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Physiology

Senior Lecturer or Associate Professor – Teaching & Research – Exercise Science job with FLINDERS UNIVERSITY | 222798 – Times Higher Education…

Clinical Exercise Physiology

Classification:Academic Level C or DSalaryRange:Level C: $119,641 to $137,625 pa,Level D: $143,623 to $158,010 paEmployment Type:Continuing, Full-TimePosition Reports to:Dean (People & Resources), or DelegatePlease Direct Application Enquiries to:cnhs.pc@flinders.edu.auClosing Date:Monday, 21 September 2020 at 11:00 am

Position Summaries:

Senior Lecturer:

The Senior Lecturer will be a key member of the academic staff of Exercise Science and Clinical Exercise Physiology in the College of Nursing and Health Sciences. In addition to contributing to quality research, the position will contribute to administration and leadership within the College and play a lead role in the planning and delivery of topics, including development of teaching materials, delivery of lectures/tutorials or other innovative teaching and learning, including assessment and/or professional activities.

The Senior Lecturer may also be involved in teaching across other courses in the College of Nursing and Health Sciences or other Colleges, where appropriate.

The position will also involve strengthening existing partnerships or exploring new partnerships with external stakeholders that have potential for providing improved teaching, learning and/or research outcomes for the University.

The Senior Lecturer will prioritise, coordinate, monitor workflow and provide informal dayto-day feedback to research support staff and casual academic teaching staff according to the Universitys policies, practices, and standards.

Associate Professor:

The Associate Professor will be a senior member of the academic staff of Exercise Science and Clinical Exercise Physiology in the College of Nursing and Health Sciences. The position will provide leadership in research, teaching and contribute significantly to administrative processes. The Associate Professor may also be involved in teaching across other courses in the College Nursing and Health Sciences, where appropriate.

The position of Associate Professor will provide leadership in strengthening existing partnerships and exploring new partnerships with external stakeholders that have potential for providing improved teaching, learning and/or research outcomes for the University.

The Associate Professor will prioritise, coordinate, monitor workflow and provide informal day-to-day feedback to research support staff and casual academic teaching staff according to the University's policies, practices and standards.

The Associate Professor will also make a significant contribution to leadership and managerial activities of the College and/or University and be recognised for their contribution to the profession at the local, national, and international level.

Please note: Pursuant to Child Safety (Prohibited Persons) Act 2016 (SA) this position has been deemed prescribed. It is an inherent requirement of the position that the successful candidate maintains a current Working With Children Check which is satisfactory to the University.

Avalid National Police Certificate which is satisfactory to the University will also be required before the successful applicant can commence in this position.

Information For Applicants:

You are required to provide asuitability statement ofno more than three pages,addressing the key capabilities of the position description. In addition, you are required to upload your CV.

We are seeking to increase the diversity to improve equal opportunity outcomes for employees, and therefore we encourage female applicants, people with a disability and/or people from Aboriginal or Torres Strait Islander descent to apply.

This position closes onMonday, 21 September 20202 at 11:00 am (ACST), however, we reserve the right to progress late applications.

Please note, applications sent via agencies will not be accepted.

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Senior Lecturer or Associate Professor - Teaching & Research - Exercise Science job with FLINDERS UNIVERSITY | 222798 - Times Higher Education...

Physiology

Scientists Explore Why Some People Are Able To Live With An Infection Unscathed – Public Radio Tulsa

One of the reasons Covid-19 has spread so swiftly around the globe is that for the first days after infection, people feel healthy. Instead of staying home in bed, they may be out and about, unknowingly passing the virus along. But in addition to these pre-symptomatic patients, the relentless silent spread of this pandemic is also facilitated by a more mysterious group of people: the so-called asymptomatics.

According to various estimates, between 20 and 45 percent of the people who get COVID-19 and possibly more, according to a recent study from the Centers for Disease Control and Prevention sail through a coronavirus infection without realizing they ever had it. No fever or chills. No loss of smell or taste. No breathing difficulties. They don't feel a thing.

Asymptomatic cases are not unique to COVID-19. They occur with the regular flu, and probably also featured in the 1918 pandemic, according to epidemiologist Neil Ferguson of Imperial College London. But scientists aren't sure why certain people weather COVID-19 unscathed. "That is a tremendous mystery at this point," says Donald Thea, an infectious disease expert at Boston University's School of Public Health.

The prevailing theory is that their immune systems fight off the virus so efficiently that they never get sick. But some scientists are confident that the immune system's aggressive response, the churning out of antibodies and other molecules to eliminate an infection, is only part of the story.

These experts are learning that the human body may not always wage an all-out war on viruses and other pathogens. It may also be capable of accommodating an infection, sometimes so seamlessly that no symptoms emerge. This phenomenon, known as disease tolerance, is well-known in plants but has only been documented in animals within the last 15 years.

Hints that 'disease tolerance' is at work

Disease tolerance is the ability of an individual, due to a genetic predisposition or some aspect of behavior or lifestyle, to thrive despite being infected with an amount of pathogen that sickens others. Tolerance takes different forms, depending on the infection. For example, when infected with cholera, which causes watery diarrhea that can quickly kill through dehydration, the body might mobilize mechanisms that maintain fluid and electrolyte balance. During other infections, the body might tweak metabolism or activate gut microbes whatever internal adjustment is needed to prevent or repair tissue damage or to make a germ less vicious.

"Why, if they have these abnormalities, are they healthy? Potentially because they have disease tolerance mechanisms engaged. These are the people we need to study." - Janelle Ayres, physiologist, Salk Institute for Biological Studies

Researchers who study these processes rely on invasive experiments that cannot be done in people. Nevertheless, they view asymptomatic infections as evidence that disease tolerance occurs in humans. At least 90 percent of those infected with the tuberculosis bacterium don't get sick. The same is true for many of the 1.5 billion of people globally who live with parasitic worms called helminths in their intestines. "Despite the fact that these worms are very large organisms and they basically migrate through your tissues and cause damage, many people are asymptomatic. They don't even know they're infected," says Irah King, a professor of immunology at McGill University. "And so then the question becomes, what does the body do to tolerate these types of invasive infections?"

While scientists have observed the physiological processes that minimize tissue damage during infections in animals for decades, it's only more recently that they've begun to think about them in terms of disease tolerance. For example, King and colleagues have identified specific immune cells in mice that increase the resilience of blood vessels during a helminth infection, leading to less intestinal bleeding, even when the same number of worms are present.

"This has been demonstrated in plants, bacteria, other mammalian species," King says.

"Why would we think that humans would not have developed these types of mechanisms to promote and maintain our health in the face of infection?" he adds.

Maybe germs aren't the enemy: A more nuanced view

In a recent Frontiers in Immunology editorial, King and his McGill colleague Maziar Divangahi describe their long-term hopes for the field: A deeper understanding of disease tolerance, they write, could lead to "a new golden age of infectious disease research and discovery."

Scientists have traditionally viewed germs as the enemy, an approach that has generated invaluable antibiotics and vaccines. But more recently, researchers have come to understand that the human body is colonized by trillions of microbes that are essential to optimal health, and that the relationship between humans and germs is more nuanced.

Meddlesome viruses and bacteria have been around since life began, so it makes sense that animals evolved ways to manage as well as fight them. Attacking a pathogen can be effective, but it can also backfire. For one thing, infectious agents find ways to evade the immune system. Moreover, the immune response itself, if unchecked, can turn lethal, applying its destructive force to the body's own organs.

"With things like COVID, I think it's going to be very parallel to TB, where you have this Goldilocks situation," says Andrew Olive, an immunologist at Michigan State University, "where you need that perfect amount of inflammation to control the virus and not damage the lungs."

Some of the key disease tolerance mechanisms scientists have identified aim to keep inflammation within that narrow window. For example, immune cells called alveolar macrophages in the lung suppress inflammation once the threat posed by the pathogen diminishes.

Much is still unknown about why there is such a wide range of responses to COVID-19, from asymptomatic to mildly sick to out of commission for weeks at home to full-on organ failure. "It's very, very early days here," says Andrew Read, an infectious disease expert at Pennsylvania State University who helped identify disease tolerance in animals. Read believes disease tolerance may at least partially explain why some infected people have mild symptoms or none at all. This may be because they're better at scavenging toxic byproducts, he says, "or replenishing their lung tissues at faster rates, those sorts of things."

Asymptomatic COVID-19 infections

The mainstream scientific view of asymptomatics is that their immune systems are especially well-tuned. This could explain why children and young adults make up the majority of people without symptoms because the immune system naturally deteriorates with age. It's also possible that the immune systems of asymptomatics have been primed by a previous infection with a milder coronavirus, like those that cause the common cold.

Asymptomatic cases don't get much attention from medical researchers, in part because these people don't go to the doctor and thus are tough to track down. But Janelle Ayres, a physiologist and infectious disease expert at the Salk Institute For Biological Studies who has been a leader in disease tolerance research, studies precisely the mice that don't get sick.

The staple of this research is something called the "lethal dose 50" test, which consists of giving a group of mice enough pathogen to kill half. By comparing the mice that live with those that die, she pinpoints the specific aspects of their physiology that enable them to survive the infection. She has performed this experiment scores of times using a variety of pathogens. The goal is to figure out how to activate health-sustaining responses in all animals.

A hallmark of these experiments and something that surprised her at first is that the half that survive the lethal dose are perky. They are completely unruffled by the same quantity of pathogen that kills their counterparts. "I thought going into this ... that all would get sick, that half would live and half would die, but that isn't what I found," Ayres says. "I found that half got sick and died, and the other half never got sick and lived."

Ayres sees something similar happening in the COVID-19 pandemic. Like her mice, asymptomatic people infected with the novel coronavirus seem to have similar amounts of the virus in their bodies as the people who fall ill, yet for some reason they stay healthy. Studies show that their lungs often display damage on CT scans, yet they are not struggling for breath (though it remains to be seen whether they will fully escape long-term impacts). Moreover, a small recent study suggests that people who are asymptomatic mount a weaker immune response than those who get sick suggesting that mechanisms are at work that have nothing to do with fighting infection.

"Why, if they have these abnormalities, are they healthy?" asks Ayres. "Potentially because they have disease tolerance mechanisms engaged. These are the people we need to study."

The goal of disease tolerance research is to decipher the mechanisms that keep infected people healthy and turn them into therapies that benefit everyone. "You want to have a drought-tolerant plant, for obvious reasons, so why wouldn't we want to have a virus-tolerant person?" Read asks.

A 2018 experiment in Ayres' lab offered proof of concept for that goal. The team gave a diarrhea-causing infection to mice in a lethal dose 50 trial, then compared tissue from the mice that died with those that survived, looking for differences. They discovered that the asymptomatic mice had utilized their iron stores to route extra glucose to the hungry bacteria, and that the pacified germs no longer posed a threat. The team subsequently turned this observation into a treatment. In further experiments, they administered iron supplements to the mice and all the animals survived, even when the pathogen dose was upped a thousandfold.

When the pandemic hit, Ayres was already studying mice with pneumonia and the signature malady of COVID-19, acute respiratory distress syndrome, which can be triggered by various infections. Her lab has identified markers that may inform candidate pathways to target for treatment. The next step is to compare people who progressed to severe stages of COVID-19 with those who are asymptomatic to see whether markers emerge that resemble the ones she's found in mice.

If a medicine is developed, it would work differently from anything that's currently on the market because it would be lung-specific, not disease-specific, and would ease respiratory distress regardless of which pathogen is responsible.

But intriguing as this prospect is, most experts caution that disease tolerance is a new field and tangible benefits are likely many years off. The work involves measuring not only symptoms but the levels of a pathogen in the body, which means killing an animal and searching all of its tissues. "You can't really do controlled biological experiments in humans," Olive says.

In addition, there are countless disease tolerance pathways. "Every time we figure one out, we find we have 10 more things we don't understand," King says. Things will differ with each disease, he adds, "so that becomes a bit overwhelming."

Nevertheless, a growing number of experts agree that disease tolerance research could have profound implications for treating infectious disease in the future. Microbiology and infectious disease research has "all been focused on the pathogen as an invader that has to be eliminated some way," says virologist Jeremy Luban of the University of Massachusetts Medical School. And as Ayres makes clear, he says, "what we really should be thinking about is how do we keep the person from getting sick."

Emily Laber-Warren directs the health and science reporting program at the Craig Newmark Graduate School of Journalism at CUNY.

This story was produced by Undark, a nonprofit, editorially independent digital magazine exploring the intersection of science and society.

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Scientists Explore Why Some People Are Able To Live With An Infection Unscathed - Public Radio Tulsa

Cell Biology

Cells Solve an English Hedge Maze with the Same Skills They Use to Traverse the Body – Scientific American

From the embryonic stages to late life, cells often make incredible journeys, sometimes even traversing an entire organism. They reach their destination by chemotaxis, following signals that lead them to the goal like a chemical yellow brick road. The catch is that different levels, or gradients, of a chemical drawing cells to a target only work over short distances. What guides them over the hills and valleys of a longer journey through the body has been unclear.

Findings reported on August 27 in Science show how two kinds of cellsone a dirt-dwelling amoeba and the other a mouse cancer cell linemanage these seemingly impossible journeys. The key is that the cells do not work along a preexisting gradient but create one themselves by breaking down the chemical lure as they encounter it. Like gathering string while finding ones way out of a labyrinth, the chemical-free path they leave behind keeps them binding toand followingthe guide in front of them.

Take melanoma cells, which are among the most avidly metastasizing tumor cells. Once they have broken down a chemoattractant called lysophosphatidic acid locally in the tumor, they move toward higher levels of the molecule away from the tumor. The cells forge a path into the bloodstream, where lysophosphatidic acid is relatively uniformly distributed. The melanoma cells break the chemical down as they go, leaving a high concentration of it in front of them that they follow and consume, Pac-Man-like, whereas low levels remain behind.

The research team confirmed the use of this tactic in both an amoeba and a mammalian cell line, suggesting a commonality among cells engaged in long-distance orienteering. That outcome is really interesting and demonstrates that self-generated gradients are a universal mechanism for steering directional migration of groups of cells for long distances, says Pablo Sez, a professor and group leader in the department of biochemistry and molecular cell biology at the University Medical Center HamburgEppendorf in Germany, who was not involved in the work. He adds that the result highlights the usefulness of some of the techniques the researchers used, including mathematical modeling to predict how the cells might behave and employing mazes to test those predictions.

In navigating real mazes, cells broke down an attractant chemical (purple), creating a gradient that left more of it ahead and less of it behind. This high-to-low gradient drew the Pac-Man-like cells forward. Credit: Luke Tweedy, Michele Zagnoni and Cancer Research UK

In fact, Luke Tweedy, a postdoctoral research associate at the Beatson Institute for Cancer Research in Scotland and his colleagues reasoned that following a winding path through the complex topography of an organism might be a lot like navigating a labyrinth. To test their idea, they used two kinds of cells: the amoeba Dictyostelium discoideum, or Dicty for short, and mouse pancreatic cancer cells. Dicty cells were especially of interest because of their proficiency at breaking down the chemical yellow brick road as they travel it so that the right path is always before them. With this tendency to gather string as it moves along, Dicty was an exemplary candidate for maze solvinga chemotactic prodigy, as Tweedy puts it.

Tweedy and his colleagues found that Dicty lived up to its reputation, rapidly solving a complex maze in an hour that could take the tortoiselike pancreatic cancer cells several days. The researchers tested the cells in a lot of different mazes, some with shorter versus longer dead ends and different forks. When cells faced a choice between a dead end and a true path, a few wayward ones would dispatch all of the chemoattractant trapped in the cul-de-sac, and the rest of them would orient to the other fork that was still flowing with the alluring molecules.

The most memorable test the investigators used was the one they modeled on the famous maze at Hampton Court Palace near London. They chose it, Tweedy says, for the razzle-dazzle and to capture the imagination. Dicty, the prodigy protist, not only solved this maze but also managed to use its self-generating gradient skills to find a shortcut.

Researchers also brought incomputational modelsto predict cell behavior, which could have implications for human conditions that involve migrating cells. An example is human cancer cells that have something in common with amoebaswhether that connection involves the normal migration of immune cells or the pathological journey of metastatic cancer cells They use the same fundamental mechanism of migration, [in which] receptors detect attractants and guide the cytoskeleton to move the cell.

In fact, the similarities are strong enough that Tweedy sees many ways to bridge the amoeba-human-cell gap, including applying maze-solving ideas to predicting the path that the cancer cells of glioblastoma follow.

The results could also offer a rare window into some early processes in mammalian embryos. The cells that eventually set up shop in the gonads start far away from their target early in an embryos development. These so-called germ cells have to move over embryonic hill and dale to get to the appropriate destination. If the behavior of Dicty or the much slower pancreatic cancer cells is universal, then these germ cells may use a similar tactic to get to the future gonads and avoid taking a wrong turn toward, say, the gut. The implication is that building complex organisms sometimes means that cells only get where they are going by making their own way.

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Cells Solve an English Hedge Maze with the Same Skills They Use to Traverse the Body - Scientific American

Cell Biology

How Plants Close the Door on Infection – Technology Networks

Plants have a unique ability to safeguard themselves against pathogens by closing their poresbut until now, no one knew quite how they did it. Scientists have known that a flood of calcium into the cells surrounding the pores triggers them to close, but how the calcium entered the cells was unclear.

A new study by an international team including University of Maryland scientists reveals that a protein called OSCA1.3 forms a channel that leaks calcium into the cells surrounding a plants pores, and they determined that a known immune system protein triggers the process.

The findings are a major step toward understanding the defense mechanisms plants use to resist infection, which could eventually lead to healthier, more resistant and more productive crops. The research paper was published on August 26, 2020 in the journal Nature.

This is a major advance, because a substantial part of the worlds food generated by agriculture is lost to pathogens, and we now know the molecular mechanism behind one of the first and most relevant signals for plant immune response to pathogensthe calcium burst after infection, said Jos Feij, a professor of cell biology and molecular genetics at UMD and co-author of the study. Finding the mechanism associated with this calcium channel allows further research into its regulation, which will improve our understanding of the way in which the channel activity modulates and, eventually, boosts the immune reaction of plants to pathogens.

Plant porescalled stomataare encircled by two guard cells, which respond to calcium signals that tell the cells to expand or contract and trigger innate immune signals, initiating the plants defense response. Because calcium cannot pass directly through the guard cell membranes, scientists knew a calcium channel had to be at work. But they didnt know which protein acted as the calcium channel.

To find this protein, the studys lead author, Cyril Zipfel, a professor of molecular and cellular plant physiology at the University of Zurich and Senior Group Leader at The Sainsbury Laboratory in Norwich, searched for proteins that would be modified by another protein named BIK1, which genetic studies and bioassays identified as a necessary component of the immune calcium response in plants.

When exposed to BIK1, one protein called OSCA1.3 transformed in a very specific way that suggested it could be a calcium channel for plants. OSCA1.3 is a member of a widespread family of proteins known to exist as ion channels in many organisms, including humans, and it seems to be specifically activated upon detection of pathogens.

To determine if OSCA1.3 was, in fact, the calcium channel he was looking for, Zipfel's team reached out to Feij, who is also an affiliate professor in the College of Agriculture and Natural Resources at UMD and is well known for identifying and characterizing novel ion channels and signaling mechanisms in plants. Erwan Michard, a visiting assistant research scientist in Feijs lab and co-author of the paper, conducted experiments that revealed Zipfels BIK1 bait triggers OSCA1.3 to open up a calcium channel into a cell and also explained the mechanism for how it happens.

BIK1 only activates when plants get infected with a pathogen, which suggests that OSCA1.3 opens a calcium channel to close stomata as a defensive, immune system response to pathogens.

This is a perfect example of how a collaborative effort between labs with different expertise can bring about important conclusions that would be difficult on solo efforts, Feij said. This fundamental knowledge is badly needed to inform ecology and agriculture on how the biome will react to the climatic changes that our planet is going through.

Feij will now incorporate this new knowledge of the OSCA1.3 calcium channel into other areas of research in his lab, which is working to understand how the mineral calcium was co-opted through evolution by all living organisms to serve as a signaling device for information about stressors from infection to climate change.

Despite the physiological and ecological relevance of stomatal closure, the identity of some of the key components mediating this closure were still unknown, Zipfel said. The identification of OSCA1.3 now fills one of these important gaps. In the context of plant immunity this work is particularly apt in 2020, the UN International Year of Plant Health.

ReferenceThor, K., Jiang, S., Michard, E. et al. The calcium-permeable channel OSCA1.3 regulates plant stomatal immunity. Nature (2020). https://doi.org/10.1038/s41586-020-2702-1

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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How Plants Close the Door on Infection - Technology Networks

Cell Biology

Hamilton Thorne to Present at the Baird 2020 Global Healthcare Conference – GlobeNewswire

BEVERLY, Mass. and TORONTO, Aug. 27, 2020 (GLOBE NEWSWIRE) -- Hamilton Thorne Ltd. (TSX-V: HTL), a leading provider of precision instruments, consumables, software and services to the Assisted Reproductive Technologies (ART), research, and cell biology markets, today announced that David Wolf, President and CEO of Hamilton Thorne Ltd., will deliver a virtual presentation at the upcomingBaird 2020 Global Healthcare Conference on Wednesday, September 9, 2020 at 3:45 EDT. Mr. Wolf will also be available for virtual one-on-one meetings during the conference.

About Hamilton Thorne Ltd. (www.hamiltonthorne.ltd)

Hamilton Thorne is a leading global provider of precision instruments, consumables, software and services that reduce cost, increase productivity, improve results and enable breakthroughs in Assisted Reproductive Technologies (ART), research, and cell biology markets. Hamilton Thorne markets its products and services under the Hamilton Thorne, Gynemed, Planer, and Embryotech Laboratories brands, through its growing sales force and distributors worldwide. Hamilton Thornes customer base consists of fertility clinics, university research centers, animal breeding facilities, pharmaceutical companies, biotechnology companies, and other commercial and academic research establishments.

Neither the TSX Venture Exchange, nor its regulation services provider (as that term is defined in the policies of the exchange), accepts responsibility for the adequacy or accuracy of this release.

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Hamilton Thorne to Present at the Baird 2020 Global Healthcare Conference - GlobeNewswire

Cell Biology

Genetic mutations may be linked to infertility, early menopause – Washington University School of Medicine in St. Louis

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Gene in fruit flies, worms, zebrafish, mice and people may help explain some fertility issues

Researchers at Washington University School of Medicine in St. Louis have identified a gene that plays an important role in fertility across multiple species. Pictured is a normal fruit fly ovary (left) and a fruit fly ovary with this gene dialed down (right). Male and female animals missing this gene had substantially defective reproductive organs. The study could have implications for understanding human infertility and early menopause.

A new study from Washington University School of Medicine in St. Louis identifies a specific genes previously unknown role in fertility. When the gene is missing in fruit flies, roundworms, zebrafish and mice, the animals are infertile or lose their fertility unusually early but appear otherwise healthy. Analyzing genetic data in people, the researchers found an association between mutations in this gene and early menopause.

The study appears Aug. 28 in the journal Science Advances.

The human gene called nuclear envelope membrane protein 1 (NEMP1) is not widely studied. In animals, mutations in the equivalent gene had been linked to impaired eye development in frogs.

The researchers who made the new discovery were not trying to study fertility at all. Rather, they were using genetic techniques to find genes involved with eye development in the early embryos of fruit flies.

We blocked some gene expression in fruit flies but found that their eyes were fine, said senior author Helen McNeill, PhD, the Larry J. Shapiro and Carol-Ann Uetake-Shapiro Professor and a BJC Investigator at the School of Medicine. So, we started trying to figure out what other problems these animals might have. They appeared healthy, but to our surprise, it turned out they were completely sterile. We found they had substantially defective reproductive organs.

Though it varied a bit by species, males and females both had fertility problems when missing this gene. And in females, the researchers found that the envelope that contains the eggs nucleus the vital compartment that holds half of an organisms chromosomes looked like a floppy balloon.

This gene is expressed throughout the body, but we didnt see this floppy balloon structure in the nuclei of any other cells, said McNeill, also a professor of developmental biology. That was a hint wed stumbled across a gene that has a specific role in fertility. We saw the impact first in flies, but we knew the proteins are shared across species. With a group of wonderful collaborators, we also knocked this gene out in worms, zebrafish and mice. Its so exciting to see that this protein that is present in many cells throughout the body has such a specific role in fertility. Its not a huge leap to suspect it has a role in people as well.

To study this floppy balloon-like nuclear envelope, the researchers used a technique called atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleuss membrane. The amount of force required to penetrate the membranes gives scientists a measure of their stiffness. While the outer membrane was of normal stiffness, the nucleuss membrane was much softer.

Its interesting to ask whether stiffness of the nuclear envelope of the egg is also important for fertility in people, McNeill said. We know there are variants in this gene associated with early menopause. And when we studied this defect in mice, we see that their ovaries have lost the pool of egg cells that theyre born with, which determines fertility over the lifespan. So, this finding provides a potential explanation for why women with mutations in this gene might have early menopause. When you lose your stock of eggs, you go into menopause.

On the left is a normal fruit fly ovary with hundreds of developing eggs. On the right is a fruit fly ovary that is totally missing the NEMP gene. It is poorly developed and no eggs are visible.

McNeill and her colleagues suspect that the nuclear envelope has to find a balance between being pliant enough to allow the chromosomes to align as they should for reproductive purposes but stiff enough to protect them from the ovarys stressful environment. With age, ovaries develop strands of collagen with potential to create mechanical stress not present in embryonic ovaries.

If you have a softer nucleus, maybe it cant handle that environment, McNeill said. This could be the cue that triggers the death of eggs. We dont know yet, but were planning studies to address this question.

Over the course of these studies, McNeill said they found only one other problem with the mice missing this specific gene: They were anemic, meaning they lacked red blood cells.

Normal adult red blood cells lack a nucleus, McNeill said. Theres a stage when the nuclear envelope has to condense and get expelled from the young red blood cell as it develops in the bone marrow. The red blood cells in these mice arent doing this properly and die at this stage. With a floppy nuclear envelope, we think young red blood cells are not surviving in another mechanically stressful situation.

The researchers would like to investigate whether women with fertility problems have mutations in NEMP1. To help establish whether such a link is causal, they have developed human embryonic stem cells that, using CRISPR gene-editing technology, were given specific mutations in NEMP1 listed in genetic databases as associated with infertility.

We can direct these stem cells to become eggs and see what effect these mutations have on the nuclear envelope, McNeill said. Its possible there are perfectly healthy women walking around who lack the NEMP protein. If this proves to cause infertility, at the very least this knowledge could offer an explanation. If it turns out that women who lack NEMP are infertile, more research must be done before we could start asking if there are ways to fix these mutations restore NEMP, for example, or find some other way to support nuclear envelope stiffness.

This work was supported by the Canadian Institutes of Health, research grant numbers 143319, MOP-42462, PJT-148658, 153128, 156081, MOP-102546, MOP-130437, 143301, and 167279. This work also was supported, in part, by the Krembil Foundation; the Canada Research Chair program; the National Institutes of Health (NIH), grant number R01 GM100756; and NSERC Discovery grant; and the Medical Research Council, unit programme MC_UU_12015/2. Financial support also was provided by the Wellcome Senior Research Fellowship, number 095209; Core funding 092076 to the Wellcome Centre for Cell Biology; a Wellcome studentship; the Ontario Research FundsResearch Excellence Program. Proteomics work was performed at the Network Biology Collaborative Centre at the Lunenfeld-Tanenbaum Research Institute, a facility supported by Canada Foundation for Innovation funding, by the Ontarian Government, and by the Genome Canada and Ontario Genomics, grant numbers OGI-097 and OGI-139.

Tsatskis Y, et al. The NEMP family supports metazoan fertility and nuclear envelope stiffness. Science Advances. Aug. 28, 2020.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Genetic mutations may be linked to infertility, early menopause - Washington University School of Medicine in St. Louis

Cell Biology

The Merging Of Human And Machine. Two Frontiers Of Emerging Technologies – Forbes

Molecular Science as a Scientific Field of Study

An amazing aspect of living in The Fourth Industrial Era is that we are at a new inflection point in bringing emerging technologies to life. We are in an era of scientific breakthroughs that will change the way of life as we currently know it. While there are many technological areas of fascination for me, the meshing of biology with machine is one of the most intriguing. It fuses many elements of technologies especially artificial intelligence and pervasive computing. I have highlighted two frontiers of mind-bending developments that are on the horizon, Neuromorphic technologies, and human-machine biology.

Neuromorphic Technologies

Human computer interaction (HCI) was an area of research that started in the 1980s and has come a long way in a short period of time. HCI was the foundation for what we call neuromorphic computing, the integration of systems containing electronic analog circuits to mimic neuro-biological architectures present in the biological nervous system.

In 2018, in research funded by the Defense Advanced Projects Agency (DARPA) demonstrated that a person with a brain chip could pilot a swarm of drones using signals from the brain. There have been a variety of studies and experiments since then, and no doubt science combining neural networks and artificial intelligence is on a path to enhance and even upgrade human cognition capabilities.

Recently, a research team from Columbia University tested the convergence of neural networks. They combined brain implants, artificial intelligence, and a speech synthesizer to translate brain activity into recognizable robotic words. The implications of this neuromorphic technology are mind-boggling, including allowing paralyzed people the ability to communicate and the potential to read human thoughts via cognitive imaging. (1)

A Frontiers in Science publication involving the collaboration of academia, institutes, and scientistssummed up the promise of the human computer interface, They concluded that We can imagine the possibilities of what may come next with the human brain machine interface. A human B/CI system mediated by neural nanorobotics could empower individuals with instantaneous access to all cumulative human knowledge available in the cloud and significantly improve human learning capacities and intelligence. Further, it might transition totally immersive virtual and augmented realities to unprecedented levels, allowing for more meaningful experiences and fuller/richer expression for, and between, users. These enhancements may assist humanity to adapt emergent artificial intelligence systems as human-augmentation technologies, facilitating the mitigation of new challenges to the human species. (2)

This week, Elon Musk announced that his neuroscience company, NeuraLink, created to develop cranial computers that can rapidly upload and process information, will demonstrate their lasts device that would let humans control computers with their mind via surgically implant electrodes. Linking brains to computers is no longer the stuff of science fiction.

Human-Machine Biology

The field of human and biological applications has many applications for medical science. This includes precision medicine, genome sequencing and gene editing (CRISPR), cellular implants, and wearables that can be implanted in the human body The medical community is experimenting with delivering nano-scale drugs (including anti-biotic smart bombs to target specific strains of bacteria. Soon they will be able to implant devices such as bionic eyes and bionic kidneys, or artificially grown and regenerated human organs. Succinctly, we are on the cusp of significantly upgrading the human ecosystem. It is indeed revolutionary.

This revolution will expand exponentially in the next few years. We will see the merging of artificial circuitries withsignaturesof our biological intelligence, retrieved in the form of electric, magnetic, and mechanical transductions. Retrieving these signatures will be like taking pieces of cells (including our tissue-resident stem cells) in the form of code for their healthy, diseased or healing states, or a code for their ability to differentiate into all the mature cells of our body. This process will represent an unprecedented form of taking a glimpse of human identity. (3)

In the future biocomputers may be able to store on the DNA of living cells. This technology could store almost unlimited amounts of data and allow the biocomputers to perform complex calculations beyond our current capabilities.

Researchers at the Technion have already created a biological computer, constructed within a bacterial cell. developed a complex biocomputer, that is, a programmed biological system that fulfills complex tasks. The research by Ph.D. student Natalia Barger and Assistant Professor Ramez Daniel, head of the Synthetic Biology and Bioelectronics Lab at the Technion's Faculty of Biomedical Engineering, was published in September 2019 in the journalNucleic Acids Research(NAR) "We built a kind ofbiological computerin the livingcells. In this computer, as in regular computers, circuits carry out complicated calculations," said Barger. "Only here, these circuits are genetic, not electronic, and information are carried by proteins and not electrons." (4)

The Human-machine synergies now being explored offer us a glimpse into the not so distant future. Clearly, from the perspective of human augmentation, the promise is exciting. The future will also encompass moral issues to address such as containing super artificial intelligence, ensuring cyborg rights, and a whole host of other related ethical topics. It is evident is that human-machine interface will help pave our futures. How we harness it for good should be our focus. Perhaps that will be what the Fifth Industrial Revolution will codify.

Footnote:this past year I designed and wrote a graduate course for Georgetown University called Disruptive Technologies and Organizational Management. I am now enjoying teaching it. What excites me is receiving back insights on my assignments. Paraphrasing Leonardo Da Vinci, you should never stop learning in life. The imagination of my students as they contemplate the applications and fusion of emerging technologies in society and security is an inspiration.

Sources:

1) The New Techno-fusion by Chuck Brooks

2)Human Brain/Cloud Interface

3) Emerging Bio-Science and Health Security Implications for Biometrics by Chuck Brooks

4) Researchers turn bacterial cell into biological computer

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The Merging Of Human And Machine. Two Frontiers Of Emerging Technologies - Forbes

Cell Biology

Study may help develop new types of non-addictive pain therapies – News-Medical.Net

A team of scientists from ASU's School of Molecular Sciences and the Biodesign Institute have recently published a study in Nature Communications that helps clarify the contributions to an ion channel's temperature - dependent activation. This in turn should aid in the development of new types of non-addictive pain therapies.

The ability to sense and respond to temperature is fundamental in biology. Ion channels are formed by membrane proteins that allow ions to pass through the otherwise impermeable lipid cell membrane, where they are used as a communication network.

TRPV1 is an ion channel that is widely expressed in various tissues and plays a variety of roles in biology. It is best known for its role as the primary hot sensor in humans; it is the main way that we sense heat in our environment."

Wade Van Horn, Professor and Senior Author, School of Molecular Sciences and the Biodesign Institute, Arizona State University

Although important contributions have been made in the investigation of TRPV1 thermosensing, its mechanism has remained elusive.

TRPV1 is also a common taste and pain sensor, think spicy foods and pepper spray. Beyond these roles, it has been implicated in longevity, inflammation, obesity, and cancer. For decades it has been a target in the search for new types of pain medication, ones that are not addictive.

"However, to date, a common feature is that while TRPV1 targeting compounds can relieve pain, they also cause off-target effects, especially causing changes in body temperature, which has limited their utility. These off-target effects happen because TRPV1 is activated by many distinct stimuli, including ligands (i.e., capsaicin - the main ingredient in pepper spray), heat, and protons (acidic pH)," says Van Horn.

Also particularly limiting, is the uncertainty about the mechanisms that underlie temperature-sensing and how the different activation mechanisms are linked together.

This study used a variety of techniques, from cellular to atomic in nature, to investigate the domain of TRPV1 that is key to its ligand activation.

The techniques included Nuclear Magnetic Resonance spectroscopy experiments (like an MRI) aided by Brian Cherry (Associate Research Professional in the Magnetic Resonance Research Center), intrinsic fluorescence carried out in SMS associate professor Marcia Levitus' lab.

Levitus is also part of the Biodesign Center for Single Molecule Biophysics. Other techniques included far ultraviolet circular dichroism and temperature dependent electrophysiology.

Van Horn explains that this work identifies for the first time, both functionally and thermodynamically, that a particular region (of TRPV1) is crucial to heat activation. The team proposes, and provides experimental validation for, the heat activation mechanism and details a number of structural changes that happen as the temperature is changed.

This study provides a framework that the team anticipates will be foundational for future studies to further refine how we sense high temperatures and, importantly, how we can distinguish and target specific activation mechanisms that should promote the development of new types of non-addictive pain therapies.

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Study may help develop new types of non-addictive pain therapies - News-Medical.Net

Biochemistry

The Road to a COVID-19 Vaccine and Treatment: a Biochemistry Student Explains – The Whit Online

In just five months, a nonliving particle one hundredth the diameter of a human hair has claimed the lives of more U.S. citizens than the Vietnam and Korean wars combined. This particle is, of course, the novel coronavirus known as COVID-19. Can scientists and medical professionals find a way to stop it before it reaps further destruction?

With the ability to switch from a nonliving to a living state after hijacking a host cells replication machinery, viruses are intricate rogue proteins that occupy a mysterious realm between biochemistry and quantum mechanics. You cannot kill viruses as they are not even alive in the first place, and the field of biochemistry is currently not advanced enough to annihilate all of these sub-microscopic parasites outright without harming you, too. However, viruses utilize a variety of chemicals to accomplish their replication cycles, and it is these specific chemicals that are vulnerable to attack.

Possible treatments for viruses are classified into one of two groups: drugs that inhibit viral replication and drugs that modify your immune response.

To understand how antiviral drugs work, you must know the substances involved in viral replication. COVID-19, aka SARS-CoV-2 (severe acute respiratory system coronavirus 2), is a single-stranded RNA virus that enters your cells by binding to a specific receptor on their surfaces, triggering endocytosis (cell entry). The virus reverse transcribes its RNA into double-stranded DNA, the blueprint for protein synthesis, using an enzyme called RNA polymerase. This enzyme lacks a proofreading function, so the resulting DNA code will mutate over time. When COVID-19s completed DNA is integrated into your cells genome, your cell exhausts its own resources manufacturing more viruses.

The viruses escape and infect other cells, eventually killing them.

Remdesivir is the most promising antiviral drug to date, and is the only one authorized by the U.S. Food and Drug Administration for emergency use. Its molecular structure mimics that of adenine, a nucleic acid in DNA. When the viruses RNA polymerase mistakenly adds a Remdesivir molecule in place of adenine, the reverse transcription process is stopped. The drugs developer, Gilead, applied for FDA approval Aug. 10 for regular use after presenting preliminary evidence proving the drugs effectiveness. Remdesivir is not a cure for COVID-19; according to the study, treatment only reduces the recovery time of infected patients and does not protect against death. FDA approval is currently pending.

Why prioritize usage of drugs when you could just prevent people from contracting COVID-19 in the first place?

This is where drugs that modify your immune response vaccines come into play. Vaccination is the best way to drastically reduce COVID-19 transmission and to grant immunity to the general public. Antibodies are protective proteins naturally synthesized by your body whenever antigens (foreign substances) invade it. By introducing a weakened form of the virus or a portion of the viruses protein structure into your body, vaccines train your immune system to manufacture its own antibodies in a phenomenon known as active immunity. When you are infected with the actual virus, your immune system swiftly identifies the pathogens protein pattern, induces apoptosis (cell death) in all affected cells, and stops viral spread in its tracks.

Unfortunately, vaccine development is a long and arduous process often riddled with complications, and rushing the development process can sacrifice drug effectiveness and even trigger dangerous immune reactions in patients. To be deemed safe and effective, immunological response data from thousands of testing subjects from specific populations (especially those with underlying health issues and senior citizens) must be compiled and analyzed. This procedure alone can take months or even years. After a vaccine is considered safe and effective, there is the additional hurdle of manufacturing and distributing the vaccine to the entire population.

The rate of vaccine development is progressing at historically fast speeds. According to Johns Hopkins Coronavirus Resource Center, the first COVID-19 vaccine was developed for testing just six weeks after the viral sequence was decoded. In comparison, the vaccine for Influenza another RNA virus infecting the respiratory system took 20 years to be developed and 26 years to be approved. In fact, by the time regular citizens were inoculated with this flu vaccine, it was ineffective because the virus had mutated by then.

The most promising SARS-CoV-2 vaccine, Moderna, entered its final phase of testing among 30,000 patients on July 27. Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, has predicted that researchers will be able to determine Modernas effectiveness by November or December this year, perhaps sooner. The vaccine does its job by transmitting mRNA (messenger RNA) molecules transcribed from DNA to your cells genomes, which causes them to assemble portions of COVID-19 proteins. By introducing these inactive foreign proteins into your body, the vaccine compels your immune system to manufacture antibodies that will identify and eliminate the actual virus. The introduction of a vaccine to the American public would finally allow our country to regain some semblance of normalcy.

The way each person responds to SARS-CoV-2 infection depends on individual genetics, age and pre-existing health conditions. Some patients are not even aware of infection, while others exhibit life-threatening symptoms. COVID-19 enters cells by binding a receptor called the angiotensin enzyme converting 2 (ACE2) receptor. Angiotensin 2 is a powerful enzyme that causes your blood pressure levels to skyrocket and is implicated in inflammation in a way that is still not fully understood. For some, SARS-CoV-2 wreaks havoc on the cardiovascular system, which then damages vascularized organs requiring a constant blood supply. Despite having a 3-4% mortality rate, evidence suggests that COVID-19 is capable of inflicting lasting damage on highly vascularized organs including the lungs and brain.

Scientific advancement is not based on a couple of scientific studies or published papers. Instead, it is founded upon decades of research. Medical professionals, scientists and governments across the globe are engaged in a race unlike any other in history to develop a safe and effective vaccine, and we have learned about COVID-19 faster than any infectious disease in history.

Unanswered questions, however maddening they may be, are powerful catalysts for scientific advancement. As we expand the breadth and depth of our knowledge, not only will we have more answers, but we will have a better understanding of the right questions to ask. To quote Douglas Adams, author of The Hitchhikers Guide to the Galaxy, Phrasing the right question is much harder than finding the right answer.

Ultimately, it is questions not answers that are the driving force behind the growth of humanitys collective intelligence and the development of a successful vaccine.

Special thanks to Johns Hopkins University & Medicine Coronavirus Resource Center and RowanSOM Family Medicine Department.

For comments/questions about this story, email editor@thewhitonline.com or tweet @TheWhitOnline.

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The Road to a COVID-19 Vaccine and Treatment: a Biochemistry Student Explains - The Whit Online

Biochemistry

Itaconic Acid Market with Competitive Analysis, New Business Developments and Top Companies: Kehai Biochemistry, Guoguang Biochemistry – The Daily…

Itaconic Acid Industry Analysis 2020

TheItaconic Acid Marketreport enlightens its readers about its products, applications, and specifications. The research enlists key companies operating in the market and also highlights the roadmap adopted by the companies to consolidate their position in the market.By extensive usage of SWOT analysis and Porters five force analysis tools, the strengths, weaknesses, opportunities, and combination of key companies are comprehensively deduced and referenced in the report.Every single leading player in this global market is profiled with their related details such as product types, business overview, sales, manufacturing base, applications, and other specifications.Itaconic Acid is a naturally occurring unsaturated 5-C dicarboxylic acid which is also known as methylenesuccinic acid or methylenebutanedioic acidCurrently, the largest applications for itaconic acid are Plasticizer, accounting for 56.10% ofMajor Market Players Covered In This Report:, Kehai Biochemistry, Guoguang Biochemistry, Huaming Biochemistry, Alpha Chemika, Zhongshun Science & Technology,

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The Global Itaconic AcidMarket Can Be Segmented As

The key product type of Itaconic Acidmarket are:, Synthesis, Fermentation,

Itaconic AcidMarket Outlook by Applications:, Plasticizer, Lubricating Oil Additive, Other

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What Itaconic AcidMarket report offers:Itaconic AcidMarket share assessments for the regional and country-level segmentsMarket share analysis of the highest trade playersItaconic AcidMarket Trends (Drivers, Constraints, Opportunities, Threats, Challenges, Investment Opportunities, and Recommendations)Strategic recommendations on key business segments

The Report Answers Following Questions:Over successive few years, which Itaconic Acidapplication segment can perform well?Within which market, the businesses ought to establish a presence?Which product segments are exhibiting growth?What are the market restraints which are likely to impede the growth rate?However, market share changes their values by completely different producing brands?

To Know More About The Assumptions in This Market Report:http://grandviewreport.com/industry-growth/Itaconic-Acid-Market-17428

The report entails detailed profiling of each company, and information on capacity, production, price, revenue, cost, gross, gross margin, sales volume, sales revenue, consumption, growth rate, import, export, supply, future strategies, and the technological developments, are also included within the scope of the report. In the end, the Itaconic AcidMarket Report delivers a conclusion which includes Breakdown and Data Triangulation, Consumer Needs/Customer Preference Change, Research Findings, Market Size Estimation, Data Source. These factors are expected to augment the overall business growth.

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Itaconic Acid Market with Competitive Analysis, New Business Developments and Top Companies: Kehai Biochemistry, Guoguang Biochemistry - The Daily...