Culture

Among the African countries, South Africa has significantly high prevalence rate of overweight and obesity, especially, among women, courtesy certain factors such as nutrition transition and socio-demographic factors. Currently, there is little information about the socio-demographic determinants of overweight/obesity, especially in the rural settings.

Dr. Perpetua Modjadji, serving in School of Health Care Sciences, Department of Public Health, Sefako Makgatho Health Sciences University, South Africa, conducted research to identify and assess the socio-demographic determinants of overweight and obesity among mothers of primary school children living in a rural Dikgale Health and Demographic Surveillance System Site in South Africa. Interviewer-administered questionnaire was used to determine the socio-demographic factors.

The researcher concluded that socio-demographic and economic factors such as the decision-making authority of the spouse, income level and number of children have an impact on the health of women in South Africa in terms of the incidents of overweight and obesity. They recommend evidence based measures to address these factors in case policy makers wish to tackle the obesity epidemic among the female population specific to the region.

This article is open access (free-to-access). To download the article, please visit: https://benthamopen.com/ABSTRACT/TOPHJ-13-518

In the middle of the pandemic this spring, researchers at the Norwegian University of Science and Technology (NTNU) conducted a survey among members of Kondis, a Norwegian fitness training organization.

Since this survey was sent out in the middle of the lockdown in Norway, participants were asked whether they had changed their exercise habits as a result of the COVID-19 pandemic.

The aim of these initial analyses was to map mental health and sleep problems, and to investigate whether changes in exercise habits had consequences for sleep.

"Not surprisingly, we found that the incidence of anxiety and depression was significantly lower in this relatively fit sample than among other people. And this was the case despite the fact that we conducted the survey in the middle of the toughest part of the COVID time," says associate professor Linda Ernstsen from NTNU's Department of Public Health and Nursing.

These findings come as little surprise to the researchers. The connection between physical and mental health has been known for a long time, not least through the 240 000 people who have participated in a series of health studies starting in 1984 called the HUNT Surveys.

But the new study still offers some surprises, especially related to the fact that a lot of people changed their exercise habits this spring.

Ernstsen carried out the study together with project manager and associate professor Audun Havnen from NTNU's Department of Psychology.

"It was surprising that so many people increased their amount of exercise during the coronavirus pandemic. Since people were encouraged to avoid public spaces and stay home, the fact that so many used the extra time they had to move more was a positive effect," says Havnen.

This survey is the first of three to be conducted among Kondis members. The overall goal of the questionnaires is to study the relationship between different aspects of physical activity, mental health and quality of life in a sample assumed to be fit, and how this changes over time.

Although active people generally suffer less depression and anxiety than others, some of them still do get depressed and anxious.

When COVID-19 struck this spring, many Kondis members modified their training habits, regardless of whether they were struggling with mental health problems or not. You would think that this change would affect their quality of sleep as well. But that didn't happen.

"We thought the connection between mental health and sleep problems would be more pronounced in people who changed how much they exercised. But we found no differences," says Ernstsen.

The two groups were thus affected in exactly the same way, regardless of changes in their exercise habits.

This doesn't mean that there is no connection between mental health and sleep, even in this active group.

"We found a connection between anxiety symptoms and sleep problems and a connection between depressive symptoms and sleep problems," Ernstsen says.

People with depression and anxiety consistently sleep less well than others. This is true for the most physically fit among us as well.

"Since all the participants answered the questions at the same time this spring, so far we only know that there's a connection between physical activity, mental health and sleep. To investigate what leads to what, we've invited the participants to take the survey again after six and twelve months to study changes over time," says Havnen.

Upon a heart infarct or stroke, rapid restoration of blood flow, and oxygen delivery to the hypo perfused regions is of eminent importance to prevent further damage to heart or brain. Arterial diameter is a critical determinant of blood flow conductance. Scientists of the Karlsruhe Institute of Technology (KIT) have now discovered a novel mechanism to structurally increase arterial diameter by selectively increasing the size of arterial endothelial cells, thereby allowing rapid increases in flow. The team has published their results in Nature Communications (DOI: 10.1038/s41467-020-19008-0).

Research team leader Professor Ferdinand le Noble of the Department of Cell and Developmental Biology at the KIT explains that the prevalence of complex vascular disease is steadily rising and it is especially this patient population that will benefit from adjunct therapy to conventional revascularization methods. Unfortunately, many recent clinical therapeutic vascular growth trials failed, thus emphasizing the need for a more rational approach to this important area of clinical cardiovascular medicine, le Noble explains.

His research team now identified a novel mechanism to improve arteriogenesis involving enlargement of the endothelial cells lining the arteries. Larger endothelial cells allow a structural increase of arterial diameter in developing vascular networks. "This is important, as already small increases in arterial diameter considerably augment flow conductance, a simple physical principle," le Noble explains.

The process of cell enlargement is coordinated by a molecule called Trio. Trio is located inside the endothelial cell and plays a pivotal role in determining endothelial shape. Trio does this by selectively activating specific molecules, so called small Rho GTPases, that affect the structure and rigidity of the endothelial cytoskeleton in the cell periphery. The authors show that Trio can be activated selectively in developing arteries by precisely titrating Vegf signaling strength in the arterial wall. This is achieved by targeting soluble Vegf receptor Flt1, a decoy receptor for the growth factor VEGF. Endothelial cell enlargement is a fast process, independent of shear stress or inflammatory processes and within several hours results in 2-3 fold structurally larger arterioles that can attract flow to hypoperfused regions. Due to the rapid nature of this process, the authors believe that this approach has significant advantages over the (relatively slow) conventional angiogenesis approaches aimed at improving vessel number.

"We hope that our research can contribute to improving the treatment of ischemic cardiovascular diseases" le Noble says. "Our data derived from experimental models and human endothelial cells suggest that Trio is an interesting therapeutic target, and together with our collaboration partners, we envision to extend our work to pre-clinical models."

Researchers from Erasmus University, The Ohio State University, York University, and London Business School published a new paper in the Journal of Marketing that examines the tension between AI's benefits and costs and then offers recommendations to guide managers and scholars investigating these challenges.

The study, forthcoming in the Journal of Marketing, is titled "Consumers and Artificial Intelligence: An Experiential Perspective" and is authored by Stefano Puntoni, Rebecca Walker Reczek, Markus Giesler, and Simona Botti.

Not long ago, artificial intelligence (AI) was the stuff of science fiction. Now it is changing how consumers eat, sleep, work, play, and even date. Consumers can interact with AI throughout the day, from Fitbit's fitness tracker and Alibaba's Tmall Genie smart speaker to Google Photo's editing suggestions and Spotify's music playlists. Given the growing ubiquity of AI in consumers' lives, marketers operate in organizations with a culture increasingly shaped by computer science. Software developers' objective of creating technical excellence, however, may not naturally align with marketers' objective of creating valued consumer experiences. For example, computer scientists often characterize algorithms as neutral tools evaluated on efficiency and accuracy, an approach that may overlook the social and individual complexities of the contexts in which AI is increasingly deployed. Thus, whereas AI can improve consumers' lives in very concrete and relevant ways, a failure to incorporate behavioral insight into technological developments may undermine consumers' experiences with AI.

This article seeks to bridge these two perspectives. On one hand, the researchers acknowledge the benefits that AI can provide to consumers. On the other hand, they build on and integrate sociological and psychological scholarship to examine the costs consumers can experience in their interactions with AI. As Puntoni explains, "A key problem with optimistic celebrations that view AI's alleged accuracy and efficiency as automatic promoters of democracy and human inclusion is their tendency to efface intersectional complexities."

The article begins by presenting a framework that conceptualizes AI as an ecosystem with four capabilities: data capture, classification, delegation, and social. It focuses on the consumer experience of these capabilities, including the tensions felt. Reczek adds, "To articulate a customer-centric view of AI, we move attention away from the technology toward how the AI capabilities are experienced by consumers. Consumer experience relates to the interactions between the consumer and the company during the customer journey and encompasses multiple dimensions: emotional, cognitive, behavioral, sensorial, and social."

The researchers then discuss the experience of these tensions at a macro level, by exposing relevant and often explosive narratives in the sociological context, and at the micro level, by illustrating them with real-life examples grounded in relevant psychological literature. Using these insights, the researchers provide marketers with recommendations regarding how to learn about and manage the tensions. Paralleling the joint emphasis on social and individual responses, they outline both the organizational learning in which firms should engage to lead the deployment of consumer AI and concrete steps to design improved consumer AI experiences. The article closes with a research agenda that cuts across the four consumer experiences and ideas for how researchers might contribute new knowledge on this important topic.

CORVALLIS, Ore. - Corals that appear healthy are more prone to getting sick when they're home to too many parasitic bacteria, new research at Oregon State University shows.

Supported by the National Science Foundation, the study, published in Environmental Microbiology, adds fresh insight to the fight to save the Earth's embattled coral reefs, particularly those in the Caribbean.

"The clear relationship we've discovered between this kind of bacteria and disease resistance in Caribbean staghorn coral is a crucial piece of the puzzle for coral restoration efforts in that region," said study co-author Becca Maher, a Ph.D. candidate at Oregon State.

Found in less than 1% of the ocean but home to nearly one-quarter of all known marine species, coral reefs help regulate the sea's carbon dioxide levels and are a crucial hunting ground that scientists use in the search for new medicines.

Between 2014 and 2017, more than 75% of the world's reefs experienced bleaching-level heat stress, and 30% suffered mortality-level stress. Bleaching refers to the breakdown of the symbiotic relationship between corals and the algae they rely on for energy.

A complex composition of dinoflagellates, viruses, fungi, bacteria and archaea make up the coral microbiome, and shifts in microbiome composition are connected to changes in coral health.

In 2019, scientists in the lab of OSU microbiologist Rebecca Vega Thurber identified a new genus of parasitic bacteria that flourishes when reefs become polluted with nutrients, siphoning energy from the corals and making them more susceptible to disease.

The bacteria are in the order Rickettsiales, and the new genus is associated primarily with aquatic organisms. Scientists named the genus Candidatus Aquarickettsia and the coral-associated species in the 2019 study, Candidatus A. rohweri, was the first in the new genus to have its genome completely sequenced.

Since their first appearance 425 million years ago, corals have branched into more than 1,500 species, including the one at the center of this research: the critically endangered Acropora cervicornis, commonly known as the Caribbean staghorn coral.

"The bacterial genus we've identified is found around the world and in multiple types of corals, but is most notably found in high abundance in the microbiomes of Caribbean staghorn coral," said study co-author Grace Klinges, also a Ph.D. candidate in the Vega Thurber lab. "Now we've uncovered significant evidence that a high abundance of Ca. Aquarickettsia is a marker of disease susceptibility in corals that otherwise seem healthy."

Disease-resistant corals were found to host a much more even mix of many types of bacteria, she said. Additionally, as corals experienced heat stress from a warming ocean, the microbiome dominance of Ca. Aquarickettsia eroded.

"That's apparently because the bacteria rely on host nutritional resources that become scarce during periods of stress," Vega Thurber said. "And then the sudden loss of a dominant community member frees up niche space and creates openings for opportunistic pathogens to proliferate and sicken the coral."

Erinn Muller of the Mote Marine Laboratory in Sarasota, Florida, led the study.

To build the machinery that enables bacteria to swim, over 50 proteins have to be assembled according to a logic and well-defined order to form the flagellum, the cellular equivalent of an offshore engine of a boat. To be functional, the flagellum is assembled piece by piece, ending with the helix called flagellar filament, composed of six different subunits called flagellins. Microbiologists from the University of Geneva (UNIGE) have demonstrated that adding sugar to the flagellins is crucial for the flagellum's assembly and functionality. This glycosylation is carried out by a newly discovered enzyme FlmG, whose role was hitherto unknown. Based on this observation - which you can read all about in the journal eLife - the researchers followed up with a second discovery published in Developmental Cell. Among the six flagellins of Caulobacter crescentus, the model bacterium in the two studies, one is the special one serving a signalling role to trigger the final assembly of the flagellum.

The flagellum is the locomotive engine of bacteria. Thanks to the flagellum, bacteria can swim towards food whether in the lake Geneva (Léman) or inside the host during an infection. The flagellum - which, due to its complexity, is similar to an offshore engine - is made up of a basic structure, a rotary motor and a helical propeller. It is synthesized inside the bacteria in their cytosol. "The 50 proteins must be produced sequentially and assembled in the right order", begins Patrick Viollier, a researcher in UNIGE's Department of Microbiology and Molecular Medicine. At the same time the flagellum must be embedded within the bacterial envelope that contains up to three cell layers before ending up on the outside. While the flagellar subunits are known many of the subtleties in flagellar assembly control and targeting mechanisms are still poorly understood.

Sweet suprise

The UNIGE microbiologists studied the bacterium Caulobacter crescentus. &laquoThese bacteria are very interesting for studying flagella since they produce two different daughter cells: one has a flagellum and the other doesn't. They're ideal for understanding what is needed for building a flagellum ", explains Nicolas Kint, co-author of the study. Another peculiarity is that the flagellar filament of this bacterium is an assembly consisting of six flagellin sub-units, meaning it isn't the result of the polymerisation of a single protein, as is the case for many other bacteria. "When analysing these six flagellins, we discovered they were decorated with sugars, indicating that a glycosylation step - an enzymatic reaction adding sugars to proteins - was taking place and was needed for assembly. It was a surprising discovery, since this reaction is not very common and not well understood in bacteria," continues Professor Viollier.

Viollier's research team succeeded in demonstrating that the glycosylation of the six flagellins that make up the filament is essential for the formation and functionality of the flagellum. "To demonstrate this, we first identified the gene that produces the glycosylation enzyme, FlmG. When it's absent, it results in bacteria without flagellum. Secondly, we genetically modified another type of bacterium, Escherichia coli, to express one of the six flagellins, the glycosylation enzyme and sugar producing enzymes from Caulobacter crescentus. All these elements are required to obtain a modified flagellin", adds Nicolas Kint.

A versatile black sheep

"The different elements of the flagellum are produced one after the other: the molecules of the base first, then those of the rotor and finally the propeller. The scientific literature indicates that this sequential process is important. However, we don't know how the order of manufacturing the sub-units is controlled ." The researcher and his team focused on the synthesis of the six flagellins, discovering a black sheep among them: a sub-unit that has only 50% sequence homology with the other five. "This sub-unit serves as become a checkpoint protein, a repressive molecular traffic cop restraining the synthesis of the other flagellin proteins," says Professor Viollier. It is present before the synthesis of the other five sub-units, and it acts as a negative regulator. As long as it is present in the cytosol, the synthesis of the other sub-units is prevented. Once the elements of the flagellum are assembled, apart from the filament, the cop is exported to the membrane and thus removed. Then the synthesis of the last five sub-units can then begin. "It is a sensor for the protein synthesis and a component of the flagellar filament at the same time: a dual function that is unique of its kind," says the microbiologist with great enthusiasm.

This discovery is fundamental for understanding the motility of bacteria and the assembly of proteins. "It also provides clues for understanding the synthesis and assembly of tubulin, an essential part of the cytoskeleton", concludes Professor Viollier.

Massive galaxies were already much more mature in the early universe than previously expected. This was shown by an international team of astronomers who studied 118 distant galaxies with the Atacama Large Millimeter/submillimeter Array (ALMA).

Most galaxies formed when the universe was still very young. Our own galaxy, for example, likely started forming 13.6 billion years ago, in our 13.8 billion-year-old universe. When the universe was only ten percent of its current age (1-1.5 billion years after the Big Bang), most of the galaxies experienced a "growth spurt". During this time, they built up most of their stellar mass and other properties, such as dust, heavy element content, and spiral-disk shapes, that we see in today's galaxies. Therefore, if we want to learn how galaxies like our Milky Way formed, it is important to study this epoch.

In a survey called ALPINE (the ALMA Large Program to Investigate C+ at Early Times), an international team of astronomers studied 118 galaxies experiencing such a "growth spurt" in the early universe. "To our surprise, many of them were much more mature than we had expected," said Andreas Faisst of the Infrared Processing and Analysis Center (IPAC) at the California Institute of Technology (Caltech).

Galaxies are considered more "mature" than "primordial" when they contain a significant amount of dust and heavy elements. "We didn't expect to see so much dust and heavy elements in these distant galaxies," said Faisst. Dust and heavy elements (defined by astronomers as all elements heavier than hydrogen and helium) are considered to be a by-product of dying stars. But galaxies in the early universe have not had much time to build stars yet, so astronomers don't expect to see much dust or heavy elements there either.

"From previous studies, we understood that such young galaxies are dust-poor," said Daniel Schaerer of the University of Geneva in Switzerland. "However, we find around 20 percent of the galaxies that assembled during this early epoch are already very dusty and a significant fraction of the ultraviolet light from newborn stars is already hidden by this dust," he added.

Many of the galaxies were also considered to be relatively grown-up because they showed a diversity in their structures, including the first signs of rotationally supported disks - which may later lead to galaxies with a spiral structure as is observed in galaxies such as our Milky Way. Astronomers generally expect that galaxies in the early universe look like train wrecks because they often collide. "We see many galaxies that are colliding, but we also see a number of them rotating in an orderly fashion with no signs of collisions," said John Silverman of the Kavli Institute for the Physics and Mathematics of the Universe in Japan.

ALMA has spotted very distant galaxies before, such as MAMBO-9 (a very dusty galaxy) and the Wolfe Disk (a galaxy with a rotating disk). But it was hard to say whether these discoveries were unique, or whether there were more galaxies like them out there. ALPINE is the first survey that enabled astronomers to study a significant number of galaxies in the early universe, and it shows that they might evolve faster than expected. But the scientists don't yet understand how these galaxies grew up so fast, and why some of them already have rotating disks.

Observations from ALMA were crucial for this research because the radio telescope can see the star formation that is hidden by dust and trace the motion of gas emitted from star-forming regions. Surveys of galaxies in the early universe commonly use optical and infrared telescopes. These allow the measurement of the unobscured star formation and stellar masses. However, these telescopes have difficulties measuring dust obscured regions, where stars form, or the motions of gas in these galaxies. And sometimes they don't see a galaxy at all. "With ALMA we discovered a few distant galaxies for the first time. We call these Hubble-dark as they could not be detected even with the Hubble telescope," said Lin Yan of Caltech.

To learn more about distant galaxies, the astronomers want to point ALMA at individual galaxies for a longer time. "We want to see exactly where the dust is and how the gas moves around. We also want to compare the dusty galaxies to others at the same distance and figure out if there might be something special about their environments," added Paolo Cassata of the University of Padua in Italy, formerly at the Universidad de Valparaíso in Chile.

ALPINE is the first and largest multi-wavelength survey of galaxies in the early universe. For a large sample of galaxies the team collected measurements in the optical (including Subaru, VISTA, Hubble, Keck and VLT), infrared (Spitzer), and radio (ALMA). Multi-wavelength studies are needed to get the full picture of how galaxies are built up. "Such a large and complex survey is only possible thanks to the collaboration between multiple institutes across the globe," said Matthieu Béthermin of the Laboratoire d'Astrophysique de Marseille in France.

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. The authors of this study aimed to determine human exposure to LHQW components. Based on the human exposure analysis, several ACE2 binding components with good enzyme inhibitory effects were screened out by ACE2 biochromatography. The results obtained by the authors demonstrated chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to humans.

The research also demonstrated the utility of the human exposure-based approach to identifying pharmaceutically active components in Chinese herb medicines.

COLUMBUS, Ohio - New research shows that when vampire bats feel sick, they socially distance themselves from groupmates in their roost - no public health guidance required.

The researchers gave wild vampire bats a substance that activated their immune system and made them feel sick for several hours, and then returned the bats to their roost. A control group of bats received a placebo.

Data on the behavior of these bats was transmitted to scientists by custom-made "backpack" computers that were glued to the animals' backs, recording the vampire bats' social encounters.

Compared to control bats in their hollow-tree home, sick bats interacted with fewer bats, spent less time near others and were overall less interactive with individuals that were well-connected with others in the roost.

Healthy bats were also less likely to associate with a sick bat, the data showed.

"Social distancing during the COVID-19 pandemic, when we feel fine, doesn't feel particularly normal. But when we're sick, it's common to withdraw a bit and stay in bed longer because we're exhausted. And that means we're likely to have fewer social encounters," said Simon Ripperger, co-lead author of the study and a postdoctoral researcher in evolution, ecology and organismal biology at The Ohio State University.

"That's the same thing we were observing in this study: In the wild, vampire bats - which are highly social animals - keep their distance when they're sick or living with sick groupmates. And it can be expected that they reduce the spread of disease as a result."

The study was published today (Oct. 27, 2020) in the journal Behavioral Ecology.

Ripperger works in the lab of co-lead author Gerald Carter, assistant professor of evolution, ecology and organismal biology at Ohio State. The two scientists and their co-author on this paper, University of Texas at Austin graduate student Sebastian Stockmaier, are also affiliated with the Smithsonian Tropical Research Institute in Panama.

Carter and Ripperger have partnered on numerous studies of social behavior in vampire bats. Among their previous findings: Vampire bats make friends through a gradual buildup of trust, and vampire bat moms maintained social connections to their offspring even when both felt sick.

For this work, the researchers captured 31 female common vampire bats living inside a hollow tree in Lamanai, Belize. They injected 16 bats with the molecule that induced the immune challenge - but did not cause disease - and 15 with saline, a placebo.

After returning the bats to their roost, the scientists analyzed social behaviors in the colony over three days, including a "treatment period" from three to nine hours after the injections during which the researchers attributed behavior changes to the effects of treated bats feeling sick.

"We focused on three measures of the sick bats' behaviors: how many other bats they encountered, how much total time they spent with others, and how well-connected they were to the whole social network," Carter said.

On average, compared to control bats, the sick bats associated with four fewer groupmates over the six-hour treatment period and spent 25 fewer minutes interacting per partner, and the time any two bats spent near each other was shortest if the encounter involved at least one sick bat.

"One reason that the sick vampire bats encountered fewer groupmates is simply because they were lethargic and moved around less," Carter said. "In captivity, we saw that sick bats also groom others less and make fewer contact calls. These simple changes in behavior can create social distance even without any cooperation or avoidance by healthy bats. We had previously studied this in the lab. Our goal here was to measure the outcomes of these sickness behaviors in a natural setting.

"The effects we showed here are probably common in many other animals. But it is important to remember that changes in behavior also depend on the pathogen. We did not use a real virus or bacteria, because we wanted to isolate the effect of sickness behavior. Some real diseases might make interactions more likely, not less, or they might lead to sick bats being avoided."

Although the study did not document the spread of an actual disease, combining the social encounter data with known links between exposure time and pathogen transmission allows researchers to predict how sickness behavior can influence the spread of a pathogen in a social network.

Clearly identifying each bat's behavior in the colony's social network was possible only because the proximity sensors - miniaturized computers that weigh less than a penny and fall off within a week or two - took measures every few seconds of associations involving sick or healthy bats or a combination of the two. Visualizations of the proximity sensors' recordings showed growth in the number of connections made in the colony's social network from the treatment period to 48 hours later.

"The proximity sensors gave us an amazing new window into how the social behavior of these bats changed from hour to hour and even minute to minute during the course of the day and night, even while they are hidden in the darkness of a hollow tree," said Ripperger, who is also a visiting scientist at the Museum of National History in Berlin, Germany.

CHAPEL HILL, NC - MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs - bits of genetic code that serve as critical gene regulators in many aspects of biological processes important for human health. Due to their essential roles in gene regulation, miRNAs are tightly regulated, and abnormal miRNA expressions have been linked to cancer, neurological disorders, cardiovascular diseases, and other diseases.

Understanding how miRNAs are regulated has been the focus of intense recent study. Over the years, scientists have discovered multiple protein regulators of miRNA biogenesis cellular pathways, and it is often perceived that these protein factors act on largely passive miRNA processing intermediates to direct their maturation. Now, the lab of Qi Zhang, PhD, associate professor in the UNC Department of Biochemistry and Biophysics, discovered a new RNA-centric mechanism by which miRNA processing intermediates can play direct, active roles in regulating miRNA biogenesis.

These findings, published in the journal Nature Chemical Biology, unveil that a 'hidden' layer of regulation by which the intrinsic dynamic ensemble of miRNA processing intermediates can direct the outcome of important biological processes in response to environmental and cellular stimuli in the absence of protein factors. If these processes go awry, then disease could result. Understanding the roles of miRNAs in disease is a needed step in finding new routes to better therapeutics.

MicorRNA-21 (miR-21) is involved in the creation, progression, metastasis of cancerous tumors, and it is involved in cell survival. When Zhang's lab studied miR-21 using NMR relaxation dispersion - an advanced imaging technique capable of detecting sparsely populated transient states that often evade conventional detection techniques - they found the precursor of miR-21 exists as an ensemble of dynamic conformational states, which is surprisingly sensitive to the acidity of the environment.

They discovered that, across physiological conditions, about 1 - 15% of the miR-21 precursor carries one additional proton, the smallest chemical modification known as protonation. With a lifetime of approximately 0.8 milliseconds, this protonated state sequesters a key residue into a new structure that substantially enhances the efficiency of processing the precursor into mature miR-21.

With these powerful "imaging" techniques, scientists can now unveil transient RNA states as the 'hidden' layers of regulation, including a fleeting riboswitch state important in controlling gene transcription - a state the Zhang laboratory discovered in 2017.

"We think these techniques add more promise for new strategies to create RNA-targeted therapeutics," said Zhang, a member of the UNC Lineberger Comprehensive Cancer Center. "And that is our goal; we need better targeted therapies for many diseases including cancers."

CLEVELAND - An international team of researchers led by Cleveland Clinic's Lerner Research Institute has performed for the first time a wide-scale characterization of missense variants from 1,330 disease-associated genes. Published in Proceedings of the National Academy of Sciences, the study identifies features associated with pathogenic and benign variants that reveal the effects of the mutations at a molecular level.

"Our study serves as a powerful resource for the translation of personal genomics to personal diagnostics and precision medicine, and can aid variant interpretation, inform experiments and help accelerate personalized drug discovery," said Dennis Lal, PhD, assistant staff, Genomic Medicine, and the study's lead author.
Recent large-scale DNA sequencing efforts have detected millions of missense variants, where mistakes in the DNA code change the amino acid (molecular building block of a protein) makeup of proteins. Some of these variants are pathogenic, meaning they alter the structure and function of a protein in a way that leads to disease, while others are benign with no impact on health. The vast majority, however, are considered variants of uncertain significance because their effects remain unknown.

While methods to predict variant pathogenicity exist, they do not elucidate why some variants are more or less likely to cause disease than others or establish their functional impact. Additionally, pathogenic and benign variants can co-exist in almost every disease-associated gene. As such, gaining a better understanding of the mechanistic differences between benign and pathogenic variants will be a critical next step in the development of novel therapies for genetic disorders.

Considering that a protein's function is closely linked to its three-dimensional structure, in this study the research team identified and compared the protein features of amino acids affected by pathogenic versus benign missense variants. Features that are more frequently mutated in pathogenic variants compared to benign variants (3D mutational hotspots) are likely crucial to protein fitness and thus could help explain the molecular determinants of pathogenicity.

Looking at 1,330 disease-associated genes, the researchers analyzed a set of 40 features and found that 18 were significantly associated with pathogenic variants, 14 were significantly associated with benign variants and the remaining eight had no significant association with any variant type.

"By considering genetic variation in the context of proteins' three-dimensional organization, we present for the first time an atlas of molecular properties of pathogenic mutations that addresses the differences between benign and disease-causing mutations," said Lal. "This study focused on 1,330 genes associated with rare types of genetic disorders, so we are currently extending our project to look at more genes and milder disorders."
Data from this study (including precomputed P3DFiDAGS1330 and P3DFiProteinclass values for every possible amino acid exchange in proteins encoded by 1,330 disease-associated genes, along with the explicit listing of the 3D features of the altered site as the rationale for the index) is available through the dedicated web server MISCAST.

An environmentally friendly and sustainable synthesis of "heavyweight" polymers with very narrow molecular weight distributions is an important concept in modern polymer chemistry. Thanks to a new photoenzymatic process, Chinese researchers have been able to increase the range of possible monomers. As reported in the journal Angewandte Chemie, the researchers were able to obtain well-defined linear and star-shaped polymers with ultrahigh molecular weights.

Because many polymer properties depend heavily on molecular weight, it is desirable to have as narrow a molecular weight distribution as possible. Precision polymers with ultrahigh molecular weights (> 1 t/mol) would be interesting candidates for high-performance elastomers, low-concentration hydrogels, photonic materials, durable coatings, and flocking agents. However, such heavyweight polymers are not easy to produce with a uniform distribution of molecular weights. The radical polymerizations in widespread use are especially difficult to control in this respect. Modern methods, such as RAFT polymerization (RAFT: reversible addition-fragmentation chain transfer) offer a significantly higher degree of control by keeping the concentration of reactive radicals very small. A special agent reacts reversibly with the growing polymer chains to form a nonradical species. Whenever the intermediate dissociates, new active radicals are formed. This slows the reaction and results in longer, more uniform polymer chains.

Ultraheavy polymers with narrow weight distributions were previously only attainable from conjugated monomers, meaning compounds with at least two C=C double bonds separated by a single bond. It has never been possible to make such polymers from nonconjugated polymers whose vinyl group (-CH=CH(2)) is bound directly to a noncarbon atom.

Zesheng An (Jilin University, Changchun) and Ruoyu Li (Shanghai University) have overcome this challenge with a simple, environmentally friendly, RAFT polymerization that is based on enzymatic photocatalysis. The enzyme glucose oxidase (GOx) oxidizes glucose with oxygen, reducing the flavin-containing cofactor FAD to FADH(?). The latter acts as a photocatalyst when irradiated with visible light, starting the radical chain reaction. GOx consumes the oxygen present in the solution--another advantage because oxygen disrupts conventional radical polymerizations and must be removed beforehand. The chain propagation agents they use are xanthates (sulfur-containing carboxylic acid derivatives).

The researchers attained well-defined linear and star-shaped polymers in nearly quantitative yield, as well as various copolymers with previously unattainable uniform ultrahigh molecular weights, starting from nonconjugated monomers. The reaction, which offers outstanding control over composition, molecular weight, and architecture, is simple to carry out and takes place under mild conditions (10 °C) in water.

LAWRENCE -- Politicians discuss the ins and outs of health care while trying to win votes, but for some Americans, policymakers do not seem to be listening. University of Kansas researchers have published a study about perspectives of individuals with disabilities on health care policy, and respondents overwhelmingly stated access to health care is vital and they would like policymakers to pay more attention to their needs.

Scholars analyzed data from 35 phone interviews and survey responses from more than 475 individuals with disabilities about health policy. While the respondents largely reflect the political opinions of American society at large, they tended to agree that health care should be viewed as a human right and that feelings of social exclusion and stigma inform what they would like to tell officials who make health policy in the United States.

"We found that people with disabilities are marginalized and stigmatized and that policymakers don't listen to them," said Sarah Smith, a doctoral candidate in sociology, graduate research assistant at KU and lead author of the study. "They also felt that access to health insurance was important in order to be able to take part in society and that policymakers did not consider how the policies they make affected their lives."

The study, published in the Journal of Disability & Policy Studies, was co-written by Smith; Jean Hall, professor of applied behavioral science and director of KU's Institute for Health & Disability Policy Studies, and Noelle Kurth, senior research assistant at the institute. The interviews and surveys revealed five key themes about health policy perspectives among people with disabilities.

Access to health insurance and health care is critical for their ability to participate in society

They felt that politicians did not understand or prioritize the needs and experiences of people with disabilities

Participants used a variety of arguments why policymakers and society should care about people with disabilities

They felt access to health care is a human right or moral imperative

Participants expressed largely positive views regarding the Affordable Care Act.

Respondents nearly uniformly reported how important employment was to their lives in terms of financial security, access to health insurance, not depending on state programs for health coverage and for personal dignity. However, they also faced many barriers to employment, especially those living in states that have not expanded Medicaid who tend to lose eligibility when they are employed.

"Employment is a key component of being part of society and a big part of personal identity," Smith said. "But it can be very hard to access, and most health insurance is tied to employment, which also makes insurance difficult to access, especially if you're not employed full time."

Many study participants also shared that policymakers do not consider the needs of constituents with disabilities.

"I hear politicians on the TV talking about me as if I am the cause of the budget deficit," one respondent said. "They seem to lump us into a group of people--well, not people: 'You're the budget deficit, you're this, you're that,' instead of saying, 'These are people who need care.' Maybe the number one thing, then, is an attitude change. You're not dealing with line items on a budget; you're dealing with what real people need."

Previous research has shown political leanings of people with disabilities are representative of those of American society at large, and participants used a variety of arguments for a matter they agreed on: Policymakers should care about individuals with disabilities. The arguments included that no one chooses to be disabled, anyone can become disabled, better health care access will lead to more productive society, all individuals should matter to policymakers as human beings and that politicians should make the health care policy for all like what they want for themselves and their families.

Health care was viewed as a human right, not something that should only be available to certain members of society, the findings showed.

"Policymakers already know that restricting access to health care has outcomes that range from loss of income to loss of life," one participant said. "True access means that all citizens, regardless of their ability to pay, have access to the same range of services. Like water and an unpolluted environment, health services are essential to life, liberty and the pursuit of happiness."

The study's participants also expressed largely positive opinions about the Affordable Care Act. Many reported that they still struggled with health care costs but were at least able to get health insurance through the act. Primarily, the law's health insurance premium subsidies, coverage for preexisting conditions and Medicaid expansion were important to study participants.

Taken as a whole, the results show the connections among disability stigma, health policy and politics. Previous research has shown that people with disabilities face barriers to political participation, similar to those they face with employment and participation in society, and as a result their voices are often underrepresented in health policy discussions, even though their lives are greatly affected by the policies enacted. As key participants in programs such as Medicare, Medicaid and Social Security, the population can provide vital insight into the functioning and outcomes of those programs, the authors wrote. As America's population ages and the COVID-19 pandemic affects more people's long-term health, new complications to health care access can be expected, which the authors plan to address in future research.

"This is a population that knows a lot about health policy, because they have to know a lot about navigating insurance and health care systems. Policymakers should listen to them," Smith said.

Low muscle quality and quantity are both predictive of poor outcomes in colon resection surgery, according to a new study published in JAMA Surgery.

Carla Prado, a researcher in the University of Alberta's Faculty of Agricultural, Life & Environmental Sciences, and her team followed 1,630 patients who received a diagnosis of Stage I to Stage III colon cancer. The researchers examined various outcomes including length of hospital stay, need for readmission and mortality in patients with colon cancer following colon resection surgery.

They found that low muscle mass was linked to greater post-operative complications, hospitalization and mortality.

According to the Canadian Cancer Society, in 2020, colorectal cancer is expected to be the second-leading cause of death from cancer in Canadian men and the third-leading cause of death from cancer in women. Surgery is often used to remove the cancer, and post-operative complications can affect a patient's quality of life.

Prado noted that the ability to predict who may suffer poor outcomes after surgery would allow for more personalized treatment and improved patient care.

Patients in the study were assessed using preoperative computerized tomography (CT) scans, a technique that involves taking a series of X-ray images from different angles and using computer technology to create cross-sectional images of the body. Scans are taken during cancer diagnosis, and researchers can also use the images to analyze body composition.

The CT technology is what allows for the added analysis of muscle radiodensity, which is the quality of the muscle itself.

"It's like you're looking at a steak and you have fat inside the steak. Our muscles can be like that too, and that's not good for us--so our study looked at both the mass (the quantity) and also the quality of the muscles, which is the amount of fat infiltration," said Prado.

Prado said colon cancer patients were of particular interest for a variety of reasons. The CT images obtained span the body to the third lumbar vertebrae, a frame that is ideal for assessing body composition. Many patients with colon cancer also commonly fall into the obese weight range, and studying low muscle mass in patients at higher weights can offer added insight.

According to Prado, the knowledge that low muscle quantity and quality are indicative of poor post-operative outcomes can have a major impact on patient care through targeted patient interventions.

"It is possible to preoperatively improve muscle, and through that intervention we can better people's quality of life. So I think exploring ways that we can successfully use this approach is the way of the future," she said.

Boston - Results from a new study led by Boston Medical Center (BMC) demonstrate the disproportionate impact of COVID-19 on Hispanic groups within the US, with the most severe outcomes, including death and intensive care, among Hispanic Black individuals. Analyzing data from the Centers for Disease Control and Prevention, researchers found differences between Hispanic groups, with higher rates of hospitalization and increased risk of death for Hispanic Black compared to Hispanic multiracial individuals. Published online in the Journal of Immigrant and Minority Health, the results highlight that Hispanic populations as a whole have worse COVID-19 outcomes compared to the Hispanic white population, demonstrating the need for more accurate demographic data collection efforts in order to better address the disparities among Hispanic individuals impacted by COVID-19.

Results from previous COVID-19 research have shown that Latinx populations, as a whole, have worse outcomes compared to other ethnic groups. This study, the first to use a nationally representative COVID-19 database, delves further into the data to investigate the differential impact of COVID-19 on different racial groups within the Hispanic community.

For this study, researchers analyzed data reported to the Centers for Disease Control and Prevention between April 5 and May 18, 2020, with a cohort of 78,323 individuals. They compared hospitalization, intensive care unit admission, need for breathing support, and death rates among Hispanic white, Hispanic Black, and Hispanic multiracial/other groups. Next, they compared these results with the data on the above criteria for non-Hispanic white individuals.

Hispanic Black individuals in the cohort had the highest rate of comorbidities, at 51 percent, as well as hospitalizations, which were 45 percent. Hispanic/multiracial individuals were more frequently admitted to the intensive care unit (10 percent), had the highest incidence of requiring breathing support through mechanical ventilation (10 percent) and more frequent rates of death due to COVID-19 (16.1 percent). Overall, Hispanic groups fared worse than non-Hispanic white individuals. The relative risk of death was 1.36, 1.72 and 1.68 times higher for Hispanic white, Hispanic Black and Hispanic multiracial compared to non-Hispanic white individuals.

"Our results clearly show that Hispanic individuals are more likely to be hospitalized and die from COVID-19 infection than non-Hispanic individuals, with the worst outcomes among Hispanic Black individuals," said Sarah Kimball, MD, co-director of BMC's Immigrant & Refugee Health Center and the study's corresponding author. One of the challenges, the authors note, is the incomplete information on race and ethnicity included in the reported data given variations among how the information is collected and reported. At this time, there are no universal standards or processes in place at health care institutions related to how racial or ethnic information is collected from patients.

"The dilemma is that we know these disparities among racial groups aren't biological, and reflect the systemic impacts of racism and inequality. Yet, we need better data collection on racial and ethnic groups, in order to develop interventions tailored to address the COVID-19 disparities among specific patient populations," added Kimball, who is also an assistant professor of medicine at Boston University School of Medicine. "The better data we have access to, the more targeted we can be in our public health and treatment approaches to dismantle the effects of racism and the disparities that we see among different groups within the Hispanic community, which can help decrease COVID-19-specific disparities in these individuals."