathways can be tweaked, suppressed or activated to quell pain or sensation. How the body senses external stimuli is among the oldest excursions of natural philosophy. Entire schools of philosophy were based on speculating how the senses influenced the nature of the reality we perceive. Only when physiology developed as an independent discipline and anatomy came into its own did it become widely accepted that specific sensations were the result of different categories of nerves getting stimulated. Thus, a caress or a punch induces cells in our bodies to react differently and convert into specific patterns of electrical stimulation that is then conveyed via the nerves to the central nervous system. Since the Nobel Prizes came to be, at least three of them were for establishing key principles for how sensations travelled along skin and muscle sensory nerve fibres. Much like the length, thickness, material and incident force on their strings elicit specific tones out of a guitar or a piano, there are specific nerve fibre types that in tandem create a response to touch, heat and proprioception, or the sense of our bodys movement and position in space. However, the prominence of molecular biology means that physiology wanted to go a level deeper and find out what specific proteins and which genes are responsible in this symphony of the nerves.

What is the contribution of David Julius towards this?

Capsaicin (8-methyl-N-vanillyl-6-nonenamide), the active component of chili peppers, generates the burning sensation when eating spicy food. Studies on capsaicin showed that when it acted on sensory nerves it induced ionic currents, or the gush of charged particles along a membrane. In the late 1990s, Professor Julius pursued a project to identify a nerve receptor for capsaicin. He thought that understanding the action of capsaicin could provide insights into how the body sensed pain. He and his team went about this by looking for a gene that could induce a response to capsaicin in cells that usually wouldnt react to it. They found one in a novel ion channel protein, later called TRPV1, where TRP stands for transient receptor potential, and VR1 is vanilloid receptor1. They were part of a super family of TRP and it was found that TRPV1 was activated when temperatures were greater than 40 degrees Celsius, which is close to the bodys pain threshold. Several other TRP channels were found, and this ion channel could be activated by various chemical substances, as well as by cold and heat in a way that differs between mammalian species.

What did Ardem Patapoutian find?

Growing up in Beirut as an Armenian, during the Lebanese Civil War, Patapoutian has related stories of being captured by militants at university, before he moved to the United States. Patapoutian and his colleagues were working on how pressure and force affected cells. Following an approach similar to that of Professor Julius, they identified 72 potential genes that could encode an ion channel receptor and trigger sensitivity to mechanical force, and it emerged that one of them coded for a novel ion channel protein, called Piezo1. Via Piezo1, a second gene was discovered and named Piezo2. Sensory neurons were found to express high levels of Piezo2 and further studies firmly established that Piezo1 and Piezo2 are ion channels that are directly activated by the exertion of pressure on cell membranes. The breakthrough by Professor Patapoutian led to a series of papers from his and other groups, demonstrating that the Piezo2 ion channel is essential for the sense of touch. Moreover, Piezo2 was shown to play a key role in proprioception as well as regulate blood pressure, respiration and urinary bladder control. Independently of one another, Professor Julius and Professor Patapoutian used the chemical substance menthol to identify TRPM8, a receptor activated by cold.

What applications do these discoveries have?

Along with the discoveries of specific genes, proteins and pathways, the scientists pioneered experimental methods that allow insight into the structure of these pain and temperature sensors. The challenge for pain relieving drugs is to precisely target regions without causing imbalance in other necessary functions. These scientists work, the Nobel Prize committee said, significantly helped towards reaching that goal.

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Explained | The 2021 Nobel Prize in Physiology or Medicine - The Hindu

Physiology

Charter to establish clinical exercise physiology as a recognised allied health profession in the UK: a call to action – DocWire News

This article was originally published here

BMJ Open Sport Exerc Med. 2021 Sep 21;7(3):e001158. doi: 10.1136/bmjsem-2021-001158. eCollection 2021.

ABSTRACT

The UK population is growing, ageing and becoming increasingly inactive and unfit. Personalised and targeted exercise interventions are beneficial for ageing and the management of chronic and complex conditions. Increasing the uptake of effective exercise and physical activity (PA) interventions is vital to support a healthier society and decrease healthcare costs. Current strategies for exercise and PA at a population level mostly involve self-directed exercise pathways, delivered largely via the fitness industry. Even for those who opt-in and manage to achieve the current recommendations regarding minimum PA, this generic one-size-fits-all approach often fails to demonstrate meaningful physiological and health benefits. Personalised exercise prescription and appropriate exercise testing, monitoring and progression of interventions for individuals with chronic disease should be provided by appropriately trained and recognised exercise healthcare professionals, educated in the cognate disciplines of exercise science (eg, physiology, biomechanics, motor control, psychology). This workforce has operated for >20 years in the Australian public and private healthcare systems. Accredited exercise physiologists (AEPs) are recognised allied health professionals, with demonstrable health and economic benefits. AEPs have knowledge of the risks and benefits of distinct forms of exercise, skills in the personalised prescription and optimal delivery of exercise, and competencies to support sustained PA behavioural change, based on the established scientific evidence. In this charter, we propose a road map for the training, accreditation and promotion of a clinical exercise physiology profession in the UK.

PMID:34631147 | PMC:PMC8458347 | DOI:10.1136/bmjsem-2021-001158

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Charter to establish clinical exercise physiology as a recognised allied health profession in the UK: a call to action - DocWire News

Physiology

Nobel Prize winners 2021: Here’s the complete list of awardees and their contributions – Republic World

Every year in October, the Nobel Committee recognises and awards individualsor organisations for their contributions in specific fields. Fields considered for the awards includephysiology or medicine, physics, chemistry, literature, peace work, and economic science.

The Nobel Prize is given to people who "have conferred the greatest benefit to humankind" bya foundation established by Swedish inventor Alfred Nobel inhis will, read in Stockholm on 30 December 1896.

The Nobel Prizes and the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel have been awarded 609 times to 975 people and organisations between the years 1901 and 2021. Atotal of 943 individuals and 25 organisationsare awarded as some have receivedthe Nobel Prize more than once.

Nobel Peace Prize 2021

Maria Ressa continues to expose abuse of power, use of violence, and growing authoritarianism in her native country, the Philippines by using freedom of expression. On the other hand, for several decades, Dmitry Andreyevich Muratov has defended freedom of speechin Russia amid challenging conditions.

Nobel Prize in Literature 2021

Gurnah is known for hisnovels and a number of short stories that arethemed around the disruption of refugees

Nobel Prize in Physics 2021

Syukuro Manabe,thefirst person to explore the interaction between radiation balance and the vertical transport of air masses,discovered theories to help makeclimate models that assist in detecting weather patterns.

Klaus Hasselmann's methods have proven that global warming is a result of human emissions of carbon dioxide into the atmosphere, andGiorgio Parisi'sdiscoveries makemany different and apparently entirely random phenomena understandable. Their application is not only limited to physics and extends toother fieldsincludingmathematics, biology, neuroscience, and machine learning.

Nobel Prize in Chemistry 2021

List and MacMillan have been recognised for their contribution in making molecular construction easier by inventing a tool that helps in catalysis for producing asymmetric molecules.

Nobel Prize in Physiology or Medicine 2021

Julius and Patapotian's breakthrough discoveries launched intense research activities leading to a rapid increase in the understanding of how the humannervous system senses heat, cold, and mechanical stimuli.

Sveriges Riksbank Prize in Economic Sciences

The three laureates havenew insights about the labour market and have shown what conclusions about cause and effect can be drawn from natural experiments. Their approach has spread to other fields and has revolutionised empirical research.

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Nobel Prize winners 2021: Here's the complete list of awardees and their contributions - Republic World

Physiology

Jeff Ramirez to be Inducted into American Academy of Nursing – gonzaga.edu

SPOKANE, Wash. Jeffery Ramirez, Ph.D., a psychiatric nurse practitioner and a professor of nursing in the School of Nursing and Human Physiology at Gonzaga University, has been selected to become a Fellow of the American Academy of Nursing.

Professor Ramirez and the other 2021 inductees will be recognized for their significant contributions to health care at the Academys annual Health Policy Conference, Oct. 7-9. This years conference and induction ceremony is offered in a hybrid format, allowing attendees to participate in-person (at the Marriott Marquis in Washington, D.C.) or virtually, allowing for maximum attendance through an inclusive format where colleagues, friends, and family members who may not be able to attend the event in person are able to participate. This years induction ceremony will feature personalized video vignettes and live streaming of each inductee.

Induction into the Academy is a significant milestone in a nurse leaders career in which their accomplishments are honored by their colleagues within and outside the profession. Fellows are selected based on their contributions and impact to advance the publics health.

The Academy is an honor society that recognizes nursings most accomplished leaders in policy, research, practice, administration, and academia. Academy Fellows, from nearly 40 countries, hold a wide variety of roles influencing health care. Induction into the Fellowship represents more than recognition of ones accomplishments within the nursing profession. Fellows contribute their collective expertise to the Academy, engaging with health leaders nationally and globally to improve health and achieve health equity by impacting policy through nursing leadership, innovation, and science.

Through a competitive, rigorous application process, the Academys Fellow Selection Committee reviewed hundreds of applications to select the 2021 Fellows. Ramirez was one of 225 individuals selected to be inducted into the 2021 class, which represents 38 states, the District of Columbia, and 18 countries.

Ramirez also was inducted as a Fellow in the American Association of Nurse Practitioners (FAANP) in 2019 and a Distinguished Fellow in the National Academies of Practice in 2020. He is the first nurse practitioner faculty member from Gonzaga to receive these honors.

Dr. Ramirez has held hospital leadership positions as a Nurse Manager, Clinical Nurse Specialist, and Director of Quality Management. He shared his clinical expertise in psychiatric nursing by consulting throughout the country advocating for system changes to improve the care and treatment of psychiatric hospitalized patients. He has been an invited speaker at the local, state, and national level. He has served on expert nursing panels, state and national nursing professional organization boards.

Professor Ramirez is a recognized leader in psychiatric-mental health nurse practitioner (PMHNP) education and has educated PMHNPs to serve in rural and underserved communities in multiple states. He has held educational leadership positions including as lead faculty for the PMHNP program, chairperson for the nursing department and program director for the Doctor of Practice.

I am honored to be chosen to this distinguished and respected academy, Ramirez said. This is certainly one of the greatest recognitions a nursing scholar can receive. I am looking forward to joining this esteemed group of nursing leaders and carrying out the mission of the American Academy of Nursing and improving health through leadership and innovations.

For more information, please contact Professor Ramirez at (509) 313-6484.

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Jeff Ramirez to be Inducted into American Academy of Nursing - gonzaga.edu

Physiology

Busted body clocks mess with fight or flight response – Futurity: Research News

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New research in mice digs into how the bodys internal clocks manage release of important hormones.

For humans and animals, many aspects of normal behavior and physiology rely on the proper functioning of the bodys circadian clocks.

for a normal hormone rhythm to proceed, you need clocks in both the central pacemaker and this downstream region to work in tandem.

Heres how its supposed to work: Your brain sends signals to your body to release different hormones at certain times of the day. For example, you get a boost of the hormone cortisolnatures built-in alarm systemright before you usually wake up.

But hormone release actually relies on the interconnected activity of clocks in more than one part of the brain.

The new research shows how daily release of glucocorticoids depends on coordinated clock-gene and neuronal activity rhythms in neurons found in two parts of the hypothalamus, the suprachiasmatic nucleus (SCN) and paraventricular nucleus (PVN).

The new study, conducted with freely behaving mice, appears in Nature Communications.

Normal behavior and physiology depends on a near 24-hour circadian release of various hormones, says Jeff Jones, who led the study as a postdoctoral research scholar in biology atWashington University in St. Louis and recently started work as an assistant professor of biology at Texas A&M University.

When hormone release is disrupted, it can lead to numerous pathologies, including affective disorders like anxiety and depression and metabolic disorders like diabetes and obesity.

We wanted to understand how signals from the central biological clocka tiny brain area called the SCNare decoded by the rest of the brain to generate these diverse circadian rhythms in hormone release, says Jones, who worked with Erik Herzog, a professor at Washington University and senior author of the new study.

The daily timing of hormone release is controlled by the SCN. Located in the hypothalamus, just above where the optic nerves cross, neurons in the SCN send daily signals that are decoded in other parts of the brain that talk to the adrenal glands and the bodys endocrine system.

Cortisol in humans (corticosterone in mice) is more typically known as a stress hormone involved in the fight or flight response, Jones says. But the stress of waking up and preparing for the day is one of the biggest regular stressors to the body. Having a huge amount of this glucocorticoid released right as you wake up seems to help you gear up for the day.

Or for the night, if youre a mouse.

The same hormones that help humans prepare for dealing with the morning commute or a challenging work day also help mice meet their nightly step goals on the running wheel.

Using a novel neuronal recording approach, Jones and Herzog recorded brain activity in individual mice for up to two weeks at a time.

Recording activity from identified types of neurons for such a long period of time is difficult and data intensive, Herzog says. Jeff pioneered these methods for long-term, real-time observations in behaving animals.

Using information about each mouses daily rest-activity and corticosterone secretion, along with gene expression and electrical activity of targeted neurons in their brains, the scientists discovered a critical circuit between the SCN and neurons in the PVN that produce the hormone that triggers release of glucocorticoids.

Turns out, its not enough for the neurons in the SCN to send out daily signals; the local clock in the PVN neurons also has to be working properly in order to produce coordinated daily rhythms in hormone release.

Experiments that eliminated a clock gene in the circadian-signal-receiving area of the brain broke the regular daily cycle.

Theres certain groups of neurons in the SCN that communicate timing information to groups of neurons in the PVN that regulate daily hormone release, Jones says. And for a normal hormone rhythm to proceed, you need clocks in both the central pacemaker and this downstream region to work in tandem.

The findings in mice could have implications for humans down the road, Jones says. Future therapies for cortisol-related diseases and genetic conditions in humans will need to take into account the importance of a second internal clock.

Source: Washington University in St. Louis

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Busted body clocks mess with fight or flight response - Futurity: Research News

Physiology

Weed goes off script to resist herbicides – EurekAlert

image:University of Illinois researchers (from left) Seth Strom, Dean Riechers, and Crystal Concepcion discovered multiple ways waterhemp is devising new biochemical strategies to evade herbicide control. view more

Credit: Lauren Quinn, University of Illinois

URBANA, Ill. Cementing waterhemps reputation as a hard-to-kill weed in corn and soybean production systems, University of Illinois researchers have now documented the weed deviating from standard detoxification strategies to resist an herbicide that has never been commercialized.

The chemical in question, syncarpic acid-3 (SA3), is the great-great grandfather of the HPPD-inhibiting herbicide Callisto. SA3 has never been used in corn because it has the rather unfortunate effect of killing the crop along with the weeds. Corn can tolerate Callisto and other herbicides because it has a robust detoxification system to neutralize and cordon off the harmful chemical. But corns neutralizing systems dont work on SA3.

Weeds like waterhemp typically evolve detoxification systems that mimic corns. Thats why it's especially surprising that HPPD-resistant waterhemp can detoxify SA3.

"This is probably the first known example where waterhemp has evolved a detox mechanism that a crop doesn't have. Its using a completely different mechanism, adding to the complexity of controlling this weed, says Dean Riechers, professor in the Department of Crop Sciences at U of I and co-author on a new study in New Phytologist.

The discovery means waterhemp could theoretically be resistant to new herbicide products before they even hit the shelves.

Weve always known metabolic resistance is dangerous because it could confer resistance to a yet-to-be-discovered herbicide. Weve just shown that this is a reality, Riechers says. Companies don't want to invest 10-15 years in developing a new herbicide, patent and release it, and find it doesn't work on day one. Our research reinforces that we need to rely more on non-chemical control methods and make sure weeds don't go to seed.

Riechers and postdoctoral associate Crystal Concepcion traced the biochemical reactions inside resistant waterhemp plants when treated with SA3.

Detoxification of herbicides and other toxic compounds usually happens in distinct phases. The first involves a group of enzymes known as p450s that remove electrons from toxic compounds, making them less reactive inside plant cells. But in resistant waterhemp, the opposite happened: electrons were added to SA3 molecules.

Phase-two enzymes known as GSTs are normally not activated for Callisto because p450s get the job done so quickly and efficiently in corn. But for SA3, GSTs did the heavy lifting of detoxification.

Along with the removal of a water molecule in the first phase, the addition of those electrons prepared the phase-two GST enzymes to detoxify SA3, Concepcion says. Its surprising because not only did the phase-one reactions not proceed as expected, we didnt even anticipate GSTs to be involved for this class of herbicides. We dont see corn preparing chemicals for attack by GSTs. This is very, very rare for herbicides.

Riechers says this deviation from standard biochemical detoxification patterns represents something truly novel and potentially damaging for crop producers. Its definitely challenging, he says.

The research group is on a roll with unexpected findings.

Scientists have known for years that corn, soybeans, and sorghum use GSTs to metabolize S-metolachlor, a soil-applied herbicide offering residual weed control. Therefore, they assumed waterhemp used the same mechanism to detoxify the chemical. But in a recent paper, published in Plant and Cell Physiology, Riechers research team documented another example of waterhemp going off script.

In this case, we were thinking it was GSTs all the way. But the data told us otherwise. The metabolomics approach we took informed us that GSTs arent the main mechanism to detoxify S-metolachlor in resistant waterhemp. Its actually p450s, Riechers says.

Last year, Riechers worked with former doctoral student Seth Strom, extension weed scientist and crop sciences professor Aaron Hager, and others to show waterhemp employs both p450s and GSTs in detoxifying Group 15 herbicides. But when they dug deeper in the new Plant and Cell Physiology study, the researchers found GST enzyme activity was detectable in both resistant and sensitive waterhemp but much lower than in corn. In contrast, p450 activity in resistant waterhemp was 20 times greater than in the crop and in sensitive waterhemp.

Studying resistance to soil-applied herbicides like S-metolachlor can be challenging, especially in waterhemp where there were not any templates or previous methods to follow. Developing methods to understand S-metolachlor resistance was worth every minute knowing that results could eventually help provide solutions for growers, says Strom, now a field R&D scientist at Syngenta Crop Protection.

Both studies demonstrate that waterhemp is done relying on corn for detoxification cues, and is evolving its own ways of conquering herbicides.

The New Phytologist article is available at https://doi.org/10.1111/nph.17708.The Plant and Cell Physiology article is available at https://doi.org/10.1093/pcp/pcab132.

Both projects were funded in part by Syngenta.

The Department of Crop Sciences is in the College of Agricultural, Consumer and Environmental Sciences at the University of Illinois at Urbana Champaign.

Resistance to a nonselective 4-hydroxyphenylpyruvate dioxygenase-inhibiting herbicide via novel reductiondehydrationglutathione conjugation in Amaranthus tuberculatus

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Weed goes off script to resist herbicides - EurekAlert

Physiology

Why extinctions ran amok in ancient oceans, and why they slowed down – EurekAlert

image:Brachiopod and crinoid fossils from the Late Ordovician, about 445 million years ago. view more

Credit: Seth Finnegan

Not long after the dawn of complex animal life, tens of millions of years before the first of the Big Five mass extinctions, a rash of die-offs struck the worlds oceans. Then, for reasons that scientists have debated for at least 40 years, extinctions slowed down.

A new Stanford University study shows rising oxygen levels may explain why global extinction rates slowed down throughout the Phanerozoic Eon, which began 541 million years ago. The results, published Oct. 4 inProceedings of the National Academy of Sciences, point to 40 percent of present atmospheric oxygen levels as a key threshold beyond which viable ocean habitat expands and the global extinction rate sharply falls.

Theres a whole set of high-magnitude extinctions earlier in the history of animal life, and then they taper off until theres just these huge mass extinctions. And theres never been an explanation for why we have all those high-magnitude extinctions early on, said senior study authorErik Sperling, an assistant professor of geological sciences at StanfordsSchool of Earth, Energy & Environmental Sciences(Stanford Earth).

The new study reveals that even five degrees of warming extreme for our current climate but common in Earths deep past would be more than enough to trigger mass die-offs early in the Phanerozoic. The research shows this is because, in a low oxygen world, marine animals were already on the razors edge of their ability to breathe and maintain their body temperatures. The finding has implications for understanding the fate of ocean creatures in todays warming world.

The authors used computer models of Earths climate to simulate seawater temperatures and the amount of oxygen that would be dissolved in the ocean as atmospheric carbon dioxide and oxygen fluctuated throughout the Phanerozoic. They paired these simulations with mathematical models of interactions between animal physiology and local environments, then estimated the proportion of marine animal types that would be lost with every 5 degrees Celsius of ocean warming, as would be expected from roughly every fourfold increase in atmospheric carbon dioxide. Such warming events are extreme but not infrequent throughout Earth history.

The approach allowed the authors to effectively populate virtual oceans with realistic organisms, then crank up the heat to see who would survive. These are fully three-dimensional models with the physics of the water circulating around the continents in different configurations and all the biogeochemistry, Sperling said. Thats a huge computational advance.

The results are consistent with a series of major extinction events during the first 50 to 100 million years of the Phanerozoic being a direct consequence of low oxygen levels and physiological responses to heat. We dont need to invoke something outside of climatic change to explain these anomalously severe extinction rates and anomalously common mass extinctions early in the animal fossil record, said lead study authorRichard Stockey, a Stanford PhD student in geological sciences.

The need, rather, is to consider how oxygen scarcity hindered the ability of animals to cope with heat. Thats because as oceans warm, their oxygen content declines while animals need for oxygen grows. This is particularly true for cold-blooded species that rely on the external environment to regulate body temperature and metabolism. The way we looked at things puts oxygen change and temperature change in a common currency and evaluates them at once, Sperling said. Were treating fossils as ancient living organisms and thinking about how they feed, live and breathe how they get through a day.

The researchers found several additional factors that influenced the proportion of species that died out during warmer periods over the past 541 million years, including the configuration of Earths continents, the efficiency of carbon cycling between ocean and atmosphere and the state of the climate at the start of a given warming event. However, atmospheric oxygen is the dominant predictor of extinction vulnerability, the authors write. Changes in atmospheric oxygen were likely much more important than those other factors, Stockey said.

The study reinforces previous findings fromSperlings groupthat underline oxygen and temperature as interlocking keys to understanding extinction and survival patterns in ancient oceans. The geological and paleontological record is telling us over and over that it is the combination of oxygen and temperature change that are the big killers for marine animals, Sperling said.

In areas of todays oceans that have low oxygen levels, including deeper waters of the continental margin off the California coast, any further drop in oxygen or change in temperature may be catastrophic for organisms that are already pushing the limits of their aerobic capacity. Those are some of the places that are potentially in the gravest danger as climate change drives further ocean warming and deoxygenation, Sperling said. For the first hundred million years or so of animal evolution, almost the entire ocean was like that.

Sperling is also Assistant Professor, by courtesy, of Biology and a Center Fellow, by courtesy, at Stanford Woods Institute for the Environment. Coauthors are affiliated with University of California, Riverside; Universit Bourgogne Franche-Comt; and University of California, Berkeley.

The research was supported by the National Science foundation, the NASA Astrobiology Institute Early Career Collaboration Award, the Heising-Simons foundation and the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant.

Proceedings of the National Academy of Sciences

Computational simulation/modeling

Not applicable

Decreasing Phanerozoic extinction intensity as a consequence of Earth surface oxygenation and metazoan ecophysiology

4-Oct-2021

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Why extinctions ran amok in ancient oceans, and why they slowed down - EurekAlert

Physiology

Quixplained: Who won 2021 Nobel Prizes in science, and for what? – The Indian Express

The 2021 Nobel Prizes saw seven winners in science. Ardem Patapoutian and David Julius received the Nobel for physiology while Giorgio Parisi, Syukuro Manabe and Klaus Hasselmann together won the physics gong for their work deciphering chaotic climate. Benjamin List and David MacMillan received the chemistry accolade for developing a tool for molecule building.

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Quixplained: Who won 2021 Nobel Prizes in science, and for what? - The Indian Express

Physiology

2021 Nobel Prize in Physiology or Medicine Awarded for Discoveries in Sensing Temperature and Touch – Scientific American

After a year and a half characterized by a devastating pandemic and a Herculean effort to develop several highly effective vaccines, this years Nobel Prize in Physiology or Medicine was something of a surprise. It was awarded for discoveries related to how the human body senses temperature and touch.

The prize went to David Julius of the University of California, San Francisco, and Ardem Patapoutian of Scripps Research in La Jolla, Calif., for discovering the molecular bases of how nerves convert stimulithe burn of a chili pepper, or the soft pressure of a huginto signals that can be sensed by the brain.

Humans abilities to sense heat, cold, pressure and position are vital for perceiving and reacting to our surroundings. Understanding how they work is critical for treating chronic pain and other conditions.

The work by David Julius and Ardem Patapoutian has unlocked one of the secrets of nature, said Patrik Ernfors, a member of the Nobel Committee, in a press conference announcing the award on Monday in Sweden.

U.C.S.F.sJulius and his colleagues worked to find the receptor for capsaicin, a component in chilies that causes a painful burning sensation. They identified the gene that encodes a new protein, called TRPV1an ion channel in the membranes of cells that opens in response to heat.Julius got the idea to do his capsaicin experiments while shopping in a grocery store: Walking through the supermarket aisle one day, seeing all these hot chili pepper sauces, et cetera, I was thinking, We really have to get this project done, he said in a press conference on Monday. And my wife said, Well, then you should get on it!

Julius and Patapoutian independently identified another protein: TRPM8, which is sensitive to cold and menthol. Additionally, Patapoutian and his colleagues identified the genes for proteins that sense touch, known as Piezo1 and Piezo2. He showed that these two proteins were force-activated ion channels. Piezo2 was also found to be important for sensing the positions of limbs in space, an ability known as proprioception.

Patapoutian, an Armenian-American who grew up in war-torn Lebanon before coming to the U.S. at age 18, says he has learned not to take the opportunities he has had for granted. And in a press conference on Monday, he acknowledged the work of many other colleagues. I just want to emphasize that theres a whole field behind these studiesand, specifically within my lab, a big group of young, enthusiastic, smart scientists, of graduate students and postdocs who actually do the work.

Erhu Cao,who was formerly a postdoctoral researcher in Juliuss lab and is now an assistant professor of biochemistry at the University of Utah,says he was not surprised that the U.C.S.F. researcher won a Nobel Prize for this work. Temperature sensing is a very fundamental sense, Cao adds. If you cannot sense temperature, you can drink very hot coffee without noticing. The pain response is fundamentally protective, but if it goes awry, it can cause chronic pain, he notes.

With these discoveries, and the discovery of Piezo ion channels, in particular, it's so exciting, because it gives us tools to really understand a multitude of different aspects of our physiologyeverything from touch to how you control your blood pressureand sense the need to go to the bathroom,saysKara Marshall, a postdoctoral studentin the Patapoutian lab and an incoming assistant professor at Baylor College of Medicine in Houston. These are things that we take for granted, because they're really important for all of these different aspects of our physiology and our sensory world,Marshall adds.

The Nobel Prize is wonderful recognition of these discoveries, said Scripps Researchs president and CEO Peter Schultz in a statement. I have followed Ardems career closely since he first came to Scripps and can say that he is an extraordinary scientist, mentor, and colleague and a wonderful person.

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2021 Nobel Prize in Physiology or Medicine Awarded for Discoveries in Sensing Temperature and Touch - Scientific American

Physiology

Cerebral and systemic physiological effects of wearing face masks in young adults – pnas.org

Abstract

The COVID-19 pandemic led to widespread mandates requiring the wearing of face masks, which led to debates on their benefits and possible adverse effects. To that end, the physiological effects at the systemic and at the brain level are of interest. We have investigated the effect of commonly available face masks (FFP2 and surgical) on cerebral hemodynamics and oxygenation, particularly microvascular cerebral blood flow (CBF) and blood/tissue oxygen saturation (StO2), measured by transcranial hybrid near-infrared spectroscopies and on systemic physiology in 13 healthy adults (ages: 23 to 33 y). The results indicate small but significant changes in cerebral hemodynamics while wearing a mask. However, these changes are comparable to those of daily life activities. This platform and the protocol provides the basis for large or targeted studies of the effects of mask wearing in different populations and while performing critical tasks.

Many governments have mandated the wearing of face masks in response to the coronavirus disease 2019 (COVID-19) pandemic in order to mitigate the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. The effectiveness of this measure is currently being evaluated (1). This has led to ongoing discussions about possible adverse effects of mask wearing (e.g., dizziness, headaches, fainting), especially within the elderly, during long-term continuous mask usage and during physical activity. Chan et al. (2) reported that the arterial oxygenation (SpO2) did not change in elderly subjects after 1 h, while Law et al. (3) reported a significant effect on baseline cerebral hemodynamics and end-tidal carbon dioxide pressure (EtCO2) using functional MRI (fMRI) on middle-aged adults. No task-induced hemodynamic changes were found in this study. The bulk of these concerns arise due to potential hypercapnic effects of carbon dioxide rebreathing, which has not yet been evaluated in a thorough manner. Also, the brain function was evaluated only at the level of a surrogate of oxygen consumption. Noninvasive functional near-infrared spectroscopy (fNIRS) and functional diffuse correlation spectroscopy (fDCS) use near-infrared light to measure microvascular cerebral hemodynamics without the constraints of the fMRI scanners. When combined together, they allow us to relate cerebral blood/tissue oxygen saturation and blood flow to the cerebral oxygen metabolism. Their main disadvantage is the potential signal contamination due to the extracerebral tissues and the limited penetration depth. Nevertheless, the advantage of studying mask effects on brain function in realistic settings merits their uses for a thorough study to look at the physiology in a holistic manner.

To this end, we have investigated the effect of mask wearing (FFP2 [European Union standard, similar to N95 in North America and KN95 in China] versus surgical) on cerebral hemodynamics, blood/tissue oxygenation, and oxygen metabolism as well as the systemic physiology with a multimodal platform of custom near-infrared spectroscopies and commercial physiological monitors in healthy young adults.

Thirteen volunteers (median age: 27.0 y [23 to 33 y], six females) took part in the study. Fig. 1 summarizes the findings. Small but significant changes in cerebral blood flow (CBF) and cerebral blood oxygen saturation (StO2) were detected for both mask types: 1) CBF increased by 6.5% (95% CI: 2.6, 10.5%) for the FFP2 mask and 6.2% (95% CI: 2.4, 9.9%) for the surgical mask; 2) StO2 increased by 0.9% (95% CI: 0.2, 1.7%) for the FFP2 mask and also 0.9% (95% CI: 0.1, 1.6%) for the surgical mask; 3) total hemoglobin concentration (tHb) increased significantly only for the FFP2 mask by 0.9 M (95% CI: 0.3, 1.5 M). Changes in oxygen extraction fraction (OEF) and cerebral metabolism (CMRO2) (defined in SI Appendix) were not statistically significant: 1) OEF decreased by 1.7% (85% CI: 4.1, 0.8) for the FFP2 mask and by 2.4% (95% CI: 4.7, 0.0) for the surgical mask; 2) CMRO2 increased by 4.5% (95% CI: 1.3, 10.4%) for the FFP2 mask and by 3.6% (95% CI: 1.7, 9.0%) for the surgical mask. None of these changes were statistically significantly different between the two mask types.

(Left) Changes in the different parameters are shown for FFP2 masks (red) and surgical masks (blue). denotes a difference and r is a ratio. The arrow indicates a significant change (P < 0.05) whose direction is an increase or a decrease. Additionally, for cerebral hemodynamics, we have reported (green) changes during typical tasks such as basic cognitive, visual, or motor tasks (4, 8) for comparison. (Right) Time series of the population mean of all parameters are shown for both mask types (same color code). Time 0 is the time when the mask was placed and the shaded area indicates the time taken for placing the mask, which was excluded from the analysis. Data to the Right of the 3-min mark (magenta) were used for analysis to allow the physiology to stabilize after placing the mask. The data were normalized to 300 s prior to the mask placement.

EtCO2 showed a significant change but was discarded since the probe was affected by the air trapped within the mask. Transcutaneous carbon dioxide partial pressure (TcCO2) and SpO2 did not significantly change due to wearing a mask, while mean arterial pressure (MAP) and heart rate (HR) increased significantly for the surgical mask by 4.1 mmHg (95% CI: 0.5, 7.6 mmHg) and 2.0 beats/min (95% CI: 1.0, 3.1 beats/min), respectively. Respiratory rate (RR) decreased significantly for the FFP2 mask by 3.2 breaths/min (95% CI: 5.4, 1.1 breaths/min). A significant difference in HR between mask types of 1.2 beats/min (95% CI: 0.0, 2.4 beats/min) was detected.

Our findings show that wearing a face mask leads to statistically significant changes in the cerebral hemodynamics and oxygenation (CBF and StO2) in healthy young subjects at rest, even for this first relatively short period of mask usage. However, the changes observed are minimal and are comparable to those typically observed during daily life (4). Within the limitations of the study, we cannot claim any concerns for mask use during daily life activities for healthy, young individuals. In order to draw a stronger conclusion, the duration of mask wearing could have been longer (harder to disentangle its effects from other physiological variables such as fatigue), the study population should be more heterogeneous representing the society in general, and the sample sizes can be increased. Another limitation is the fact that the order of the masks was fixed, therefore one should be critical about the results regarding differences in the mask types and additional differences may be revealed in the future. The noticeable differences in variance of the time traces are related to the intersubject variability, which may be related to the fit of the mask, mask types, and the individuals physiology.

Furthermore, we did not observe significant changes in TcCO2 and SpO2. The increase in MAP and HR for the surgical mask may have been caused by the discomfort of probes, placement of masks, and the order of studies. Here, we did not account for these stressors as potential confounding effects, since they are also part of daily life. This observation is further strengthened since TcCO2 did not change, i.e., the hypothesized hypercapnic effect was not observed. We stress that in the literature mainly EtCO2 is utilized as a surrogate of blood carbon dioxide levels, which, however, is influenced by the trapped carbon dioxide under the mask with standard equipment (5). TcCO2 provides insights as a better surrogate for the partial pressure of carbon dioxide.

Overall, our study provides a holistic view of understanding the potential effects of mask wearing in healthy, young adults by a thorough characterization of both the systemic physiology, the presumed driving biomarker of carbon dioxide rebreathing effect, and cerebral hemodynamics. The large intersubject variability while wearing a mask suggests that individuals may have differing responses and the platform/protocol that we introduce here could be utilized on elderly subjects or those with preexisting respiratory or cerebrovascular problems. These populations may behave differently. Finally, the potential effect of mask wearing on individuals performing critical tasks needs to be studied with future investigations. Investigations of these effects are important for policy making in order to maintain quality of life for individuals and for minimizing risks in persons carrying out critical tasks.

The study protocol was approved by the ethical committee of Hospital Clinic Barcelona and all participants signed informed consent. Young healthy adults (range for inclusion: 20 to 35 y of age) were recruited. Participants sat in a chair and read a scientific text during the experiments. The experimental paradigm involved two 10-min periods: 1) without wearing a mask and 2) with a mask. A commonly used three-layer surgical mask and a FFP2 mask (RM101 FFP2 NR, Zhejiang Yinghua Technology Co. Ltd.) were tested. Cerebral blood flow, oxygenation, and oxygen metabolism were measured bilaterally over the prefrontal cortex using transcranial diffuse correlation spectroscopy (DCS) and time-resolved near-infrared spectroscopy (TR-NIRS) (6). Changes in CBF, StO2, and tHb were determined. MAP, HR, SpO2, RR, EtCO2, and TcCO2 were monitored. Signal processing was performed with Matlab (R2019a, MathWorks) and statistical analysis (R, v4.0.3) was applied to determine whether mask wearing was leading to a significant change in the signals. Raw DCS and TR-NIRS data were fitted using the analytical solution. Artifacts were manually removed, the data were smoothed (30-s window), and the changes were averaged over both hemispheres since no difference between them was detected (P >> 0.5, paired Wilcoxon test). For further details see SI Appendix.

This work was funded by la Fundaci La Marat de TV3 (201709.31, 201724.31); Fundaci CELLEX Barcelona; Agencia Estatal de Investigacin (PHOTOMETABO, PID2019-106481RB-C31, PRE2018-085082); the Severo Ochoa (CEX2019-000910-S); laCaixa (LlumMedBcn); Instituci Centres de Recerca de Catalunya (CERCA), Agncia de Gesti d'Ajuts Universitaris i de Recerca (AGAUR)-Generalitat (2017SGR1380); RIS3CAT (CECH, 001-P-001682); LASERLAB-EUROPE V and EU Horizon 2020 (BitMap 675332, VASCOVID 101016087, LUCA 688303, TinyBrains 101017113).

Author contributions: J.B.F., L.K.F., F.S., R.D.-M., M.M., and T.D. designed research; J.B.F. and L.K.F. performed research; J.B.F. and L.K.F. analyzed data; J.B.F., F.S., and T.D. wrote the paper; J.B.F., L.K.F., F.S., R.D.-M., M.M., and T.D. interpreted data; F.S., M.M., and T.D. provided supervision; and R.D.-M. and T.D. provided administrative, technical, and material support.

Competing interest statement: T.D. and J.B.F. are inventors on relevant patents. Institut de Cincies Fotniques (ICFO) has equity ownership in the spin-off company HemoPhotonics S.L. Potential financial conflicts of interest and objectivity of research have been monitored by ICFOs Knowledge and Technology Transfer Department.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2109111118/-/DCSupplemental.

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Cerebral and systemic physiological effects of wearing face masks in young adults - pnas.org