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Pheasants fall into two groups in terms of how they find their way around - and the different types prefer slightly different habitats, new research shows.

University of Exeter scientists tested whether individual pheasants used landmarks (allocentric) or their own position (egocentric) to learn the way through a maze.

The captive-bred pheasants were later released into the wild, and their choice of habitat was observed.

All pheasants favoured woodland, but allocentric navigators spent more time out in the open, where their landmark-based style is more useful.

"Humans tend to use both of these navigational tactics and quite frequently combine them, but when animals are tested, they often seem to rely more on one or the other," said Dr Christine Beardsworth.

"It is assumed that species favour whichever strategy suits their habitat, rather than using habitats which suit their strategy.

"Pheasants generally favour woodland, where an allocentric strategy is difficult because there are lots of trees close together, so it is hard to pick out landmarks.

"So, we might expect most pheasants to use an egocentric strategy - turning left, turning right or moving forward based on their own position and previous movements.

"However, in our study about half of pheasants reared in identical conditions used an allocentric strategy, while the other half used an egocentric or mixed strategy."

In the experiments, 20 pheasants first learned how to navigate through a simple maze, then faced a rotated version.

By altering the orientation of the maze but keeping the placement of "landmarks" the same, including the position of a human observer, the scientists were able to establish the preferred navigation strategy of each pheasant.

The discovery of individual variation suggest pheasants are either born with an "inherent cognitive bias", or develop one early in life.

Resulting differences in habitat selection may indicate that these biases help them to navigate more effectively in particular environments, perhaps outperforming other pheasants in relocating resources. However, it is not yet clear whether this is the case.

COLUMBUS, Ohio - Politicization of the COVID-19 pandemic had a powerful influence over adherence to social distancing guidelines in the United States and why people did, or did not, comply during the lockdown days, a new study has found.

The analysis boiled down to whom study participants trusted most: scientists or President Donald Trump.

"People who expressed a great deal of faith in President Trump, who thought he was doing an effective job of guiding us through the pandemic, were less likely to socially distance," said Russell Fazio, senior author of the study and a professor of psychology at The Ohio State University. "In contrast, the people who expressed a great deal of trust in scientists showed the exact opposite pattern: They were more likely to engage in social distancing.

"We were getting two-sided messages at the time from our government officials and public health scientists, so we had these two sources that were, in effect, working in opposition to one another. That pointed to the politicization of the pandemic."

The study is published today (Feb. 24, 2021) in PLOS ONE.

Fazio's lab studies how personal beliefs and attitudes influence behavior. When COVID-19's emergence in the United States led to lockdowns and stay-at-home orders, the national directive to socially distance became an enormous science experiment.

"On the basis of everything we've known for decades of social psychology, it seemed clear that people's pre-existing beliefs would affect their interpretations of the seriousness of the pandemic and the extent to which they would comply with these recommendations," Fazio said. "We thought we needed to directly assess that empirically, find out who was indeed complying or not complying, and get some idea about which beliefs mattered."

According to the authors' theoretical framework, three components were at play when the information campaign began: the source of the message, what kind of challenge the context presented - is the virus really a threat? - and the self-views of the targets, in this case the entire U.S. population.

The researchers recruited participants from Amazon's Mechanical Turk crowdsourcing marketplace. The sample in this study consisted of 2,001 U.S. adults representing a range of ages, geographical locations and political ideologies.

The team surveyed the participants in early May about their personal beliefs on a range of issues associated with the pandemic: how much they trusted the sources of information, the extent of their worry about the dangers of the virus, and how concerned they were for others' vulnerability to getting sick. Did they believe in the value of science, trust the federal government's handling of the pandemic, weigh economic concerns over public health, consider themselves compassionate?

"We were interested in the extent to which an individual had a self-view as a compassionate person, because at least part of the reason we were all engaging in social distancing was to protect one another. We were also interested, because of all of the misinformation that was floating around, in people's general tendency toward conspiratorial thinking," Fazio said.

Questions about beliefs and political leanings were combined with a knowledge check: a true-or-false quiz on 13 facts and myths about the coronavirus.

To gauge participants' social distancing behavior, the researchers presented study participants with 10 virtual behavior scenarios of various public settings - a grocery store, a crowded beach, a crosswalk - and asked them to place themselves or fictional people in those contexts based on their social distancing preferences. Though the researchers also asked participants to self-report their social distancing practices, the virtual scenarios requiring "in the moment" decisions about reactions to different situations were considered more representative of how people actually behaved in real life.

In fact, a recently published study involving follow-up data showed that the more participants demonstrated a preference for social distancing in the virtual scenarios, the less likely they were to have gotten sick with COVID-19 in the subsequent four months - a finding that established the validity of the virtual measures.

Statistical analyses revealed several correlations. Trust in scientists, support for the guidelines, belief that the virus threat was not exaggerated, concern about its spread, general science literacy and COVID-19 knowledge were strongly associated with the practice of social distancing. Trust and confidence in President Trump and the federal government's effectiveness, belief in conspiracy theories, a political lean toward conservatism and an opinion that economic health was more important than safety were linked to lower odds of practicing social distancing.

Fazio said the findings may make one wonder what might have been had the U.S. populace been exposed to more consistent messaging.

"If there had been a single coherent voice communicating information, leading people to understand how serious the threat was and encouraging all of these preventive behaviors, including social distancing, I think we would have seen far more compliance," he said. "That is what comes through the data very clearly."

UCLA materials scientists and their colleagues have developed a new method to make synthetic biomaterials that mimic the internal structure, stretchiness, strength and durability of tendons and other biological tissues.

The researchers developed a two-pronged process to enhance the strength of existing hydrogels that could be used to create artificial tendons, ligaments, cartilage that are 10 times tougher than the natural tissues. Although the hydrogels contain mostly water with little solid content (about 10% polymer), they are more durable than Kevlar and rubber, which are both 100% polymer. This kind of breakthrough has never been achieved in water-laden polymers until this study, which was recently published in Nature. The new hydrogels could also provide coating for implanted or wearable medical devices to improve their fit, comfort and long-term performance.

"This work shows a very promising pathway toward artificial biomaterials that are on par with, if not stronger than, natural biological tissues," said study leader Ximin He, an assistant professor of materials science and engineering at the UCLA Samueli School of Engineering.

Hydrogels are a broad class of materials with interior structures made up of crisscrossing polymers or gels. They show promise for use as replacement tissues, either to temporarily close wounds or as a long-term or even permanent solution. In addition, the gels may have applications for soft robots and wearable electronics.

However, current hydrogels are not strong or durable enough to mimic or replace tissues that need to move and flex repeatedly while bearing weight. To address these issues, the UCLA-led team employed a combination of molecular and structural engineering approaches that were not previously utilized together to make hydrogels.

First, the researchers used a method called "freeze-casting" -- a solidifying process that results in porous and concentrated polymers, similar to a sponge. Second, they used a "salting-out" treatment to aggregate and crystalize polymer chains into strong fibrils. The resulting new hydrogels have a series of connecting structures across several different scales -- from molecular levels up to a few millimeters. The hierarchy of these multiple structures, similar to that of biological counterparts, enables the material to be stronger and more stretchable.

As demonstrated by the team, this versatile method is highly customizable and could replicate various soft tissues in the human body.

The researchers used polyvinyl alcohol, a material already approved by the U.S. Food and Drug Administration, to make their hydrogel prototype. They tested its durability, seeing no signs of deterioration after 30,000 cycles of stretch testing. Under light, the new hydrogel produced a vivid shimmer, similar to real tendons, confirming the micro/nano structures that formed in the gel.

In additional to biomedical applications, the advance may hold potential for surgical machines or bioelectronics that operate innumerable cycles, and 3D printing of previously unachievable configuration, thanks to the hydrogel's flexibility. In fact, the team demonstrated that such 3D-printed hydrogel architectures could transform into other shapes pending changes in temperature, acidity or humidity. Acting as artificial muscles, they are much more resilient and could exert great force.

What The Study Did: This randomized clinical trial compares the effects of once-weekly subcutaneous semaglutide versussplacebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity.

Authors: Thomas A. Wadden, Ph.D., of the University of Pennsylvania in Philadelphia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2021.1831)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Many genetic variants have been found to have a linkage with genetic diseases, but the understanding of their functional roles in causing diseases are still limited. An international research team, including a biomedical scientist from City University of Hong Kong (CityU), has developed a high-throughput biological assay technique which enabled them to conduct a systematic analysis on the impact of nearly 100,000 genetic variants on the binding of transcription factors to DNA. Their findings provided valuable data for finding key biomarkers of type 2 diabetes for diagnostics and treatments. And they believe that the new technique can be applied to studies of variants associated with other genetic diseases.

The study was co-led by Dr Yan Jian, Assistant Professor in the Department of Biomedical Sciences at CityU, Professor Bing Ren from the University of California San Diego and Professor Jussi Taipale from the University of Cambridge. Their findings were published in the prestigious scientific journal Nature, titled "Systematic analysis of binding of transcription factors to noncoding variants".

"Based on our findings, we believe that our high-throughput experimental method can be applied in the study of different genetic diseases, including colorectal cancer and prostate cancer. It can help dissect the mechanism of the genetic inheritance of the disease and find the biomarkers for clinical diagnosis," said Dr Yan.

Unveiling the roles of noncoding variants in diseases

Genome-wide association studies (GWAS), which investigate the entire genome, has been the most important strategy in finding the genes associated with complex genetic diseases. Researchers have found hundreds of thousands of genetic variants in association with human diseases and traits. But studies on the functions of these variants are still limited.

"Understanding the molecular functions of the noncoding variants will help us find out why people carrying these mutations are more susceptible to genetic diseases. This will help us develop methods or strategies to prevent, to detect or to cure the diseases early," explained Dr Yan.

One of the variants' functions is to affect the binding of transcription factors to DNA. The transcription factors will then control the gene expression in cells, turning the specific genes "on" and "off", modulating the cellular functions.

To systematically characterise the effects of genetic variants on the transcription factor binding, the team modified their previously developed experimental method into an ultra-high-throughput multiplex protein-DNA binding assay, termed "single-nucleotide polymorphism evaluation by systematic evolution of ligands by exponential enrichment" (SNP-SELEX). Then they chose the genetic variants from the gene locations on the genome (called "gene loci") that are known to be associated with the risk of type 2 diabetes as the object of analysis.

Utilising the SNP-SELEX, they successfully analysed the impact of 95,886 genetic variants on the binding of 270 distinct human transcription factors to DNA. They demonstrated that noncoding genetic variant SNP rs7118999 that increases the risk of type 2 diabetes can affect the DNA binding with one of the transcription factors, and the resulting molecular mechanism regulates the blood lipid level.

"This is a clear example of applying the data generated by SNP-SELEX that it can help identify the genetic variants which play key roles in the inheritance of type 2 diabetes. This would help the subsequent investigation in finding diagnostic biomarkers and therapeutic targets," said Dr Yan.

Speeding Up Analysis Significantly

Moreover, previous studies could only single out one or a few variants to find out its molecular mechanism. Each study took around 2-3 years. "So it was impossible to completely understand the complex genetic diseases like type 2 diabetes which are associated with hundreds of genetic variants within a short period. But with the SNP-SELEX, we could systematically analyse approximately 100,000 variants within a much shorter timeframe," said Dr Yan.

"In this study, we only covered a relatively small portion of variants and transcription factors. So we will expand our study. By utilising the SNP-SELEX, hopefully it will help us uncover the underlying mechanisms of more and more of these noncoding variants very soon," said Professor Ren.

RESEARCHERS MAY HAVE UNCLOUDED THE MYSTERY OF COVID-19 'BRAIN FOG'

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

People who survive a severe case of COVID-19 have reported a variety of lingering aftereffects, but perhaps none as unusual as what has been popularly called "brain fog." Clinically known as dysexecutive syndrome, the condition is a COVID-19-kindled delirium, initially experienced by patients -- mostly older -- while sick as a state of confusion and impaired awareness. It then often stays on after recovery to torment as persistent cognitive sluggishness. Unfortunately, the origin of brain fog has remained unclear.

Now, pathologists at Johns Hopkins Medicine in Baltimore and Brigham and Women's Hospital in Boston have found evidence that large bone marrow cells known as megakaryocytes may be responsible for the brain fog. They suggest that megakaryocytes migrate to the brain in a journey precipitated by the destructive activity of SARS-CoV-2, the virus that causes COVID-19.

There, the researchers believe, the out-of-place cells may reduce or completely block the flow of nourishing blood through individual capillaries in the cerebral cortex -- the area of the brain where most information processing occurs. Such capillary occlusions, they say, could lead to neurological impairment.

The team's findings are reported in a research letter published Feb. 12 in JAMA Neurology.

Megakaryocytes are the cells responsible for production of platelets --blood components that are necessary for clotting and wound repair.

Interestingly, the researchers say, a scientific literature search they conducted indicates this may be the first time that megakaryocytes have been found in blood vessels in the human brain.

The researchers evaluated brain tissue from autopsies of 15 patients who died of COVID-19. In five of the samples, they discovered large cell nuclei resembling those of megakaryocytes in the cortical capillaries. Immunohistochemical testing confirmed that the nuclei were those of megakaryocyte immigrants from bone marrow.

No megakaryocyte nuclei were found in post-mortem brain tissues from decedents who were negative for the COVID-19 coronavirus and served as the study's control group.

What isn't clear is how the COVID-19-associated megakaryocytes are signaled to leave the bone marrow or how they can navigate the fine network of lung blood vessels on their way to the brain, says David Nauen, M.D., Ph.D., study lead author and assistant professor of pathology at the Johns Hopkins University School of Medicine.

"We suspect that SARS-CoV-2 damages lung tissue, leading to the release of chemical signals that induce the megakaryocytes to travel there from the bone marrow," says Nauen. "When that happens, these large cells somehow find a way to pass through the lung capillaries and get to the brain."

"We don't yet know if the megakaryocytes we found in the brain are just the result of blood flow carrying them there or if a specific change occurs in the brain vessels that trap them," he adds.

Nauen says the researchers plan next to characterize what happens in the brain tissue and cortical capillaries during severe cases of COVID-19 to better understand how megakaryocytes are signaled and recruited.

"Because standard brain autopsy sections represent only a minute portion of the cerebral cortex, the actual numbers of these cells in the brain as a result of COVID-19 could be considerable -- as could their potentially negative neurological impacts on those who survive," says Nauen.

Nauen is available for comment about these research findings.

SCIENTISTS ARE BUILDING MORE COMPREHENSIVE TESTS FOR COVID-19

Media Contact: Vanessa Wasta, wasta@jhmi.edu

New strains of SARS-CoV-2, the virus that causes COVID-19, may have greater transmissibility or altered virulence, or may exhibit resistance to the current vaccines. Now, scientists are racing to develop better ways to detect emerging SARS-CoV-2 strains among the high number of diagnosed infections.

Johns Hopkins assistant professor of pathology Ben Larman, Ph.D., and his team have been working to improve the analysis of genetic material called RNA that forms the genome of many viruses.

Specifically, the Johns Hopkins team is developing a technique to scan biological specimens, including saliva or specimens obtained with nasal swabs, using specialized DNA probes that sift through a complex "forest" of RNA sequences. The probes can detect specific RNA sequences of viruses and other disease-causing pathogens.

A report describing the development and application of the test (cRASL-seq), led by Larman and postdoctoral fellow Joel Credle, Ph.D., appeared online Feb. 3 in the journal Modern Pathology.

A key feature of the newly developed test, says Larman, is its ability to analyze and detect the many subtle changes that can occur in the SARS-CoV-2 viral genome -- so-called variants, such as those first identified in the United Kingdom and South Africa.

Read more about development of the test.

Larman is available for interviews.

PHILADELPHIA -- A second study of the injectable anti-obesity medication, semaglutide, has confirmed the large weight losses reported in a study earlier this month, establishing the reliability and robustness of this new drug. With obesity affecting more than 40 percent of American adults, the findings could have a major impact on weight management in primary care and other settings. The study is published today in the Journal of the American Medical Association.

The 68-week study was conducted at 41 sites in the United States from August 2018 to April 2020 and was designed to boost total weight loss with semaglutide by combining the medication with a more intensive diet and physical activity program than what was used in the STEP 1 trial, published online February 10th in the New England Journal of Medicine. All participants in the new STEP 3 study received 30 sessions of intensive behavioral therapy consisting of diet and physical activity counseling, which was combined with an initial 8-week, 1000-1200 kcal/day meal-replacement diet, consisting of shakes, meal bars, and prepared entrees.

"We wanted to induce a large weight loss with rigorous behavioral therapy and see how much additional weight loss semaglutide could add," said lead author Thomas Wadden, PHD, a professor of psychology in the Department of Psychiatry at the Perelman School of Medicine at the University of Pennsylvania.

The 611 participants in the STEP 3 trial had an average starting weight of 233 pounds with a body mass index of 38 kg/m2. The participants taking semaglutide were given a 2.4 mg dose once weekly. After 68 weeks of treatment, the semaglutide group lost an average of 16 percent of baseline body weight, equal to 37 pounds, compared with 5.7 percent, 14 pounds for those assigned to intensive behavioral therapy combined with placebo. Substantially greater proportions of semaglutide-treated participants (75 percent), compared with placebo (27 percent), achieved weight losses of 10 percent or more of baseline weight.

"These are remarkable weight losses, particularly the one third of participants who lost 20 percent of baseline weight, a reduction that approaches that achieved with sleeve gastrectomy, a widely used bariatric surgery procedure," Wadden said. "Further study is needed to determine if patients can sustain these substantial losses with long-term use of semaglutide 2.4 mg."

The larger weight losses achieved with semaglutide than with placebo were associated with greater improvements in cardiometabolic risk factors, including changes in waist circumference, systolic blood pressure, hemoglobin A1c, and triglycerides.

"These metabolic benefits and marked improvements in risk factors hold great promise for the prevention and treatment of diabetes and cardiovascular disease," said W. Timothy Garvey, MD, a study co-author and professor of medicine in the Department of Nutrition Sciences at the University of Alabama at Birmingham. "The unprecedented degree of weight loss is also sufficient to prevent and treat other complications of obesity including osteoarthritis, sleep apnea, and non-alcoholic fatty liver disease," he added.

Gastrointestinal side effects were reported by 83 percent of semaglutide participants and included mild-to-moderate nausea and diarrhea that generally improved over time, without the need to discontinue the drug.

Semaglutide is a glucagon-like-peptide 1 (GLP-1) receptor agonist which, at a dose of 1.0 mg once weekly, is approved (as Ozempic) by the U.S. Food and Drug Administration for the management of type 2 diabetes. The higher dose of 2.4 mg, currently being evaluated by the FDA for chronic weight management, appears to affect appetite centers in the brain that control hunger and cravings, leading to a reduction in food and calorie intake. Patients also report feeling full more quickly when eating. The medication is taken once weekly by self-injection under the skin.

"The results with semaglutide appear to be the breakthrough in weight management that health care providers and their patients with obesity have been waiting for," said Wadden. "It's clear that adding semaglutide to intensive behavioral therapy could substantially increase the proportions of patients who lose 10 percent or more of their starting weight, with accompanying improvements in health and mobility."

A question left unanswered by the present study is how much lifestyle counseling is needed with semaglutide to lose an average of approximately 15 percent of baseline weight. Semaglutide-treated participants in the STEP 1 trial lost 14.9 percent of starting weight, with 18 sessions of lifestyle counseling, compared with 2.4 percent for placebo.

"For the placebo-treated participants in STEP 3, the 30 intensive behavioral therapy sessions and meal-replacement diet appeared to increase weight loss by approximately 3 percentage points, as compared with the less intensive lifestyle counseling provided in the STEP 1 trial," Wadden noted. "However, a comparable benefit was not observed in combining rigorous behavioral treatment with semaglutide, suggesting that further study is needed of the optimal program of lifestyle counseling required with semaglutide at the higher dose currently being evaluated."

SAN ANTONIO -- Feb. 24, 2021 -- A Southwest Research Institute® (SwRI®) scientist examined 11 Mars years of image data to understand the seasonal processes that create linear gullies on the slopes of the megadune in the Russell crater on Mars. In early spring images, captured by two different cameras on the Mars Reconnaissance Orbiter, SwRI's Dr. Cynthia Dinwiddie noticed airborne plumes of dusty material associated with the linear dune gullies on the sand dune's downwind slope. These clues point to active processes involving chunks of frozen CO2, or dry ice, sliding down the sand dune, kicking up sand and dust along the way.

Russell crater, on Mars, is home to the largest known sand dune in the solar system, providing a frequently imaged locale to study modern surface activity on the Red Planet.

"For two decades, planetary scientists have had many ideas about how and when very long, narrow gullies formed on frost-affected sand dunes on Mars," said Dinwiddie, first author of a paper outlining new research that has been accepted for publication in the journal Geophysical Research Letters. "Initially, scientists thought linear dune gullies were remnants of an ancient time when the climate on Mars supported liquid water on its surface. Then, repeat imaging showed that changes were happening now, when Mars is cold and arid. Several hypotheses have since been proposed, usually involving either CO2 ice or water ice."

Other scientists found imagery showing bright CO2 ice blocks at rest in dune gullies, suggesting a causal relationship between the blocks and the gullies.

"In this paper, we offer compelling new evidence that venting CO2 gas dislodges CO2 ice blocks that carve and modify linear dune gullies," Dinwiddie said.
"While trace amounts of seasonally condensed water are present, it behaves like an innocent bystander, not actively participating in the processes," said coinvestigator Dr. Tim Titus of the U.S. Geological Survey.

During the bleak Martian fall and winter, cold temperatures condense part of the CO2 atmosphere onto the dune field's surface, creating ice deposits. Previous research has shown that in the winter and early spring, the translucent slab of CO2 ice allows radiation from the Sun to heat the dark sand under the ice, causing some ice to transition to gas (or sublimate) and become pressurized in the contact zone. This pressurized CO2 gas escapes to the atmosphere via weak zones in the ice, also expelling sand and dust in a jet of gas.

The ejected material falls back to the surface and forms dark spots around the vent. This research proposes that as the season wears on, repetitive venting breaks up the slab ice into discrete blocks on steep slopes near the crest of the dune. Venting gas eventually dislodges the blocks, and sends them sliding downslope, deepening and modifying existing gullies or carving new ones.

The airborne plumes consist of fine dust disturbed by the sliding block, whereas coarse dust is redeposited near the gullies, creating a seasonal, relatively bright fringe around active gullies. The off-gassing ice blocks temporarily clean dust from the dark gully sand, resulting in telltale brightness (albedo) variations in and around gullies.

"We observe this bright fringe pattern around active gullies for a short period of time, say, the equivalent of the last three weeks of October, which is early to mid-spring in the Earth's southern hemisphere," Dinwiddie said. "Shortly after this 'spring break,' Mars' dusty atmosphere blankets the area with a more homogenous façade, disturbed only by dust devils in the late spring and summer."

SwRI led this program, with thermal modeling of ice and dust provided by Titus and the U.S. Geological Survey. A NASA Mars Data Analysis Program grant funded this 12-month pilot study of seasonal dune processes in Russell crater. Dinwiddie and Titus have proposed to extend this research to other craters in the southern hemisphere of Mars, where craters provide low-lying traps for sand to accumulate and form frost-affected dune fields.

Immunologists at St. Jude Children's Research Hospital have discovered that tumors use a unique mechanism to switch on regulatory T cells to protect themselves from attack by the immune system. Surprisingly, the mechanism does not affect regulatory T cell function outside the tumor and may therefore limit the immune-associated toxicities of targeting regulatory T cells.

The finding offers the promise of drug treatment to selectively shut down regulatory T cells in a tumor, rendering the tumor vulnerable to cancer immunotherapies that activate the immune system to kill the tumor. The researchers showed that blocking tumor-associated regulatory T cell activity eliminated tumors cells in mice and sensitized the cells to cancer immunotherapy called anti-PD-1 therapy.

The research appeared today in the journal Nature.

A tumor-controlled metabolic pathway to ward off the immune system

Regulatory T cells keep the immune system in check, preventing it from attacking the body's own tissues in autoimmune diseases such as lupus and rheumatoid arthritis.

"There has certainly been a great deal of interest in targeting regulatory T cells for cancer therapy, because they are central to keeping the immune system in check in tumors," said corresponding author Hongbo Chi, Ph.D., of the St. Jude Department of Immunology. "But the risk of such targeting is possibly inducing autoimmune disease because these T cells are crucial to balancing the body's immune response.

"Our finding is exciting because we have identified a metabolic pathway that tumors use to independently reprogram regulatory T cells," he said. "Thus, we believe there is the potential for inhibiting regulatory T-cell activation in tumors to unleash effective antitumor immune responses without triggering autoimmune toxicity."

Tracking gene regulation to a surprise

Researchers discovered the pathway by challenging mice with melanoma cells and then analyzing which genes were switched on in regulatory T cells. Investigators compared tumor-infiltrating regulatory T cells with regulatory T cells in other tissues to compare gene activation.

The experiment revealed a master genetic switch that was activated only in regulatory T cells in the tumor microenvironment. The switch was a transcription factor family called SREBP.

"We were surprised to find this context-dependent pathway functioning selectively in the tumor microenvironment," Chi said. Seon Ah Lim, Ph.D., a first author of the study, added, "It is incredible we can target metabolic pathways in regulatory T cells for cancer immunotherapy while maintaining immune homeostasis."

The researchers determined that the tumor-specific regulatory T cell pathway was switched on in a range of cancers--melanoma, breast cancer and head and neck cancer. The tumor-specific pathway was not switched on in animal models of inflammation or autoimmune disease.

Genetically blocking the SREBP pathway selectively in regulatory T cells led to rapid clearance of tumor cells in mice with melanoma and colon adenocarcinoma. Targeting the pathway also reduced tumor growth in mice with established tumors. Blocking the pathway had no effect on the proliferation of regulatory T cells or their overall function in the body.

Blocking a pathway unleashes the anti-cancer immune response

Blocking the SREBP pathway also unleashed a potent antitumor response in mice with melanoma treated with immunotherapy called anti-PD-1. Anti-PD-1 treatment alone was otherwise ineffective in the mice. This form of immunotherapy inhibits the biochemical switch known as programmed cell death protein 1, or PD-1. PD-1 is a checkpoint switch that protects tumors by suppressing the immune response to them.

"Anti-PD-1 therapy currently works in only about 20% of cancer patients, although when it works, the response is durable in those cases," Chi said. "Many pediatric cancers are not responsive to anti-PD-1. Our experiments showed that blocking this lipid pathway had quite a remarkable effect in sensitizing mice to the therapy.

"While we still have a long research path ahead of us, these findings suggest that if we can develop drugs to control this context-specific regulatory T cell pathway in cancer patients, we can make them even more responsive to immunological checkpoint therapies," he said.

BROOKLYN, New York, Wednesday, February 24, 2021 -The Governance Lab (The GovLab) at the NYU Tandon School of Engineering released a report, "The Power of Virtual Communities," which examines the role online groups play in creating opportunities for people to build new kinds of meaningful communities they often could not form in real space.

This first-of-its-kind research was built on interviews with 50 Facebook community leaders in 17 countries, 26 global experts from academia and industry, unique access to Facebook's underlying research and an original global survey conducted by YouGov of 15,000 people in 15 countries who are currently members of online and in-person communities, which found that in 11 of those countries the majority of people said that the most meaningful communities to which they belong are primarily online.

"Around the world, people who are otherwise voiceless in physical space are becoming powerful leaders of groups that confer a true sense of meaning and belonging for their members," said Beth Simone Noveck, director of The GovLab. "This brief report, which tells the stories of several of those leaders and how they govern global communities is, we hope, the beginning of greater and much needed study of online groups and their impact on social and political life."

Many of these Facebook groups cut across traditional social groupings and bring together people around a shared trait or interest:

Female IN (FIN), created as a safe space for women in the Nigerian diaspora to discuss and seek support for problems associated with such challenges as relationship struggles, health issues, abuse, grief and loss. Female IN grew by word-of-mouth into a 1.8 million-person community with members in more than 100 countries.

Surviving Hijab encourages its 920,000 female members to take up or continue wearing the Muslim head covering in the face of political and social criticism.

Blind PenPals enables its 7,000 blind and visually impaired members to share stories and advice.

Canterbury Residents Group acts as a public square in the British city of Canterbury and has 38,000 members, about the same size as the city's population.

Subtle Asian Traits, which began as a modest initiative among nine young Australians of Chinese background to share funny memes about their Asian heritage, has expanded to a group of 1.82 million people who discuss and share the experience of growing up Asian in mostly majority-White societies.

The GovLab's report findings note that:

Membership in online communities confers a strong sense of community, the lack of physical proximity notwithstanding.

Online groups are a still fluid form of human organization that in many cases attract members and leaders who are marginalized in the physical societies they inhabit, and who use the platform to build new kinds of communities that would be difficult to form otherwise.

Many of these groups have counter-cultural norms and are what political scientists might call "cross-cleavage" communities. These groups cut across traditional social groupings, and bring together people normally divided by geography around a shared trait or interest.

The flexible affordances of online platforms have enabled new kinds of leaders to emerge in these groups with unique skills in moderating often divisive dialogues, sometimes among millions of members.

Most groups are run as a labor of love; many leaders are neither trained nor paid and the rules that govern their internal operations are often uncodified and the hosting platform - in this case Facebook - holds significant power over their operations and future.

These groups, some of which have huge memberships, remain emergent and largely unrecognized: they are outside traditional power structures, institutions and forms of governance.

More research is needed to understand whether and how these groups will operate as genuine communities over the long term, especially given the tensions that derive from conducting public life on a private platform such as Facebook, and how such groups and their leaders can be supported to ensure they provide maximum voice, participation and benefit to their members

Further, results from the YouGov survey and the interviews with group leaders indicated that the three most essential traits and behaviors for leaders to exhibit were welcoming differences of opinions, being visible and communicating well, and acting ethically at all times.

This report, published in six languages, further shines a light on the role leaders have and why it is important to further support them in running their community.

Aged cheeses pack a punch of nutty, sharp flavor. Before they're fully mature, aged cheeses are either waxed or placed in brine for weeks to create a natural rind. However, the high salt content in brined cheeses deters some consumers. Now, researchers reporting in ACS Food Science & Technology present a shortened brining time for Parmigiano Reggiano that results in a less salty product, while still potentially maintaining the cheese's distinctive texture and flavor compounds.

Parmigiano Reggiano is a lactose-free, crumbly and hard cheese. Manufactured in select provinces in Italy, its protected designation of origin status requires that certain production processes, such as a minimum 12-month ripening period, be performed. Ripening or maturing imparts the cheese's recognizable taste as milk solids are converted to flavor compounds. But before that, cheese wheels are placed in a saturated brine solution for weeks. The added salt plays a key role in the ripening process by modulating microbial growth, enzyme activity and the separation of solids from liquids, hardening the final product. One enzyme-mediated reaction is lipolysis, in which triglyceride fats in milk break down into their key components -- free fatty acids and diacylglycerides. Free fatty acids not only contribute to the taste of the cheese but are also precursors to other flavor molecules. So, Silvia Marzocchi and colleagues wanted to test the impact of brining time on the lipolysis reactions responsible for the free fatty acids involved in Parmigiano Reggiano's flavor profile and distinctive characteristics.

The researchers had five Parmigiano Reggiano dairies brine several cheese wheels by immersing them in a saturated salt solution for either 18 days or a shorter 12-day period. Then the wheels were ripened for 15 months under conditions typical for this type of cheese. Salt content in fully ripened cheese was 9% lower in the samples brined for a shorter time than the group with the longer procedure. Unexpectedly, the researchers found no difference in the moisture level, cholesterol and total fat in the two sets of cheeses. The team also observed no major variations in compounds involved in the flavor profile, as most of the 32 free fatty acids had overlapping concentration ranges between the two groups. Yet in the cheeses with the shorter salting time, overall, the total free fatty acids and the total diacylglycerides concentration ranges were 260% and 100% higher, respectively, than the traditionally brined version, suggesting the lower salt to moisture ratio resulted in more water available to lipolysis reactions and more rapid enzymatic activity breaking down triglycerides. The researchers say a reduced brining time for Parmigiano Reggiano could result in a product appealing to salt-conscious consumers, but sensory tests are still needed to indicate if they can detect differences to the overall taste and texture.

Scientists have made a pivotal breakthrough in the quest to understand how single-cell green algae are able to keep track of the light as they swim.

A team of researchers from the University of Exeter's flagship Living Systems Institute has discovered how the model alga Chlamydomonas is seemingly able to scan the environment by constantly spinning around its own body axis in a corkscrewing movement. This helps it respond to light, which it needs for photosynthesis.

The tiny alga, which is found abundantly in fresh-water ponds across the world, swims by beating its two flagella, hair-like structures that adopt a whip-like movement to move the cell. These flagella beat in much the same way as the cilia in the human respiratory system.

Chlamydomonas cells are able to sense light through a red eye spot and can react to it, known as phototaxis. The cell rotates steadily as it propels itself forwards using a sort of breaststroke, at a rate of about once or twice a second, so that its single eye can scan the local environment.

However, the intricate mechanism that allows the alga to achieve this helical swimming has been previously unclear.

IN the new study, the researchers first performed experiments which revealed that the two flagella in fact beat in planes that are slightly skewed away from each other.

Then, creating a sophisticated computer model of Chlamydomonas, they were able to simulate the flagella movement and reproduce the observed swimming behaviour.

The researchers discovered that the flagella were able to move the Chlamydomonas in a clockwise fashion with each power stroke, and then anticlockwise on the reverse stroke - akin to how a swimmer rocks back and forth when switching from one arm to another. Except here the cell feels no inertia.

Furthermore, they also deduced how simply by exerting slightly different forces on the two flagella, the alga can even steer, rather than just move in a straight line.

The researchers were able to show that by adding in an additional influence, such as light, the alga can navigate left or right by knowing which flagellum to stroke harder than the other.

Dr Kirsty Wan, who led the study said: "The question of how a cell makes these types of precise decisions can be a matter of life or death. It's quite a remarkable feat of both physics and biology, that a single cell with no nervous system to speak of is able to do this...It's an age-old mystery that my group is currently working hard to solve."

For the study, the researchers were able to test various scenarios to determine which variables were influencing the trajectory. Their study showed that by varying different parameters, such as if one flagella is slightly stronger than another, the tilt plane of the flagella or its beat pattern, the algae can manipulate its own movement.

Team member Dr Dario Cortese added: "The agreement of our model with the experiments is surprising really, that we could effectively capture the complex 3D beat of the flagella with a very simple movement of a bead going around in circles."

Chemical & Engineering News (C&EN), the newsmagazine of the American Chemical Society (ACS), is celebrating Black chemists and chemical engineers with a special issue highlighting Black chemists who work across the fields of biotechnology, solar energy, pharmaceuticals and more. Guest edited by Massachusetts Institute of Technology (MIT) drug delivery pioneer Paula Hammond, Ph.D., this special issue showcases Black scientists, spotlighting their scientific passions and career accomplishments.

"In bringing into focus the unique lives of this set of accomplished Black scientists in chemistry and chemical engineering, it is my hope that we open the door to more frequent and constant recognition of our presence in the field," Hammond wrote in her introductory remarks. "We have always been present in the sciences -- but now more than ever, we must appreciate and acknowledge the presence of Black people and other people of color. We must find ways to continue to raise our voices and celebrate our work. As a nation, we all benefit from the huge talent gained when all are included in the science enterprise."

Among the chemists and chemical engineers featured in the 2021 Trailblazers issue are Karen Akinsanya, Ph.D., of Schr?dinger, Inc., on artificial-intelligence-driven drug discovery; Oluwatoyin Asojo, Ph.D., of Hampton University on her calling to develop drugs for neglected diseases; Squire J. Booker, Ph.D., of Penn State University on the catalytic moments of his career; Cato T. Laurencin, M.D., Ph.D., of the University of Connecticut on his twin passions for surgery and biomedical engineering; and Kristala L. J. Prather, Ph.D., of MIT on harnessing the synthetic power of microbial systems. The print issue, which features original content and photography by Black creators, was released on February 22.

More U.S. adults reported receiving or planning to receive an influenza vaccination during the 2020-2021 flu season than ever before, according to findings from a national survey.

The survey of 1,027 adults, conducted by the University of Georgia, found that 43.5% of respondents reported having already received a flu vaccination with an additional 13.5% stating they "definitely will get one" and 9.3% stating they "probably will get one." Combined, 66.3% have received or intend to receive an influenza vaccination.

By comparison, 48.4% of adults 18 and older received the vaccine during the 2019-2020 flu season, according to the Centers for Disease Control and Prevention, an increase of 3.1 percentage points from 2018-2019.

The survey was led by professor Glen Nowak, director of UGA's Center for Health and Risk Communication in the Grady College of Journalism and Mass Communication, and associate professor Michael Cacciatore, CHRC research director. The respondents came from the National Opinion Research Center's AmeriSpeak panel, which uses a prescreened, nationally representative pool of participants to obtain rapid and projectable survey findings.

"Our survey shows that most Americans have or planned to act on the advice to get a flu vaccination this season," said Nowak. "Further, these results strongly suggest the U.S. will be crossing an important threshold this flu season, which is over half of U.S. adults getting a flu vaccination."

The survey results indicate much of the increase in flu vaccine uptake is being driven by people 60 years old and older. A total of 61.5% said they had already received the influenza vaccine in December, with another 12% stating they "would definitely get it" and 5.8% stating they "would probably get it."

Demographic differences

The survey results also indicated many demographic differences when it came to having received a flu vaccination. Forty-eight percent of white respondents reported having a flu vaccination by December, compared to 35.1% of Hispanic respondents and 30.1% of Black respondents. Having already received a flu vaccination was also much higher for respondents with a college or higher education and those with annual household incomes of $75,000 a year or more.

Conversely, flu vaccination uptake and plans to get a flu vaccination were lowest for those 18-29 years old, those with some college or a high school education, and those with annual incomes less than $25,000. The survey found that 50.7% of those making more than $75,000 had already been vaccinated for the flu, while only 35% of those making less than $25,000 had been vaccinated.

"It was disappointing to see that significant differences by race, age, education and income persisted during a flu vaccination season that took place during a COVID pandemic," Cacciatore said. "It's important that we continue to learn more about why these disparities exist so we can take steps that will reduce them."

"Overall, it is good news to find that many people, particularly those at highest risk for serious flu or COVID-19 illness, followed the advice to get the flu vaccine. Hopefully, we can sustain that level of success in the years ahead," Nowak said. "It also remains worrisome to find much lower flu vaccination rates and intentions in so many groups. We continue to have much work to do among Hispanic and Black adults and those with lower income and years of formal education when it comes to flu vaccination."

A new analysis of education debates on both social media and in traditional media outlets suggests that the education sector is being increasingly influenced by populism and the wider social media 'culture wars'.

The study also suggests that the type of populism in question is not quite the same as that used to explain large-scale political events, such as the UK's 'Brexit' from the European Union, or Donald Trump's recent presidency in the United States.

Instead, the researchers - from the University of Cambridge, UK, and Queensland University of Technology, Australia - identify a phenomenon called 'micropopulism': a localised populism which spotlights an aspect of public services, such as the education sector. Micropopulism is populist, they argue, in the sense that it expresses a fervent division between a disregarded 'people' and an unjust elite.

The paper, by Dr Steve Watson and Dr Naomi Barnes, sketches out how think tanks, among other organisations, propagate such controversies using both new media and old. They highlight how 'wedge' issues are being used to prompt bitter disputes on social media between those with traditional views of education, and those who are more progressive.

'Traditional' teachers, in this context, argue that their authority in the classroom has been undermined by a largely university-based and ideologically-progressive 'elite' which, they claim, has used its institutional power to force them to use student-centred teaching methods which are not supported by scientific evidence. The polarised debate that ensues disguises the complexity of real classrooms, which in practice can be neither purely traditional, nor purely progressive.

The authors argue that 'the claim that educational micropopulism is abroad in England and Australia is almost self-evident' and offer a theoretical analysis of how and why it is happening. As potential examples, they cite increasingly vitriolic and adversarial online standoffs over issues such as teaching methods, discipline, or free speech on university campuses. Many of these appear to be linked to, or directly involve, think thanks or other groups with an interest in shaping policy. The paper calls for more evidence-gathering to understand the conditions which precipitate increasingly bitter debates within the education community, and warns that some vested interests may be using micropopulist tactics to influence policy.

Dr Steve Watson, a lecturer at the Faculty of Education, University of Cambridge, said: "We've reached the stage where there is enough evidence to indicate this issue requires more analysis and attention than it has received to date. There is clearly a relationship between education, policy-making, think tanks, media, and micropopulism - but its extent and consequences have yet to be fully determined."

Dr Naomi Barnes, from the Faculty of Education, Queensland University of Technology, said: "One concern is that at present, teachers and educators who are actively involved in these online discussions may not be aware of how controversy is being perpetuated and how bitter discussions go viral to help achieve policy-making objectives. There is a need to understand this more."

The authors argue that controversies in the media and on social channels enable would-be reformers to position progressives in education (often abbreviated to 'progs') as an out-of-touch elite. Most obviously, this idea seems to match Michael Gove's infamous demonisation of progressive 'bureaucrats, academics and teachers' unions' as 'The Blob'. One reformist government advisor has similarly praised social media 'trads' for instigating 'a reformation of the church of education'.

They also suggest that this reductive version of the debate now defines many of the most toxic arguments about education online. Watson, in particular, identifies Twitter - especially the popular #EduTwitter - as the site of unpleasant confrontations about matters such as the #BanTheBooth debate on discipline in schools, or the use of phonics in primary education.

In higher education, the researchers document a similar pattern in which university leaders are demonised as lazy, careless, distant and heavy-handed. In Australia, this seems to parallel a recent upswing in efforts by the right-wing Institute of Public Affairs (IPA) and Centre for Independent Studies (CIS) to actively publicise their policy arguments as research 'findings'.

The paper highlights 10 recent examples of this activity, which prompted national media headlines such as: 'Our universities have caved in to lazy groupthink'; and 'Don't bail out bloated unis'. Similarly provocative articles are increasingly appearing in the UK media, concerning issues such as free speech on campus, or claims about infiltration by foreign governments.

Watson's own experiences suggest that some of the online confrontations, if not deliberately instigated, certainly involve strange forms of behaviour. Last year, he published a paper highlighting possible evidence of micropopulist strategies on #EduTwitter. Within hours, this had provoked multiple angry responses on Twitter accusing him of fabricating a conspiracy theory - although many teachers and academics also posted messages of agreement.

As a result, the paper scored unusually well on Altmetric.com: a tool that tracks engagement with scholarly content online. Once this became apparent, the Twitter attacks not only ceased, but disappeared, with several critics deleting their posts as if attempting to stifle its popularity. "Extraordinarily, the paper may have gone some way to proving its own theory through the backlash it created," Watson said.

The authors believe that, at the very least, further research is needed to understand how today's education debates have become so schismatic. They warn that reasoned discussion about the future of education is being compromised. "We would recommend considering a digital citizenship initiative for education professionals to counter this," Barnes added.