Culture

Scientists across the globe are rushing to find inhibitors of SARS-CoV-2, the new coronavirus behind the COVID-19 pandemic. Some are using computer simulations to identify promising compounds before conducting actual experiments in the lab. Now, researchers reporting in ACS Nano have used computer modeling to assess four peptides that mimic the virus-binding domain of the human protein that allows SARS-CoV-2 to enter cells.

To infect cells, SARS-CoV-2 uses its spike protein to attach to the ACE2 receptor, a protein on the surfaces of certain human cells. This attachment lets the virus fuse with the host cell membrane and gain entry. Many researchers have been trying to find compounds that block key regions of the spike protein, preventing the virus from infecting cells. Yanxiao Han and Petr Král wanted to use computer modeling to design compounds that mimic the spike protein's natural target, ACE2.

To do so, the researchers examined the recently published X-ray crystal structure of the receptor-binding domain of SARS-CoV-2 when it is bound to ACE2. They identified 15 amino acids from ACE2 that interact directly with the viral protein. Then, the researchers designed four inhibitors that contain most or all of these amino acids, with additional sequences that they thought would stabilize the structures. Through computer simulations, the team studied how the inhibitors might attach to the spike protein in the body and the energies needed for binding. One of the compounds showed a particularly good fit with the viral protein. The peptide still needs to be tested in the lab and in patients, but being able to narrow down drug candidates on the computer could help expedite this process, the team says.

Philadelphia, April 16, 2020 - A team of researchers at Children's Hospital of Philadelphia (CHOP) has characterized how the gut microbiome develops in the first hours of infancy, providing a critical baseline for how changes in this environment can impact health and disease later in life. The findings were published online by the journal Nature Microbiology.

While researchers understand the important connection between the many species of bacteria in the gut microbiome and human health, how these species emerge in infancy and what functions they serve are not fully understood.

"Eventually, the gut in children will hold hundreds of different species of bacteria, but at birth, there might only be 10 or fewer species," said Kyle Bittinger, PhD, the Analytics Core Director of the Microbiome Center at CHOP and first author of the study. "We wanted to understand why those particular bacteria are the first to emerge and what they are doing in those first hours of life."

The study team focused on three species of bacteria - Escherichia coli, Enterococcus faecalis, and Bacteroides vulgatus - because to date those species have been observed in the highest number of babies. They analyzed the genomes of these bacteria to determine why they are growing in infants. Additionally, the team characterized the proteins and metabolites, or small molecules, that were present in the microbiome at this stage of development.

One of the challenges for collecting this information is that for the first several hours of life, any DNA collected from a stool sample is not from the bacteria but from the infant itself. The researchers did not see bacteria emerge in detectable concentrations until the infants were about 16 hours old.

The study team found evidence that the initial environment of the gut microbiome is anaerobic, contrary to the prevailing model which holds that the gut becomes anerobic only after bacteria grow and consume oxygen. The evidence came from observing the order in which amino acids were consumed by bacteria.

The study team also observed that metabolite levels were generally consistent with the detection of bacteria. Molecules typically produced by gut bacteria, like acetate and succinate, went up in samples where bacteria were detected. Additionally, the levels of select proteins went down in samples containing bacteria, suggesting that bacteria might have been consuming those proteins to promote growth.

Analysis of the three bacterial species studied in these infants revealed that multiple strains of each bacterium were already emerging.

"With the information we have, as we continue to follow these infants, we can track them and see how long these early strains of bacteria linger," Bittinger said. "We can then see the consequences of this initial chemical activity in later samples and hopefully pinpoint early changes that might impact health later in childhood."

The researchers hope to use the study findings to determine how the development of the gut microbiome may influence excess weight gain. The infants involved in this study will be followed through the first two years of life. Additionally, all 88 infants involved in the study are African American, a population for whom childhood obesity is a growing concern.

"There are remarkably few studies that have looked at infant growth patterns in African Americans," said Babette Zemel, PhD, the Associate Program Director of the Center for Human Phenomic Science, the Director of the Nutrition and Growth Laboratory, an academic investigator with the Healthy Weight Program at CHOP, a research professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and senior co-author of the study. "With this important first piece in the puzzle, we can follow these healthy term infants and learn what a normal growth pattern looks like so that, in the future, we may be able to intervene when changes in the microbiome can adversely affect children."

Orange, Calif. - In research published in the Journal of Economic Psychology, scientists explore whether people trust robots as they do fellow humans. These interactions are important to understand because trust-based interactions with robots are increasingly common in the marketplace, workplace, on the road and in the home. Results show people extend trust similarly to humans and robots but people's emotional reactions in trust-based interactions vary depending on partner type.

The study was led by Chapman University's Eric Schniter, Ph.D. and Timothy Shields, Ph.D. along with University of Montreal's Daniel Sznycer, Ph.D.

Experiment

The researchers used an anonymous trust game experiment during which a human trustor decided how much of a $10 endowment to give to a trustee - a human, a robot, or a robot whose payoffs go to another human. The human trustor knows there were potential gains from the transfer and the trustee would determine whether to reciprocate by transferring back an amount. Robots were programmed to mimic previously observed reciprocation by human trustees.

It is well established that in trust games like this, most people make decisions that lead to both trustor and trustee benefit. After the interaction, participants rated various positive and negative emotions.

The experimental design allowed researchers to explain two important aspects of trust in explainable robots: how much humans trust robots compared to fellow humans and patterns of how humans react emotionally following interactions with robots versus other humans.

Results

The experiment shows people extend similar levels of trust to humans and robots. This is not what we would find if humans blindly trusted or refused to t
rust robots. This would also not be the outcome if we believe people extend trust with the sole intention of improving other humans' welfare, since trusting a robot does not improve another person's welfare.

The result is consistent with the view that people extend trust for both monetary gain and to discover information about human behavioral propensities. Through their trust interactions with the robots, participants learned about the cooperativeness of fellow humans.

Social emotions are more than feelings - they regulate social behavior. More specifically, social emotions such as guilt, gratitude, anger, and pride affect how we treat others and influence how others treat us in trust-based interactions.

Participants in this experiment experienced social emotions differently depending on whether their partner was a robot or human. A failure to reciprocate the trustor's investment in the trustee triggered more anger when the trustee was a human than when the trustee was a robot. Similarly, reciprocation triggered more gratitude when the trustee was a human than when the trustee was a robot.

Further, participants' emotions finely discriminated among robot types. They reported feeling more intense pride and guilt when the robot trustee's payoff went to a human than when the robot acted alone.

Prospects and Implications

Given that initial trust did not differ across partner type, but social emotions did, a distinct possibility is that trust re-extension in repeated interactions will differ when the partner is a human, a robot, or a robot linked to a human beneficiary.

In the future, driving will present interaction opportunities where it will matter whether decisions are being made by humans or robots and if they serve humans or not. Some cars used for delivery or pickups may drive without human occupants, other cars will drive with passive human occupants and yet other cars will be driven by human drivers. Analogous interactions occur with automated or robotic check-in agents, bank tellers, surgeons, etc.

Partnerships with consistent reciprocators may consolidate into stronger, more productive partnerships when the reciprocators are fellow humans, because humans elicit more gratitude than robots do. Conversely, partnerships with inconsistent reciprocators may be more stable when the reciprocators are robots, because robots elicit less anger than humans do. Further, humans experienced pride and guilt more intensely in interactions where robots served a beneficiary, which suggests people will be more likely to re-extend trust to similar partners.

The human cognitive architecture evolved to have enough structure and content to promote our ancestors' survival and reproduction while also having the flexibility to navigate novel challenges and opportunities. These features enable humans to design and rationally interact with artificial intelligence and robots. Still, interactions with automata, and science's ability to explain these interactions are imperfect because automata lack the psychophysical cues that we expect in an interaction and are often guided by unexplainable or unintuitive decision logics.

Scientists at the University of South Florida have reached a new milestone in the development of two-dimensional supramolecules - the building blocks that make areas of nanotechnology and nanomaterial advancement possible.

Since the 2004 discovery of graphene, the world's thinnest (one-atom-thick) and strongest (200 times stronger than steel) material, researchers have been working to further develop similar nanomaterials for industrial, pharmaceutical and other commercial uses. Thanks to its conductive properties and strength, graphene can be used in microelectronics to fortify mechanical materials and has recently enabled precise 3D imaging of nanoparticles.

While work to develop new supramolecules capable of further applications has seen some success, those molecular formations are either small - less than 10 nanometers in size - or arbitrarily assemble, limiting their potential use. But now, new research published in Nature Chemistry, outlines a profound leap forward in supramolecular progress.

"Our research team has been able to overcome one of the major supramolecular obstacles, developing a well-defined supramolecular structure that pushes the 20-nanometer scale," said Xiaopeng Li, an associate professor in the USF Department of Chemistry and the study's lead researcher. "It's essentially a world record for this area of chemistry."

Li, along with his USF research team, collaborated with Saw Wai Hia's team at the Argonne National Laboratory and Ohio University, as well as several other U.S. and international research institutes on this effort.

Supramolecules are large molecular structures made up of individual molecules. Unlike traditional chemistry, which focuses on covalent bonds between atoms, supramolecular chemistry studies the noncovalent interactions between molecules themselves. Many times, these interactions lead to molecular self-assembly, naturally forming complex structures capable of performing a variety of functions.

In this latest study, the team was able to build a 20-nm-wide metallo-supramolecular hexagonal grid by combining intra- and intermolecular self-assembly processes. Li says the success of this work will advance further understanding of the design principles governing these molecular formations and could one day lead to the development of new materials with yet-to-be-discovered functions and properties.

After eluding researchers for more than 30 years, the VP3 protein of rotavirus has finally revealed its unique structure and function to a team led by scientists at Baylor College of Medicine. The researchers discovered that VP3 consists of four molecular modules that uniquely integrate five enzymatic activities that are necessary for capping messenger-RNA (mRNA), a process essential for the synthesis of viral proteins and for evading the host's immune response.

The researchers report in the journal Science Advances that, in addition to two previously known enzymatic activities, VP3 presents two more unanticipated activities, altogether enabling this capping machine to carry out a function essential for viral replication. The findings open opportunities to design antiviral drugs to counter rotavirus infection, the most common cause of diarrhea in children worldwide, resulting in approximately 200,000 deaths annually.

"Viruses cannot replicate on their own. They take over the machinery of the cells they infect to produce viral particles," said co-corresponding author Dr. B. V. Venkataram Prasad, professor and Alvin Romansky Chair of the Verna and Marrs McLean Department of Biochemistry and Molecular Biology and professor of molecular virology and microbiology at Baylor.

One of the strategies viruses use to highjack the cells they invade involves capping or preparing viral mRNA so that it mimics the capped mRNA of the host cells. Capping of mRNA is an essential step to engage the cellular machinery that synthesizes proteins. Imitating the cell's capping enables the virus to take over the host's machinery to produce viral proteins.

Several viruses use this strategy, but in different ways. In the case of rotavirus, it was known that the viral protein VP3 was involved in capping, but for more than three decades determining the structure of VP3 and understanding how it carried out mRNA capping had been a challenge.

Rotavirus VP3 protein is a unique capping machine

"Combining cryo-electron microscopy, X-ray crystallography and biochemical assays, we discovered that VP3 has all the enzymatic activities required to effectively cap rotavirus mRNA. We also found that, opposed to what has been seen in many viruses that have individual proteins for each enzymatic activity, rotavirus integrates all the enzymatic actitivities as modules into one protein, VP3," said first author Dr. Dilip Kumar, postdoctoral fellow in the Prasad lab.

"What makes rotavirus different from most other viruses is that capping takes place inside the tight confines of the viral capsid, the protein shell of the virus, that is inside the cell. Once capping is complete, viral mRNA exits the capsid through channels and enters the cytoplasm of the cell where it engages the protein-making machinery to produce viral proteins," said co-author Dr. Mary K. Estes, Cullen Foundation Endowed Chair and Distinguished Service Professor of molecular virology and microbiology at Baylor.

"Solving this puzzle was very exciting," Kumar said. "We were able to isolate VP3 and its modules and show that they self-assemble into a stable molecule capable of capping at least two mRNAs simultaneously, making the process efficient."

Crucial to this work were the collaborations with Dr. Zhao Wang, assistant professor in the Verna and Marrs McLean Department of Biochemistry and Molecular Biology and co-director of the CryoEM Core at Baylor, and his postdoctoral fellow Dr. Xinzhe Yu as well as Dr. Sue Crawford, assistant professor in the molecular virology and microbiology for the enzymatic and functional assays, and Dr. Liya Hu, assistant professor in the Verna and Marrs McLean Department of Biochemistry and Molecular Biology, for the modeling of cryo-EM-data.

Next steps

Knowing the structure of VP3 and how it works offers the opportunity to design antiviral drugs to prevent or treat rotavirus infection. In addition, it makes it possible to further investigate the role VP3 plays in rotavirus replication and how it interferes with the host's immune response.

"For nearly 30 years, my lab and Dr. Estes's have collaborated to unravel the complex structure of rotavirus and better understand how it works," Prasad said. "Determining the structure and function of VP3 is a major milestone that opens new doors for continuing our collaboration."

CHAPEL HILL, NC - April 16, 2020 - Most research about the genetics of schizophrenia has sought to understand the role that genes play in the development and heritability of schizophrenia. Many discoveries have been made, but there have been many missing pieces. Now, UNC School of Medicine scientists have conducted the largest-ever whole genome sequencing study of schizophrenia to provide a more complete picture of the role the human genome plays in this disease.

Published in Nature Communications, the study co-led by senior author Jin Szatkiewicz, PhD, associate professor in the UNC Department of Genetics, suggests that rare structural genetic variants could play a role in schizophrenia.

"Our results suggest that ultra-rare structural variants that affect the boundaries of a specific genome structure increase risk for schizophrenia," Szatkiewicz said. "Alterations in these boundaries may lead to dysregulation of gene expression, and we think future mechanistic studies could determine the precise functional effects these variants have on biology."

Previous studies on the genetics of schizophrenia have primarily involved using common genetic variations known as SNPs (alterations in common genetic sequences and each affecting a single nucleotide), rare variations in the part of DNA that provide instructions for making proteins, or very large structural variations (alterations affecting a few hundred thousands of nucleotides). These studies give snapshots of the genome, leaving a large portion of the genome a mystery, as it potentially relates to schizophrenia.

In the Nature Communications study, Szatkiewicz and colleagues examined the entire genome, using a method called whole genome sequencing (WGS). The primary reason WGS hasn't been more widely used is that it is very expensive. For this study, an international collaboration pooled funding from National Institute of Mental Health grants and matching funds from Sweden's SciLife Labs to conduct deep whole genome sequencing on 1,165 people with schizophrenia and 1,000 controls - the largest known WGS study of schizophrenia ever.

As a result, new discoveries were made. Previously undetectable mutations in DNA were found that scientists had never seen before in schizophrenia.

In particular, this study highlighted the role that a three-dimensional genome structure known as topologically associated domains (TADs) could play in the development of schizophrenia. TADs are distinct regions of the genome with strict boundaries between them that keep the domains from interacting with genetic material in neighboring TADs. Shifting or breaking these boundaries allows interactions between genes and regulatory elements that normally would not interact.

When these interactions occur, gene expression may be changed in undesirable ways that could result in congenital defects, formation of cancers, and developmental disorders. This study found that extremely rare structural variants affecting TAD boundaries in the brain occur significantly more often in people with schizophrenia than in those without it. Structural variants are large mutations that may involve missing or duplicated genetic sequences, or sequences that are not in the typical genome. This finding suggests that misplaced or missing TAD boundaries may also contribute to the development of schizophrenia. This study was the first to discover the connection between anomalies in TADs and the development of schizophrenia.

This work has highlighted TADs-affecting structural variants as prime candidates for future mechanistic studies of the biology of schizophrenia.

"A possible future investigation would be to work with patient-derived cells with these TADs-affecting mutations and figure out what exactly happened at the molecular level," said Szatkiewicz, an adjunct assistant professor of psychiatry at UNC. "In the future, we could use this information about the TAD effects to help develop drugs or precision medicine treatments that could repair disrupted TADs or affected gene expressions which may improve patient outcomes."

This study will be combined with other WGS studies in order to increase the sample size to further confirm these results. This research will also help the scientific community build on the unfolding genetic mysteries of schizophrenia.

Leesburg, VA, April 16, 2020--To date, the radiology literature on coronavirus disease (COVID-19) pneumonia has consisted of limited retrospective studies that do not substantiate the use of CT as a diagnostic test for COVID-19, according to an open-access Clinical Perspective article in the American Journal of Roentgenology (AJR).

"This is not to say these studies are not valuable," maintained lead investigator Constantine A. Raptis of Washington University in Saint Louis. As Raptis, Travis S. Henry of the University of California-San Francisco, and nine co-authors from six institutions across the United States noted of the most frequently cited studies on the subject, reporting the various CT features of COVID-19 pneumonia remains "an important first step" in helping radiologists identify patients who may have COVID-19 in the appropriate clinical environment.

"However," they continue, "test performance and management issues arise when inappropriate and potentially overreaching conclusions regarding the diagnostic performance of CT for COVID-19 pneumonia are based on low-quality studies with biased cohorts, confounding variables, and faulty design characteristics."

CT Sensitivity

Because misdiagnosing even a single patient (i.e., obtaining a false-negative finding) could result in large outbreaks among future contacts, understanding the potential effects of selection bias is important in determining sensitivity. As Raptis and colleagues explained, "if a study cohort contains patients who are more likely to have a true-positive finding and less likely to have a false-negative finding, sensitivity will be overestimated."

CT Specificity

The specificity and positive predictive value of a laboratory test--in the case of COVID-19, reverse transcription-polymerase chain reaction (RT-PCR)--are based on its ability to limit false-positive findings. Acknowledging false-positive RT-PCR results are possible, Raptis, Henry, et al. maintained they are often caused by contamination and are likely insignificant in the setting of assays for COVID-19. CT, on the other hand, does not test for singular features unique to the disease, and even those features most characteristic of COVID-19 pneumonia--peripheral, bilateral ground-glass opacities typically in the lower lobes--have been reported in a number of other conditions, both infectious and noninfectious.

CT in Clinical Practice

Finally, Raptis and colleagues addressed the hazards of wide deployment of CT: overuse of hospital resources, including the use of PPE already limited in availability but required to safely perform CT studies; clustering of affected and nonaffected patients in the radiology department, increasing the risk of disease transmission among imaging staff.

"At present," the authors of this AJR article concluded, "CT should be reserved for evaluation of complications of COVID-19 pneumonia or for assessment if alternative diagnoses are suspected."

Moderated by AJR Cardiopulmonary Imaging Section Editor Patrick M. Colletti, Constantine A. Raptis and Travis S. Henry served as speakers for a recent AJR Live Webinar exploring the radiography and CT findings associated with EVALI and COVID-19--including the limitations of imaging in their diagnosis.

Dr. Ayse Sena Mutlu, a postdoctoral fellow at Baylor's Huffington Center On Aging, had an intriguing question. Is it possible to change the body's fat storage without changing eating habits?

Working with the laboratory worm C. elegans, Mutlu and her colleagues conducted a broad screen to investigate whether neurons can actively send signals that, without affecting feeding habits, could alter lipid metabolism.

"When we found a connection with the sense of smell, we were very surprised. We expected a link with taste or related to eating," said Mutlu, who works in the laboratory of Dr. Meng Wang, professor of molecular and human genetics, a member of the Huffington Center On Aging and a Howard Hughes Medical Institute investigator at Baylor.

How scents can affect fat storage

The connection between the sense of smell and fat metabolism is not new, but the underlying mechanisms are still not clear. Olfactory perception is complex and highly regulated, explained Mutlu.

"There are many scents in the environment that can be detected by specific olfactory neurons through specific receptors. Olfactory neurons relay the information to interneurons that interpret the information to command other neurons and peripheral tissues," Mutlu said.

Olfactory perception in C. elegans is simpler than in larger organisms, such as humans, which helps researchers like Mutlu and her colleagues to study how olfaction regulates bodily processes. The laboratory worm has three pairs of olfactory neurons that detect a variety of airborne scents. "Some odors selectively activate or inhibit a single olfactory neuron, while others can stimulate a group of neurons," Mutlu said.

The researchers tested several odors in C. elegans and discovered that only certain scents dynamically regulate fat mobilization by interacting with specific olfactory neurons through specific receptors. Using a laboratory method called optogenetics that uses light to activate or inhibit these neurons, the researchers were able to promote the loss or gain of fat storage, respectively. They also determined that the neurons act through a selective neural circuit and a neuroendocrine pathway to directly regulate fat metabolism.

"Our findings bring a new perspective on how lipid metabolism is regulated and may help understand why some people may be more resistant to metabolic problems while others are more vulnerable," said Wang.

In addition, the findings are relevant to the observations that have been made between olfaction, fat metabolism and neurodegenerative diseases.

"For example, we know that patients with Alzheimer's disease tend to have metabolic problems, Mutlu said. "Also, our study suggests a link between the scents each individual can perceive and his or her susceptibility to obesity."

"Although more research is needed, it is possible that certain scents might trigger changes in fat metabolism resulting in weight loss," Wang said. "We may have to watch not only what we eat, but what we smell."

New research published in the British Ecological Society's Journal of Ecology finds that ash dieback is far less severe in the isolated conditions ash is often found in, such as forests with low ash density or in open canopies like hedges, suggesting the long term impact of the disease on Europe's ash trees will be more limited than previously thought.

The research looked at a 22km2 area in North-eastern France, where ash dieback was first observed in 2010. Although the environment had little impact on the initial spread of the disease, the researchers found that after ten years, the disease remained mild in many places.

"We found that the disease had spread to virtually all ash present in the studied landscape within two years. Nevertheless, in many areas ash trees remained relatively healthy" said lead author of the study Dr Benoit Marçais, French National Institute for Agriculture, Food, and Environment (INRAE).

"The view that only the most resistant part of the ash population, just a few percent of the individuals, will survive the ash dieback pandemic is wrong. We see that in many environments not favourable to ash dieback, the proportion of ash that remain heathy is closer to 80-95% than to 5%, although the disease may be locally very severe." added Dr Marçais.

As well as being further apart from each other, isolated ash trees or those in open canopies tended to have higher crown temperatures than those in shaded forests. This is less favourable for the development of the fungal pathogen that causes ash dieback, Hymenoscyphus fraxineus.

High summer temperatures, even in temperate climates like North-eastern France, could further help to reduce the severity of the disease. Climate change is expected to increase the frequency of summer temperatures above 35°C, which the disease cannot survive at.

Reducing the density of threatened tree species by promoting diversity in forest stands could be a valuable strategy in limiting vulnerability to invasive pathogens like ash dieback. With these invasive pathogens occurring more frequently, mixed forest stands may offer protection without the need to target specific pathogens.

Ash dieback originated in Asia and was reported in Poland in the 1990s, it then reached France in 2008 and the UK four years later. The fungal spores infect leaves in the summer before moving to the stem, causing shoot mortality and crown dieback. The fungus survives the winter in leaves in the forest litter before spores are released again in summer. This makes dense stands of ash trees with closed canopies highly susceptible to the fungus.

To understand the impact of landscape on the severity of ash dieback, the researchers performed a landscape survey on a 22km2 area around the village of Champenoux in North-eastern France shortly after the disease arrived, with further surveys taking place annually. Using 25m plots around the study area, the researchers recorded the presence of ash trees and ash dieback, with samples tested for Hymenoscyphus fraxineus.

Dr Marçais cautions that this research applies to the climatic context of North-eastern France. "We show that the low impact of Ash dieback in trees isolated or in hedges is partly linked to high crown temperature during heat waves. In more oceanic climates like northern and western France or Great Britain, this might not be as prominent."

The researchers are looking to further explore the impacts of climate: "We are working on how climate affects ash dieback risk. We have already shown that in south-Eastern France, ash dieback will have very little impact because of high summer temperature." Said Dr Marçais.

Observations made with ESO's Very Large Telescope (VLT) have revealed for the first time that a star orbiting the supermassive black hole at the centre of the Milky Way moves just as predicted by Einstein's general theory of relativity. Its orbit is shaped like a rosette and not like an ellipse as predicted by Newton's theory of gravity. This long-sought-after result was made possible by increasingly precise measurements over nearly 30 years, which have enabled scientists to unlock the mysteries of the behemoth lurking at the heart of our galaxy.

"Einstein's General Relativity predicts that bound orbits of one object around another are not closed, as in Newtonian Gravity, but precess forwards in the plane of motion. This famous effect -- first seen in the orbit of the planet Mercury around the Sun -- was the first evidence in favour of General Relativity. One hundred years later we have now detected the same effect in the motion of a star orbiting the compact radio source Sagittarius A* at the centre of the Milky Way. This observational breakthrough strengthens the evidence that Sagittarius A* must be a supermassive black hole of 4 million times the mass of the Sun," says Reinhard Genzel, Director at the Max Planck Institute for Extraterrestrial Physics (MPE) in Garching, Germany and the architect of the 30-year-long programme that led to this result.

Located 26 000 light-years from the Sun, Sagittarius A* and the dense cluster of stars around it provide a unique laboratory for testing physics in an otherwise unexplored and extreme regime of gravity. One of these stars, S2, sweeps in towards the supermassive black hole to a closest distance less than 20 billion kilometres (one hundred and twenty times the distance between the Sun and Earth), making it one of the closest stars ever found in orbit around the massive giant. At its closest approach to the black hole, S2 is hurtling through space at almost three percent of the speed of light, completing an orbit once every 16 years. "After following the star in its orbit for over two and a half decades, our exquisite measurements robustly detect S2's Schwarzschild precession in its path around Sagittarius A*," says Stefan Gillessen of the MPE, who led the analysis of the measurements published today in the journal Astronomy & Astrophysics.

Most stars and planets have a non-circular orbit and therefore move closer to and further away from the object they are rotating around. S2's orbit precesses, meaning that the location of its closest point to the supermassive black hole changes with each turn, such that the next orbit is rotated with regard to the previous one, creating a rosette shape. General Relativity provides a precise prediction of how much its orbit changes and the latest measurements from this research exactly match the theory. This effect, known as Schwarzschild precession, had never before been measured for a star around a supermassive black hole.

The study with ESO's VLT also helps scientists learn more about the vicinity of the supermassive black hole at the centre of our galaxy. "Because the S2 measurements follow General Relativity so well, we can set stringent limits on how much invisible material, such as distributed dark matter or possible smaller black holes, is present around Sagittarius A*. This is of great interest for understanding the formation and evolution of supermassive black holes," say Guy Perrin and Karine Perraut, the French lead scientists of the project.

This result is the culmination of 27 years of observations of the S2 star using, for the best part of this time, a fleet of instruments at ESO's VLT, located in the Atacama Desert in Chile. The number of data points marking the star's position and velocity attests to the thoroughness and accuracy of the new research: the team made over 330 measurements in total, using the GRAVITY, SINFONI and NACO instruments. Because S2 takes years to orbit the supermassive black hole, it was crucial to follow the star for close to three decades, to unravel the intricacies of its orbital movement.

The research was conducted by an international team led by Frank Eisenhauer of the MPE with collaborators from France, Portugal, Germany and ESO. The team make up the GRAVITY collaboration, named after the instrument they developed for the VLT Interferometer, which combines the light of all four 8-metre VLT telescopes into a super-telescope (with a resolution equivalent to that of a telescope 130 metres in diameter). The[ same team reported in 2018] - another effect predicted by General Relativity: they saw the light received from S2 being stretched to longer wavelengths as the star passed close to Sagittarius A*. "Our previous result has shown that the light emitted from the star experiences General Relativity. Now we have shown that the star itself senses the effects of General Relativity," says Paulo Garcia, a researcher at Portugal's Centre for Astrophysics and Gravitation and one of the lead scientists of the GRAVITY project.

With ESO's upcoming Extremely Large Telescope, the team believes that they would be able to see much fainter stars orbiting even closer to the supermassive black hole. "If we are lucky, we might capture stars close enough that they actually feel the rotation, the spin, of the black hole," says Andreas Eckart from Cologne University, another of the lead scientists of the project. This would mean astronomers would be able to measure the two quantities, spin and mass, that characterise Sagittarius A* and define space and time around it. "That would be again a completely different level of testing relativity," says Eckart.

The expansion of farmlands to meet the growing food demand of the world's ever expanding population places a heavy burden on natural ecosystems. A new IIASA study however shows that about half the land currently needed to grow food crops could be spared if attainable crop yields were achieved globally and crops were grown where they are most productive.

The land sparing debate, which was sparked around 2005 by conservation biologists, recognized that there is usually a limit to the extent to which farmland can be made 'wildlife friendly' without compromising yields, while most threatened species only profit from the sparing or restoration of their natural habitats. Interest in this topic recently gained new momentum through the Half Earth project, which aims to return half the area of land currently being used for other purposes to natural land cover to restrict biodiversity loss and address other impacts of land use such as greenhouse gas emissions.

According to the authors of the study published in Nature Sustainability, the need for this type of strategy is urgent, given the increasing global demand for agricultural products. The study is the first to provide insight into the amount of cropland that would be required to fulfill present crop demands at high land use efficiency without exacerbating major agricultural impacts globally.

"The main questions we wanted to address were how much cropland could be spared if attainable crop yields were achieved globally and crops were grown where they are most productive. In addition, we wanted to determine what the implications would be for other factors related to the agricultural sector, including fertilizer and irrigation water requirements, greenhouse gas emissions, carbon sequestration potential, and wildlife habitat available for threatened species," explains study lead author Christian Folberth, a researcher in the IIASA Ecosystems Services and Management Program.

The study results indicate that with high nutrient inputs and reallocation of crops on present cropland, only about half the present cropland would be required to produce the same amounts of major crops. The other half could then in principle be used to restore natural habitats or other landscape elements. The findings also show that land use is currently somewhat inefficient and not primarily due to the upper limits to crop yields as determined by climate in many parts of the world, rather, it is strongly subject to management decisions.

It is difficult to say exactly how much biodiversity is impacted as a direct result of agricultural activities, but it is estimated to exceed safe boundaries, primarily due to habitat loss. In this regard, the researchers evaluated two scenarios: the first proposes maximum land sparing without constraints, except for the present cropland extent, while the second scenario puts forward targeted land sparing that abandons cropland in biodiversity hotspots and uniformly releases 20% of cropland globally. There were only marginal differences between the two scenarios in most aspects, except for wildlife habitat, which only increased significantly with targeted land sparing. This however still enabled reducing the cropland requirement by almost 40%.

Furthermore, the researchers found that greenhouse gas emissions and irrigation water requirements are likely to decrease with a reduced area of cultivated land, while global fertilizer input requirements would remain unchanged. Spared cropland could also provide space for substantial carbon sequestration in restored natural vegetation. Yet, potentially adverse local impacts of intensive farming and land sparing such as nutrient pollution or loss of income in rural areas will need to be studied further.

"The results of our study can help policymakers and the wider public to benchmark results of integrated land use scenarios. It also shows that cropland expansion is not inevitable and that there is significant potential for improving present land use efficiency. If the right policies are implemented, measures such as improved production technologies can be just as effective as demand-side measures like dietary changes," says project lead and former IIASA Ecosystems Services and Management Program Director Michael Obersteiner. "However, in all cases such a process would need to be steered by policies to avoid unwanted outcomes."

What The Study Did: Whether visual impairment is a risk factor for dementia was the focus of this observational study that included 1,000 older women who are participants in the Women's Health Initiative studies.

Authors: Suzann Pershing, M.D., M.S., of the Stanford University School of Medicine in Palo Alto, California, 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/jamaophthalmol.2020.0959)

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

Cold Spring Harbor, NY -- In the urgent battle to treat COVID-19 patients, a group of eleven international medical research organizations is investigating whether overactive immune cells that produce Neutrophil Extracellular Traps (NETs) cause the most severe cases. The consortium, called the NETwork, includes Cold Spring Harbor Laboratory, the Feinstein Institutes for Medical Research, and the Research Institute of the McGill University Health Centre (RI-MUHC).

A paper published today in the Journal of Experimental Medicine describes that patients with severe COVID-19 infection develop Acute Respiratory Distress Syndrome (ARDS), pulmonary inflammation, thick mucus secretions in the airways, extensive lung damage, and blood clots. This late stage of the disease is difficult to manage. In the worst cases, patients require invasive mechanical ventilation, and still, a large number of patients die. The NETwork suggests that the severity of COVID-19 may result from overactive white blood cells known as the neutrophils. Part of the body's immune system, neutrophils detect bacteria and can expel their DNA to attack the bacteria with a gauzy web of DNA laced with toxic enzymes, called a NET. These NETs can ensnare and digest the unwanted pathogen but in cases of ARDS, they damage the lungs and other organs.

"Given the clear similarities between the clinical presentation of severe COVID-19 and other known diseases driven by NETs, such as ARDS, we propose that excess NETs may play a major role in the disease," said Betsy Barnes, Ph.D., lead and co-corresponding author of the paper and professor at the Feinstein Institutes. "As samples from patients become available, it will be important to determine whether the presence of NETs associates with disease severity and/or particular clinical characteristics of COVID-19."

[Watch - How NETs Harm Lungs: https://www.youtube.com/watch?v=HgrpG6n8z_c]

"NETs were identified in 2004, but many scientists have never heard of them. Most of the researchers in the NETwork have worked on NETs in other diseases, and when we started hearing about the symptoms of the COVID-19 patients, it sounded familiar," said Cold Spring Harbor Laboratory cancer biologist Mikala Egeblad, Ph.D., who coalesced the NETwork research group around COVID-19 and is senior and corresponding author of the paper.

Jonathan Spicer, M.D., Ph.D., a clinician scientist at the RI-MUHC and Assistant Professor of Surgery at McGill University is a thoracic surgeon who has witnessed the devastating effects of COVID-19 infection at the bedside. "We see in these patients severe lung damage known as ARDS, another serious problem caused by excess NETs and seen in cases of severe influenza," he said. "In addition, their airways are often clogged with thick mucus and unlike most severe lung infections, these patients tend to form small clots throughout their body at much higher rates than normal. NETs have also been found in the blood of patients with sepsis or cancer, where they can facilitate the formation of such blood clots."

Researchers at the eleven NETwork institutions are now pursuing studies into whether NETs are a common feature in COVID-19 cases. If their findings show that excess NETs cause the severe symptoms of COVID-19, then a new avenue of treatments may be deployed to help COVID-19 patients. Current treatments used in other NET and neutrophil-driven diseases--like cystic fibrosis, gout, and rheumatoid arthritis--might dampen the activity of NETs in COVID-19 patients, reducing the need for invasive mechanical ventilation.

The following research institutes comprise the NETwork: Cold Spring Harbor Laboratory, the Feinstein Institutes for Medical Research, McGill University Health Centre, Weill Cornell Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Centre Hospitalier Universitaire de Nancy, University of Michigan, University of California, San Francisco, University of Texas MD Anderson Cancer Center, University of Utah School of Medicine, and Northwell Health.

University of Phoenix today announced Harris Poll findings regarding U.S. adults' perceptions of the COVID-19 pandemic. The survey found more than two in five (41 percent) of Americans say they are most concerned about experiencing increased anxiety; more so than not being able to pay their bills (33 percent), reduced job salary/work hours (26 percent), or losing their job/not being able to get a new job (22 percent).

Respondents expressed other mental health concerns as well. More than 2 in 3 Americans (68 percent) say they feel like everything is out of their control right now and more than half (56 percent) say they are balancing more now than ever before during this pandemic.

Although Americans report feelings of being overwhelmed and anxious, they also express feelings of gratitude and hope with 65 percent saying they are thankful for their health, family and friends. Americans are also looking toward the future when social distancing guidelines are lifted. The survey found nearly 2 in 5 (38 percent) are optimistic that the country will come out of this pandemic stronger than ever and 30 percent are making plans for a post-pandemic future.

Still, many Americans are worried about the long- term mental health repercussions of being quarantined. The vast majority of Americans (84 percent) say that if the social distancing continues longer than they expect, it will have an impact on their mental health.

"While many people are currently feeling anxiety, there can be several ways to maintain good mental health by making small behavior changes," said Dr. Dean Aslinia, counseling department chair at University of Phoenix. "Instead of texting or emailing, make a phone call or use video chat to build a more meaningful connection. Build activity in your day by trying something new or setting a goal for yourself to start a new project. Remember, it is okay to seek professional help, if your negative feelings persist. Many mental health practitioners are offering virtual counseling sessions so you can have someone to talk to without leaving the house.

WHAT ARE RESPONDENTS DOING TO IMPROVE THEIR MENTAL HEALTH?

If there is a silver lining in social distancing, the survey suggests that many people are engaging in activities to maintain connections and improve their mental health.

Checked in with a loved one - 60 percent
Increased my exercise - 35 percent
Limited my news consumption - 30 percent
Performed acts of kindness for others - 29 percent

"It is encouraging to see some people take this time to practice habits that will improve their mental health, said Dr. Aslinia. "Feelings of anxiety are not solely due to isolation or social distancing. The everyday choices we make including technology overuse, impersonal interactions and engaging with people that are unhealthy for us, all lead to anxiety. If something good can come from this pandemic, we can hopefully recognize the need for intentional behaviors that maintain and improve our mental health."