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Immunology

Fighting off food poisoning depends on the time of day – UT Southwestern

Scanning electron micrograph shows segmented filamentous bacteria attaching to the intestinal surface of a mouse. More bacteria attach during the night than during the day. Credit: John F. Brooks II

DALLAS July 28, 2021 The bodys ability to prevent food poisoning by producing a natural antimicrobial compound increases during the day, when exposure to noxious bacteria is most likely, a new study by UT Southwestern scientists suggests. The findings, published online in Cell, could eventually lead to timed therapies and vaccination regimens designed to maximize this immune response.

John F. Brooks II, Ph.D.

This study shows that our immune systems are not turned on all the time, which is an unexpected result, says study leader John F. Brooks II, Ph.D., a postdoctoral fellow in the laboratory of Lora Hooper, Ph.D., study co-leader and professor of immunology and microbiology at UTSW. Our findings suggest that there are peak times in which the body is more primed to fight infections.

Researchers have long known that virtually all animals follow circadian cycles that are tied to sunrise and sunset. These cycles allow animals to anticipate and prepare for changes in their environment. Disrupting circadian rhythms can have serious health consequences; for example, chronic sleep disruption is related to increased intestinal infection in humans. However, why this occurs has been unclear.

Lora Hooper, Ph.D.

Brooks, Hooper, and their colleagues suspected that antibacterial immunity might change in the intestines on a circadian cycle. To investigate this idea, the researchers looked for rhythms in the expression of natural antimicrobial agents produced in the gut of mice to fight foodborne illness. The researchers saw that in normal lab mice, one of these antimicrobial molecules known as regenerating islet-derived protein 3g (REG3G) was more abundant at night, when these nocturnal animals are active, and less so during the day, when mice sleep. However, in mice raised to have no gut bacteria, REG3G was essentially absent throughout both the day and the night.

Searching for the microbial components driving the rhythmic pattern, the researchers found that mice with cycling amounts of REG3G had large resident populations of segmented filamentous bacteria in their guts microbes typically present in rodents, nonhuman primates, and humans that have a unique ability to attach to the intestinal lining and change their hosts gene activity. Further experiments showed that these bacteria attached to the animals intestinal lining during feeding, probably to siphon off nutrients. When they attached, REG3G production ramped up in the intestines.

This cycling had significant consequences for the ability of mice to fight off infection. When the researchers infected normal mice with bacteria, the animals had higher bacterial burdens and rates of death if they were exposed at sunset than at sunrise. Mice that cant make antimicrobial proteins, including REG3G, had similarly high rates of bacterial burden and death regardless of when they were infected.

If further research shows this phenomenon also occurs in humans, scientists may eventually be able to capitalize on it by timing the administration of synthetic antibiotics for intestinal infections and oral vaccines or finding new ways to avoid intestinal infections altogether.

These results make me think twice about waking up in the middle of the night and raiding the refrigerator, Hooper says. It may be more dangerous to eat bacteria-laden potato salad when your gut defenses are lowest.

Other UTSW researchers who contributed to this study include Cassie L. Behrendt, Kelly A. Ruhn, Syann Lee, Prithvi Raj, and Joseph S. Takahashi.

This work was supported by grants from the National Institutes of Health (R01 DK070855), The Welch Foundation (I-1874), and the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases.

Hooper holds the Jonathan W. Uhr, M.D. Distinguished Chair in Immunology, the Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell, and is an investigator of the Howard Hughes Medical Institute.

Takahashi holds the Loyd B. Sands Distinguished Chair in Neuroscience and is an investigator of the Howard Hughes Medical Institute.

Brooks is a recipient of the highly competitive Howard Hughes Medical Institute Hanna Gray Fellowship.

About UTSouthwestern Medical Center

UT Southwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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Fighting off food poisoning depends on the time of day - UT Southwestern

Immunology

iShares Trust – iShares Genomics Immunology and Healthcare ETF (IDNA) falls 0.91% for July 27 – Equities.com

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IDNA - Market Data & News

Today, iShares Trust - iShares Genomics Immunology and Healthcare ETF Incs (NYSE: IDNA) stock fell $0.4424, accounting for a 0.91% decrease. iShares - iShares Genomics Immunology and Healthcare ETF opened at $48.92 before trading between $48.92 and $47.38 throughout Tuesdays session. The activity saw iShares - iShares Genomics Immunology and Healthcare ETFs market cap fall to $317,085,500 on 93,591 shares -above their 30-day average of 89,687.

Visit iShares Trust - iShares Genomics Immunology and Healthcare ETF's profile for more information.

The New York Stock Exchange is the worlds largest stock exchange by market value at over $26 trillion. It is also the leader for initial public offerings, with $82 billion raised in 2020, including six of the seven largest technology deals. 63% of SPAC proceeds in 2020 were raised on the NYSE, including the six largest transactions.

To get more information on iShares Trust - iShares Genomics Immunology and Healthcare ETF and to follow the company's latest updates, you can visit the company's profile page here: iShares Trust - iShares Genomics Immunology and Healthcare ETF's Profile. For more news on the financial markets be sure to visit Equities News. Also, don't forget to sign-up for the Daily Fix to receive the best stories to your inbox 5 days a week.

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iShares Trust - iShares Genomics Immunology and Healthcare ETF (IDNA) falls 0.91% for July 27 - Equities.com

Immunology

Call in the T-Cell Cavalry to Fight COVID in the Immunocompromised – MedPage Today

Last year was one of collective confinement. The majority of us shuttered our doors to visitors, worked from home, and ventured out sparingly in hopes of evading the grasp of COVID-19. Now in 2021, thanks to vaccination rollout, those who have been vaccinated are hopefully on the path to normalcy. But not everyone is so fortunate. For some, 2021 will bring more isolation and loneliness than ever before, which is hard to imagine. I'm talking about immunocompromised adults and children. While much of the rest of the populace clinks glasses, hugs loved ones, and joins parties, immunocompromised individuals do not have the security of an effective vaccine, and for their health and safety will maintain their distance and watch the social revelry from the sidelines.

The normal vaccine response that elicits antibodies and immune cells to fight infection are absent in these immunocompromised individuals, who fall into two categories: those living with congenital or acquired diseases that weaken their immune system, or those with pre-existing conditions whose treatment requires dampening of the immune system (e.g., patients with blood cancers or transplant recipients). This vulnerable population represents a sizable proportion of the U.S. population. A 2018-2019 analysis in JAMA Network Open estimated that 2.8% of adults in America were on a treatment regimen that dampened their immune system. That percentage may seem small but extrapolate it to the entire U.S. population and you hit 9 million vulnerable people. This doesn't even include immunocompromised individuals who are not taking immune-suppressing medication.

The plight of immune-compromised individuals has large-scale implications. This inability to combat the virus not only can be potentially life-threatening but can also lead to the continued evolution of mutant strains that infiltrate healthy populations. The so-called New York variant (B.1.526) was identified in a patient with advanced AIDS. Similarly, the highly transmissible and more deadly Alpha strain (B.1.1.7) emerged in a patient receiving immune suppressive treatment for a blood cancer.

So, while COVID-19 vaccines administered in the U.S. have been highly effective for mounting an antibody immune response in people with functional immune systems, it's not enough to vanquish the contagion. In our fight against virus infection, another critical arm of the immune system is required: The T-cell immune response. While antibodies may prevent infection, these warriors destroy already infected cells. And initial research suggests they may be active even in absence of antibodies.

Just recently, researchers (including myself) published a study in the Journal of Clinical Immunology that showed that pediatric patients with primary immune deficiencies, who often fail to make protective immune responses to infections and vaccinations, show robust T-cell activity and immunity against SARS-CoV-2. These findings are important because if T-cell responses to COVID-19 are protective in this highly vulnerable population, this could suggest that a COVID-19-directed T-cell immunotherapy might benefit other profoundly immunocompromised patients. However, we still don't know if such responses will persist to provide protective long-term immunity, especially against mutant strains of the virus.

Indeed, earlier findings published by me and my team in Blood, show T cells can be taken from the blood of recovered COVID-19 patients and multiplied in a lab, which could then be infused into bone marrow transplant patients whose immune systems can't fight the virus on their own. In effect, this creates an army of trained coronavirus fighters to potentially provide protective T-cell immunity long-term to these highly immunosuppressed patients. My team and I submitted this coronavirus-killing T-cell therapy (CST) clinical trial proposal to the FDA and have recently received approval to start this first-in-human clinical research protocol to treat these vulnerable patients who are currently falling through the cracks in the vaccine fight against COVID-19.

Ongoing research in the race to outpace the pandemic has helped us to increasingly unravel the prominent role of T cells in long-term immunity. A study published in Nature showed patients who recovered from the 2003 SARS epidemic, whose antibodies faded within 2 to 3 years, had a robust T-cell response to SARS 17 years later. These T cells also recognize the SARS-CoV-2 nucleocapsid protein.

For immunocompromised patients, adoptive immunotherapy using T cells from recovered COVID-19 patients may be the answer when vaccines only offer partial protection. T cells could vanquish infected cells to limit the severity of disease or avoid hospitalization, and they remember a contagion for decades.

With the number of COVID-19 variants multiplying, this is an arms race. As a society, we need to deploy every weapon in our arsenal to ensure no one is left behind in the return to normalcy, especially not the most vulnerable. If antibodies were the infantry in our fight against the pandemic, then T cells are the cavalry. It's time we call them in.

Catherine Bollard, MD, MBChB, is the director of the Center for Cancer and Immunology Research at the Children's National Research Institute, director of the Program for Cell Enhancement and Technologies for Immunotherapy, and a member of the Division of the Blood and Marrow Transplantation at Children's National Hospital in Washington, D.C.

Disclosures

Bollard is co-founder and on the scientific advisory boards for Catamaran Bio and Mana Therapeutics with stock and/or ownership; is on the Board of Directors for Cabaletta Bio with stock options; has stock in NexImmune and Repertoire Immune Medicines; and has submitted patent applications on SARS-CoV-2 T cells.

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Call in the T-Cell Cavalry to Fight COVID in the Immunocompromised - MedPage Today

Physiology

Defining Physiologys Upper Limits and Again Winning the Tour de France – CU Anschutz Today

First of all, congratulations on an incredible accomplishment your top cyclist winning his second Tour de France.

It was a great victory. This year we were not the underdog anymore. Its too bad (Primoz) Roglic (last years second-place General Classification finisher) had a bad crash and had to quit the race. It was unfortunate because otherwise it would have been better (duel-wise between the two top-rated Slovenians). He crashed in the first week.

We did all the homework for the Tour de France in Sestriere, which is in the Italian Alps. I told the team the first day of pre-training camp, Guys, lets take this seriously. Lets focus, because we have never been in this situation. We have never had to defend a Tour de France, and since the very last day of last years Tour, everybody has tried to figure out how to beat Tadej. Everybodys guns are loaded to shoot at us this year. Be ready for that.

Our strategy was to try to control the race as best as we could, and that was the most stressful part to put together that block of riders. Out of 29 riders we have on the team, to select that block of seven who could help Tadej do the job. Ineos Grenadiers would be the team to bring the race. They have a very strong roster, and they are signing from other teams their leaders, so its difficult to compete as a block against Ineos. But we were able to put a good block together, and yeah, it worked out.

Yeah, it was a coincidence (laughs). It was the last time trial, and that was when we kind of said, OK, boom, now we won the Tour, and we celebrated. Also, that is an area of the world with some of the best wines some are $3,000 a bottle. Im crazy about wine, so that area was very special because of Tadej, because of the wine and because of my last name (laughs).

He has an amazing recovery capacity. Each stage of the Tour is like (playing) about three soccer games, or five American football games. So, imagine playing five games for 21 days in a row. By day 10, many players would be gone, right? Only the best, the fittest ones, will make it to day seven, 10 and so on. This is how fit these cyclists are. Their (physiologic) machinery is some of the best you will ever find in humans. These athletes and marathon runners, but probably more so cyclists, because they have to recover between stages.

And while everybody might start (a stage) at 100%, some people finish at 60% because they go lower and lower and lower. And maybe Tadej finishes at 80%, so that 20% extra at the end is what makes one of his parameters. Contenders at the Tour all recover well. But at the same time, you also have other physiological capabilities which are the ability to clear lactate, to have very good mitochondrial function. You need to have a very economical and efficient engine, but its both the recovery capacity and the ability to go at a very hard pace without utilizing a lot of energy.

No, we didnt do that this year at the Tour because the logistics have been difficult. We (Angelo DAlessandro, PhD, Travis Nemkov, PhD, and San Milln) are developing the first metabolomics platform in the world of sports. Were very close to the finish line. We learned a lot from last year, but from this year also. We did a training camp and at another race, so we looked at more parameters, and all of it keeps telling us the same story: Tadejs recovery capacity and mitochondrial function are spectacular, at a whole different level. He has an ability to burn fat and use fuels very efficiently.

Its like the 23andMe or the DNA test kits you can buy in the supermarket and do yourself and send through the mail to a laboratory. In a few days you get the whole report. This (platform) would be for metabolomics, which is more precise than genetics. Genetics is the science of probability, and metabolomics is the science of reality.

Genetics is the science of probability, and metabolomics is the science of reality. Inigo San Millan

In genetic testing, especially for sports, the accuracy might be less than 20%. A few years ago, athletes would get these genetic tests and they showed, Oh, youre not a good sprinter or Youre not a good climber or You dont have much strength or power. Thats only because a few genes showed that, but you can improve the signal, the expression, of those genes through training, through nutrition, through recovery, through the right psychology. This is where you can transform a normal athlete into a very good athlete. And this is what we capture through metabolomics.

Genes are transcribed into proteins, and proteins into multiple biological actions. So, the genes are the very first step of the journey, but by no means do they mean an athlete is going to become something. Thats why the accuracy is less than 20%, whereas in metabolomics its, Hey, this is who you are right now, and now we know how you can improve.

This is what were developing. Its a platform where someone can send a blood sample put on a small card before and after exercise, and we can then give them those metabolomic parameters.

Yes, exactly, so we know the upper levels of human physiology and metabolic health.

It was really bad. And 10 or 15 kilometers later, there was another bad crash, and I forget in which of them Tadej received a minor cut. It didnt affect him much.

We have patterns or signatures at the research level we call them signatures and this is what we see as who you are now. With this, we can help athletes to improve. At the same time and this is our ultimate goal we want to take this into the fitness, wellness and even the clinical space. Because with the lessons we have learned from these athletes, we can understand the many pathologies people are having at the metabolic level, as athletes are the absolute gold standard of metabolic health.

For example, people with Type 2 diabetes are at the opposite metabolic pole of someone like Pogaar. They dont burn fat very well at all, they dont burn glucose. They have very poor mitochondrial function, and they have inflammation, whereas Pogaar is completely the opposite. This is something Ive been pushing at the university for years, since I arrived, using elite athletes as the gold standard.

I think some people are finally understanding this concept that, yes, you cannot understand imperfection if you dont first understand perfection. In my modest opinion, the best way to understand a faulty metabolism, like people with Type 2 diabetes, is to in the first place understand how does a perfect metabolism work? And who do you go to to understand that? You dont go to the sedentary people who, until recently, have been the gold standard. Thats not the best population to go to (for study). You need to go to the elite athletes.

To our advantage we have access to these populations which most scientists dont have access to. So, we are very lucky to have this unique population to be able to understand what perfection is. And now we know better how to get there and how bad imperfection is. So, we can use all of these technologies for diagnoses and also therapeutics down the road for people with chronic diseases.

Absolutely. For someone his age, hes amazing. It seems like youre dealing with a 30-plus-year-old professional athlete who has been a professional for 10 or 15 years. Its unbelievable. And also, how calm he is. He doesnt feel so much the stress of the competition as others. Some great athletes have amazing physiological capabilities, but they cant sleep well the day before an event, or they have anxiety and are nervous the day of the competition, and they cant give their 100%. Its not uncommon at all and its too bad, because some of them could have been incredible athletes. But I guess thats what it takes to be a big, big champion to have all these qualities together.

So far, nobody in (cycling) history has done what Tadej has done at this age. The best rider ever is Eddy Merckx and Tadej has done more than what Merckx had done at his age. So this is the unusual and special thing about Tadej.

From the Tour he went to Tokyo for the Summer Olympics where took the bronze medal in the road race, and he was the one who broke the entire race. Also, we have an American from the UAE team at the Olympics, too, Brandon McNulty, who I also personally coach. He was in the Tour with Tadej. Brandon can be one of the best time trialists in the world. He placed sixth in the road race in Tokyo and was the best finish of an American cyclist since 2012.

Regarding Tadej, absolutely, a third Tour win in a row is the goal. You always want to win and keep breaking records. We are already thinking about next year, how we can keep improving. We still have some margin for improvement, but the other (teams) do, too. As were speaking, theyre trying to figure out how to do things better for next year. This is why next year it will be harder than this year for sure. We better be prepared and not sleep on our laurels.

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Defining Physiologys Upper Limits and Again Winning the Tour de France - CU Anschutz Today

Physiology

Microphysiological Systems: Approaches, Applications and Opportunities – Technology Networks

Microphysiological systems (MPS), also commonly referred to as organ-on-a-chip or body-on-a-chip technologies, have gained considerable attention in recent years. They provide a more physiologically relevant setting compared to static two-dimensional cell culture assays or animal models, as they more closely recapitulate human physiology and the downstream effects of drugs on multiple tissues. The development of MPS technologies has been driven by advances in several areas 3D cell culture techniques, microfluidics, tissue engineering and bioprinting enabling the creation of various key components. In this article, we highlight advances in the field that have been instrumental to the development of MPS, as well as key applications and future opportunities.

However, building a device that encompasses several tissue constructs to produce an interconnected multi-organ environment is no easy feat, as Dokmeci explains, Finding a universal media that satisfies the needs of multiple cells or organs is one of the main challenges.

Also, being able to control the fluid flow between different systems sometimes requires microvalves, which enables automation but complicates the design and manufacturing of the system. Overall, adding more components complicates the design, he adds.

In recent years, there have been efforts to improve the in vitro models used in preclinical drug development and disease research. In particular the use of microphysiological systems (MPS), also sometimes referred to as organ-on-a-chip (OOC) technologies, has become more widespread. Download this app note to discover a gut MPS that has physiologically relevant morphology, reduced barrier integrity and mucus expression. It can also be used to predict drug permeability across an intestinal barrier.

To prevent loss of the drug compounds, the team chose to assemble their MPS using polymethyl methacrylate (PMMA) rather than polydimethylsiloxane (PDMS). While PDMS has been widely used to build microfluidic chips until now, it can cause small molecules to be absorbed into the walls of the chip, reducing the free concentration of drug within the circulated medium, affecting drug bioavailability.

Atala explains that to create the MPS they employed strategies like those used to implant engineered tissues in patients. We first determine the major cell types present in the specific organ, and we use normal cells in the same proportions as present in humans. We also use the tissue-specific glue that holds cells together, the extracellular matrix, he says. The team then combined the different organoids of interest into a single system by immobilizing them in hydrogels within individual chambers.

Atala elaborates, We can therefore test many parameters, such as the effects of one drug on a specific organ, and how the drug gets metabolized and processed, or its bystander effects on other organs. The system, depending on how many tissues it uses, can be designed to fit an area about the size of a matchbox.

This is one of the main promises of the organ-on-a-chip field being able to borrow cells from patients and test the drugs on individual patients beforehand, explains Dokmeci.

The invention of induced pluripotent stem cells (iPSCs) has helped to expedite research in this field, he adds. Personalized MPS can be created using blood samples, primary human tissue and cells derived from iPSCs, as Dokmeci emphasized above.

There are efforts by different groups in this area, explains Prof. Nureddin Ashammakhi, ex-associate director of the Center for Minimally Invasive Therapeutics, UCLA. Ashammakhis research is focused on 3D bioprinting and the development of organ-on-a-chip models for regenerative and personalized medicine.

In a recent study, published in Bio-Design and Manufacturing, Ashammakhi and colleagues reviewed the development of lung MPS to model the pathology of COVID-19. According to Ashammakhi, when designing a lung MPS it is important to mirror the organs unique organization and function.

This is achieved by designing a chip with one chamber for air, representing alveolus and one chamber lined with endothelial cells, representing the blood vessel. The two chambers are separated by a porous membrane that allows the movement of molecules between the two sides, says Ashammakhi.

It is even possible to emulate the motion of in vivo breathing by applying a vacuum to chambers surrounding the epithelialcapillary membrane, causing it to stretch. This is an important element as stress has been shown to influence permeability of the membrane and the release of reactive oxygen species, as well as other molecules.

COVID-19 pathology can be organized into the following stages: SARS-CoV-2 viral entry by the ACE2 receptor; inflammation or malfunction of the innate immune response; coagulopathy or clotting dysregulation; edema or swelling and fluid accumulation; and fibrosis or scarring through the buildup of fibrotic connective tissue, explains Ashammakhi.

While there are surely benefits to assessing COVID-19 using a single lung-on-a-chip device, as Ashammakhi eludes above, the systemic nature of the disease means that a multi-organ MPS would be needed to reflect secondary and systemic effects of the drugs being tested. The inclusion of other cell types such as immune cells is also of utmost importance in developing relevant models especially for infection-related studies, he stresses.

AI is very important in this sense, it can make the big data obtained from multiple MPS chips, for a multitude of variables comprehendible relations [can be] identified and conclusions can be drawn, says Ashammakhi.

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Microphysiological Systems: Approaches, Applications and Opportunities - Technology Networks

Physiology

A blood test for your body clock? It’s on the horizon – CU Boulder Today

What time is your body clock set on?

The answer, mounting research suggests, can influence everything from your predisposition to diabetes, heart disease and depression to the optimal time for you to take medication. But unlike routine blood tests for cholesterol and hormone levels, theres no easy way to precisely measure a persons individual circadian rhythm.

At least not yet.

New CU Boulder research, published in the Journal of Biological Rhythms, suggests that day could come in the not-too-distant future. The study found its possible to determine the timing of a persons internal circadian or biological clock by analyzing a combination of molecules in a single blood draw.

If we can understand each individual persons circadian clock, we can potentially prescribe the optimal time of day for them to be eating or exercising or taking medication, said senior author Christopher Depner, who conducted the study while an assistant professor of integrative physiology at CU Boulder. From a personalized medicine perspective, it could be groundbreaking.

For decades, researchers have known that a central master clock in a region of the brain called the hypothalamus helps to regulate the bodys 24-hour cycle, including when we naturally feel sleepy at night and have the urge to wake up in the morning.

More recently, studies reveal that nearly every tissue or organ in the body also has an internal timing device, synced with that master clock, dictating when we secrete certain hormones, how our heart and lungs function throughout the day, the cadence of our metabolism of fats and sugars, and more.

As many as 82% of protein-coding genes that are drug targets show 24-hour time-of-day patterns, suggesting many medications could work better and yield fewer side effects if administration was timed appropriately.

And when our internal rhythm is at odds with our sleep-wake cycle, that can boost risk of an array of diseases, said study co-author Ken Wright, a professor of integrative physiology and director of the Sleep and Chronobiology Laboratory at CU Boulder.

If we want to be able to fix the timing of a persons circadian rhythm, we need to know what that timing is, he said. Right now, we do not have an easy way to do that.

Even among healthy people, sleep-wake cycles can vary by four to six hours.

Simply asking someone, are you a morning lark, a night owl or somewhere in-between? can provide hints to what a persons circadian cycle is.

But the only way to precisely gauge the timing of an individuals circadian clock (including where the peaks and troughs of their daily rhythm) is to perform a dim-light melatonin assessment. This involves keeping the person in dim light and drawing blood or saliva hourly for up to 24 hours to measure melatoninthe hormone that naturally increases in the body to signal bedtime and wanes to help wake us up.

In pursuit of a more precise and practical test, Wright and Depner brought 16 volunteers to live in a sleep lab on the CU Anschutz Medical campus in Aurora for 14 days under tightly controlled conditions.

In addition to testing their blood for melatonin hourly, they also used a method called metabolomicsassessing levels of about 4,000 different metabolites (things like amino acids, vitamins and fatty acids that are byproducts of metabolism) in the blood.

They used a machine learning algorithm to determine which collection of metabolites were associated with the circadian clockcreating a sort of molecular fingerprint for individual circadian phases.

When they tried to predict circadian phase based on this fingerprint from a single blood draw, their findings were surprisingly similar to those using the more arduous melatonin test.

It was within about one hour of the gold standard of taking blood every hour around the clock, said Depner, now an assistant professor of kinesiology at the University of Utah.

He noted the test was significantly more accurate when people were well rested and hadnt eaten recentlya requirement that could make the test challenging outside of a laboratory setting. And to be feasible and affordable, a commercial test would likely have to narrow down the number of metabolites its looking for (their test narrowed it down to 65).

But the study is a critical first step, said Wright.

We are at the very beginning stages of developing these biomarkers for circadian rhythm, but this promising study shows it can be done.

Other research, including some from Wrights lab, is exploring proteomics (looking for proteins in blood) or transcriptomics (measuring the presence of ribonucleic acid, or RNA) to assess circadian phase.

Ultimately, the researchers imagine a day when people can, during a routine physical, get a blood test to precisely determine their circadian phaseso doctors can prescribe not only what to do, but when.

This is an important step forward in paving the way for circadian medicinefor providing the right treatment to the right individual at the right time of day, said Depner.

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A blood test for your body clock? It's on the horizon - CU Boulder Today

Physiology

Adapting Roots to a Hotter Climate Could Reduce Pressure on Food Supply – Technology Networks

The shoots of plants get all of the glory, with their fruit and flowers and visible structure. But it's the portion that lies below the soil the branching, reaching arms of roots and hairs pulling up water and nutrients that interests plant physiologist and computer scientist, Alexander Bucksch, associate professor of Plant Biology at the University of Georgia.

The health and growth of the root system has deep implications for our future.

Our ability to grow enough food to support the population despite a changing climate, and to fix carbon from the atmosphere in the soil are critical to our, and other species', survival. The solutions, Bucksch believes, lie in the qualities of roots.

"When there is a problem in the world, humans can move. But what does the plant do?" he asked. "It says, Let's alter our genome to survive.' It evolves."

Until recently, farmers and plant breeders didn't have a good way to gather information about the root system of plants, or make decisions about the optimal seeds to grow deep roots.

In a paper published this month in Plant Physiology, Bucksch and colleagues introduce DIRT/3D (Digital Imaging of Root Traits), an image-based 3D root phenotyping platform that can measure 18 architecture traits from mature field-grown maize root crowns excavated using the Shovelomics technique.

In their experiments, the system reliably computed all traits, including the distance between whorls and the number, angles, and diameters of nodal roots for 12 contrasting maize genotypes with 84 percent agreement with manual measurements. The research is supported by the ROOTS program of the Advanced Research Projects AgencyEnergy (ARPA-E) and a CAREER award from National Science Foundation (NSF).

"This technology will make it easier to analyze and understand what roots are doing in real field environments, and therefore will make it easier to breed future crops to meet human needs " said Jonathan Lynch, Distinguished Professor of Plant Science and co-author, whose research focuses on understanding the basis of plant adaptation to drought and low soil fertility.

DIRT/3D uses a motorized camera set-up that takes 2,000 images per root from every perspective. It uses a cluster of 10 Raspberry Pi micro-computers to synchronize the image capture from 10 cameras and then transfers the data to the CyVerse Data Store the national cyberinfrastructure for academic researchers for 3D reconstruction.

The system generates a 3D point cloud that represents every root node and whorl "a digital twin of the root system," according to Bucksch, that can be studied, stored, and compared.

The data collection takes only a few minutes, which is comparable to an MRI or X-Ray machine. But the rig only costs a few thousand dollars to build, as opposed to half a million, making the technology scalable to perform high-throughput measurements of thousands of specimens, which is needed to develop new crop plants for farmers. Yet, the 3D scanner is also enabling basic science and addresses the problem of pre-selection bias because of sample limitations in plant biology.

"Biologists primarily look at the one root structure that is most common what we call the dominant root phenotype," Bucksch explained. "But people forgot about all of the other phenotypes. They might have a function and a role to fulfill. But we just call it noise," Bucksch said. "Our system will look into that noise in 3D and see what functions these roots might have."

Individuals who use DIRT/3D to image roots will soon be able to upload their data to a service called PlantIT that can perform the same analyses that Bucksch and his collaborators describe in their recent paper, providing information on a wide range of traits from young nodal root length to root system eccentricity. This data lets researchers and breeders compare the root systems of plants from the same or different seeds.

The framework is made possible by massive number-crunching capabilities behind the scenes. These are provided by the Texas Advanced Computing Center (TACC) which receives massive amounts of data from the CyVerse Cyberinfrastructure for computing.

Though it takes only five minutes to image a root crown, the data processing to create the point cloud and quantify the features takes several hours and requires many processors computing in parallel. Bucksch uses the NSF-funded Stampede2 supercomputer at TACC through an allocation from the Extreme Science and Engineering Discovery Environment (XSEDE) to enable his research and power the public DIRT/2D and DIRT/3D servers.

DIRT/3D is an evolution on a previous 2D version of the software that can derive information about roots using only a mobile phone camera. Since it launched in 2016, DIRT/2D has proven to be a useful tool for the field. Hundreds of plant scientists worldwide use it, including researchers at leading agribusinesses.

The project is part of ARPA-E's ROOTS program, which is working to develop new technologies that increase carbon storage within the soil and root systems of plants.

"The DIRT/3D platform enables researchers to identify novel root traits in crops, and breed plants with deeper, more extensive roots," said ARPA-E ROOTS Program Director Dr. David Babson. "The development of these kind of technologies will help promote climate change mitigation and resilience while also giving farmers the tools to lower costs and increase crop productivity. We're excited to see the progress that the team at PSU and UGA has made over the course of their award."

The tool has led to the discovery of several genes responsible for root traits. Bucksch cites a recent study of Striga hermanthica resistance in sorghum as the kind of outcome he hopes for users of DIRT/3D. Striga, a parasitic weed, regularly destroys sorghum harvests in huge areas of Africa.

The lead researcher, Dorota Kawa, a post-doc at UC Davis, found that there are some forms of sorghum with Striga-resistant roots. She derived traits from these roots using DIRT/2D, and then mapped the traits to genes that regulate the release of chemicals in the roots that triggers Striga germination in plants.

DIRT3D improves the quality of the root characterizations done with DIRT/2D and captures features that are only accessible when scanned in 3D.

The challenges facing farmers are expected to rise in coming years, with more draughts, higher temperatures, low-soil fertility, and the need to grow food in less greenhouse-gas producing ways. Roots that are adapted to these future conditions will help ease pressure on the food supply.

"The potential, with DIRT/3D, is helping us live on a hotter planet and managing to have enough food," Bucksch said. "That is always the elephant in the room. There could be a point where this planet can't produce enough food for everybody anymore, and I hope we, as a science community, can avoid this point by developing better drought adapted and CO2 sequestering plants."

Reference:Liu S, Barrow CS, Hanlon M, Lynch JP, Bucksch A. DIRT/3D: 3D root phenotyping for field-grown maize (Zea mays). Plant Physiol. 2021;(kiab311). doi:10.1093/plphys/kiab311

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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Adapting Roots to a Hotter Climate Could Reduce Pressure on Food Supply - Technology Networks

Physiology

In the hot seat: U of T expert on Tokyo’s weather and how athletes can beat the heat – News@UofT

This week, Spanish tennis player Paula Badosa was forced to retire from the quarter final at Tokyo 2020 due to heatstroke, using a wheelchair to leave the court. Novak Djokovic and Daniil Medvedev have also complained about the heat and scheduling of matches during the day.

As a result, International Tennis Federation officials decided to schedule Olympic tennis matches later in the afternoon, starting at 3 p.m. local time.

Ira Jacobs, a professor of exercise physiology in the University of Toronto's Faculty of Kinesiology & Physical Education, spoke to U of T's Jelena Damjanovicabout the temperatures in Tokyo and what athletes can do to prepare for the heat.

How do heat and humidity affect athlete performance?

The healthy human body is very sensitive to changes in both internal body temperature as well as air temperature. For example, we have neurons sensitive to temperature changes throughout our bodies, many located close to the skin surface. They act as temperature sensors resulting in many physiological changes. One of the most rapid changes that occurs within seconds of the sensing of warm air is the vasodilation, or expansion of the diameter of blood vessels, particularly the smaller ones closer to the skin surface. That enables more blood to be shunted to the skin surface, facilitating a more rapid and effective transfer of heat from the blood to the skin surface and away from the body to the surrounding environment.

When it comes to physical performance and sports there is a downside to that shunting of blood to the skin surface. Because our bodies give a higher priority to trying to maintain body temperature within a critical range, the heart has to work all that much harder to both continue to shunt blood to the skin surface while also trying to provide oxygenated blood flow to the exercising muscles. The end result is that the cardiovascular strain during intense exercise is much higher when its hot. Therefore, that intensity cannot be sustained for as long as when its done at a comfortable temperature.

Another example of how our bodies try to regulate internal body temperature is sweating. The evaporation of sweat from the skin surface is one of the most important avenues of heat transfer out of human bodies when we are exercising. Anything that impedes sweat secretion or evaporation will have a negative effect on exercise or physical performance. How much and how quickly sweat can be evaporated is dramatically affected by air humidity. The higher the humidity, the lower is the capacity of that air to accept more moisture which means that less sweat will be evaporated. More sweat simply drips off our bodies without being evaporated, and without removing as much heat from our bodies.

Recent research has also suggested that there is a central nervous system component to the regulation of body temperature that senses and predicts the rate of body temperature increase, and will cause us to involuntarily reduce our internal heat production by making us feel more fatigued. One of the underlying theories is that this a protective mechanism whereby the fatigue will cause us to slow down and thereby reduce the rate of increase of body temperatures to critical levels associated with serious damage to vital organs.

What can athletes do to adapt to extreme heat?

Fortunately, healthy humans can quickly improve their ability to cope with exercise in the heat. A period of 10 to14 days of daily exposure to a combination of heat stress and exercise will significantly improve the ability to exercise in the heat. Sweat rate increases, the volume of blood pumped by the heart per heart beat increases, heart rate decreases, blood plasma volume increases, the perception of how hard exercise feels decreases.These are but a few of the adaptations that help to preserve and increase exercise performance in the heat after a period of adaptation to heat stress.

So, Olympic athletes hopefully either went through a heat acclimation process a couple of weeks before their competitions in Japan, or they moved to Japan in sufficient time to give them a couple of weeks of natural acclimatization to Japans heat and humidity.

Is there something the International Tennis Federation (ITF) can do to protect players' health? Perhaps schedule matcheswhen it's cooler?

Frankly, I was surprised to learn that the scheduling of outdoor events like tennis at the Olympics did not start off with matches being scheduled to times that corresponded with reduced environmental heat stress. I read that they have now done so.

Many industrial, military and sporting organizations have standards whereby no hard work, training or competitions can take place when the heat index (an index of the combined effects of air temperature and air humidity) exceeds certain limits.

Longer rest intervals between sets; a longer break when changing courts within a set; cooling stations courtside where players could insert the arms and hands into cold water while on a break these are all examples of simple strategies that are employed in many other occupational and sport settings to reduce the health risks of high intensity physical exertion in the heat.

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In the hot seat: U of T expert on Tokyo's weather and how athletes can beat the heat - News@UofT

Physiology

R. Barry Dale Named Chair of Physical Therapy for College of Health Professions – UTHSC News

R. Barry Dale, DPT, PhD, MBA, has been named chair of the Department of Physical Therapy for the College of Health Professions at the University of Tennessee Health Science Center. He will begin his role July 30.

Dr. Dale brings significant experience to our college, said Stephen E. Alway, PhD, FACSM, dean of the UTHSC College of Health Professions. He is passionate about students and taking the training of Physical Therapy students to higher levels of excellence at UTHSC. He will provide outstanding energy for reshaping the Department of Physical Therapy and elevate its national visibility, clinical impact, teaching prominence and research productivity. We are delighted to recruit a leader of the caliber of Dr. Dale to our college.

The UTHSC Department of Physical Therapy is a proud and storied program with excellent faculty, students, and staff, Dr. Dale said. It is humbling to be a part of it.I am really looking forward to working with the faculty, students, and staff to continue the quest for programmatic excellence.

A nationally recognized leader in physical therapy, Dr. Dale joins UTHSC from the University of South Alabama, where he served as professor,department chair, and program director of the Department of Physical Therapy with expertise in Orthopedics, Sports, and Kinesiology.

Dr. Dales clinical expertise and research focuses on experimental sports-related and orthopedic areas of tendinopathy,rotator cuff fatigue, kinematics and kinetic analysis pertaining to the lumbar spine and thermoregulation. He has contributed to multiple textbook chapters pertaining to orthopedic and sports rehabilitation, exercise physiology and motor control. An active researcher, Dr. Dale has published 33 peer reviewed publications and has presented his research nationally and internationally.

Dr. Dale is certified as a Myofascial Trigger Point Therapist (CMTPT), Orthopedic Certified Specialist (OCS), and as a Sports Certified Specialist (SCS). In addition, he is Athletic Trainer Certified (ATC) and is a Certified Strength and Conditioning Specialist (CSCS).

Dr. Dale earned his bachelors degree from the University of South Alabama and a masters in Education in Exercise Science from the University of Alabama, Birmingham. He earned his PhD in Kinesiology with a specialization in Exercise Physiology from the University of Alabama, Tuscaloosa; a Doctor of Physical Therapy degree from University of Tennessee, Chattanooga; and his MBA from the University of South Alabama.

One facet of my role will be supporting student and faculty growth so that we may lead PT education in Tennessee, the region, and the nation, Dr. Dale said. Our department has a strong reputation, and we will only be getting better with time.

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R. Barry Dale Named Chair of Physical Therapy for College of Health Professions - UTHSC News

Physiology

Laurel Hubbard will make Olympic history on Monday before winning a medal despite the naysayers – ABC News

This weekend one Olympic athlete is preparing to make history.

Whether she wins or not is irrelevant, because just by taking part she will become one of those rare few who will be described as "the first ever".

There's no certainty that her history-making effort will be widely celebrated.

Certainly, it is controversial and yet the athlete herself is playing entirely by the rules.

New Zealand weightlifter Laurel Hubbard will become the first openly transgender woman to compete at the Olympics when she joins nine other competitors in the women's 87+ kilogram event at the Tokyo International Forum on Monday evening.

AAP:Dean Lewins

That's about the only simple thing to say about the story because everything else is highly complex and emotive.

Even the science is divided.

In years gone by there used to be rooms full of men making decisions for women, without hearing from the women themselves.

Then it was rooms full of white people making decisions for people of colour, without hearing their voices.

Now there are also rooms full of cisgender people making decisions for transgender people.

Some of those with the loudest voices and most forthright opinions have never actually discussed their views with a transgender athlete.

The most common view against transgender women competing in the women's category is:"Sooner or later there'll be no women left." By that, they mean cisgender women.

That line has been around for the best part of a decade and there is still no evidence of it happening.

One expert who worksin the field described it this week as "vastly overblown".

Australian weightlifter Charisma Amoe-Tarrant voices her support for Laurel Hubbard following her inclusion in New Zealand's squad for the Tokyo Games.

Significant numbers of men are not going to wakeup in the morning and decide, for a laugh, they'll become women so they can win a sporting contest.

Overwhelmingly, transgender women speak of knowing at age three or four that their bodies did notmatch what they knew themselves to be on the inside.

They describe living in a parallel world where the way people saw them was not who they were.

That experience alone can be psychologically traumatic.

When a male transitions to female, under the current International Olympic Committee (IOC) consensus, athletes need to prove they have reduced their testosterone levels to under 10 nanomoles per litre and maintain those levels for a period of 12months prior to their first competition.

Some experts argue 10nm is still too high, with most cisgender women registering levels between one and five nanomoles per litre.

Some are happy with the ratio but want the time period extended from one to two years or longer before being allowed to compete.

Transgender athletes have spoken of the impact testosterone reduction has.

Explained basically, the skeletal and muscular development of a male body that has gone through puberty requires a certain amount of hormonal "fuel"to sustain the speed and muscular strength to carry that body.

Reducing testosterone impacts the entire endocrine system, with flow-on effects formoods, metabolism and the way thebody's organs function.

Canadian cyclist and transgender woman Kristen Worley described the impact on her body as "spontaneous menopause".

Put another way, there was not enough fuel to continue to drive the vehicle andeverything steadily declined.

One of Australia's first transgender athletes was middle-distance runner Ricki Coughlan.

Speaking at a recent Association of International Sports Press (AIPS) e-College session, Coughlan said her experience was different.

"I experienced very little in the way of a full-blown puberty," she said.

"When I began my transition, the doctors didn't put me on a testosterone blocker because I didn't need one.

"My testosterone levels are lower than the average females.

"This points to the fact that all of our lives are different; where we start from and where we finish and where we go are very different."

Australian rugby player and sprinterCaroline Laytsaidbefore transitioning she was running 100 metres in "very low 11 seconds".

"Six years after surgery I was running 13.5 seconds, so I was about two and a half seconds slower over 100 metres," she said.

As part of a PhD thesis, Loughborough University's Joanna Harper has been collecting data on "changing athletic attributes as trans athletes transition".

Layt said she hadgiven all her statistical information to Harper, including how the amount she could bench press decreased from around 115 kilogramsto about 70kg.

Her data showed as a male athlete she was graded at around 85 per cent whileas a female she was graded at around 80 per cent. In other words, compared to most others in each category, she was more competitive as a manthan as a woman.

"But I'm only one person," Layt said.

"As we know, there are people that don't take hormones, there are people who are non-binary, so I think it's going to be a case-by-case basis.

"There's not one set rule for all."

The IOC will make a significant announcement in the coming months regarding a transgender framework which individual sports can use in devising their own policies.

It is expected to be a major shift, looking at the inclusion of transgender athletes through a multi-dimensional prism including human rights, legal, medical, social and scientific aspects.

The IOC's medical and scientific director, Richard Budgett, saidthere was still more science needed.

"There's quite a large amount of research being done at the moment to ascertain the residual advantage after going through male puberty, but you have to weigh that against all the other disadvantages of going through transition, and it's not something any individual would ever take lightly," he said.

"There are lots of aspects of physiology and anatomy, and the mental side, that can contribute to elite performance and it's very difficult to say, 'Yes, she has an advantage because she went through male puberty,' when there's so many other factors to be taken into account.

"It's not simple.I think each sport has to make their own assessment depending on the physiology of that sport so that they can ensure that there's fair competition but also inclusion of everyone, whether they're male or female able to take part in the sport that they so love."

He paid tribute to Hubbard's courage and tenacity in competing at the Olympic Games.

Hubbard rarely gives interviews but on Friday issued a message.

"I see the Olympic Games as a global celebration of our hopes, ideals and values and I would like to thank the IOC for its commitment to making sport inclusive and accessible," she said.

Come Monday, Hubbard will make history.

By Tuesday we'll know how widely that will be celebrated.

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Laurel Hubbard will make Olympic history on Monday before winning a medal despite the naysayers - ABC News