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Even if a black hole can be described with a mathematical model, it doesn't mean it exists in reality. Some theoretical models are unstable: though they can be used to run mathematical calculations, from the point of view of physics they make no sense. A physicist from RUDN University developed an approach to finding such instability regions. The work was published in the Physics of the Dark Universe journal.

The existence of black holes was first predicted by Einstein's general theory of relativity. These objects have so strong gravitational pull that nothing, not even light, can escape them. Dense and massive, black holes deform space-time (a physical construct with three spatial and one temporal dimension). Many mathematical models used to describe black holes include corrections to account for such space-time curvatures. The main condition of existence for every black hole model is its stability in cases of minor spatial or temporal changes. Mathematically unstable black holes make no physical sense, as the objects they describe cannot exist in reality. A physicist from RUDN University suggested a method to identify black hole instability parameters in 4D space-time.

"For a model to be considered feasible, a black hole described by it has to remain stable in case of minor space-time fluctuations. One of the most promising approaches to developing alternative gravity theories includes adding corrections to Einstein's equation, including the fourth-order Gauss-Bonnet correction and the Lovelock correction that provides a higher level of generalization," said Roman Konoplya, a researcher at the Educational and Research Institute of Gravitation and Cosmology, RUDN University.

The physicist studied stability in the Einstein-Gauss-Bonnet theory in which a black hole is described by Einstein's equation with a fourth additional component. Previously, he had focused on a different mathematical description of a black hole, the so-called Lovelock theory, that describes a black hole as a sum of an infinite number of components. The instability region turned out to be closely associated with the values of the so-called coupling constants: numerical coefficients by which the corrections to Einstein's equation are multiplied.

According to the physicist, the Einstein-Gauss-Bonnet model does not provide for the existence of small black holes, because if coupling constants are relatively big compared to other parameters (such as the radius of a black hole), the model almost always turns out to be unstable. The stability region is much bigger if the coupling constant has a negative value. Based on these calculations, he and his team developed a program to calculate black hole stability based on any of its parameters.

"Our approach helps test black hole models for stability. We made the code publicly available so that any of our colleagues could use it to calculate instability regions for models with an unspecified set of parameters," added Roman Konoplya.

Zoologists at the University of Cologne studied the nervous systems of insects to investigate principles of biological brain computation and possible implications for machine learning and artificial intelligence. Specifically, they analysed how insects learn to associate sensory information in their environment with a food reward, and how they can recall this information later in order to solve complex tasks such as the search for food. The results suggest that the transformation of sensory information into memories in the brain can inspire future machine learning and artificial intelligence applications to solving complex tasks. The study has been published in the journal PNAS.

Living organisms show remarkable abilities in coping with problems posed by complex and dynamic environments. They are able to generalize their experiences in order to rapidly adapt their behaviour when the environment changes. The zoologists investigated how the nervous system of the fruit fly controls its behaviour when searching for food. Using a computer model, they simulated and analysed the computations in the fruit fly's nervous system in response to scents emanated from the food source. 'We initially trained our model of the fly brain in exactly the same way as insects are trained in experiments. We presented a specific scent in the simulation together with a reward and a second scent without a reward. The model rapidly learns a robust representation of the rewarded scent after just a few scent presentations and is then able to find the source of this scent in a spatially complex and temporally dynamic environment,' said computer scientist Dr Hannes Rapp, who created the model as part of his doctoral thesis at the UoC's Institute of Zoology.

The model created is thus capable to generalize from its memory and to apply what it has learned previously in a completely new and complex odour molecule landscape, while learning required only a very small database of training samples. 'For our model, we exploit the special properties of biological information processing in nervous systems,' explained Professor Dr Martin Nawrot, senior author of the study. 'These are in particular a fast and parallel processing of sensory stimuli by means of brief nerve impulses as well as the formation of a distributed memory through the simultaneous modification of many synaptic contacts during the learning process.' The theoretical principles underlying this model can also be used for artificial intelligence and autonomous systems. They enable an artificial agent to learn much more efficiently and to apply what it has learned in a changing environment.

One of the novel coronavirus' most insidious tricks is that it can block the ability of cells to produce protective proteins without hindering its own ability to replicate.

Now, a multidisciplinary team of Yale researchers has discovered how SARS-CoV-2, the virus that causes COVID-19, accomplishes this trick by blocking production of cellular proteins, including immune molecules, and contributes to severe illness in its host.

"The virus essentially reprograms host cells, and by understanding this mechanism we can hopefully design new therapeutics,'' said Yong Xiong, professor of molecular biophysics and biochemistry and co-corresponding author of the research published in the journal Molecular Cell.

Previous studies had implicated a viral protein, nonstructural protein 1 or Nsp1, in the COVID-19 virus' ability to block cells' ability to produce new proteins. But exactly how NsP1 works in a cell was not known.

Using advanced genetic screening and cryogenic electron microscopy (cryo-EM), the Yale team was able to show that Nsp1 is one of SARS-CoV-2's most pathogenic viral proteins. In human lung cells, it can drastically alter host cell gene expression and essentially form a plug that prevents the ribosome, the cell's protein-making machinery, from receiving genetic instructions for new proteins encoded in messenger RNA.

"This is the entry channel for genetic material, and when it is blocked no protein can be made," Xiong explained. "We didn't understand this mechanism before, but now we know."

This process affects protein production in many parts of the body, and high levels of Nsp1 may help explain why some people fare poorly after infection by the virus, he said.

However, it remains unknown how the virus is still able to produce its own proteins, using the same ribosome, to replicate in the cell after it disables the cell's ability to make normal proteins, Xiong said.

New research by BAT has found that smokers who switched completely from smoking cigarettes to using BAT's flagship tobacco heating product (THP), glo, substantially reduced their exposure to certain cigarette smoke toxicants over three months.

For many of the toxicants measured, the levels found in participants were similar to those in people that stopped using tobacco completely.

This supports BAT's ambition to build A Better Tomorrow by reducing the health impact of its business, given respected public health agencies say that to be considered a modified risk tobacco product, switching completely should have a similar outcome for the smoker to quitting.

Scientists at BAT are conducting the UK's first ever year-long controlled study to see what impact switching from cigarettes to glo will have on general health as well as smoke-toxicant exposure.

Today's results find that smokers who switch from cigarettes to glo exclusively significantly reduce the levels of harmful toxicants they are exposed to, potentially reducing their risk of developing smoking-related diseases. Further results from this study will provide more evidence to help understand the impact of switching to glo and will be announced once the study has been completed.

Dr James Murphy, Group Head of Potentially Reduced-Risk Product Science, commented: "These initial results regarding glo are extremely encouraging - glo provides smokers who wish to continue using tobacco and nicotine products with a potentially reduced risk alternative to cigarettes. The results are another positive step for BAT as we continue our journey to reduce the health impact of our business by offering consumers a range of enjoyable and potentially reduced-risk products."

EUGENE, Ore. -- Nov. 5, 2020 -- Conservation efforts on the edges of the Amazon forest, especially in light of recent deforestation by human disturbance, could help the region weather the storm of climate change, researchers say.

That assessment comes from an analysis of vegetation changes and carbon isotope signatures in the soil at 83 sites. The project, led by University of Oregon doctoral student Jamie Wright, established a record of soil changes associated with both climate and human activity over the last 1,600 years based on radiocarbon dating.

The study was published online Oct. 30 ahead of print in Global Change Biology.

Woody vegetation expansion into savannas, the research team found, had continued amid increasing moisture levels regardless of human impacts until only recently, mostly from rapid deforestation in the last decade. Climate modeling previously has suggested that local water and carbon cycles, as well as global climate patterns, are at risk.

"The past, like most things, leaves a trace behind and with it a rich history left to be told," said Wright, a member of the UO's Soil Plant Atmosphere Lab headed by co-author Lucas Silva, a professor in the Environmental Studies Program.

The forest-savanna borderlands, known as the Amazon-Cerrado transition, experience broad climatic and ecological influences. The study helped address uncertainties of those influences in the tropical ecosystem.

"Through the use of soil science, specifically with carbon isotopes, we unearthed a history of forest expansion over several millennia. This region is at the epicenter of deforestation and socio-ecological transformations that cause and drive climate change," Wright said.

Previous studies had suggested that forest expansion was primarily driven by increased precipitation, but that work, Silva noted, did not fully consider the impacts of local influences, such as fire frequency and intensity or whether it was occurring because of climate dynamics in the region. Focusing on soil changes, he said, allowed for these factors to be examined.

"Carbon storage in woody savannas and forests plants at this large of scale can be a significant carbon sink," Wright said. "Increasing tree cover also can ameliorate adverse climatic change impacts, such as droughts, by influencing the hydrological cycle and generating rain clouds."

In total, 742 soil samples were taken from forests, savannas and transition zones across a large swath of north-central Brazil, between latitudes 4 to 16 degrees south and longitudes 46 to 56 degrees west -- an area where precipitation and distribution vary significantly.

The research team also measured the leaf index of the ecosystem's cover, mostly the forest canopy, to understand changes in carbon isotope signatures in the soil. Such changes reflect land usage. To determine changes over time, radiocarbon activity and isotopic ratios were profiled in 43 selected depths that represented the different sites.

While the research affirmed that forest expansion has occurred in most of the past 1,600 years, the researchers found a trend of decreasing woody vegetation in the study area's easternmost sites. The decline, they said, may reflect the prevalence of dry deciduous or semi-deciduous tree species in those areas.

The observed incremental expansion into savannas, they wrote, could have significant impacts on carbon-water relations, potentially affecting the balance between precipitation and evapotranspiration as seen in previous research. However, they noted, they did not see a clear effect of changes in vegetation on soil carbon stocks.

Future studies, they said, are needed to focus on the mechanisms that drive the permanence of carbon derived from woody vegetation expansion, especially because of recent documentation of hotter and longer dry seasons, as well as rising mortality rates of wet climate species.

The next phase of understanding, they said, will come from integrating plant, soil and atmospheric data to understand the influence of human activity on ecosystem-climate feedbacks as a path towards improving carbon sequestration and water conservation.

"Our data indicate a regional increase in tree cover prior to modern deforestation, which could help inform conservation and management for climate change mitigation," said Silva, who also is a professor of geography and member of the Institute of Ecology and Evolution. "We hope that our research will lead to a greater appreciation of ecological processes in the region and their importance for global climatic stability."

In addition to Silva and Wright, the study's co-authors are Barbara Bomfim, a former postdoctoral researcher in Silva's lab who is now at the Lawrence Berkeley National Laboratory, Corrine Wong of Boston College, and Ben Hur Marimon-Junior and Beatriz Marimon, both of the State University of Mato Grosso in Nova Xavantina, Brazil.

The research team is continuing to work closely with collaborators in the Amazon region in an effort to secure funding to launch a reforestation project, Silva said.

Peculiar hybrid structures called retrons that are half RNA, half single-strand DNA are found in many species of bacteria. Since their discovery around 35 years ago, researchers have learned how to use retrons for producing single strands of DNA in the lab, but no one knew what their function was in the bacteria, despite much research into the matter. In a paper published today in Cell, a Weizmann Institute of Science team reports on solving the longstanding mystery: Retrons are immune system "guards" that ensure the survival of the bacterial colony when it is infected by viruses. In addition to uncovering a new strategy used by bacteria to protect themselves against viral infection -- one that is surprisingly similar to that employed by plant immune systems -- the research revealed many new retrons that may, in the future, add to the genome-editing toolkit.

The study, conducted in the lab of Prof. Rotem Sorek of the Institute's Molecular Genetics Department, was led by Adi Millman, Dr. Aude Bernheim and Avigail Stokar-Avihail in his lab. Sorek and his team did not set out to solve the retron mystery; they were seeking new elements of the bacterial immune system, specifically elements that help bacteria to fend off viral infection. Their search was made easier by their recent finding that bacteria's immune system genes tend to cluster together in the genome within so-called defense islands. When they uncovered the unique signature of retron within a bacterial defense island, the team decided to investigate further.

Their initial research showed that this retron was definitely involved in protecting bacteria against the viruses known as phages that specialize in infecting bacteria. As the researchers looked more closely at additional retrons located near known defense genes, they found that the retrons were always connected - physically and functionally - to one other gene. When either the accompanying gene or the retron was mutated, the bacteria were less successful in fighting off phage infection.

The researchers then set out to look for more such complexes in defense islands. Eventually, they identified some 5,000 retrons, many of them new, in different defense islands of numerous bacterial species.

To check if these retrons function, generally, as immune mechanisms, the researchers transplanted many retrons, one by one, into laboratory bacterial cells that were lacking retrons. As they suspected, in a great number of these cells they found retrons protecting the bacteria from phage infection.

How do retrons do this? Focusing back on one particular kind of retron and tracing its actions in the face of phage infection, the research team discovered that its function is to cause the infected cell to commit suicide. Cell suicide, once thought to belong solely to multicellular organisms, is a last-ditch means of aborting widespread infection - if the suicide mechanism works fast enough to kill the cell before the virus finishes making copies of itself and spreading out to other cells.

Further investigation showed that retrons do not sense the phage invasion itself, but rather keep watch on another part of the immune system known as RecBCD, which is one of the bacterium's first lines of defense. If it realizes that the phage has tampered with the cell's RecBCD, the retron activates its program through the second, linked genes to kill the infected cell and protect the rest of the colony.

"It's a clever strategy, and we found it works in a similar way to a guard mechanism employed in plant cells," says Sorek. "Just like viruses that infect plants, phages come equipped with a variety of inhibitors to block assorted parts of the cell immune response. The retron, like a guard mechanism known to exist in plants, does not need to be able to identify all possible inhibitors, just to have a handle on the functioning of one particular immune complex. Infected plant cells apply this 'abortive infection' method, killing off a small region of a leaf or root, in an effort to save the plant itself. Since most bacteria live in colonies, this same strategy can promote the survival of the group, even at the expense of individual members."

Retrons are so useful to biotechnology because they begin with a piece of RNA, which is the template for the synthesis of the DNA strand. This template in the retron sequence can be swapped out for any desired DNA sequence and used, sometimes in conjunction with another tool borrowed from the bacterial immune toolkit - CRISPR - to manipulate genes in various ways. Sorek and his team believe that within the diverse list of retrons they identified may be hiding more than a few that could provide better templates for specific gene editing needs.

Since the Affordable Care Act's (ACA) Medicaid expansion program went into effect 10 years ago, the U.S. has seen a larger reduction in the number of uninsured low-income, rural residents, compared to their urban contemporaries.

But the likelihood of repeated visits to emergency rooms for non-urgent reasons has not decreased.

That's what Washington State University's Bidisha Mandal discovered in a new paper published in the journal Applied Economic Perspectives and Policy.

"Using emergency departments for non-urgent care is often a sign that people don't have convenient access to doctors," said Mandal, a professor in WSU's School of Economic Sciences. "With more people having insurance under the ACA, demand has increased for doctors. Supply seems to have gone up in cities, but not in rural areas."

Non-urgent visits put an additional strain on emergency rooms, and cost more for patients as well, she said.

One potential reason that non-urgent emergency room visits haven't decreased with more insurance is that Medicaid reimbursements for doctors are lower than other insurances. Physicians don't have a monetary incentive to increase the number of low-income patients they see.

"I was surprised to see that low-income rural residents actually had more insurance gains than urban residents," Mandal said. "But providers just don't have enough incentive to accept new Medicaid patients."

Low-income people benefited from the ACA's Medicaid expansion, and the Supreme Court ruling that made the expansion optional for states allowed researchers to compare outcomes between states that accepted or rejected the expansion, Mandal said.

She also found that the number of annual checkups has increased for low-income people in rural areas. But those additional visits haven't led to fewer non-urgent ER visits.

Mandel hopes policymakers looking to improve the ACA will read papers like hers to see and fix weaknesses in the law.

"There are definite gaps in the ACA, and I hope this paper helps fill some of them," Mandal said. "Having access to proper medical care is really important for our entire population."

Scientists at the University of Cambridge, in collaboration with Justus-Liebig University, Germany, have uncovered how the genome of SARS-CoV-2 - the coronavirus that causes COVID-19 - uses genome origami to infect and replicate successfully inside host cells. This could inform the development of effective drugs that target specific parts of the virus genome, in the fight against COVID-19.

SARS-CoV-2 is one of many coronaviruses. All share the characteristic of having the largest single-stranded RNA genome in nature. This genome contains all the genetic code the virus needs to produce proteins, evade the immune system and replicate inside the human body. Much of that information is contained in the 3D structure adopted by this RNA genome when it infects cells.

The researchers say most current work to find drugs and vaccines for COVID-19 is focused on targeting the proteins of the virus. Because the shape of the RNA molecule is critical to its function, targeting the RNA directly with drugs to disrupt its structure would block the lifecycle and stop the virus replicating.

In a study published today in the journal Molecular Cell, the team uncovered the entire structure of the SARS-CoV-2 genome inside the host cell, revealing a network of RNA-RNA interactions spanning very long sections of the genome. Different functional parts along the genome need to work together despite the great distance between them, and the new structural data shows how this is accomplished to enable the coronavirus life cycle and cause disease.

"The RNA genome of coronaviruses is about three times bigger than an average viral RNA genome - it's huge," said lead author Dr Omer Ziv at the University of Cambridge's Wellcome Trust/Cancer Research UK Gurdon Institute.

He added: "Researchers previously proposed that long-distance interactions along coronavirus genomes are critical for their replication and for producing the viral proteins, but until recently we didn't have the right tools to map these interactions in full. Now that we understand this network of connectivity, we can start designing ways to target it effectively with therapeutics."

In all cells the genome holds the code for the production of specific proteins, which are made when a molecular machine called a ribosome runs along the RNA reading the code until a 'stop sign' tells it to terminate. In coronaviruses, there is a special spot where the ribosome only stops 50% of the times in front of the stop sign. In the other 50% of cases, a unique RNA shape makes the ribosome jump over the stop sign and produce additional viral proteins. By mapping this RNA structure and the long-range interactions involved, the new research uncovers the strategies by which coronaviruses produce their proteins to manipulate our cells.

"We show that interactions occur between sections of the SARS-CoV-2 RNA that are very long distances apart, and we can monitor these interactions as they occur during early SARS-CoV-2 replication," said Dr Lyudmila Shalamova, a co-lead investigator at Justus-Liebig University, Germany.

Dr Jon Price, a postdoctoral associate at the Gurdon Institute and co-lead of this study, has developed a free, open-access interactive website hosting the entire RNA structure of SARS-CoV-2. This will enable researchers world-wide to use the new data in the development of drugs to target specific regions of the virus's RNA genome.

The genome of most human viruses is made of RNA rather than DNA. Ziv developed methods to investigate such long-range interactions across viral RNA genomes inside the host cells, in work to understand the Zika virus genome. This has proved a valuable methodological basis for understanding SARS-CoV-2.

Quick flashes of light in the night sky have been linked to the growing mass of satellites and debris zipping around Earth's orbit.

The orbital flashes, often mistaken for stars, are extremely common, occurring 1,000 times an hour, according to new research led by the University of North Carolina at Chapel Hill that may improve the accuracy of astronomical data.

Stargazers have long been tantalized by the inexplicable glimmers and the study published Nov. 5 in The Astrophysical Journal Letters provides a potential explanation for those mysterious flashes.

Most of the flashes require powerful telescopes for viewing, but up to 100 of them are bright enough to see with the naked eye in a suburban community.

"Astronomical surveys have seen occasional reflected light glints from satellites; those flashes can cause false alarms in surveys looking for new events in the sky," said lead study author Hank Corbett, graduate student at the UNC-Chapel Hill Department of Physics and Astronomy.

"For the first time, we have studied the flashes in a systematic way that will help reduce their impact on astronomical discoveries."

The team at UNC-Chapel Hill, along with collaborators from San Diego State University and the University of Barcelona, reported more than 100,000 flashes over a six-month period.

The flashes were observed with the Evryscopes, telescopes in California and Chile constructed and funded by the National Science Foundation. The pair of robotic, gigapixel-camera telescopes observe the entire sky above their observatories every two minutes.

"These measurements allow us to predict the impact of reflected-light flashes on both current and future professional observatories and develop techniques to mitigate their effects on data," Corbett said.

The orbital flashes are reflected not only from the satellites relied on for navigation, communication, weather forecasting, and more, but also from space trash such as dead satellites, paint chips and errant nuts and bolts that has accumulated since space exploration began six decades ago.

These short duration flashes can be indistinguishable from stars in images from professional observatories and are typically visible for only a fraction of a second.

"Millions of stargazers have likely observed these quick glimmers of light in the night sky," Corbett said. "Reflected-light flashes happen so fast that observers may dismiss them as visual noise, but this research provides a potential explanation for those mysterious flashes.

Rogue reflections from Earth satellites take two forms: short duration flashes that can lead to mistaken astrophysical events and streaks associated with fast-moving or slowly rotating satellites like SpaceX Starlink.

Companies are competing to launch thousands of satellites capable of beaming internet coverage to Earth. However, in the new study, researchers conclude that the upcoming satellite internet constellations, like SpaceX Starlink, are unlikely to contribute significantly to the appearance of flashes, though there are other potential impacts of satellite constellations on astronomers.

Bright streaks caused by sun-illuminated satellites moving across an image are a separate class of events that needs to be studied.

CAMBRIDGE, MA -- Dealing with a global pandemic has taken a toll on the mental health of millions of people. A team of MIT and Harvard University researchers has shown that they can measure those effects by analyzing the language that people use to express their anxiety online.

Using machine learning to analyze the text of more than 800,000 Reddit posts, the researchers were able to identify changes in the tone and content of language that people used as the first wave of the Covid-19 pandemic progressed, from January to April of 2020. Their analysis revealed several key changes in conversations about mental health, including an overall increase in discussion about anxiety and suicide.

"We found that there were these natural clusters that emerged related to suicidality and loneliness, and the amount of posts in these clusters more than doubled during the pandemic as compared to the same months of the preceding year, which is a grave concern," says Daniel Low, a graduate student in the Program in Speech and Hearing Bioscience and Technology at Harvard and MIT and the lead author of the study.

The analysis also revealed varying impacts on people who already suffer from different types of mental illness. The findings could help psychiatrists, or potentially moderators of the Reddit forums that were studied, to better identify and help people whose mental health is suffering, the researchers say.

"When the mental health needs of so many in our society are inadequately met, even at baseline, we wanted to bring attention to the ways that many people are suffering during this time, in order to amplify and inform the allocation of resources to support them," says Laurie Rumker, a graduate student in the Bioinformatics and Integrative Genomics PhD Program at Harvard and one of the authors of the study.

Satrajit Ghosh, a principal research scientist at MIT's McGovern Institute for Brain Research, is the senior author of the study, which was published last month in the Journal of Internet Medical Research. Other authors of the paper include Tanya Talkar, a graduate student in the Program in Speech and Hearing Bioscience and Technology at Harvard and MIT; John Torous, director of the digital psychiatry division at Beth Israel Deaconess Medical Center; and Guillermo Cecchi, a principal research staff member at the IBM Thomas J. Watson Research Center.

A wave of anxiety

The new study grew out of the MIT class 6.897/HST.956 (Machine Learning for Healthcare), in MIT's Department of Electrical Engineering and Computer Science. Low, Rumker, and Talkar, who were all taking the course last spring, had done some previous research on using machine learning to detect mental health disorders based on how people speak and what they say. After the Covid-19 pandemic began, they decided to focus their class project on analyzing Reddit forums devoted to different types of mental illness.

"When Covid hit, we were all curious whether it was affecting certain communities more than others," Low says. "Reddit gives us the opportunity to look at all these subreddits that are specialized support groups. It's a really unique opportunity to see how these different communities were affected differently as the wave was happening, in real-time."

The researchers analyzed posts from 15 subreddit groups devoted to a variety of mental illnesses, including schizophrenia, depression, and bipolar disorder. They also included a handful of groups devoted to topics not specifically related to mental health, such as personal finance, fitness, and parenting.

Using several types of natural language processing algorithms, the researchers measured the frequency of words associated with topics such as anxiety, death, isolation, and substance abuse, and grouped posts together based on similarities in the language used. These approaches allowed the researchers to identify similarities between each group's posts after the onset of the pandemic, as well as distinctive differences between groups.

The researchers found that while people in most of the support groups began posting about Covid-19 in March, the group devoted to health anxiety started much earlier, in January. However, as the pandemic progressed, the other mental health groups began to closely resemble the health anxiety group, in terms of the language that was most often used. At the same time, the group devoted to personal finance showed the most negative semantic change from January to April 2020, and significantly increased the use of words related to economic stress and negative sentiment.

They also discovered that the mental health groups affected the most negatively early in the pandemic were those related to ADHD and eating disorders. The researchers hypothesize that without their usual social support systems in place, due to lockdowns, people suffering from those disorders found it much more difficult to manage their conditions. In those groups, the researchers found posts about hyperfocusing on the news and relapsing back into anorexia-type behaviors since meals were not being monitored by others due to quarantine.

Using another algorithm, the researchers grouped posts into clusters such as loneliness or substance use, and then tracked how those groups changed as the pandemic progressed. Posts related to suicide more than doubled from pre-pandemic levels, and the groups that became significantly associated with the suicidality cluster during the pandemic were the support groups for borderline personality disorder and post-traumatic stress disorder.

The researchers also found the introduction of new topics specifically seeking mental health help or social interaction. "The topics within these subreddit support groups were shifting a bit, as people were trying to adapt to a new life and focus on how they can go about getting more help if needed," Talkar says.

While the authors emphasize that they cannot implicate the pandemic as the sole cause of the observed linguistic changes, they note that there was much more significant change during the period from January to April in 2020 than in the same months in 2019 and 2018, indicating the changes cannot be explained by normal annual trends.

Mental health resources

This type of analysis could help mental health care providers identify segments of the population that are most vulnerable to declines in mental health caused by not only the Covid-19 pandemic but other mental health stressors such as controversial elections or natural disasters, the researchers say.

Additionally, if applied to Reddit or other social media posts in real-time, this analysis could be used to offer users additional resources, such as guidance to a different support group, information on how to find mental health treatment, or the number for a suicide hotline.

"Reddit is a very valuable source of support for a lot of people who are suffering from mental health challenges, many of whom may not have formal access to other kinds of mental health support, so there are implications of this work for ways that support within Reddit could be provided," Rumker says.

The researchers now plan to apply this approach to study whether posts on Reddit and other social media sites can be used to detect mental health disorders. One current project involves screening posts in a social media site for veterans for suicide risk and post-traumatic stress disorder.

PITTSBURGH, Nov. 5, 2020 - Today in Science, researchers at the University of Pittsburgh School of Medicine describe a new method to extract tiny but extremely powerful SARS-CoV-2 antibody fragments from llamas, which could be fashioned into inhalable therapeutics with the potential to prevent and treat COVID-19.

These special llama antibodies, called "nanobodies," are much smaller than human antibodies and many times more effective at neutralizing the SARS-CoV-2 virus. They're also much more stable.

"Nature is our best inventor," said senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. "The technology we developed surveys SARS-CoV-2 neutralizing nanobodies at an unprecedented scale, which allowed us to quickly discover thousands of nanobodies with unrivaled affinity and specificity."

To generate these nanobodies, Shi turned to a black llama named Wally--who resembles and therefore shares his moniker with Shi's black Labrador.

Shi and colleagues immunized the llama with a piece of the SARS-CoV-2 spike protein and, after about two months, the animal's immune system produced mature nanobodies against the virus.

Using a mass spectrometry-based technique that Shi has been perfecting for the past three years, lead author Yufei Xiang, a research assistant in Shi's lab, identified the nanobodies in Wally's blood that bind to SARS-CoV-2 most strongly.

Then, with the help of Pitt's Center for Vaccine Research (CVR), the scientists exposed their nanobodies to live SARS-CoV-2 virus and found that just a fraction of a nanogram could neutralize enough virus to spare a million cells from being infected.

These nanobodies represent some of the most effective therapeutic antibody candidates for SARS-CoV-2, hundreds to thousands of times more effective than other llama nanobodies discovered through the same phage display methods used for decades to fish for human monoclonal antibodies.

Shi's nanobodies can sit at room temperature for six weeks and tolerate being fashioned into an inhalable mist to deliver antiviral therapy directly into the lungs where they're most needed. Since SARS-CoV-2 is a respiratory virus, the nanobodies could find and latch onto it in the respiratory system, before it even has a chance to do damage.

In contrast, traditional SARS-CoV-2 antibodies require an IV, which dilutes the product throughout the body, necessitating a much larger dose and costing patients and insurers around $100,000 per treatment course.

"Nanobodies could potentially cost much less," said Shi. "They're ideal for addressing the urgency and magnitude of the current crisis."

In collaboration with Cheng Zhang, Ph.D., at Pitt, and Dina Schneidman-Duhovny, Ph.D., at the Hebrew University of Jerusalem, the team found that their nanobodies use a variety of mechanisms to block SARS-CoV-2 infection. This makes nanobodies ripe for bioengineering. For instance, nanobodies that bind to different regions on the SARS-CoV-2 virus can be linked together, like a Swiss army knife, in case one part of the virus mutates and becomes drug-resistant.

"As a virologist, it's incredible to see how harnessing the quirkiness of llama antibody generation can be translated into the creation of a potent nanoweapon against clinical isolates of SARS-CoV-2," said study coauthor and CVR Director Paul Duprex, Ph.D.

LOS ANGELES (Nov. 5, 2020) -- An enzyme that helps COVID-19 (coronavirus) infect the body also plays a role in inflammation and patient outcomes in inflammatory bowel disease (IBD), according to a new study led by Cedars-Sinai. The findings raise the possibility that anti-inflammatory drug therapies for IBD may aid recovery from coronavirus.

The multisite study, led by Cedars-Sinai and published today in the journal Gastroenterology, focused on angiotensin-converting enzyme 2 (ACE2), which normally plays a crucial health role by activating a hormone that helps regulate blood pressure. But in COVID-19 infections, the SARS-CoV-2 virus binds to ACE2 and uses it to invade and infect cells, "hijacking" them to spread the virus.

To learn more about how ACE2 affects the body, investigators examined its role in Crohn's disease and ulcerative colitis - two types of IBD that can cause inflammation and scarring (fibrosis) in the digestive tract along with diarrhea, cramping and loss of appetite.

"We chose these disorders because COVID-19, while known for attacking the lungs, frequently causes gastrointestinal symptoms," said Dermot P. McGovern, MD, PhD, the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and senior author of the new study. "It was important for us to understand how COVID-19 might affect IBD patients who are treated with anti-inflammatory medications. Also, there is increasing evidence that the GI tract may serve as an alternate route for uptake of SARS-COV-2 in general."

By examining records of nearly 1,000 patients at Cedars-Sinai, Washington University in St. Louis, Missouri, and multiple other centers across North America, the team found that levels of ACE2 in the small bowel were lower in Crohn's patients and higher in the colons of ulcerative colitis patients than they were in patients without IBD. The differing ACE2 levels were associated with poorer outcomes and more severe disease in the IBD patients.

"We saw that the effect of ACE2 depended on both its specific location in the gastrointestinal tract and the specific disease involved," said McGovern, professor of Medicine and Biomedical Sciences. "So, this enzyme was a double-edged sword."

In both types of IBD, treatment with infliximab, an anti-inflammatory drug, normalized the levels of ACE2 and was associated with improved disease outcomes in patients. This finding suggests these drugs, commonly used in autoimmune diseases, also might improve outcomes in COVID-19, the investigators said, "Overall, our study supports the potential paradoxical function of ACE2 in inflammation and COVID-19," McGovern explained. "Individuals with higher ACE2 expression may be at increased risk of infection with SARS-CoV-2. But judging from our discoveries of how ACE2 works in IBD, this enzyme likely has anti-inflammatory and anti-fibrotic functions that also could help certain COVID-19 patients recover from the virus."

Further research is needed to delineate the processes involving ACE2 and what they might mean for treating COVID-19 patients, he said. In support of that effort, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health recently awarded a two-year grant of $677,036 to McGovern to examine overlaps in the mechanisms that drive inflammation in IBD and COVID-19.

NEW YORK, NY (Nov. 5, 2020)--Children and adults produce different types and amounts of antibodies in response to infection with the new coronavirus, SARS-CoV-2, a new study from researchers at Columbia University Vagelos College of Physicians and Surgeons has found.

The differences in antibodies suggest the course of the infection and immune response is distinct in children and most children easily clear the virus from their bodies. 

"Our study provides an in-depth examination of SARS-CoV-2 antibodies in kids, revealing a stark contrast with adults," says Columbia University immunologist Donna Farber, PhD, the George H. Humphreys II Professor of Surgical Sciences in the Department of Surgery, who led the study with Matteo Porotto, PhD, associate professor of viral molecular pathogenesis in Columbia's Department of Pediatrics. The first authors, Stuart Weisberg, MD, PhD, assistant professor of pathology & cell biology, and Thomas Connors, MD, assistant professor of pediatrics, enrolled patients into the study and conducted the data analysis.

"In kids, the infectious course is much shorter and probably not as disseminated as in adults," Porotto adds. "Kids may clear this virus more efficiently than adults and they may not need a strong antibody immune response to get rid of it."

Children Less Affected by SARS-CoV-2

One of the striking manifestations of the COVID-19 pandemic is that the majority of children cope well with the virus while older people struggle.

"This is a new infection for everybody," Farber says, "but children are uniquely adapted to see pathogens for the first time. That's what their immune system is designed to do. Children have a lot of naive T cells that are able to recognize all sorts of new pathogens, whereas older people depend more on our immunological memories. We're not as able to respond to a new pathogen like children can."

Children Make Fewer SARS-CoV-2 Neutralizing Antibodies

Among the 47 children in the study, 16 were treated at Columbia University Irving Medical Center for MIS-C and 31 children of similar ages had tested positive for the virus after visiting the medical center for the treatment of other conditions. Half of the children without MIS-C had no COVID-19 symptoms. The 32 adults in the study ranged from severely affected patients admitted to the hospital to those with milder disease who recovered at home.

Both groups of children produced the same antibody profile, the study found, which differed from that of adults. 

Compared with adults, children produced fewer antibodies against the virus's spike protein--which the virus uses to infect human cells. The children's antibodies had the least neutralizing activity, while all adults, including young adults in their 20s, produced neutralizing antibodies. The sickest adults had the most neutralizing activity.

Though it may seem counterintuitive that the sickest patients produce antibodies with the greatest neutralizing activity, Farber says that likely reflects the amount of time the virus is present in the sickest patients. 

"There is a connection between the magnitude of your immune response and the magnitude of the infection: The more severe the infection, the more robust the immune response, because you need to have more immune cells and immune reactions to clear a higher dose of a pathogen." 

Other Antibody Differences Show Children's Infections Are Limited

In contrast to adults, children also produced very few antibodies against a viral protein that is only visible to the immune system after the virus infects human cells.

"That suggests that in kids, the infection doesn't really spread a lot and doesn't kill a lot of their cells," Farber says.

"Because children clear the natural virus rapidly, they do not have a widespread infection and they do not need a strong antibody response," Porotto says. 

The reduced course of infection in children may signify that they are infectious for a shorter period of time compared with adults and therefore less likely to spread the virus, although the researchers did not measure viral load in the children.

"Current studies in other countries indicate that younger school-age children are not vectors for the new coronavirus, so our data are consistent with those findings," Farber says.

Children Should Respond Well to Vaccine

The antibody responses found in children do not suggest that children will have a weaker response to a vaccine, the researchers say. 

Vaccines under development for SARS-CoV-2 contain pieces of the virus and do not mimic the normal route of infection.

"Even though children don't produce neutralizing antibodies in response to a natural infection with SARS-CoV-2, vaccines are designed to generate a protective immune response in the absence of an infection," Farber says. "Children respond very well to vaccines, and I think they will develop good neutralizing antibody responses to a SARS-CoV-2 vaccine, and they'll probably be better protected than the adults.

"That said, very few vaccine studies are currently enrolling children and we will need this data to really understand how well the vaccines work in children."

What Does the Adult Immune System Lack?

Though the findings suggest the course of infection in children and adults is different, it's still not known how the children are able to clear the virus more easily--and what the adult immune system lacks.

Farber, Porotto, and their colleagues at Columbia are now looking for differences in T-cell response (antibodies are produced by the immune system's B cells), especially T cells that reside in the lung. [Previous research from Farber's lab has shown these "stay-at-home" T cells are more important in fighting lung infections than T cells that travel through the body via the bloodstream].

Children infected with SARS-CoV-2 also may generate a stronger response from the innate immune system, which deploys interferon and cells called macrophages to indiscriminately attack cells infected by pathogens. Earlier studies suggest that the innate immune response may be delayed in adults infected with SARS-CoV-2.

"If the innate response is really strong, that can reduce the viral load in the lungs, and the antibodies and T cells of the adaptive response have less to clear up," Farber says. 

It's also possible that the virus is less able to infect children's cells, possibly because children's cells express fewer proteins the virus needs to infect human cells.

The Columbia researchers are now testing these possibilities with cells from children versus adults.

"There are still all these issues that we have very little information about," Porotto says. "The interaction between the virus and the host is the reason why we see so much diversity in responses to this virus, but we don't understand enough about this virus yet to really determine what leads to severe disease and what leads to mild disease."

November 5, 2020 - Studies using repetitive transcranial magnetic stimulation (rTMS), a noninvasive technique, to help veterans and active-duty service members living with depression, post-traumatic stress disorder (PTSD), and other lasting consequences of concussion have shown promise. However, there's an urgent need for studies designed to address the unique patterns of post-concussion symptoms seen in military populations, concludes a review in the November/December issue of the Journal of Head Trauma Rehabilitation (JHTR). The official journal of the Brain Injury Association of America, JHTR is published in the Lippincott portfolio by Wolters Kluwer.

"rTMS represents a novel innovative, and possibly transformative approach to the treatment of chronic neuropsychiatric and neurocognitive symptoms associated with military concussion," write David L. Brody, MD, PhD, of the Center for Neuroscience and Regenerative Medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md., and colleagues. They highlight the need for higher-quality evidence to guide the use of rTMS for service members and veterans with post-concussion symptoms.

rTMS for post-concussive symptoms in veterans: 'Smarter trials' needed

More than 342,000 US service members have experienced concussion over the past two decades. Many of them are living with post-concussive symptoms - especially depression, PTSD, and cognitive issues, often in combination. Despite the high impact of these chronic neuropsychiatric and neurocognitive symptoms, there is a lack of effective, evidence-based treatments.

One potentially useful approach is rTMS, consisting of repeated sessions of noninvasive magnetic stimulation, targeted to specific areas of the brain. Specific rTMS protocols are approved for the treatment of selected patients with major depressive disorder. A growing body of evidence suggests that rTMS may be effective for PTSD and cognitive issues as well.

However, the effectiveness of rTMS for post-concussion symptoms remains unclear; many studies have specifically excluded patients with brain injury or head trauma. In addition, the nature of military concussions and post-concussion symptoms may be very different than in civilian populations.

To assess the current state of knowledge, Dr. Brody and colleagues reviewed the research literature on rTMS for post-concussion symptoms. They identified a total of nine clinical trials, mainly small-scale pilot studies. Evidence for the effectiveness of rTMS for specific types of symptoms was mixed, at best:

Depression. Of six studies evaluating the effects of rTMS for depression, three reported positive results but three found no improvement. Three of the studies did not assess veterans or service members.

PTSD. Three of the depression studies did include patients with military concussions, and all of them also included data on PTSD. However, just one study reported improvement in PTSD symptoms with rTMS.

Cognitive issues. Five studies included data on cognitive outcomes of rTMS; none found significant improvement. One recent trial designed for veterans with mild to moderate traumatic brain injury reported no improvement in executive functioning: a key aspect of cognitive performance.

Based on the results, "there is simply insufficient data" to support the effectiveness of any specific rTMS protocol, Dr. Brody and coauthors write. They do note that rTMS appears safe, and that the negative results in preliminary trials don't necessarily mean that rTMS is ineffective. Key questions remain as to the best stimulation settings and number of sessions, as well as the optimal approach to military and other patients with multiple clinical issues.

"The importance of optimizing feasibility and efficacy of rTMS to treat service members and veterans with chronic neuropsychiatric and neurocognitive symptoms associated with concussion cannot be overstated," Dr. Brody and colleagues conclude. "We need to begin to design smarter trials that are powered to answer research questions to confidently assess and recommend rTMS as a treatment option for this population."

Scientists have found that insulin has met an evolutionary cul-de-sac, limiting its ability to adapt to obesity and thereby rendering most people vulnerable to Type 2 diabetes.

A recent study from scientists at Indiana University School of Medicine, the University of Michigan and Case Western Reserve University has determined that the sequence of insulin has become entrenched at the edge of impaired production, an intrinsic vulnerability unmasked by rare mutations in the insulin gene causing diabetes in childhood. The study exploits biophysical concepts and methods to relate protein chemistry to the emerging field of evolutionary medicine.

Insulin is produced by a series of highly specific processes that occur in specialized cells, called beta cells. A key step is the folding of a biosynthetic precursor, called proinsulin, to achieve the hormone's functional three-dimensional structure. Past studies from this and other groups have suggested that impaired biosynthesis could be the result of diverse mutations that hinder the foldability of proinsulin.

This group sought to determine if the evolution of insulin in vertebrates--including humans--has encountered a roadblock. Has a complex series of steps imposed constraints that have frozen the sequence of insulin at a precipice of non-foldability? And if so, has this left humankind vulnerable to Type 2 diabetes as a pandemic disease of civilization?

According to the study published in the Proceedings of the National Academy of Sciences, the answers are yes and yes.

"Biological processes ordinarily evolve to be robust, and this protects us in the majority of cases from birth defects and diseases," said Michael Weiss, MD, PhD, Distinguished Professor at IU School of Medicine and lead investigator of the study. "Yet diabetes seems to be an exception."

Weiss and team looked at a subtle mutation in human insulin in relation to the insulins of other animals, such as cows and porcupines. The mutant human insulin functions within the range of natural variation among animal insulins, and yet this mutation has been excluded by evolution. The answer to this seeming paradox is that the forbidden mutation selectively blocks the folding of proinsulin and stresses beta cells.

The group discovered that even the slightest variation of the insulin-sequencing process not only impairs insulin folding (and eventual insulin secretion) but also induces cellular stress that leads to beta cell dysfunction and eventually permanent damage.

Weiss, who is also Chair of the Department of Biochemistry and Molecular Biology and a Precision Health Initiative Professor, said that the study highlights the importance of folding efficiency as a critical but hidden factor in the evolution of insulin over the past 540 million years. Humans have evolved to be vulnerable to diverse mutations in the insulin gene and that this vulnerability underlies a rare monogenic form of diabetes and provides an evolutionary backdrop to the present obesity-related diabetes pandemic.

National experts agree that this discovery provides key insight to better understanding the development of Type 2 diabetes in adults and children--which both are rising at alarming rates in Indiana and around the world.

"This study is a tour de force unraveling key elements of the structural biology of insulin that affect its synthesis and function," said Barbara Kahn, MD, George R. Minot Professor of Medicine at Harvard Medical School. "The authors highlight the fact that the insulin gene has been susceptible throughout evolution to mutations that impair insulin's function or stress beta cells. As we approach the 100th anniversary of the discovery of insulin, these elegant observations might lead to a better understanding of the pathogenesis of Type 2 diabetes."

Director of the University of Chicago Kolver Diabetes Center Louis Philipson, MD, agreed, adding that findings will shape future approaches to research in this area.

"The present findings define a major question for the future: whether harmful misfolding of proinsulin seen in patients bearing INS gene variants may also occur, at lower levels perhaps, but more broadly in the population of human Type 2 diabetes patients around the world," Philipson said.

Next, the group will work to fully define the sequence determinants that make proinsulin foldable in beta cells. Their hope is that this work will eventually lead to a new category of drugs that mitigate the cellular stress caused by proinsulin's precarious foldability and target cellular stress in beta cells, thereby preserving insulin-production for high-risk patients.