Culture

The structure of a biomolecule can reveal much about its functioning and interaction with the surrounding environment. The double-helical structure of DNA and its implications for the processes of transmission of genetic information form an obvious example. In a new study by SISSA - Scuola Internazionale Superiore di Studi Avanzati, published in Nucleic Acids Research, experimental data were combined with computer simulations of molecular dynamics to examine the conformation of an RNA fragment involved in protein synthesis and its dependence on the salts present in the solution. The research has led to a new method for high-resolution definition of the structures of biomolecules in their physiological environments.

"X-ray crystallography, as used to discover the double-helical conformation of DNA, remains one of the most common techniques for studying biomolecule structures", explains SISSA physicist Giovanni Bussi. "This technique allows us to reconstruct the image of the molecule in solid state crystalline form. However, this yields a static view of the structure that may not correspond to that assumed in the aqueous natural environment in which biomolecules are normally found."

This is why researchers began to use the small-angle X-ray scattering (SAXS) technique in the last decade to study RNA molecules, which can have highly dynamic structures. This method can be used directly in aqueous solutions that reproduce the physiological environment. Furthermore, the composition of the solutions can be modified to study how the molecules adapt to different conditions. Unfortunately, however, SAXS has limited resolution, in the order of a nanometer. Giovanni Bussi and Mattia Bernetti, a research fellow at SISSA, therefore decided to enhance SAXS via a 'computational microscope', combining it with molecular dynamics simulations that allow computerised reconstruction of molecular structures at the atomic level.

"We studied a fragment of ribosomal RNA involved in protein synthesis," explain the researchers. "We used SAXS data, derived from aqueous solutions containing different mixtures of salts, that was provided by Kathleen B. Hall of the Washington University School of Medicine in St Louis, and combined them with molecular dynamics simulations. By this means we discovered the existence of two distinct conformations: one more compact and functional to the protein synthesis process, the other more extended, confirming the dynamic nature of RNA. In particular, we noticed how the prevalence of one structure over the other varies with the salts dissolved in solution, further underlining the importance of studying these molecules in an environment as similar as possible to that of the cell."

Bernetti and Bussi conclude that the results of the study, published in Nucleic Acids Research, have significance beyond the specific case and indicate an innovative method offering two advantages: "In this work, we combined molecular dynamics simulations and SAXS experimental data to obtain high-resolution structures of RNA biomolecules. This is a useful approach in two senses: on one hand, it allows detail to be added to SAXS experimental data, which in fact give a very approximate view; on the other hand, it allows results of molecular dynamics to be corrected if the models used in the simulations are insufficiently accurate."

Coronavirus disruption to weddings has highlighted the complexity and antiquity of marriage law and reinforced the need for reform, a new study shows.

During the pandemic the ease and speed with which couples were able to marry has depended on their chosen route into marriage - religious or civil - experts have found.

Rules to prevent the spread of the pandemic attempted to strike a balance between getting married as a legal event and a wedding as a social event, and this has failed to please anyone, according to the research.

As lockdown loomed, couples marrying in the Anglican church were able to apply for a common or special licence rather than waiting to have their banns read. During the first lockdown alone, the Church of England's Faculty Office issued 104 special licences in order to enable the marriages of those who were terminally ill, or who had a close family member who was terminally ill, whereas it would normally issue only 40 for this purpose in a whole year. By contrast, the Registrar-General - who is responsible for civil weddings - issued fewer licences than usual for this purpose.

The research was carried out by Professor Rebecca Probert, from the University of Exeter, and Dr Stephanie Pywell, from The Open University. They surveyed 1,449 people whose plans to marry in England and Wales had been affected by COVID-19 during the first lockdown in summer 2020.

Of these, 625 had been unable to marry on their intended wedding date as it fell during the period of lockdown. Just 10 managed to bring the date forward and marry before the start of lockdown, while 615 had to postpone their plans. A further 793 couples had been planning to marry between the end of lockdown and the end of 2020 and had had to change their plans in some way.

The remainder had either been prompted to marry in England and Wales on account of COVID-19, or had decided to postpone their wedding indefinitely, were no longer planning to marry, or were unable to marry.

Dr Pywell said: "The limited number of venues in which couples can marry made it impossible for most couples to marry during the pandemic, although they were able to do so in some other countries. We argue that the laws governing marriage in England and Wales must be fit for purpose in the twenty-first century, so that couples can marry with relative ease if there is a similar nationwide crisis in the future."

The survey asked couples whether they would have wanted to marry in a virtual ceremony. One in 11 said they would have considered a wedding via video-link had this been available. Couples were also asked if they would have been willing to marry in a socially-distanced ceremony with the minimum number of persons present required by law for a valid marriage. One in nine would have been happy to do so outdoors, and one in seven would have considered doing so indoors if different households were separated by screens. Overall, one in five would have considered at least one of these options.

The researchers say all these options deserve serious consideration, and that legislation should be amended to make this option available during any future emergency.

Dr Pywell said: "For those couples who simply wanted to be married, having to wait until weddings were permitted to go ahead with 30 guests was particularly frustrating, especially since pubs, restaurants, and gyms had been able to open earlier. Allowing marriages to go ahead earlier, with the minimum number of persons required by law, would have mitigated some of their anger and upset."

Professor Probert said: "Reform is clearly needed, but any such reform has to be holistic rather than piecemeal, and we hope that our findings will strengthen the case for making weddings law simpler and more flexible for the future. The fact that for much of 2020 and for 2021 so far couples were either unable to marry, or unsure as to whether their planned wedding would go ahead, led many to reflect on just how important it was to them. A wedding should be available to couples at the best and worst of times."

LOUISVILLE, Ky. - A clinical trial conducted at the University of Louisville has shown for the first time that heart failure treatments using cells derived from the patient's own bone marrow and heart resulted in improved quality of life and reduced major adverse cardiac events for patients after one year.

"This is a very important advance in the field of cell therapy and in the management of heart failure. It suggests that a treatment, given only once, can produce long-term beneficial effects on the quality of life and prognosis of these patients," said Roberto Bolli, M.D., director of the UofL Institute of Molecular Cardiology, who led the study at UofL. "The results pave the way for a larger, Phase 3 trial of cell therapy in heart failure."

UofL led enrollment among seven institutions participating in CONCERT-HF, a Phase 2 clinical trial testing the safety, feasibility and efficacy of two types of adult cells, used alone and in combination, in patients with heart failure.

CONCERT-HF evaluated the use of two types of cells - autologous mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs) - alone or in combination, in patients with heart failure caused by chronic ischemic cardiomyopathy, a decrease in heart pumping effectiveness due to heart attacks and a lack of blood getting to the heart. Autologous MSCs are derived from the patient's bone marrow and CPCs are from the patient's heart tissue. Both are known as "autologous" cells because they come from the same patient in whom they are returned for the treatment.

In the study, patients treated with CPC cells alone had a significant reduction in major adverse cardiac events, particularly hospitalization. Patients treated with MSC cells alone and with a combination of both types of cells experienced significantly improved quality of life compared with patients who received no treatment. Quality of life was assessed using patient responses to the Minnesota Living with Heart Failure Questionnaire, which gauges the degree to which physical, emotional and socioeconomic effects of heart failure adversely affect the patient's life and the extent to which they prevented the patient from living as they wanted to live.

"The results of this trial show for the first time that cell therapy reduces hospitalization for heart failure and improves clinical outcome, providing a cogent rationale for undertaking a pivotal Phase 3 trial" that could be the next step on the pathway to FDA approval, Bolli said.

The results of the CCTRN CONCERT-HF Trial were published in the European Journal of Heart Failure. The Phase 2, randomized, placebo-controlled trial, funded by NIH National Heart, Lung and Blood Institute, was conducted by the Cardiovascular Cell Therapy Research Network (CCTRN), a network of clinical trial researchers involved in cell therapy for heart disease that includes UofL. UofL led enrollment in the study, accounting for 25% of the 125 trial participants.

Bolli's expertise and long career in successful cardiac research led to the establishment of the CCTRN center at UofL in 2011. This consortium of leading cardiovascular research organizations includes Stanford University, the University of Miami, Indiana University, the Texas Heart Institute, the University of Florida and the Minneapolis Heart Institute Foundation in addition to UofL. The School of Public Health at the University of Texas Health Science Center at Houston serves as the data coordinating center.

Bolli is a pioneer in research using adult stem cells for cardiac disease. Over the past two decades, he has shown that CPCs are beneficial in many preclinical models of heart failure, thus paving the way for the CONCERT-HF trial. He also led the recent CCTRN SENECA Trial - the first study to show safety and potential efficacy of cell therapy in cancer survivors with heart failure caused by anticancer therapy.

Does evolution explain why we can't resist a salty chip? Researchers at NC State University found that differences between the elemental composition of foods and the elemental needs of animals can explain the development of pleasing tastes like salty, umami and sweet.

Taste tells us a lot about foods before they are swallowed and digested, and some tastes correspond with the elemental composition of foods. For example, an aged steak lights up the umami taste receptors, because it has a high concentration of the element nitrogen, which occurs in amino acid molecules. Nitrogen is essential for survival, but often occurs in low concentrations relative to the demand by animals. Likewise, sodium is limited in many foods in nature - think of life before supermarkets. So if you need sodium to survive - and all animals do - you are more likely to have adapted a taste for, and seek out, salty foods.

"Nutritional imbalances, even at the elemental level, can limit the growth and metabolism of animals," says Lee Demi, a co-author of the study and postdoctoral researcher in NC State's Department of Applied Ecology. "We posited that animals should have evolved the ability to taste, and enjoy, certain elements and nutrients that are most likely to be limiting for growth, due to their low concentrations in typical foods."

To investigate this hypothesis, Demi and colleagues compared the body elemental composition of three animal groups (mammals, fish, and insects) to the elemental composition of plants, the base of most food webs. They predicted that animals who eat foods composed of particular elements that are rare or unpredictable are more likely to have taste receptors that reward them for finding those same elements.

"Because animals have very limited ability to change their elemental composition, the old adage that 'You are what you eat' doesn't really apply," says Demi. "Rather, animals are rewarded with pleasing tastes for 'eating what they are', at least from an elemental composition perspective, which helps reduce the prospect of dietary nutrient limitation."

This is particularly important for omnivorous and herbivorous animals that eat a variety of different foods which vary in nutritional quality. Within this framework, taste becomes a tool that helps consumers prioritize which foods they should search for and consume, so they don't waste time on foods that have less of these necessary elements. Equally, taste can also inform consumers to avoid foods that contain too much of an element they need. This is why eating a handful of chips is more attractive than eating a handful of table salt.

Where you are on the food chain can predict the complexity of your taste systems. Some top predators, like orcas, have lost many taste receptors over evolutionary time. This study suggests that predators are less likely to experience strong elemental imbalances in their diet than herbivores or omnivores. Because their prey already match their elemental needs, predators experience less selective pressure to maintain elaborate taste systems. However, these top predators have kept their taste for salt, which can be harmful if overconsumed.

"Affinity for certain foods must have strong evolutionary drivers, because without taste, animals would be forced to overconsume everything in the hopes of hitting the magic ratio of elements needed for growth and development," says Benjamin Reading, co-author of the study and a professor in NC State's Department of Applied Ecology. "They would need to eat way too much and end up excreting huge quantities of those things they need less of, which is not efficient."

The research team also found strong evidence of convergent taste evolution in mammals, fish, and insects. Each group, although far apart on the phylogenetic tree, all have adapted tastes that prioritize the same infrequent elements, including sodium, nitrogen and phosphorus.

"Phosphorus is particularly intriguing because this recently discovered taste is most strongly linked to phosphate, which is also the primary form of phosphorus in many nucleic acids, ATP, phospholipids, etc.," says Brad Taylor, a co-author of the study and professor in NC State's Department of Applied Ecology. "Phosphate is the most readily available form of phosphorus for uptake by plants, and often the primary growth limiting element in organisms and ecosystems. So, links between the elemental form, taste receptors, organismal needs, and ecosystem are really direct."

While the neurobiological process of taste has been extensively researched, this study is the first to explore taste as an evolutionary tool for optimal foraging. The researchers suggest that this may open a new area of thought on how taste can indicate how animals impact their environments through foraging, nutrient-cycling, and other core principles of ecology.

Syracuse, N.Y. - A study of nearly 550 adults with intellectual and developmental disabilities receiving residential services in New York City found that age, larger residential settings, Down syndrome and chronic kidney disease were the most common risk factors for COVID-19 diagnosis, and heart disease was most associated with COVID-19 deaths.

The study, "Risk Factors Associated With COVID-19 Outcomes Among People With Intellectual and Developmental Disabilities Receiving Residential Services," was published June 8 by JAMA Network Open and provided the first evidence of the risk factors leading to COVID-19 diagnosis and death among people with IDD who receive residential services.

The study's findings suggest that the risk factors for COVID-19 diagnosis and mortality for people with IDD who receive residential services are similar to the general population. It also provided more evidence of increased risk for severe COVID-19 outcomes for people with Down syndrome.

"The results from this study reinforce early findings from the U.K. of increased risk for people with Down syndrome during the pandemic," said researcher Scott Landes. "While it will take time for scientists to fully discern the reasons for this increased risk, it is imperative that people with Down syndrome, their families, care providers and medical providers are fully aware of this trend and take all necessary precautions during this time."

The researchers also found that, similar to the nursing home population, an increased number of residents with IDD living in a group home was associated with more severe COVID-19 outcomes.

"We are to a place in the U.S. where access to COVID-19 vaccines is universal," Landes said. "While this will help alleviate some of the spread of the virus, it is necessary to continue monitoring and testing, especially in congregate settings such as group homes.

"However, unlike nursing homes, group homes for people with IDD have not always been afforded the resources necessary to perform routine COVID-19 testing for residents and staff," Landes added. "This is unacceptable. The results from this study indicate that all U.S. states should ensure that group homes are provided the same level of protection as nursing homes or other congregate care settings."

The research team for the study includes Landes, an associate professor of sociology and a faculty associate for the Aging Studies Institute at Syracuse University's Maxwell School of Citizenship and Public Affairs; Dr. Margaret Turk, Distinguished Service Professor of Physical Medicine and Rehabilitation at SUNY Upstate Medical Center in Syracuse, N.Y.; Marco Damiani, Chief Executive Officer, AHRC New York City; Philip Proctor, Enterprise Technology Strategy, AHRC New York City; and Sarah Baier, Licensed Clinical Social Worker, AHRC New York City.

The researchers set out by asking which individual and residential characteristics were associated with COVID-19 outcomes for people with IDD who receive residential services. They tracked COVID-19 outcomes for 543 people with IDD who were receiving support services and residential services from AHRC New York City in the city's five boroughs from March 1 through Oct. 1, 2020.

The researchers found that, like the general population, people with IDD who were older and/or had pre-existing health conditions were more likely to be diagnosed with, and die from, COVID-19. Chronic kidney disease and COPD were associated with an increased risk of being diagnosed; heart disease and cancer were associated with increased risk of death.

The researchers say that all of these risk factors point to the long-term need for to provide sufficient funding for IDD services.

"If we want to ensure the best health and quality of life outcomes for people with IDD, it's imperative that states do not cut funding for IDD services," Landes said. "In fact, the pandemic has underscored the critical need to increase our commitment to IDD services, including guaranteeing public health prioritization for people with IDD, providing medical care staff training on how to provide quality care for people with IDD, and increasing the pay for care staff."

A discovery from researchers at the University of Illinois Chicago may lead to new treatments for individuals who suffer from alcohol use disorder and depression.

The study, "Transcriptomics identifies STAT3 as a key regulator of hippocampal gene expression and anhedonia during withdrawal from chronic alcohol exposure," is published in the journal Translational Psychiatry by researchers at UIC's Center for Alcohol Research in Epigenetics.

"During withdrawal from long-term alcohol use, people often suffer from depression, which may cause them to start drinking again as a way to self-medicate. If we can treat that aspect, we hope we can prevent people from relapsing," said Amy Lasek, UIC associate professor of psychiatry and anatomy and cell biology at the College of Medicine, and an author of the study.

Withdrawal from chronic alcohol drinking can often result in depression. For this study, researchers removed postmortem hippocampus samples of rats in alcohol withdrawal. The hippocampus is a brain region that plays a role in depression and cognitive function. Researchers conducted RNA sequencing of all the RNA transcripts in the hippocampus and looked for those that were changed during withdrawal from alcohol.

One of the RNA transcripts that was changed makes a protein called STAT3. STAT3 is a transcription factor that controls the expression of many different genes, including immune response genes. Notably, several known STAT3-regulated genes were also increased in the hippocampus during withdrawal from alcohol, indicating that STAT3 might be a "master regulator" of several genes in the hippocampus during withdrawal.

The rats were treated during withdrawal with a compound that blocks STAT3 activity. The rats' withdrawal-induced anhedonia, or inability to feel pleasure, was alleviated.

Additionally, researchers looked at the same genes in human postmortem hippocampus samples of individuals who had a medical diagnosis of alcohol use disorder, alcoholism. They found that STAT3 and its target genes were elevated in the postmortem hippocampus of human subjects who died without alcohol in their systems -- in withdrawal or abstinent from alcohol -- when compared to samples from control subjects who did not have alcohol use disorder. These results were strikingly similar to the results found in the rat study.

"The human and rat studies are similar, which might mean that our rat results can potentially be applied to humans. We haven't done any treatments of people with alcohol use disorder, but we can see from the rat data that if we block STAT3 during withdrawal we can alleviate depression," Lasek said.

Some genes regulated by STAT3 are involved in the innate immune response in the brain. There is a known connection between hyperactive immune response and major depressive disorder, Lasek said.

"We know that chronic alcohol use can induce an immune response in the brain. By inhibiting STAT3, we think that we are dampening that hyperactive immune response by blocking the ability of STAT3 to increase the expression of these immune-response genes during withdrawal, Lasek said.

Lasek said inflammation in the brain is currently a hot research topic and further research may determine if dampening the brain's inflammatory response could treat psychiatric disorders.

Antidepressants currently available are not effective in reducing alcohol drinking. And other drugs available to treat alcohol use disorder are not universally effective. Further study for a better understanding of how STAT3 works could hopefully lead to more effective interventions for alcohol use disorder and related depression, Lasek said.

The spin of the Milky Way's galactic bar, which is made up of billions of clustered stars, has slowed by about a quarter since its formation, according to a new study by researchers at University College London (UCL) and the University of Oxford.

For 30 years, astrophysicists have predicted such a slowdown, but this is the first time it has been measured.

The researchers say it gives a new type of insight into the nature of dark matter, which acts like a counterweight slowing the spin.

In the study, published in the Monthly Notices of the Royal Astronomical Society, researchers analysed Gaia space telescope observations of a large group of stars, the Hercules stream, which are in resonance with the bar - that is, they revolve around the galaxy at the same rate as the bar's spin.

These stars are gravitationally trapped by the spinning bar. The same phenomenon occurs with Jupiter's Trojan and Greek asteroids, which orbit Jupiter's Lagrange points (ahead and behind Jupiter). If the bar's spin slows down, these stars would be expected to move further out in the galaxy, keeping their orbital period matched to that of the bar's spin.

The researchers found that the stars in the stream carry a chemical fingerprint - they are richer in heavier elements (called metals in astronomy), proving that they have travelled away from the galactic centre, where stars and star-forming gas are about 10 times as rich in metals compared to the outer galaxy.

Using this data, the team inferred that the bar - made up of billions of stars and trillions of solar masses - had slowed down its spin by at least 24% since it first formed.

Co-author Dr Ralph Schoenrich (UCL Physics & Astronomy) said: "Astrophysicists have long suspected that the spinning bar at the centre of our galaxy is slowing down, but we have found the first evidence of this happening.

"The counterweight slowing this spin must be dark matter. Until now, we have only been able to infer dark matter by mapping the gravitational potential of galaxies and subtracting the contribution from visible matter.

"Our research provides a new type of measurement of dark matter - not of its gravitational energy, but of its inertial mass (the dynamical response), which slows the bar's spin."

Co-author and PhD student Rimpei Chiba, of the University of Oxford, said: "Our finding offers a fascinating perspective for constraining the nature of dark matter, as different models will change this inertial pull on the galactic bar.

"Our finding also poses a major problem for alternative gravity theories - as they lack dark matter in the halo, they predict no, or significantly too little slowing of the bar."

The Milky Way, like other galaxies, is thought to be embedded in a 'halo' of dark matter that extends well beyond its visible edge.

Dark matter is invisible and its nature is unknown, but its existence is inferred from galaxies behaving as if they were shrouded in significantly more mass than we can see. There is thought to be about five times as much dark matter in the Universe as ordinary, visible matter.

Alternative gravity theories such as modified Newtonian dynamics reject the idea of dark matter, instead seeking to explain discrepancies by tweaking Einstein's theory of general relativity.

The Milky Way is a barred spiral galaxy, with a thick bar of stars in the middle and spiral arms extending through the disc outside the bar. The bar rotates in the same direction as the galaxy.

An international team of researchers led by the University of Bonn (Germany) has identified the cause of a rare, severe muscle disease. According to these findings, a single spontaneously occurring mutation results in the muscle cells no longer being able to correctly break down defective proteins. As a result, the cells perish. The condition causes severe heart failure in children, accompanied by skeletal and respiratory muscle damage. Those affected rarely live beyond the age of 20. The study also highlights experimental approaches for potential treatment. Whether this hope will be fulfilled, however, will only become clear in a few years. The results are published in the journal Nature Communications.

Anyone who has ever snapped a spoke on their bike or broken down with their car knows that mechanical stresses sooner or later result in damage that needs to be repaired. This also applies to the human musculature. "With each movement, structural proteins are damaged and have to be replaced," explains adjunct professor Dr. Michael Hesse from the Institute of Physiology at the University of Bonn, who led the study together with his colleague Prof. Dr. Bernd Fleischmann.

The defective molecules are normally broken down in the cell and their components are then recycled. An important role in this complex process is played by a protein called BAG3. The results of the new study show how important this is: The researchers were able to demonstrate that a single change in the genetic blueprint of BAG3 results in a fatal disease.

"The mutation causes BAG3 to form insoluble complexes with partner proteins that grow larger and larger," Hesse says. This brings the repair processes to a standstill - the muscles become less and less efficient. Moreover, toxic levels of proteins accumulate over time, eventually resulting in the death of the muscle cell. "The consequences are usually first seen in the heart," Hesse says. "There, muscle is successively replaced by scar tissue. This causes the heart's elasticity to decrease until it can barely pump blood."

Affected individuals therefore usually require a heart transplant in childhood. Even this measure only provides temporary relief, as the disease also affects the skeletal and respiratory muscles. As a result, sufferers often die at a young age.

Very rare condition, therefore little research

The lethal mutation can arise spontaneously during embryo development. Fortunately, this is a very rare occurrence: There are probably only a few hundred affected children worldwide. However, due to its rarity, the disease has received little research attention to date. "Our study now takes us a great deal further," stresses Bernd Fleischmann.

This is because the researchers have succeeded for the first time in replicating the disease in mice and using the new animal model to identify its causes. This allows it to be researched better than before - also with regard to possible therapies. Maybe the effect of the mutation can at least be reduced. Humans have two versions of each gene, one from the mother and the other from the father. This means that even if one version of BAG3 mutates during embryo development, there is still a second gene that is intact.

Unfortunately, however, the defective BAG3 also clumps with its intact siblings. The mutation in one of the genes is therefore sufficient to stop the breakdown of the defective muscle proteins. However, if the mutated version could be eliminated, the repair should work again. It would also prevent the massive accumulation of proteins in the cell that eventually results in its death.

There are indeed methods to specifically inhibit the activity of individual genes. "We used one of them to treat the sick mice," explains Kathrin Graf-Riesen of the Institute of Physiology, who was responsible for most of the experiments along with Dr. Kenichi Kimura and her colleague Dr. Astrid Ooms. The animals treated in this way then showed significantly fewer symptoms. Whether this approach can be transferred to humans, however, remains the subject of further research.

Our ability to confront global crises, from pandemics to climate change, depends on how we interact and share information.

Social media and other forms of communication technology restructure these interactions in ways that have consequences. Unfortunately, we have little insight into whether these changes will bring about a healthy, sustainable and equitable world. As a result, researchers now say that the study of collective behavior must rise to a "crisis discipline," just like medicine, conservation and climate science have done, according to a new paper published June 14 in the Proceedings of the National Academy of Sciences.

"We have built and adopted technology that alters behavior at global scales without a theory of what will happen or a coherent strategy for reducing harm," said Joseph B. Bak-Coleman, the lead author and a post-doctoral researcher at the University of Washington's Center for an Informed Public.

Social media and other technological developments have radically reshaped the way that information flows on a global scale. These platforms are driven to maximize engagement and profitability, not to ensure sustainability or accurate information -- and the vulnerability of these systems to misinformation and disinformation poses a dire threat to health, peace, global climate and more.

No one, not even the platform creators themselves, have much understanding of how their design decisions impact human collective behavior, the authors argue.

"We urgently need to understand this and move forward with focus on developing social systems that promote well-being instead of creating shareholder value by commandeering our collective attention," said co-author Carl T. Bergstrom, a UW professor of biology and faculty at the Center for an Informed Public.

Collective behavior and other complex systems are fragile. "When perturbed, complex systems tend to exhibit finite resilience followed by catastrophic, sudden, and often irreversible changes," the authors write.

While there are studies and disciplines that focus on complex systems in the natural world, "we have a far poorer understanding of the functional consequences of recent large-scale changes to human collective behavior and decision making," the authors write.

Averting catastrophe in the medium term (e.g., coronavirus) and long term (e.g., climate change, food security) will require rapid and effective collective behavioral responses -- yet it remains unknown whether human social dynamics will yield such responses.

"We have seen individual studies about how climate-change disinformation gets over-represented even in the mainstream media, and studies that show that in digital media that problem only gets worse," said co-author Jennifer Jacquet, an associate professor of environmental studies at New York University.

Lacking a developed framework, tech companies have also fumbled their way through the ongoing coronavirus pandemic, unable to stem the "infodemic" of misinformation that impedes public acceptance of pandemic control measures such as wearing masks and widespread testing for the virus.

The situation parallels challenges faced in conservation biology and climate science, where insufficiently regulated industries optimize profits while undermining the stability of ecological and Earth systems.

"If we have a decade or so to act on climate change, we have far less time to sort out our social systems," Bak-Coleman said.

Historically collective behavior has best been understood as when animals or people exhibit coordinated action without an obvious leader. This includes how fish school to evade predators or when a crowd spontaneously breaks into applause or becomes silent.

That thinking has evolved over the past decade, the authors write, from a phenomena to a contemporary view of collective action as framework that reveals how interaction between individuals gives rise to collective action.

(Santa Barbara, Calif.) -- Scientists at UC Santa Barbara, University of Southern California (USC), and the biotechnology company Regenerative Patch Technologies LLC (RPT) have reported new methodology for preservation of RPT's stem cell-based therapy for age-related macular degeneration (AMD).

The new research, recently published in Scientific Reports, optimizes the conditions to cryopreserve, or freeze, an implant consisting of a single layer of ocular cells generated from human embryonic stem cells supported by a flexible scaffold about 3x6 mm in size. This implant is currently in clinical trial for the treatment of AMD, the leading cause of blindness in aging populations. The results demonstrate that the implant can be frozen, stored for long periods and distributed in frozen form to clinical sites where it is designed to be thawed and immediately implanted into the eyes of patients with macular degeneration. The capacity to cryopreserve this and other cell-based therapeutics will extend shelf life and enable on-demand distribution to distant clinical sites, increasing the number of patients able to benefit from such treatments.

The report published by lead author Britney Pennington and colleagues achieves a milestone that brings ocular implants one step closer to the clinic. "This is the first published report that demonstrates high viability and function of adherent ocular cells following cryopreservation, even after long-term frozen storage," said Pennington, head of process development at RPT and assistant project scientist at UC Santa Barbara.

The study demonstrates that cryopreserved implants are comparable to their non-cryopreserved counterparts in appearance, gene expression and cellular function. "It's a major advance in the development of cell therapies using a sheet of cells, or a monolayer of cells, because you can freeze them as the final product and ship them all over the world," said UCSB professor and senior author Dennis O. Clegg,

The implant used in the study consists of clinical-grade retinal pigmented epithelial (RPE) cells derived from human embryonic stem cells by collaborators at cancer hospital City of Hope, and a synthetic scaffold made of ultrathin parylene designed by engineers at California Institute of Technology and manufactured by LEAP Biomed Innovators. The resulting implant consists of cells attached to the scaffold, which permits the targeted delivery of therapeutic cells to the diseased region within the eye. A non-cryopreserved formulation of this cellular therapy is being employed in an ongoing Phase I/IIa clinical trial sponsored by RPT. The cryopreserved formulation enabled by the work of Pennington and colleagues will facilitate anticipated Phase IIb and Phase III clinical trials as well as ultimate commercialization and clinical application of the product.

A new study found higher education students are more engaged and motivated when they are taught using playful pedagogy rather than the traditional lecture-based method. The study was conducted by University of Colorado Denver counseling researcher Lisa Forbes and was published in the Journal of Teaching and Learning.

While many educators in higher education believe play is a method that is solely used for elementary education, Forbes argues that play is important in post-secondary education to enhance student learning outcomes.

Throughout the spring 2020 semester, Forbes observed students who were enrolled in three of her courses between the ages of 23-43. To introduce playful pedagogy, Forbes included games and play, not always tied to the content of that day's lesson, at the start of each class. She then provided many opportunities for role-play to practice counseling skills, and designed competitions within class activities.

During the study, students mentioned they saw more opportunities for growth while learning in a highly interactive environment. Students also described that the hands-on nature of learning through play established a means for skill acquisition, and they were able to retain the content more effectively.

"As we grow older, we're conditioned to believe that play is trivial, childish, and a waste of time," said Forbes. "This social script about play leads to it being excluded from higher education. A more interactive learning approach leads to a deeper and more rigorous connection to the material."

To maintain what Forbes described as "rigor" within higher education, the most common approach tends to be lecture-based learning. However, according to Forbes, this mode of education is counter to the very outcomes educators set out to achieve.

The results of the study suggest there is a unique and powerful classroom experience when play is valued and used in the learning process. According to Forbes, students who participated in this study also indicated that play increased positive emotions and connections with other students and the professor in the course.

"I also saw that when I introduced play, it helped students let their guard down and allowed them to reduce their stress, fear, or anxiety," said Forbes. "Play even motivated students to be vulnerably engaged, take risks, and feel more connected to the content."

Play is underutilized and devalued in higher education, according to Forbes. She suggests educators reevaluate their understanding of using play in graduate courses. Playful pedagogy creates an interactive and warm learning environment, resulting in greater understanding of the material. This method is also more aligned with the humanistic missions and values of universities and programs.

DARIEN, IL - More veterans are receiving important sleep care, especially those living in rural areas where access to sleep medicine specialists can be difficult. The Veterans Health Administration's TeleSleep Program launched telehealth services in 2017 to support the testing, diagnosis, and treatment of obstructive sleep apnea and other sleep disorders. More than one million veterans who received care from VHA in 2020 have sleep apnea.

"The implementation of these services has been very successful," said Dr. Kathleen Sarmiento, program lead for the Office of Rural Health TeleSleep Program and national lead for VHA TeleSleep. Sarmiento is also the director of a new regional VA TeleSleep program covering northern California, Nevada, and Hawai'i Pacific Islands, based out of the San Francisco VA Health Care System, modeled off best practices from the ORH program but focused on reaching both urban and rural veterans. She is an associate professor of medicine at the University of California, San Francisco. "The reach of this network is impressive, with 8% of VA's health care systems (hubs within this network) providing care to 18% of all rural Veterans seen for sleep care nationally."

A new study from VHA's Office of Rural Health (ORH) TeleSleep Program evaluated the expansion of telemedicine, home sleep apnea testing and remote sleep apnea management for veterans at 12 hubs and 63 spokes across the country. From 2017 to 2020, the number of rural veterans seen for sleep-related disorders at TeleSleep sites tripled and the number of encounters for sleep-related disorders more than doubled. In 2020, 72% of rural veterans at the TeleSleep hubs or spokes had at least one virtual sleep visit. This was significantly higher than non-TeleSleep VA sites where only 64% of rural Veterans had virtual visits.

"These results are very impactful as they demonstrate how funding a network of programs who share the same mission and purpose can result in significant return on investment for an organization like VA. This program was one of the first enterprise-wide initiatives funded through VA's Office of Rural Health and has also been one of the most successful in terms of reach," said Sarmiento.

Red seaweeds have been prevalent in the diets of Asian communities for thousands of years. In a new study, published in Marine Drugs, researchers have shown how these algae confer health benefits.

"In the past, people have wondered why the number of colon cancer patients in Japan is the lowest in the world," said Yong-Su Jin (CABBI/BSD/MME), a professor of food microbiology. "Many assumed that it was due to some aspect of the Japanese diet or lifestyle. We wanted to ask whether their seaweed diet was connected to the lower frequency of colon cancer."

Although several studies have shown that Asians who eat seaweed regularly have lower risk of colon, colorectal, and breast cancer, it was unclear which component was responsible for the anti-cancer effects.

In the study, the researchers broke down the structure of different types of red seaweed using enzymes and tested the sugars that were produced to see which one of them caused health benefits. Among the six different sugars produced, agarotriose and 3,6-anhydro-L-galactose, or AHG, showed the most promise.

"After we produced these sugars, we tested their prebiotic activity using the bacteria Bifidobacterium longum ssp. infantis," said Eun Ju Yun, a former postdoctoral researcher at the Carl R. Woese Institute for Genomic Biology. B. infantis is a probiotic bacterium; it colonizes the gut of infants and provides health benefits. Among the seaweed-derived sugars, the bacteria could only consume agarotriose, indicating that it works as a prebiotic i.e., it improves the growth of probiotic bacteria.

"We also tested another strain, B. kashiwanohense, and found that it also consumed agarotriose," Jin said. "These results show us that when we eat red seaweed, it gets broken down in the gut and releases these sugars which serve as food for the probiotic bacteria. It could help explain why Japanese populations are healthier compared to others."

The researchers also tested the sugars to see if they had any anti-cancer activity. "We found that AHG specifically inhibits the growth of human colon cancer cells and does not affect the growth of normal cells," Yun said. The anti-cancer activity of AHG is due to its ability to trigger apoptosis or cell death.

"There is a lot of information on how red seaweeds are degraded by microorganisms in the ocean and in the human body," said Kyoung Heon Kim, a professor of biotechnology and the co-advisor on the paper. "Our work explains why red seaweeds are beneficial by providing the molecular mechanism. We will continue studying their function in animal models and hopefully we will be able to use them as a therapeutic agent in the future."

HOUSTON - (June 14, 2021) - In the two decades since the Human Genome Project mapped the entire human genome, improvements in technology have helped in developing updated reference genomes used for sequencing. But while the GRCh38 (hg38) human reference genome was released more than seven years ago, the older GRCh37 (hg19) reference remains widely used by most research and clinical laboratories. In a new study published in the American Journal of Human Genetics, researchers at the Human Genome Sequencing Center at Baylor College of Medicine identify genetic variant discrepancies between the two references, creating guidance for laboratories to take advantage of an improved human reference genome.

"There's a big push to update genomic sequencing resources to use the hg38 reference because the belief is that hg38 is a significant improvement over hg19," said Moez Dawood, co-first author of the study and student in the Medical Scientist Training Program at Baylor. "We wanted to identify the differences in sequencing readouts between the two references for labs that are still using hg19."

The Baylor researchers analyzed exome sequencing samples from more than 1,500 participants in the Baylor-Hopkins Center for Mendelian Genomics program. They found 206 genes with discordant variants between hg19 and hg38, including eight genes implicated in Mendelian diseases and 53 associated with common disease phenotypes. They found 73% of the discordant variants were clustered within sections of the genome with known assembly problems that the researchers called DISCordant Reference Patches (DISCREPs).

"This study isn't a theoretical comparison of the two references; we looked at exome data from study participants and examined the impact of using the updated reference on Mendelian genes and pathogenic variants," said Dr. Aniko Sabo, a senior author of the study and assistant professor at the Human Genome Sequencing Center. "We wanted to provide the list of 206 genes enriched with discordant variants and bring this issue to the attention of the labs working on these genes."

"For variant interpretation in the 206 genes enriched for discordant variants, reference assembly differences should be accounted for in the analysis, especially when lifting over variant coordinates from one reference to the other," said Dr. He Li, co-first author of the study and a postdoctoral associate at Baylor at the time of research.

Transitioning from using the hg19 reference to the hg38 reference takes significant time and resources. Through this large-scale study of sequencing data, the researchers aim to ease the burden on labs considering the transition. The study quantifies the benefits and drawbacks of the new reference and validates its utility in a lab setting.

"It's one thing to make a better reference. It's quite another to integrate it into useful practice," said Dr. Richard Gibbs, senior author of the study, director of the Human Genome Sequencing Center and Wofford Cain Chair and Professor of Molecular and Human Genetics at Baylor. "Some labs have been hesitant to use the new reference, but this study provides reassurance and guidance for those who are considering moving over."

HOUSTON - (June 14, 2021) - Osteogenesis imperfecta (OI) is the most common genetic form of brittle bone disease and results in defects of both bone and connective tissue. OI patients can have significant problems with mobility due to joint dysfunction due in part to tendinopathy. In a new study published in the journal Proceedings of the National Academy of Sciences, researchers at Baylor College of Medicine identify a protein signaling mechanism driving this dysfunction and find that inhibiting this signaling pathway can prevent onset of tendinopathy problems in mouse models.

The researchers studied mouse models of OI in which the Fkpb10 gene was deleted in tendons and ligaments. The mice developed contracture, a condition in which the tendons harden, leading to joint rigidity and limited motion. As a result of the Fkpb10 gene deletion, researchers also observed inflammation in the joints and localized formation of cartilage pieces in the tendon, both symptoms of chronic tendinopathy. These symptoms coincided with the increased expression of a gene that impacts cell differentiation.

"We discovered an important signaling protein called Hedgehog, which is key in controlling the formation on cartilage, had been activated in the joints," said Dr. Brendan Lee, corresponding author of the study and Robert and Janice McNair Endowed Chair in Molecular and Human Genetics and professor and chair of the Department of Molecular and Human Genetics at Baylor.

The team, led by Lee and first author and postdoctoral associate in the Lee Lab, Dr. Joohyun Lim, wanted to see if genetic and drug inhibition of the Hedgehog signaling pathway could prevent the onset of symptoms of tendinopathy.

"By giving an FDA-approved Hedgehog signaling inhibitor, we delayed contracture and tendon degeneration and normalized joint function," said Lee, director of the Center for Skeletal Medicine and Biology at Baylor and co-director of the Rolanette and Berdon Lawrence Bone Disease Program of Texas. "We believe this could be a model for treating tendinopathy, not only in OI patients, but perhaps also in the general population."

In the future, the researchers will also work to determine if targeting inflammatory pathways as well as Hedgehog signaling can further prevent tendinopathy.