Culture

Soils harbour a substantial part of the world's biodiversity, yet data on the patterns and processes taking place below ground does not represent all relevant ecosystems and taxa. For example, tropical and subtropical regions largely remain a blind spot when it comes to soil biodiversity. This is one of the results of a new study published in Nature Communications and led by scientists from the German Centre for Integrative Biodiversity Research (iDiv), the Martin Luther University Halle-Wittenberg (MLU) and Leipzig University (UL).

Soils contribute to many crucial ecosystem functions and services including climate regulation, nutrient cycling, and food production. To support their conservation, it is essential to know which macroecological patterns are related to the functioning of soil organisms - only then can we understand the effects of global change drivers. Such analyses need to represent the diversity of environmental conditions that can be found worldwide. Despite the mounting number of soil ecology studies, major gaps still exist in our understanding of soil biodiversity.

To identify these environmental gaps, an international team of researchers led by the German Centre for Integrative Biodiversity Research (iDiv) performed an analysis of soil macroecological studies and over 17,000 sampling sites across the globe. "This effort involved researchers from all continents and we found not only large gaps in important spatial, environmental, and taxonomic representation, but also an almost complete absence of temporally explicit data," said lead author Dr Carlos Guerra, researcher at iDiv and MLU. Given the many legal and logistic limitations related to soil macroecology, researchers often prefer to expand their number of sites rather than seeing what is happening over time. "This prevents scientists from properly assessing the effects of climate change on soil organisms and functions, but also stakeholders from taking appropriate management actions to preserve and maintain important ecosystem services, such as food and water security, for which soils are the main provider."

Lack of data for most diverse places on Earth

In contrast to other ecosystems like aboveground terrestrial, one major issue with respect to soil biodiversity is that the data does not represent all ecosystems. Gaps exist, for example, for most tropical systems: soil biodiversity and function data is scarce or even non-existent in tropical and subtropical regions, which are among the most megadiverse places on Earth. The researcher found that temperate biomes (especially broadleaved mixed forests and Mediterranean) contain more sampling sites than tundra, flooded grasslands and savannas, mangroves, and most of the tropical biomes. "This likely reflects differences in funding availability and research focus and infrastructures across countries," said Carlos Guerra.

At the same time, for many of the best-represented regions across the globe, there is rarely a complete picture of the hidden life below the surface. Instead, records are often dominated by one or two taxa such as bacteria and fungi. "We all heavily depend on the biodiversity under our feet - it is time to better understand this underexplored part of biodiversity," said Professor Nico Eisenhauer, head of the Experimental Interaction Ecology research group at iDiv and UL.

Understanding what is happening - and why

In a changing world where land-use intensity, desertification, and rapid climate change are forecast to increase, it is important to understand if and to what extent biodiversity changes are happening in the soil. This is particularly relevant to assess the links between changes in biodiversity and ecosystem function: for example, whether changes in biodiversity occur because of changes in function, coupled with them, or despite them.

The researchers highlight the need for action to facilitate a global soil monitoring system that overcomes the current limitations. "This study is a milestone revealing the status quo and informing future soil biodiversity monitoring," said Nico Eisenhauer. "Now, the next steps require two complementary pathways: making data available and standardized for further research and globally standardized sampling. Something that we are already working to put in place," said Carlos Guerra Ultimately, this could help track the fulfilment of global or national biodiversity targets, and support policy and decision-making.

Social networks have been found to influence academic performance: students tend to perform better with high-performers among their friends, as some people are capable of inspiring others to try harder, according to Sofia Dokuka, Dilara Valeyeva and Maria Yudkevich of the HSE University. Their paper was published in PLOS ONE.

Most researchers in educational sciences recognize four factors affecting student academic performance, namely: the family's socioeconomic status, the time spent on independent learning and preparation for classes, the time spent working on a job or practicing a hobby and the university or school environment.

However, recent empirical studies indicate that the role of the social environment may be underestimated, as classmates can greatly influence one another's behaviour and academic success.

Most studies question the role of social environment. Yet the value of many such studies is limited due to serious design flaws - such as viewing a random group of classmates as one's social network or assuming that a student's position in his or her social network is static. Rather than being random, one's social network is a product of conscious and dynamic choice. Social networks, particularly among college freshmen, can change considerably over time - e.g. a student can break up with an underachieving friend and seek the company of A-graders.

Using 2013-2014 data on the social networks of 117 first-year students of the Faculty of Economics at a Russian university, researchers examined whether academic performance plays a role when students choose their friends and tutors among classmates. They also examined how friends and tutors influence each other's performance during their studies.

They analysed the data using stochastic actor-based modeling to address the dynamics and other nuances of social group members' behavior.

According to the authors, in choosing friends, students do not usually consider academic performance, but over time - often in the middle of the academic year - all members in a peer group tend to perform at about the same level.

'With the use of data on the dynamics of friendship, assistance and academic performance networks, we monitor essential differences in the functionality of these connections. We have proven that asking for help with studies does not lead to growth in performance. However, friendship with those who get good grades does,' said Sofia Dokuka, https://www.hse.ru/en/staff/sofi Research Fellow at the HSE Institute of Education.

Thus, most students who surrounded themselves with high-achievers improved their performance over time. The opposite was also true - those who befriended underachievers eventually experienced a drop in grades.

According to the authors, while underachievers have a stronger influence on their networks, high performers tend to gain popularity and expand their influence over time, particularly by helping other students with their studies.

Men were found to have larger networks than women, and all students were more likely to be friends with those whom they had known before college, classmates of the same gender, and members of their study group.

Key Takeaways:

Larger daily deal platforms with bigger consumer marketplaces can exert more bargaining power during negotiation.

Merchants can build their own businesses by choosing the right daily deal platforms. Merchants' choice of a platform depends on their characteristics and the consumer base of the platform.

Underdog platforms help merchants by providing an alternative outlet in price negotiation.

CATONSVILLE, MD, August 3, 2020 - If you've ever taken advantage of a nice discount thanks to a promotion from Groupon or LivingSocial, you've tapped the power of the daily deal market yourself. You, the consumer, benefited from the prior bargaining that took place between that big online platform and the merchant, resulting in a lower price for you.

Researchers from the University of Maryland and Harvard University analyzed the bargaining process between those daily deal platforms and merchants to identify the trade-offs made by both parties during the transaction to achieve their goals. While merchants may have less leverage and sacrifice certain net profits for the short term when selling their goods or services on the larger platforms, they can win in the long run by adding new customers and creating the opportunity for future sales to a larger customer base.

The research study, "Price Bargaining and Competition in Online Platforms: An Empirical Analysis of the Daily Deal Market," published in the July issue of the INFORMS journal Marketing Science, is authored by Lingling Zhang of the University of Maryland and Doug J. Chung of Harvard University.

"We focused on price bargaining and platform competition," said Zhang. "We asked two questions: What are the determinants of price setting and profit splitting between platforms like Groupon and LivingSocial and their suppliers? And, to what extent does price bargaining affect competition and market outcomes?"

To answer those questions, the authors used data from the U.S. daily deal market with a specific focus on the Groupon and LivingSocial platforms, each sell a daily assortment of discounted goods and services, and in doing so, they connect local merchants with consumers.

"On the demand side, consumers make a multistage decision," said Chung. "They first choose the deal platform, and then they choose which deal to purchase. On the supply side, platforms and merchants negotiate terms. The platform considers not only how much revenue can be generated from each deal, but also the extent to which the deal can help grow its customer base. For the merchant, it evaluates both the current deal revenue and the future payoff by retaining the newly acquired customers."

The researchers found that, while smaller platforms cannot offer access to a consumer market like larger platforms can, they are willing to leave more room for merchants on profit splitting. So, the long-term results of working with smaller platforms can be better for some merchants.

"We compared Groupon, the larger online platform, to LivingSocial, the smaller one, and found that LivingSocial can compensate for its smaller size by offering higher share of profit to merchants," said Zhang. "For some merchants, the tradeoff works in a way that choosing the smaller daily deal platform can be an effective way to maximize profits."

The authors said that another reason why having a smaller platform in the marketplace is beneficial for merchants is that it provides an alternative outlet for their deals. In the absence of competition from the underdog platform, the larger platform can leverage its bargaining power to negotiate a lower wholesale price, increasing its deal profits. The larger platform passes some of the discount onto the retail price; thus, the platform and consumers gain, at the cost of merchants.

A team of scientists has engineered antiviral compounds that can kill several types of coronaviruses, including SARS-CoV-2, the virus that causes COVID-19. The compounds neutralized viruses in human airway cells and improved survival in mice infected with a deadly, closely related virus that causes Middle East respiratory syndrome (MERS). The new compounds' broad activity suggest that they should be further developed as treatments for infections with emerging coronaviruses, which currently have few effective antivirals and no approved vaccines. Although many coronaviruses cause only mild cases of the common cold, emerging species such as SARS-CoV-2 and SARS-CoV (the cause of the 2003 SARS outbreak) pose a serious risk to global health and security. The spread of SARS-CoV-2 has caused one of the most dangerous pandemics in modern history, and infections with its cousin MERS-CoV have a fatality rate of almost 35%, according to the World Health Organization. In previous work, Athri Rathnayake and colleagues had developed a series of antiviral compounds named 3C-like protease inhibitors, which target an enzyme essential to the replication of coronaviruses. Here, they tested several 3C-like protease inhibitors in cells infected with SARS-CoV-2, SARS-CoV, or MERS-CoV. One of the compounds, named 6e, showed strong activity against SARS-CoV-2 and inhibited viral replication by tenfold in cultured human airway epithelial cells taken from infected donors. Another potent compound named 6j boosted the odds of survival in mice infected with MERS-CoV, slashed the amount of virus in the lungs, and prevented dangerous complications like lung edema. Rathnayake et al. plan to conduct further research to see whether one of their compounds could effectively treat both MERS and COVID-19 in humans.

With these new findings scientists can potentially better understand the subtle changes that can occur in genes and brain circuits that can lead to mental health disorders such as anxiety and autism spectrum disorders.

Although physically very different, research has found that the brains of flies, mice and humans are similar in how they form and how they function. Data has shown that the genetic mechanisms that underlie the brain development of insects and mammals are very similar but this can be interpreted in two different ways, where some believe it provides evidence of one single ancestor for both mammals and insects and others think it could support the theory that brains evolved multiple times independently.

Published in the journal Proceedings of the National Academy of Sciences (PNAS), this collaborative study between King's College London, University of Arizona, University of Leuven and Leibniz Institute DSMZ has provided strong evidence that the mechanisms that regulate genetic activity required for the formation of brain areas important to control behaviour, is the same for insects and mammals.

Most strikingly they have demonstrated that when these regulatory mechanisms are inhibited or impaired in insects and mammals they experience very similar behavioural problems. This indicates that the same building blocks that control the activity of genes are essential to both the formation of brain circuits and the behaviour-related functions they perform. According to the researchers this provides evidence that these mechanisms have been established in one common ancestor.

Senior author on the study, Dr Frank Hirth from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London said: 'To my knowledge this is the first study that provides evidence of the source of similarities between human and fly brains, how they form and how they function. Our research shows that the brain circuits essential for coordinated behaviour are put in place by similar mechanisms in humans, flies and mice. This indicates that the evolution of their very different brains can be traced back to a common ancestral brain more than a half billion years ago.'

Nicholas Strausfeld, Regents Professor of Neuroscience at the University of Arizona and a co-author on the study said: 'The jigsaw puzzle of how the brain evolved still lacks an image on the box, but the pieces currently being added suggest a very early origin of essential circuits that, over an immense span of time have been maintained, albeit with modification, across the great diversity of brains we see today.'

The study focussed on those areas of the brain known as the deutocerebral-tritocerebral boundary (DTB) in flies and the midbrain-hindbrain boundary (MHB) in vertebrates including humans. Using genomic data, researchers identified the genes that play a major role in the formation of the brain circuits that are responsible for basic motion in the DTB in flies and MHB in humans. They then ascertained the parts of the genome that control when and where these genes are expressed, otherwise known as cis-regulatory elements.

The researchers found that these cis-regulatory elements are very similar in flies, mice and humans, indicating that they share the same fundamental genetic mechanism by which these brain areas develop. By manipulating the relevant genomic regions in flies so they no longer regulate the genes appropriately, the researchers showed a subsequent impairment in behaviour. This corresponds to findings from research with people where mutations in gene regulatory sequences or the regulated genes themselves have been associated with behavioural problems including anxiety and autism spectrum disorders.

Dr Hirth commented: 'For many years researchers have been trying to find the mechanistic basis behind behaviour and I would say that we have discovered a crucial part of the jigsaw puzzle by identifying these basic genetic regulatory mechanisms required for midbrain circuit formation and function. If we can understand these very small, very basic building blocks, how they form and function, this will help find answers to what happens when things go wrong at a genetic level to cause these disorders.'

When two neutron stars slam together, the result is sometimes a black hole that swallows all but the gravitational evidence of the collision. However, in a series of simulations, an international team of researchers including a Penn State scientist determined that these typically quiet--at least in terms of radiation we can detect on Earth--collisions can sometimes be far noisier.

"When two incredibly dense collapsed neutron stars combine to form a black hole, strong gravitational waves emerge from the impact," said David Radice, assistant professor of physics and of astronomy and astrophysics at Penn State and a member of the research team. "We can now pick up these waves using detectors like LIGO in the United States and Virgo in Italy. A black hole typically swallows any other radiation that could have come out of the merger that we would be able to detect on Earth, but through our simulations, we found that this may not always be the case."

The research team found that when the masses of the two colliding neutron stars are different enough, the larger companion tears the smaller apart. This causes a slower merger that allows an electromagnetic "bang" to escape. Astronomers should be able to detect this electromagnetic signal, and the simulations provide signatures of these noisy collisions that astronomers could look for from Earth.

The research team, which includes members of the international collaboration CoRe (Computational Relativity), describe their findings in a paper appearing online in the Monthly Notices of the Royal Astronomical Society.

"Recently, LIGO announced the discovery of a merger event in which the two stars have possibly very different masses," said Radice. "The main consequence in this scenario is that we expect this very characteristic electromagnetic counterpart to the gravititational wave signal."

After reporting the first detection of a neutron-star merger in 2017, in 2019, the LIGO team reported the second, which they named GW190425. The result of the 2017 collision was about what astronomers expected, with a total mass of about 2.7 times the mass of our sun and each of the two neutron stars about equal in mass. But GW190425 was much heavier, with a combined mass of around 3.5 solar masses and the ratio of the two participants more unequal--possibly as high as 2 to 1.

"While a 2 to 1 difference in mass may not seem like a large difference, only a small range of masses is possible for neutron stars," said Radice.

Neutron stars can exist only in a narrow range of masses between about 1.2 and 3 times the mass of our sun. Lighter stellar remnants don't collapse to form neutron stars and instead form white dwarfs, while heavier objects collapse directly to form black holes. When the difference between the merging stars gets as large as in GW190425, scientists suspected that the merger could be messier--and louder in electromagnetic radiation. Astronomers had detected no such signal from GW190425's location, but coverage of that area of the sky by conventional telescopes that day wasn't good enough to rule it out.

To understand the phenomenon of unequal neutron stars colliding, and to predict signatures of such collisions that astronomers could look for, the research team ran a series of simulations using Pittsburgh Supercomputing Center's Bridges platform and the San Diego Supercomputer Center's Comet platform--both in the National Science Foundation's XSEDE network of supercomputing centers and computers--and other supercomputers.

The researchers found that as the two simulated neutron stars spiraled in toward each other, the gravity of the larger star tore its partner apart. That meant that the smaller neutron star didn't hit its mbrore massive companion all at once. The initial dump of the smaller star's matter turned the larger into a black hole. But the rest of its matter was too far away for the black hole to capture immediately. Instead, the slower rain of matter into the black hole created a flash of electromagnetic radiation.

The research team hopes that the simulated signature they found can help astronomers using a combination of gravitational-wave detectors and conventional telescopes to detect the paired signals that would herald the breakup of a smaller neutron star merging with a larger.

The simulations required an unusual combination of computing speed, massive amounts of memory, and flexibility in moving data between memory and computation. The team used about 500 computing cores, running for weeks at a time, over about 20 separate instances. The many physical quantities that had to be accounted for in each calculation required about 100 times as much memory as a typical astrophysical simulation.

"There is a lot of uncertainty surrounding the properties of neutron stars," said Radice. "In order to understand them, we have to simulate many possible models to see which ones are compatible with astronomical observations. A single simulation of one model would not tell us much; we need to perform a large number of fairly computationally intensive simulations. We need a combination of high capacity and high capability that only machines like Bridges can offer. This work would not have been possible without access to such national supercomputing resources."

A common green apple vape flavor enhances nicotine reward and is also rewarding itself, according to research in mice recently published in eNeuro.

Vaping entices adolescents into nicotine use with fun flavors like green apple and cotton candy. Nicotine-free flavored vapes have also gained popularity. But of the over 7000 available flavor chemicals, only a handful have been studied. With or without nicotine, flavored vapes pose potential risks for the brain, including addiction.

To continue unravelling these risks, Cooper et al. gave mice either nicotine, the green apple flavorant farnesene, or both in one chamber and a saline solution in another. Farnesene was rewarding by itself, as mice chose the farnesene chamber over the saline chamber. But farnesene also enhanced reward when combined with nicotine.

The research team next measured how farnesene changed nicotine receptor expression and neuron activation. Alone, farnesene partially activated nicotinic receptors, meaning it may increase nicotine's receptor activation when both substances are present. Farnesene also increased the proportion of high- to low-sensitivity receptors. A greater proportion of high-sensitivity receptors increases the effects of a standard nicotine dose, which could heighten reward and drug-seeking behavior. Despite their marketing, vape flavors are not risk-free and may exacerbate the effects of nicotine.

What The Study Did: Changes in emergency department visits and hospitalizations as the COVID-19 pandemic intensified in the U.S. are examined in this observational study that included 24 emergency departments in five health care systems in Colorado, Connecticut, Massachusetts, New York and North Carolina.

Authors: Edward R. Melnick, M.D., M.H.S., of the Yale University School of Medicine in New Haven, Connecticut, is the corresponding author.

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

(doi:10.1001/jamainternmed.2020.3288)

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

A large number of the valley networks scarring Mars's surface were carved by water melting beneath glacial ice, not by free-flowing rivers as previously thought, according to new UBC research published today in Nature Geoscience. The findings effectively throw cold water on the dominant "warm and wet ancient Mars" hypothesis, which postulates that rivers, rainfall and oceans once existed on the red planet.

To reach this conclusion, lead author Anna Grau Galofre, former PhD student in the department of earth, ocean and atmospheric sciences, developed and used new techniques to examine thousands of Martian valleys. She and her co-authors also compared the Martian valleys to the subglacial channels in the Canadian Arctic Archipelago and uncovered striking similarities.

"For the last 40 years, since Mars's valleys were first discovered, the assumption was that rivers once flowed on Mars, eroding and originating all of these valleys," says Grau Galofre. "But there are hundreds of valleys on Mars, and they look very different from each other. If you look at Earth from a satellite you see a lot of valleys: some of them made by rivers, some made by glaciers, some made by other processes, and each type has a distinctive shape. Mars is similar, in that valleys look very different from each other, suggesting that many processes were at play to carve them."

The similarity between many Martian valleys and the subglacial channels on Devon Island in the Canadian Arctic motivated the authors to conduct their comparative study. "Devon Island is one of the best analogues we have for Mars here on Earth--it is a cold, dry, polar desert, and the glaciation is largely cold-based," says co-author Gordon Osinski, professor in Western University's department of earth sciences and Institute for Earth and Space Exploration.

In total, the researchers analyzed more than 10,000 Martian valleys, using a novel algorithm to infer their underlying erosion processes. "These results are the first evidence for extensive subglacial erosion driven by channelized meltwater drainage beneath an ancient ice sheet on Mars," says co-author Mark Jellinek, professor in UBC's department of earth, ocean and atmospheric sciences. "The findings demonstrate that only a fraction of valley networks match patterns typical of surface water erosion, which is in marked contrast to the conventional view. Using the geomorphology of Mars' surface to rigorously reconstruct the character and evolution of the planet in a statistically meaningful way is, frankly, revolutionary."

Grau Galofre's theory also helps explain how the valleys would have formed 3.8 billion years ago on a planet that is further away from the sun than Earth, during a time when the sun was less intense. "Climate modelling predicts that Mars' ancient climate was much cooler during the time of valley network formation," says Grau Galofre, currently a SESE Exploration Post-doctoral Fellow at Arizona State University. "We tried to put everything together and bring up a hypothesis that hadn't really been considered: that channels and valleys networks can form under ice sheets, as part of the drainage system that forms naturally under an ice sheet when there's water accumulated at the base."

These environments would also support better survival conditions for possible ancient life on Mars. A sheet of ice would lend more protection and stability of underlying water, as well as providing shelter from solar radiation in the absence of a magnetic field--something Mars once had, but which disappeared billions of years ago.

While Grau Galofre's research was focused on Mars, the analytical tools she developed for this work can be applied to uncover more about the early history of our own planet. Jellinek says he intends to use these new algorithms to analyze and explore erosion features left over from very early Earth history.

"Currently we can reconstruct rigorously the history of global glaciation on Earth going back about a million to five million years," says Jellinek. "Anna's work will enable us to explore the advance and retreat of ice sheets back to at least 35 million years ago--to the beginnings of Antarctica, or earlier--back in time well before the age of our oldest ice cores. These are very elegant analytical tools."

Washington, DC-- New work led by Carnegie's Peng Ni and Anat Shahar uncovers new details about our Solar System's oldest planetary objects, which broke apart in long-ago collisions to form iron-rich meteorites. Their findings reveal that the distinct chemical signatures of these meteorites can be explained by the process of core crystallization in their parent bodies, deepening our understanding of the geochemistry occurring in the Solar System's youth. They are published by Nature Geoscience.

Many of the meteorites that shot through our planet's atmosphere and crashed on its surface were once part of larger objects that broke up at some point in our Solar System's history. The similarity of their chemical compositions tells scientists that they originated as part of common parent bodies, even if they arrived here centuries apart and in vastly different locations.

Deciphering the geologic processes that shaped these parent bodies could teach us more about our Solar System's history and Earth's formative years. To truly understand what makes our planet capable of sustaining life, and to look for habitable worlds elsewhere, it is crucial to understand its interior--past and present.

"Like our Solar System's rocky planets, these planetesimals accreted from the disk of dust and gas that surrounded our Sun in its youth," explained lead author Ni. "And like on Earth, eventually, the densest material sank toward the center, forming distinct layers."

Iron meteorites were thought to be the remnants of the cores of their ancient, broken-apart parent bodies.

"A history of how their layers differentiated is recorded in their chemical makeup, if we can read it," said Shahar.

There are four stable isotopes of iron. (Each element contains a unique number of protons, but its isotopes have varying numbers of neutrons.) This means that each iron isotope has a slightly different mass than the others. As a result, some isotopes are preferred by certain chemical reactions--which, in turn, affects the proportion of that isotope in the reaction's end products.

The traces of this favoritism can be found in rock samples and can help elucidate the processes that forged these meteorite parent bodies.

Previous research on the ratios of iron isotopes in iron meteorites led to a puzzling observation: compared to the raw material from which their parent bodies were constructed, they are enriched in heavy isotopes of iron.

Together with Nancy Chabot and Caillin Ryan of the Johns Hopkins University Applied Physics Laboratory, Ni and Shahar determined that this enrichment can be explained entirely by the crystallization of a parent object's core.

The researchers use lab-based mimicry to simulate the temperatures of core crystallization in iron meteorite parent bodies. Sophisticated models of the crystallization process including other elemental concentrations--for example, of gold and iridium, as well as isotopes of iron--confirmed their findings.

"This improved understanding of core crystallization adds to our knowledge about our Solar System's formative period," Ni concluded.

Advancing the understanding of synovial sarcoma, a highly aggressive and rare cancer of young people, scientists at Dana-Farber Cancer Institute have discovered how an abnormal protein misdirects and disrupts the control of gene expression in cells, causing the aberrant activation of normally repressed genes that contribute to the malignant growth of sarcoma tumors.

The investigators, led by Cigall Kadoch, PhD, say the new insight could guide efforts to develop drugs to treat synovial sarcoma, which primarily affects muscle tissues in the extremities. The root cause of the sarcoma is a cellular accident -- the abnormal joining of two proteins, resulting in a "fusion protein" that sets in motion the malignant malfunctions.

"We have for the first time defined the molecular basis for the cancer-specific targeting properties of the culprit fusion protein, SS18-SSX, found in 100% of cases of synovial sarcoma." Kadoch said. "Importantly, this provides a powerful new therapeutic identification strategy for the drug discovery industry" to develop drugs to block the interaction between the abnormal fusion protein and nucleosomes - structures that package and organize DNA in cells, said Kadoch, senior author of the study published today in Nature Structural and Molecular Biology.

Nucleosomes, spool-like structures resembling beads on a string, make up chromatin, a term to describe DNA wrapped around proteins called histones. Chromatin is found throughout the genome, which in humans contains an estimated 20,000 genes and much other genetic information. Modifications in chromatin structure, carried out by protein complexes called chromatin remodelers, regulate the turning on and off of genes for cell- and tissue-specific purposes. Malfunctions of the chromatin remodeling system have been implicated in many cancers and neurodevelopmental disorders, a major focus of the Kadoch laboratory.

In synovial sarcoma, the SS18-SSX fusion oncoprotein replaces the normal SS18 subunit, or component, in BAF chromatin remodeling complexes. As a result, BAF chromatin remodeling complexes are "dragged around the genome to all the wrong sites" on chromatin "to aberrantly activate them and drive the gene expression and proliferation of synovial sarcoma," Kadoch and her team previously showed in a 2018 study. These "wrong" sites, she explained, are regions on chromatin marked by polycomb repressive complexes, which normally keep genes such as stem cell genes from being expressed when not needed. One might think of a complex traffic system in which millions of aircraft or ships normally proceed to specified destinations along specific routes - but in the case of some cancers, the targeting of these vessels is scrambled, with disastrous results.

However, this previous work had not revealed how the SS18-SSX fusion protein and BAF complexes were erroneously targeted to those repressed sites across the genome: "it was a mystery until now," Kadoch said.

In the experiments described in the new paper, Kadoch and her co-authors found that a minimal, small segment of the SS18-SSX fusion protein binds to the so-called "acidic patch" on nucleosomes. The acidic patch is a pocket of negatively charged molecules to which chromatin remodeling complexes, such as BAF complexes, can dock. The researchers found that the small segment of SSX - which they refer to as the "tail" of the fusion protein - is made up of only 34 amino acids, but binds extremely tightly to the acidic patch. Specifically, the SSX tail binds to the acidic patch on nucleosomes that are "decorated" with a histone modification known as ubiquitination of histone H2A (H2AK119Ub).

In fact, the tail of SSX binds so powerfully that it dislodges a BAF complex subunit known as SMARCB1 (BAF47) that normally engages the complexes on chromatin. "These complexes are really stuck, so once they get to the site, they stay there and strongly activate those cancer-related genes," noted Kadoch.

According to the researchers, the full-length SSX protein is normally only active in the testes, where it likely plays a role in sperm development. But when a part of the SSX protein is fused with the BAF complex SS18 subunit (via the characteristic t(X;18) chromosomal translocation in synovial sarcoma), it prompts an "unfortunate scenario" that leads to the remodeling or opening of chromatin over the regions where the SSX tail guides BAF complexes via the acidic patch, causing the activation of cancer-related genes

With these new insights into how the oncogenic fusion protein targets BAF chromatin remodeling complexes on the genome leading to activation of synovial sarcoma-related genes, said Kadoch, "these results suggest that inhibition of the interactions between SS18-SSX-bound BAF complexes and H2AK119Ub -marked nucleosomes using small molecules or peptides may prove a viable therapeutic strategy for synovial sarcoma."

ROCHESTER, Minn. -- As COVID-19 swept into the U.S., hospitals across the country have reported that their emergency departments are emptying out. In a new study published Monday, Aug. 3, in JAMA Internal Medicine, a team of researchers from multiple institutions provides insights into this phenomenon.

"We knew there were major changes in ED (emergency department) visit volume, but we didn't know how different communities were affected. It was especially important to know how much ED visits declined in areas that had a lot of COVID-19 cases, compared to those with fewer cases. Health care providers and our communities need real evidence for decision-making," says Molly Jeffery, Ph.D., scientific director of Emergency Medicine Research at Mayo Clinic. Dr. Jeffery is the study's lead author.

The investigators collected information on emergency department visits and subsequent hospital admissions from Jan. 1 to April 30. Study data came from 24 emergency departments across five health care systems. Included in the study were four emergency departments in Colorado and five emergency departments in each of these states: Connecticut, Massachusetts, New York and North Carolina. These emergency departments spanned rural, urban and suburban settings, and included regions with a high COVID-19 caseload and regions with lower case counts. Annual baseline volume across these emergency departments ranged from 12,500 to 115,000 visits.

"We found a substantial decline in emergency department visits -- between 42% and 64% -- during the four-month period of our study, but most of that decline happened over just a few weeks in March," says Dr. Jeffery. "The largest declines were seen in the areas that had a lot of COVID-19 cases. If you think about that, it means that even more people with problems other than COVID-19 must have avoided the ED during this period."

These declining visit numbers corresponded to growing awareness of COVID-19 through increasing coverage in the national and local media, as well as the timing of a good portion of state-issued stay-at-home orders. Although the researchers were unable to determine specific numerical reductions from particular causes, they offered three likely explanations.

"Reductions in ED utilization could reflect: (1) failure to seek care by patients with serious or life-threatening conditions, including those unrelated to COVID-19; (2) avoidance of the ED for nonemergent conditions; or (3) displacement of ED care to other venues, such as telemedicine visits."

Conversely, the researchers noted that hospital admission rates from the emergency department remained relatively stable across the health systems until there was a local increase in COVID-19 cases, at which time there was an uptick.

"This increase in hospital admissions was dramatic," says Edward Melnick, M.D., an emergency medicine physician at Yale New Haven Health in Connecticut. Dr. Melnick is the study's senior author.

"Here at Yale New Haven, we saw a 36% increase, the median increase across the five systems," he says. "In New York, the epicenter of the largest outbreak of COVID in the U.S., the relative increase of hospital admissions at Mount Sinai Health was 149% -- so 2½ times the usual rate of emergency admissions."

The other systems also showed significant relative increases of emergency hospital admissions:

22%, UNC Health, North Carolina

29.4%, UCHealth, Colorado

51.7%, Baystate Health, Massachusetts

The increases in hospital admissions occurred despite the reductions in visits, allowing inferences that emergency hospitalizations for COVID-19 accounted for a substantial portion. However, the researchers note that they are unable to determine if people with serious symptoms, illnesses and injuries went untreated due to the COVID-19 pandemic.

Recently, the researchers examined May and June data from the states observed in their paper. They found that the lowest amount of visits to the emergency department occurred during the week of April 8, with increasing numbers since then -- but not a return to baseline.

Furthermore, although emergency hospital admissions initially increased in correspondence to rising rates of COVID in each state, they stabilized and began to trend downward around that same time. However, admissions have not returned to levels seen before COVID-19 either, even where the rate of new COVID-19 cases has sharply decreased.

"More widely available telehealth options may be keeping the emergency visits below historic norms," says Dr. Jeffery. "Many insurers, including Medicare, are paying for telehealth visits now that they previously did not cover. It will be important to understand how this shift from in-person to virtual visits affects both access to care and patient health outcomes."

As for emergency hospital admissions, Dr. Melnick thinks it's probably for similar reasons. "If a person stays home when sick and treats illnesses early, they may avoid increased severity and the need for emergency care."

"People should continue to seek medical assistance for serious illnesses, injuries and symptoms," says Dr. Melnick. "While nonemergencies make up a certain portion of usual visits, the steep drop in visits to the emergency department seems to indicate that many urgent health situations may have gone untreated. This could lead to worsening symptoms, disability or death. Emergency departments remain a safe place to receive care for non-COVID-related emergencies."

"Since the pandemic started, infection control measures have been increased," says Dr. Jeffery. "Appropriate measures should continue in both the emergency department and other clinical settings to reassure staff and ensure patients feel safe to pursue appropriate care."

Drs. Melnick and Jeffery echo what they and their colleagues said in the paper, "It is essential that public health authorities and health care systems provide guidance and resources to help patients determine the best place to receive care now (and) throughout the pandemic, and into the future."

What The Study Did: International professional societies developed recommendations for minimum clinical standards to determine brain death/death by neurologic criteria in adults and children to improve the consistency of these criteria within and among countries.

Authors: Gene Sung, M.D., M.P.H., of the University of Southern California in Los Angeles, is the corresponding author.

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

(doi:10.1001/jama.2020.11586)

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

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Despite decades of positive messaging to encourage women and girls to pursue education tracks and careers in STEM, women continue to fall far below their male counterparts in these fields. A new study at Carnegie Mellon University examined 25 languages to explore the gender stereotypes in language that undermine efforts to support equality across STEM career paths. The results are available in the August 3rd issue of Nature Human Behavior.

Molly Lewis, special faculty at CMU and her research partner, Gary Lupyan, associate professor at University of Wisconsin-Madison, set out to examine the effect of language on career stereotypes by gender. They found that implicit gender associations are strongly predicted by the language we speak. Their work suggests that linguistic associations may be causally related to people's implicit judgement of what women can accomplish.

"Young children have strong gender stereotypes as do older adults, and the question is where do these biases come from," said Lewis, first author on the study. No one has looked at implicit language - simple language that co-occurs over a large body of text - that could give information about stereotypical norms in our culture across different languages."

In general, the team examined how words co-occur with women compared to men. For example, how often is 'woman' associated with 'home,' 'children' and 'family,' where as 'man' was associated with 'work,' 'career' and 'business.'

"What's not obvious is that a lot of information that is contained in language, including information about cultural stereotypes, [occurs not as] direct statements but in large-scale statistical relationships between words," said Lupyan, senior author on the study. "Even without encountering direct statements, it is possible to learn that there is stereotype embedded in the language of women being better at some things and men at others."

They found that languages with a stronger embedded gender association are more clearly associated with career stereotypes. They also found that a positive relationship between gender-marked occupation terms and the strength of these gender stereotypes.

Previous work has shown that children begin to ingrain gender stereotypes in their culture by the age of two. The team examined statistics regarding gender associations embedded in 25 languages and related the results to an international dataset of gender bias (Implicit Association Test).

Surprisingly, they found that the median age of the country influences the study results. Countries with a larger older population have a stronger bias in career-gender associations.

"The consequences of these results are pretty profound," said Lewis. "The results suggest that if you speak a language that is really biased then you are more likely to have a gender stereotype that associates men with career and women with family."

She suggests children's books be written and designed to not have gender-biased statistics. These results also have implications for algorithmic fairness research aimed at eliminating gender bias in computer algorithms.

"Our study shows that language statistics predict people's implicit biases -- languages with greater gender biases tend to have speakers with greater gender biases," Lupyan said. "The results are correlational, but that the relationship persists under various controls [and] does suggest a causal influence."

Lewis notes that the Implicit Association Test used in this study has been criticized for low reliability and limited external validity. She stresses that additional work using longitudinal analyses and experimental designs is necessary to explore language statistics and implicit associations with gender stereotypes.

A team of researchers from Japan has demonstrated a light-based reaction that yields high numbers of the base chemical component required to produce bioactive compounds used in common industry products.

They published their results on June 11 in Organic Letters.

"We developed a redox potential-controlled and cost-effective method to synthesize multisubstituted cyclobutanes, which are present in the core structure of various products and bioactive components," said paper author Yujiro Hoshino, a research associate at Yokohama National University.

Cycloaddition reactions allow to prepare carbocyclic and heterocyclic organic compounds with atom-efficiency. For a long time, researchers carried out photocycloadditions of olefins such as styrenes, a chemical used in the production of plastics and rubber, by treating them with high-energy ultraviolet light or transition metal catalysts, which are known to be toxic and expensive chemical reagents. The reaction mainly provides homo-dimer, not hetero-dimer. In addition, the powerful light damages the bonds holding the chemical together, allowing it to break apart and reform in a new configuration, known as a cyclobutene ring.

Redox potential refers to how easily a chemical loses or gains electrons. Hoshino and co-workers take advantage of this characteristic and applied a green, visible light to styrenes situated in a two-by-two arrangement, allowing the chemical components and bonds to selectively reorganize as the light freed electrons from the styrenes. The newly organized chemical components were multisubstituted cyclobutanes.

"By focusing on the different redox potential between various styrenes and optimizing our light catalysts, we developed a mild and clean method to synthesize multisubstituted cyclobutanes," Kenta Tanaka, paper first author and an assistant professor at Tokyo University of Science, said.

"Emphasis will be placed on the strategy which shows the potential to synthesize multisubstituted cyclobutanes via radical cation species without any transition metal catalysts," said another corresponding author Kiyoshi Honda, a professor at Yokohama National University.

Next, the researchers plan to expand the use of various visible-light catalysis methods.

"We hope our reaction system provides an efficient and new method for green-light-driven organic chemical reactions, and that we continue to contribute to the field," Hoshino said.