Culture

For eradication of HIV-1 infection, it is important to elucidate the detailed features and heterogeneity of HIV-1-infected cells in vivo. In this study, a hematopoietic stem cell-transplanted humanized mouse model infected with a gene-modified HIV-1 was used to reveal multiple characteristics of HIV-1-producing cells in vivo.

A research group at The Institute of Medical Science, The University of Tokyo (IMSUT) using HIV-1-infected cells performed "multiomics" analyses, which are technologies recently developed to comprehensively investigate the features of biological samples.

"Our findings describe multiple characteristics of HIV-1-producing cells in vivo, which could provide clues for the development of an HIV-1 cure.", said the lead scientist, Kei Sato, Associate Professor (Principal Investigator) in the Division of Systems Virology, Department of Infectious Disease Control, IMSUT.

The results of this research were published in Cell Reports on July 14, 2020.

Study for "HIV-1 cure"

For eradication of HIV-1 infection, it is important to gain an in-depth understanding of the wide-ranging characteristics of HIV-1-infected cells in vivo.

Recently developed 'omics' analyses (*1) can be a powerful tool to identify the characteristics of HIV-1-infected cells. However, it should be noted that a large majority of the CD4+ T cells(*2) in infected individuals are uninfected, and therefore, the transcriptional profiles of "bulk" CD4+ T cells in vivo do not reflect those of "pure" HIV-1-producing cells.

Multiomics analysis to comprehensively reveal the features of HIV-1-infected cells in vivo

In this study, the research group used a human hematopoietic stem cell-transplanted humanized mouse model that maintains human leukopoiesis under relatively stable immunological conditions in vivo and a replication-competent reporter HIV-1, and used four recently developed techniques to investigate viral genomics and transcriptomics.

According to the research group, this study consisted of the four following analyses:

First, droplet digital PCR revealed the presence of potential reservoirs in infected humanized mice. Second, ligation mediated PCR showed the preference of HIV-1 to integrate into open chromatin regions, as suggested by the association of the epigenetic modifications of integration sites with viral production. Third, digital RNA-sequencing quantified the absolute copy number of viral transcripts in the HIV-1-producing cells in vivo and further identified the differentially expressed genes between virus-infected and uninfected cells. Finally, single-cell RNA-sequencing revealed and characterized the heterogeneity of the HIV-1-producing cells in vivo.

Associate Professor Sato emphasized "To our knowledge, this study is the first investigation to describe multiple aspects of HIV-1-producing cells and also the first comprehensive investigation of the characteristics of HIV-1-infected cells in vivo" .

A protein produced by the human immune system can strongly inhibit corona viruses, including Sars-Cov-2, the pathogen causing Covid-19. An international team from Germany, Switzerland and the USA successfully showed that the LY6E-Protein prevents coronaviruses from causing an infection. "This finding might lead to the development of new therapeutic approaches against coronaviruses," says Professor Stephanie Pfänder from the Department for Molecular and Medical Virology at Ruhr-Universität Bochum (RUB), lead author of the study published by the team in the journal Nature Microbiology on 23 July 2020.

Strengthening influenza viruses, impairing corona viruses

The LY6E protein plays a role in various diseases: US researchers Professor John Schoggins and Professor Charles Rice discovered that the protein enhances the infectivity of influenza viruses. In contrast, coronaviruses are inhibited by LY6E.

Funded by a Marie Curie Individual Fellowship of the European Union, Stephanie Pfänder, who was then working at the Institute of Virology and Immunology in Switzerland, visited Charles Rice's lab at Rockefeller University in New York in 2017, in order to identify genes that prevent coronavirus infections. "This led to the discovery that LY6E has the opposite effect on coronaviruses compared to influenza viruses," explains the researcher. Further investigations showed that the protein exerted this inhibitory effect on all analysed coronaviruses, including the pathogens causing Sars and Mers as well as Sars-Cov-2 which causes Covid-19.

Viruses unable to fuse

Tests with different cell cultures showed that LY6E affects the ability of the virus to fuse with the host cells. "If the virus is unable to fuse with these cells, it can't cause infection," explains corresponding author Professor Volker Thiel from the University of Bern.

The validation in an animal model succeeded thanks to a collaboration with the laboratory of John Schoggins at the Southwestern Medical Center of the University of Texas. The experiments conducted there led to the discovery that the mouse variant of the protein called Ly6e is crucial for the protection of immune cells against infections. In the absence of Ly6e, immune cells such as dendritic cells and B-cells become more susceptible to infection and their numbers decrease dramatically. Mice lacking Ly6e in immune cells are highly susceptible to a normally non-lethal mouse coronavirus and succumb to infection.

Understanding basic concepts

The researchers point out that the mouse coronavirus used in the experiment differs significantly from the pathogen causing the current Covid-19 outbreak - for example, it causes hepatisis rather than respiratory disease. Nevertheless, it is widely accepted as a model for understanding the basic concepts of coronavirus replication and immune responses in a living animal.

"Our study provides new insights into how important these antiviral genes are for the control of viral infection and for an adequate immune response against the virus," say the authors. "Since LY6E is a naturally occurring human protein, we hope that this knowledge will aid the development of therapies that may one day be used to treat coronavirus infections." A therapeutic approach that mimics the mechanism of action of LY6E may provide a first line of defence against novel coronavirus infections.

UNIVERSITY PARK, Pa. -- By reconstructing the evolutionary history of SARS-CoV-2, the virus that is responsible for the COVID-19 pandemic, an international research team of Chinese, European and U.S. scientists has discovered that the lineage that gave rise to the virus has been circulating in bats for decades and likely includes other viruses with the ability to infect humans. The findings have implications for the prevention of future pandemics stemming from this lineage.

"Coronaviruses have genetic material that is highly recombinant, meaning different regions of the virus's genome can be derived from multiple sources," said Maciej Boni, associate professor of biology, Penn State. "This has made it difficult to reconstruct SARS-CoV-2's origins. You have to identify all the regions that have been recombining and trace their histories. To do that, we put together a diverse team with expertise in recombination, phylogenetic dating, virus sampling, and molecular and viral evolution."

The team used three different bioinformatic approaches to identify and remove the recombinant regions within the SARS-CoV-2 genome. Next, they reconstructed phylogenetic histories for the non-recombinant regions and compared them to each other to see which specific viruses have been involved in recombination events in the past. They were able to reconstruct the evolutionary relationships between SARS-CoV-2 and its closest known bat and pangolin viruses. Their findings appear today (July 28) in Nature Microbiology.

The researchers found that the lineage of viruses to which SARS-CoV-2 belongs diverged from other bat viruses about 40-70 years ago. Importantly, although SARS-CoV-2 is genetically similar (about 96%) to the RaTG13 coronavirus, which was sampled from a Rhinolophus affinis horseshoe bat in 2013 in Yunnan province, China, the team found that it diverged from RaTG13 a relatively long time ago, in 1969.

"The ability to estimate divergence times after disentangling recombination histories, which is something we developed in this collaboration, may lead to insights into the origins of many different viral pathogens," said Philippe Lemey, principal investigator in the Department of Evolutionary and Computational Virology, KE Leuven.

The team found that one of the older traits that SARS-CoV-2 shares with its relatives is the receptor-binding domain (RBD) located on the Spike protein, which enables the virus to recognize and bind to receptors on the surfaces of human cells.

"This means that other viruses that are capable of infecting humans are circulating in horseshoe bats in China," said David L. Robertson, professor of computational virology, MRC-University of Glasgow Centre for Virus Research.

Will these viruses be capable of jumping directly from bats into humans or will an intermediate species be required to make the leap? According to Robertson, for SARS-CoV-2, other research groups incorrectly proposed that key evolutionary changes occurred in pangolins.

"SARS-CoV-2's RBD sequence has so far only been found in a few pangolin viruses," said Robertson. "Furthermore, the other key feature thought to be instrumental to SARS-CoV-2's ability to infect humans -- a polybasic cleavage site insertion in the Spike protein -- has not yet been seen in another close bat relative of the SARS-CoV-2 virus. Yet, while it is possible that pangolins may have acted as an intermediate host facilitating transmission of SARS-CoV-2 to humans, no evidence exists to suggest that pangolin infection is a requirement for bat viruses to cross into humans. Instead, our research suggests that SARS-CoV-2 likely evolved the ability to replicate in the upper respiratory tract of both humans and pangolins."

The team concluded that preventing future pandemics will require better sampling within wild bats and the implementation of human disease surveillance systems that are able to identify novel pathogens in humans and respond in real time.

"The key to successful surveillance," said Robertson, "is knowing which viruses to look for and prioritizing those that can readily infect humans. We should have been better prepared for a second SARS virus."

Boni added, "We were too late in responding to the initial SARS-CoV-2 outbreak, but this will not be our last coronavirus pandemic. A much more comprehensive and real-time surveillance system needs to be put in place to catch viruses like this when case numbers are still in the double digits."

While there is little doubt that COVID-19 will have lasting impacts on health and the economy, a group of researchers is bringing attention to the effects the pandemic could have on the careers of scientific researchers. Carnegie Mellon University and Max Planck Institute physicist Ulrike Endesfelder, University of Stuttgart's Dirk Pflüger and Technische Universität Braunschweig's Timo de Wolff launched a Twitter campaign #StopPandemicBias, which aims to bring broader understanding to how COVID-19 will impact scientists. Using the hashtag, they hope to crowdsource ideas that will mitigate the impact of the pandemic on research careers.

They also published their concerns in a letter in the July 30 issue of Nature.

"Being unaffected by COVID-19 is a new privilege. The disadvantaged are among both the applicants for positions, grants and publications and their selecting peers, and their voices currently are not heard in our community. Pandemic bias will hinder or even stop the careers of many in our community and prevent access to many trying to enter scientific research," said Endesfelder. Endesfelder has personally felt these challenges. She was set to move her laboratory to Carnegie Mellon in the spring of 2020 but remains in Germany due to travel restrictions.

Citing the highly collaborative and participatory nature of science, the group believes that researchers who are most greatly impacted by COVID-1¬9 -- those who are overwhelmed with care-giving responsibilities, those who are unable to do research outside of the laboratory setting, those who are unable to travel and those who are sick themselves -- will be held back from advancing in their careers. For example, a single parent who must home school their children might not have time to submit grants or review articles, or a recent graduate might not be able to travel to interview for a job. These limitations imposed by the pandemic could create barriers that do not exist for those who are not largely affected by the pandemic.

"For the disadvantaged, the obstacles are immense: you cannot compromise on safety when belonging to a risk group; find your next position amidst hiring freezes and budget cuts; pursue international careers when restrictions prevent travel; say no to dependents who need your care; or stay productive when suffering from COVID-19," said Endesfelder.

"We are concerned that scientists who cannot devote time to grant applications or aren't able to access their labs to produce the data they need for career-advancing publications or can't get a visa to report to their new job will face severe setbacks in the advancement of their careers. And if these barriers are too much to surmount, we may lose a significant number of future scientists to other industries. We also are concerned that there will be fewer diverse voices in science. With less people reviewing grants and papers, we will lose diverse opinions that are necessary for moving science forward," Pflüger said.

The researchers suggest a number of actions the scientific community can take to help prevent this bias. This includes supporting scholars who are unable to travel for opportunities, reviewing more articles and grants and taking over teaching responsibilities for affected colleagues. They also urge institutions and funders to reconsider upcoming deadlines and criteria to create more leniency to those impacted by COVID-19.

"All of us need to contribute, and all of us have something at stake. Now is the time to act. There is no silver bullet, but we all have numerous points of direct influence. We feel that there are opportunities for significant change and we need to start the conversation now," de Wolff said.

They urge members of the scientific community to join the conversation on Twitter using #StopPandemicBias, where people can submit and discuss ways to help.

An extensive international study led by Prof. Illana Gozes of Tel Aviv University's Department of Human Molecular Genetics and Biochemistry found deposits of the tau protein typically found in Alzheimer's patients in tissues taken from the postmortem brain of a 7-year-old autistic child.

The child suffered from the ADNP syndrome, a mutation that causes a deficiency/malfunctioning of the ADNP protein essential for brain development. In light of these findings, the researchers tested an experimental drug called NAP, originally developed for Alzheimer's disease, on nerve cells in a model of ADNP syndrome with the mutation that induced Alzheimer's-like symptoms. The experiment was a success, with the damaged nerve-like cells returning to normal function.

The study was conducted in close collaboration with researchers from TAU's Blavatnik School of Computer Science, Sheba Medical Center, and a variety of research institutions across Europe, including the biotechnology institute BIOCEV in the Czech Republic, the Aristotle University of Thessaloniki in Greece, the University of Antwerp in Belgium, and the University Hospital Centre in Zagreb, Croatia. The study was published on July 13 in the journal Translational Psychiatry.

Prof. Gozes explains that the current study is based on tissues taken from the brain of a 7-year-old boy with ADNP syndrome who died in Croatia. "When we compared the postmortem ADNP syndrome brain tissues to tissue from the brain of a young person without ADNP syndrome, we found deposits of the tau protein in the ADNP child, a pathology that characterizes Alzheimer's disease," Prof. Gozes says.

The researchers then "treated" damaged nerve-like cells carrying an ADNP mutation similar to the deceased child's mutation with a drug candidate called NAP. NAP was developed in Prof. Gozes's laboratory and was originally intended to be used to help treat Alzheimer's disease. "NAP is actually a short active fragment of the normal ADNP protein," says Prof. Gozes. "When we added NAP to the nerve cells carrying an ADNP mutation, the tau protein bound to the nerve cell skeleton properly, and the cells returned to normal function.

"The fact that NAP treatment has been successful in restoring the normal function of neuronal-like cell models with impaired ADNP raises hopes that it may be used as a remedy for ADNP syndrome and its severe implications, including autism," Prof. Gozes continues. "Moreover, because other genetic disorders related to autism are characterized by tau pathologies in the brain, we hope that those suffering from these syndromes will also be able to benefit from NAP treatment in the future."

NAP (also called CP201) has been classified as an "orphan drug" by the US Food and Drug Administration and is currently in the preparatory stages of a clinical trial in children with ADNP syndrome through the company Coronis Neurosciences.

In another phase of the study, the researchers sought to broaden their understanding of the effects of the mutation that causes ADNP syndrome. To do this, they extracted the genetic material mRNA (messenger RNA) from the tissues of the deceased child and performed an expression analysis of about 40 proteins in the same child, encoded by the mRNA. Full genetic sequencing was also performed to determine protein expression in white blood cells taken from three other children with ADNP syndrome.

An in-depth study was carried out on all of the data obtained in the genetic sequencing using advanced bioinformatics computational tools. The data were compared to online databases of protein expression data from healthy individuals, revealing a variety of characteristics that were common to the children with the syndrome but very different from the normal appearance of these proteins.

Prof. Gozes concludes that "the significance of these findings is that the mutation that causes ADNP syndrome damages a wide range of essential proteins, some of which bind to the tau protein, among other things, and impair its function as well. This creates various pathological effects in the brains and other tissues of children with ADNP syndrome, one of which is the formation of tau deposits, known to be a characteristic of Alzheimer's disease.

"The vast and in-depth knowledge we have accumulated through the present study opens the door to further extensive and diverse research. We hope and believe that we will ultimately reach the goal of developing a drug or drugs that will help children with autism resulting from genetic mutations."

American Friends of Tel Aviv University supports Israel's most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. TAU is ranked ninth in the world, and first in Israel, for producing start-up founders of billion-dollar companies, an achievement that surpassed several Ivy League universities. To date, 2,500 US patents have been filed by Tel Aviv University researchers -- ranking TAU #1 in Israel, #10 outside of the US and #66 in the world.

Journal

Translational Psychiatry

DOI

10.1038/s41398-020-00904-4

Philadelphia, July 28, 2020 - Imagine a young girl with a peanut allergy, so stricken by fear of anaphylaxis that she no longer takes part in everyday activities many children take for granted. She's stopped playing with her siblings, worried that residue from their peanut butter crackers may trigger an allergic reaction. She obsessively washes her hands to make sure there is no trace of peanut on them. She worries that every stomachache could mean she accidently ate something she was allergic to.

This story is becoming more familiar to families across the country. While most children with food allergies maintain a healthy level of caution, there is a small percentage whose anxiety is excessive and impairing. The hallmark of excessive anxiety is going to extreme, medically unnecessary lengths to avoid the allergen, such as no longer visiting extended family or refusing to eat any allergen-free food that isn't familiar. While these coping mechanisms may relieve anxiety in the short term, they may ultimately cause more harm by negatively reinforcing the idea that the world is a dangerous place and that children are helpless to keep themselves safe.

Now, Children's Hospital of Philadelphia (CHOP) has launched the Food Allergy Bravery (FAB) Clinic to help children with a phobia of anaphylaxis. This revolutionary clinic, housed within the Food Allergy Center, is the first in the world to bring together psychologists and food allergy experts to treat food allergic children with severe phobia of anaphylaxis.

The three Founders of the FAB Clinic published a set of best practices in the Journal of Allergy and Clinical Immunology, providing guidance to allergists and pediatricians on how to address allergy-related phobias through Cognitive Behavioral Therapy (CBT).

"CBT works by gradually encouraging anxious children to take part in 'brave practices,' like eating with the rest of their family, playing with siblings, and trying new foods that don't contain allergens," said Katherine Dahlsgaard, PhD, ABPP, Director of the FAB Clinic at CHOP. "As a child's confidence grows, we gradually introduce them to more challenging brave practices. This could include sitting in the same room with the food they're allergic to, or even touching the food and then washing their hands thoroughly. The aim is to help children realize, through safe, structured practices in the FAB Clinic, that the world is much safer than they think and that they are capable of keeping themselves safe within it."

The FAB clinic enthusiastically employs the help of family members, coaching parents or caregivers to repeat brave practices at home.

"We want these children and their families to know they're safe and capable," said Dr. Dahlsgaard. "Our ultimate goal is to equip families with practical skills and confidence via focused treatment sessions, so that their child can safely navigate a world that can't always be allergen-free."

About Children's Hospital of Philadelphia: Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 564-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

Journal

Journal of Allergy and Clinical Immunology

According to new research, the failure to protect tropical rain forests has cost trillions of dollars stemming from the coronavirus pandemic, which has wreaked economic havoc and caused historic levels of unemployment in the United States and around the world.

For decades, scientists and environmental activists have been trying to draw the world's attention to the many harms caused by the rapid destruction of tropical forests. One of these harms is the emergence of new diseases that are transmitted between wild animals and humans, either through direct contact or through contact with livestock that is then eaten by humans. The SARS-CoV-2 virus--which has so far infected more than 15 million people worldwide--appears to have been transmitted from bats to humans in China.

"Much of this traces back to our indifference about what has been occurring at the edges of tropical forests," says Les Kaufman, a Boston University professor of biology.

He recently brought together 18 experts from Princeton University, Duke University, Conservation International, and other institutions, to better understand the economic costs of reducing transmission of viruses like the novel coronavirus. Looking at existing research, they made a startling realization.

They discovered that significantly reducing transmission of new diseases from tropical forests would cost, globally, between $22.2 and $30.7 billion each year. In stark contrast, they found that the COVID-19 pandemic will likely end up costing between $8.1 and $15.8 trillion globally--roughly 500 times as costly as what it would take to invest in proposed preventive measures. To estimate the total financial cost of COVID-19, researchers included both the lost gross domestic product and the economic and workforce cost of hundreds of thousands of deaths worldwide. They published their findings in a policy brief in Science.

The researchers say disease transmission from wild animals to humans occurs frequently near the edges of tropical forests, where human incursions increase the likelihood of contact with animals. These incursions take the form of logging, cattle ranching, and other livestock businesses, and the exotic animal trade, among others. Tropical forests are often cut down in a patchwork or checkerboard pattern, increasing the amount of land that lies at the edges of the forest and thus increasing the risk for disease transmission between species that would normally live in different ecosystems.

To reduce disease transmission, Kaufman and his collaborators propose expanding wildlife trade monitoring programs, investing in efforts to end the wild meat trade in China, investing in policies to reduce deforestation by 40 percent, and fighting the transmission of disease from wild animals to livestock.

In China alone, wildlife farming (a government-monitored effort to sustainably hunt wild animals without overhunting them) is an approximately $20 billion industry, employing 15 million people, say Kaufman and his peers. In many China communities, the purchase of wildlife and bushmeat--meat from wildlife species--is a status symbol.

The researchers also propose to increase funding for creating an open source library of the unique genetic signatures of known viruses, which could help quickly pinpoint the source of emerging diseases and catch them more quickly, before they can spread.

Every year, two new viruses are estimated to transfer from animals to humans, the researchers say. Historically, these have included HIV, MERS, SARS-CoV-1, H1N1, and most recently, the SARS-CoV-2 virus that causes COVID-19. Kaufman and his colleagues hope that their report will spur governments around the world, including the US government, to help fund these preventive measures.

There are some signs of hope, they say, including the February announcement by the Standing Committee of the National People's Congress that wildlife consumption for food or related trade would be banned in China.

"The pandemic gives an incentive to do something addressing concerns that are immediate and threatening to individuals, and that's what moves people," says Kaufman. "There are many people who might object to the United States fronting money, but it's in our own best interest. Nothing seems more prudent than to give ourselves time to deal with this pandemic before the next one comes."

AMES, Iowa - Exposure to the chemical glyphosate changed the level of some ovarian proteins in mice but did not impact ovarian steroid production, an indication glyphosate may not adversely affect reproduction, according to a new study.

Two studies, published in the peer-reviewed academic journals Toxicology and Applied Pharmacology and Reproductive Toxicology, analyzed how ovarian function in mice responded to various levels of exposure to glyphosate, a chemical extensively used to kill weeds. The research found the highest exposure levels included in the experiments resulted in increased ovarian weight and follicle number, but Aileen Keating, an associate professor of animal science at Iowa State University and lead author, said the research did not uncover evidence that glyphosate affects the healthy functioning of ovaries.

"The big takeaway is that while we did find some changes in ovarian proteins, many of the endpoints we examined were not altered by glyphosate exposure," Keating said.

Keating, whose research focuses on reproductive health, said it's unclear if the increased ovarian size or altered protein abundance that resulted from the highest exposure level could cause changes in the ability of mice to reproduce. Answering that question will require further study, she said. The study found glyphosate exposure did not affect heart, liver, spleen, kidney or uterus weights. Keating said the study's conclusions largely agreed with findings published years ago meant to determine how the chemical can be used safely.

The researchers introduced glyphosate to groups of mice orally, mimicking how humans could be exposed to glyphosate residue in water or in crops used for food production. Groups of mice were exposed to different glyphosate levels and for periods of 5, 10 or 20 weeks. The researchers chose the doses, measured in milligrams per kilogram of bodyweight, to approximate potential glyphosate levels that humans could be exposed to.

However, Keating noted that it remains unclear how much glyphosate humans are exposed to regularly, which made it difficult to judge what levels were appropriate for the experiments. Additionally, they used only the active compound contained in weed treatments, not the additional ingredients.

The use of glyphosate has sparked controversy regarding its proposed health effects. Accordingly, Keating said the researchers designed the study to be as unbiased as possible. For instance, the scientists didn't know the glyphosate treatment of individual samples as they conducted their analysis, which meant perceived expectations or biases could not affect the results.

"It's a commonly used chemical, and there's been some alarm in the media about its use," she said. "We need more well designed, independent studies to see if this is something we should be concerned about."

Fossil remains of a novel species of lizard that lived more than 130 million years ago have been found in the north of Minas Gerais, Brazil. It has been named Neokotus sanfranciscanus and is the oldest representative of the order Squamata ever found in South America.

Squamates are the largest reptile group, comprising lizards, snakes and amphisbaenians (worm lizards).

The discovery shows that scaled lizards were present on the continent at least 20 million years earlier than previously recorded and suggests that early South American squamates were part of a much broader global distribution, in contrast with the high levels of endemism (confinement to certain geographic regions) characteristic of modern species.

The fossil is described in an article published in Communications Biology.

The study was led by Jonathas Bittencourt, who was formerly awarded a postdoctoral research scholarship by FAPESP and is currently a professor at the Federal University of Minas Gerais (UFMG). The last author of the article is Max Langer, a professor in the Biology Department of the University of São Paulo’s Ribeirão Preto School of Philosophy, Science and Letters (FFCLRP-USP). The study was supported by the Minas Gerais Research Foundation (FAPEMIG) via a grant awarded to Bittencourt and by FAPESP via a Thematic Project led by Langer.

“This was a small lizard, approximately 10 cm long,” Langer told Agência FAPESP. “Its discovery in Brazil shows that the squamates were distributed throughout the world and were alive much earlier than we thought. This was only possible because, although the supercontinent Pangaea no longer existed, the continental lands were still relatively close to each other, allowing animals to disperse widely.”

The genus name Neokotus comes from Greek and means “novel and unfamiliar”. It was chosen because this animal’s morphology differs in several ways from that of all other species of Squamata. The specific epithet sanfranciscanus refers to the fact that the lizard’s fossilized remains were found in the Quiricó Formation, which is in the São Francisco River Basin.

“One of the morphological peculiarities of Neokotus is the shape of its ungual phalanges, which are terminal finger or toe bones. These bones end in nails in humans and in claws in other animals. In Neokotus, the base of the ungual phalanx was flat, a trait not found in any other known lizard. More detailed study of this feature is required, but it probably had something to do with locomotion,” Bittencourt said.

“Another peculiarity is the shape of its teeth, which had robust bases, tapering and curving inwards at the tip. We also have a theory about this: the shape of its teeth helped capture the insects it fed on.”

Bittencourt discovered Neokotus by chance. He was collecting scales from small sharks on a riverbank when he came across a block of sediment containing phalanges, vertebrae, teeth and other bones that did not appear to belong to fish. On assembling the bones and analyzing their mutual relationships, he realized they belonged to a lizard.

“I found approximately 30% of the fossil remains of a single individual,” he said. “The Quiricó Formation in the municipality of João Pinheiro in northern Minas Gerais must have included a large lake or several interconnected lakes in the remote past, as it’s very rich in fossils of lacustrine origin. I’ve been digging in the area since 2012. My field work consists of collecting chunks of rock, which I take back to the lab to be washed and broken up using hydrogen peroxide. I collect the tiny bones with brushes and tweezers.”

The rocks in which Neokotus was found were dated by means of microcrustaceans also embedded in the sediment.

“Many dinosaurs have been discovered in South America, but findings of small reptiles are also very important for the reconstruction of the scene at the time,” Langer said.

The article, “Discovery of the oldest South American fossil lizard illustrates the cosmopolitanism of early South American squamates”, can be read at: www.nature.com/articles/s42003-020-0926-0.

Journal

Communications Biology

DOI

10.1038/s42003-020-0926-0

Philadelphia, July 27, 2020--As the COVID-19 pandemic took hold, hospitals across the country cancelled elective procedures in an effort to flatten the transmission curve and prioritize personal protective equipment for frontline health care workers. Among those procedures were pediatric spine surgeries for patients with conditions like scoliosis and thoracic insufficiency syndrome.

Now, as hospitals resume elective procedures, including pediatric spine surgeries, surgeons from Children's Hospital of Philadelphia (CHOP) have outlined a framework for prioritizing pediatric spine surgeries amid the pandemic. The recommendations were published recently in the Journal of Bone and Joint Surgery.

"We've provided a framework for a reorientation of the thought process by which surgeons should plan pediatric spine surgery in the midst of this pandemic," said Jason B. Anari, MD, a pediatric orthopaedic surgeon with CHOP's Division of Orthopaedics and first author of the recommendations. "Although many families historically pick surgical dates that are based on school, sport seasons, or vacation schedules, we support the creation of a new urgency list to help guide rescheduling while also minimizing potential risk to patients."

The paper proposes classifying surgeries into four categories:

Class 1: Emergency surgeries that must happen right away;

Class 2: Urgent surgeries that must happen within a short timeframe;

Class 3: Semi-urgent surgeries in which a delay of several months would result in less-optimal clinical outcomes;

and Class 4: Elective surgeries that might require a prolonged stay in the intensive care unit, that will require more intensive use of health-care resources, or that involve children with competing risks of medical conditions, or cases for which the outcome will be no different if delayed up to 6 months.

The authors suggest that the classes of surgeries should occur in descending order on the epidemiological curve, with Class-1 emergency surgeries happening as soon as possible regardless of case counts, using preoperative COVID-19 screening and sufficient personal protective equipment, and the other classes happening as community case counts flatten and then decrease. Class-4 surgeries, the authors recommend, should occur once the pandemic has reached its low point.

The authors also advise health care systems and surgeons to develop strong partnerships to facilitate rescheduling patients whose surgeries had been postponed due to the pandemic. Scheduling patients beyond standard hours or on weekends, as CHOP has supported, and finding other ways to reschedule patients could potentially help decrease waiting times, which in turn could also minimize an uptick in surgeries that became more complex due to postponement. Additionally, finding alternate times for procedures helps families to social distance while in the hospital and improve overall access to care for patients.

"The pandemic has been understandably anxiety-provoking for patients in need of spine surgery and their families," Anari said. "Having a plan of action to ramp up in a safe and organized fashion benefits everyone: the health system, surgeons, care teams, and, most importantly, patients."

BROOKLYN, New York, Monday, July 27, 2020 - Fascinating opportunities are emerging from a new class of materials named two-dimensional (2D) semiconductors, which are only one atom thick. 2D materials are poised to have a bright future in the electronics and optoelectronics industry, as well as in Internet of Things devices. Any cell phone, computer, electronic device, and even solar cells, are all composed of the same basic electronic building block, the diode. Unfortunately, a major obstacle for the wide application of 2D materials in industry is the unsolved challenge of the scalable and robust nanofabrication of the core element of a diode, which is a "p-n junction".

Elisa Riedo, professor at the New York University (NYU) Tandon school of Engineering led an international team of investigators who demonstrated a novel approach based on thermal scanning probe lithography (t-SPL) to fabricate state-of-the-art "p-n junctions" on a single atomic layer of molybdeunum disulfide (MoS2) a transition metal dichalcogenide. The work, "Spatial defects nanoengineering for bipolar conductivity in MoS2," appears in Nature Communications.

To produce "p-n junctions", it is necessary to dope a semiconductor in such a way that part of it is n-doped (doped with an excess number of electrons) and another part is p-doped (doped with an excess number of positively-charged "holes"). Riedo and Davood Shahrjerdy, professor of electrical and computer engineering at NYU Tandon, showed that by combining t-SPL with defects nanoengineering was possible to obtain nanoscale-resolution bipolar doping of MoS2, yielding to both n-type and p-type conduction, which can be readily extended to other 2D semiconductors.

As part of the research, the team integrated t-SPL -- using a probe heated above 200 degrees Celsius -- with a flow-through reactive gas cell to achieve a unique nanoscale control of the local thermal activation of defects in monolayer MoS2. The defective patterns can give rise to either p- or n-type conductivity on demand, depending on the gasses used during the local heating process. Doping and defects formation mechanisms are elucidated at the molecular level by means of X-Ray photoelectron spectroscopy, transmission electron microscopy, and density functional theory.

The international team included researchers from the City University of New York (CUNY), Politecnico di Milano, the University of Illinois Urbana-Champaign, the University of Pennsylvania, and the National Research Council of Italy (CNR).

"In our previous research we showed that t-SPL outperforms electron beam lithography and other standard methods for fabricating metal electrodes on MoS2, an advance that could also decrease the cost of fabrication since t-SPL does not require markers or vacuum," said Riedo.

With this consecutive success in bipolar doping of 2D semiconductors, t-SPL is now able to offer both dopants patterning and chip manufacturing, which will rapidly advance the material science and chip design. "It is great to see how t-SPL is now taking up to enable the fabrication of functional transistor devices from 2D materials, including control of the doping levels" said Armin Knoll, from IBM Zurich, one of the pioneers together with Riedo of t-SPL.

TROY, N.Y. -- When the Shewanella oneidensis bacterium "breathes" in certain metal and sulfur compounds anaerobically, the way an aerobic organism would process oxygen, it produces materials that could be used to enhance electronics, electrochemical energy storage, and drug-delivery devices.

The ability of this bacterium to produce molybdenum disulfide -- a material that is able to transfer electrons easily, like graphene -- is the focus of research published in Biointerphases by a team of engineers from Rensselaer Polytechnic Institute.

"This has some serious potential if we can understand this process and control aspects of how the bacteria are making these and other materials," said Shayla Sawyer, an associate professor of electrical, computer, and systems engineering at Rensselaer.

The research was led by James Rees, who is currently a postdoctoral research associate under the Sawyer group in close partnership and with the support of the Jefferson Project at Lake George -- a collaboration between Rensselaer, IBM Research, and The FUND for Lake George that is pioneering a new model for environmental monitoring and prediction. This research is an important step toward developing a new generation of nutrient sensors that can be deployed on lakes and other water bodies.

"We find bacteria that are adapted to specific geochemical or biochemical environments can create, in some cases, very interesting and novel materials," Rees said. "We are trying to bring that into the electrical engineering world."

Rees conducted this pioneering work as a graduate student, co-advised by Sawyer and Yuri Gorby, the third author on this paper. Compared with other anaerobic bacteria, one thing that makes Shewanella oneidensis particularly unusual and interesting is that it produces nanowires capable of transferring electrons.

"That lends itself to connecting to electronic devices that have already been made," Sawyer said. "So, it's the interface between the living world and the manmade world that is fascinating."

Sawyer and Rees also found that, because their electronic signatures can be mapped and monitored, bacterial biofilms could also act as an effective nutrient sensor that could provide Jefferson Project researchers with key information about the health of an aquatic ecosystem like Lake George.

"This groundbreaking work using bacterial biofilms represents the potential for an exciting new generation of 'living sensors,' which would completely transform our ability to detect excess nutrients in water bodies in real-time. This is critical to understanding and mitigating harmful algal blooms and other important water quality issues around the world," said Rick Relyea, director of the Jefferson Project.

Sawyer and Rees plan to continue exploring how to optimally develop this bacterium to harness its wide-ranging potential applications.

"We sometimes get the question with the research: Why bacteria? Or, why bring microbiology into materials science?" Rees said. "Biology has had such a long run of inventing materials through trial and error. The composites and novel structures invented by human scientists are almost a drop in the bucket compared to what biology has been able to do."

The majority of U.S. gun owners support measures such as background checks, but report not vocally supporting these policies because they feel disrespected by health advocates.

A new Boston University School of Public Health (BUSPH) study sheds new light on the opinions and practices of U.S. gun owners, casting doubt on the way gun owners have been portrayed in policy discussions and media, and even how they perceive themselves.

The survey results, published in the American Journal of Preventive Medicine, show that the majority of gun owners support many gun violence prevention policies, including background checks, permit requirements, and prohibitions for individuals with domestic violence restraining orders. But most of these gun owners report that they do not make their support public because they are alienated by the rhetoric of gun violence prevention advocates.

"Most people think gun violence prevention is a contentious issue, but our survey reveals that gun owners overwhelmingly support policies such as universal background checks and red flag laws," says study co-author Claire Boine, a research scholar at BUSPH.

"Gun owners overwhelmingly support basic gun violence prevention policies, but they feel alienated because we in public health are not respecting their decision to own a gun for self-protection. This feeling of disrespect is what is keeping gun owners who support these policies from expressing their support publicly. Public health advocates must respect the decision that gun owners have made to protect themselves and their families. Educating gun owners about the risks associated with gun ownership is important, but needs to be done without criticizing gun owners or attacking gun culture," says study lead author Dr. Michael Siegel, professor of community health sciences at BUSPH.

The study is based on the responses of 2,086 gun owners in the 2019 National Lawful Use of Guns Survey.

The researchers found most gun owners in the U.S. view guns as a practical tool to protect themselves, and do not have strong identities as gun owners. Only 10% said they view guns as an important part of their identity, and 23% reported taking part in any gun-related activity more than rarely.

Ironically, only 8% of survey respondents identified themselves as being like the typical gun owner, according to the survey. "The NRA pulled one of the biggest illusions in history by making 8% of gun owners feel like they are the majority, and the other 92% feel like the minority. The NRA does not represent gun owners in this country, and it is time for the media and policymakers to give a voice to the silent majority," Boine says.

Despite the majority of the gun owners saying they support many gun violence prevention policies, 59% said they think that gun control advocates want to take their guns away. Among gun owners who said they supported universal background checks, 62% said that they nonetheless feel alienated from taking part in gun violence prevention because they perceive that gun control advocates are trying to eliminate aspects of gun culture.

"We need to view the decision to arm oneself for self-protection as a legitimate behavior," Siegel says. "We may not agree that it reduces actual risk, but if law-abiding gun owners feel disrespected, why should they believe that we are not aiming to take their guns away? That is respect that needs to be earned."

Boine notes that the survey found the policies with the least support among gun owners are the ones that ban certain types of firearms, while most gun owners support policies that instead focus on the risks associated with each potential firearm buyer. "Responsible gun owners don't want firearms to fall into the hands of people who are a danger to themselves or others," she says. "Policies that ban certain types of weapons and affect all gun owners alike make them feel like we are blaming them for the gun violence epidemic."

In previous research, Siegel and Boine have found that the policies that most effectively reduce gun violence are the ones that limit who can have a firearm, rather than what firearms are legal to own.

Analyses of lung fluid cells from COVID-19 patients conducted on the nation's fastest supercomputer point to gene expression patterns that may explain the runaway symptoms produced by the body's response to SARS-CoV-2.

A team led by Dan Jacobson of the Department of Energy's Oak Ridge National Laboratory used the Summit supercomputer at ORNL to analyze genes from cells in the lung fluid of nine COVID-19 patients compared with 40 control patients.

The computational analyses suggest that genes related to one of the body's systems responsible for lowering blood pressure -- the bradykinin system -- appear to be excessively "turned on" in the lung fluid cells of those with the virus. The results were published in eLife.

Based on their analyses, the team posits that bradykinin -- the compound that dilates blood vessels and makes them permeable -- is overproduced in the body of COVID-19 patients; related systems either contribute to overproduction or cannot slow the process. Excessive bradykinin leads to leaky blood vessels, allowing fluid to build up in the body's soft tissues.

Much attention has focused on what's known as the cytokine storm, a severe reaction in which the body releases an excess of cytokines, a variety of small proteins that help regulate the immune system. Jacobson's team thinks a bradykinin storm may instead be to blame for much of the viral pathogenesis. If the team's disease mechanism model is accurate and substantiated by experimental analysis, it may mean that existing medicines could be repurposed to slow the pathogenesis of COVID-19. This would require extensive clinical trials of drugs currently used to treat other bradykinin-related conditions.

"If we can block this pathogenesis in severe patients, we can keep the human response from going overboard and give their immune system time to fight off the virus so they can recover," Jacobson said.

The bradykinin storm could explain the wide variety of symptoms experienced by COVID-19 patients, such as muscle pain, fatigue, nausea, vomiting, diarrhea, headaches, and decreased cognitive function. Similar symptoms are also experienced by patients with other bradykinin-related conditions such as hereditary angioedema, a genetic condition that is characterized by episodes of severe swelling throughout the body.

"This is one of those rare times where you can really tie everything back to a eureka moment," said Jacobson, staff scientist in ORNL's Biosciences Division. "I was looking at data, and I suddenly saw some very distinct patterns happening in the pathways of the renin-angiotensin and bradykinin systems. That led us to do a deep dive of the gene families of the blood pressure regulatory system." The renin-angiotensin system, or RAS, and bradykinin pathway regulate blood pressure and fluid balance in the body.

Using the Summit and Rhea supercomputers at the Oak Ridge Leadership Computing Facility, the team compared the genes of COVID-19 patients against a control group and analyzed population-scale gene expression data -- 17,000 samples from uninfected individuals -- to see which genes were normally co-expressed, or turned on or off at the same time.

Summit is currently the nation's most powerful supercomputer, with a theoretical peak performance of 200 petaflops, or 200 quadrillion calculations per second. Jacobson and his colleagues required the power of Summit to run 2.5 billion correlation calculations that helped them understand the normal regulatory circuits and relationships for the genes of interest. With Summit, the team completed the calculations in one week rather than spending months doing them on a desktop computer.

Researchers found an increased expression of enzymes that can trigger the production of bradykinin and a decreased expression of enzymes that would break down bradykinin -- the perfect storm. The team also uncovered that an enzyme that forestalls the bradykinin cascade -- the angiotensin-converting enzyme, known as ACE -- was less expressed in COVID-19 patients. At least ten existing drugs are known to act on the specific pathways Jacobson's team studied, but large-scale clinical trials are needed to determine whether they might be effective at treating COVID-19.

"We believe that when you take the inhibition at the top of this pathway off, you end up with an out-of-control cascade that leads to an opening up of the blood vessels, causing them to leak," Jacobson said. "If that happens in the lung, that's not good. Immune cells that are normally contained in the blood vessels flood into the surrounding infected tissue, causing inflammation."

The lungs of COVID-19 patients are known to have an increased amount of hyaluronic acid, a gooey substance found in connective tissues that can trap around 1,000 times its own weight in water to form a hydrogel. The team also found that genes in the cells of COVID-19 patients increased the production of the substance and decreased its breakdown. The findings suggest that further experimental study of drug compounds known to slow the synthesis of hyaluronic acid and the mechanisms involved in the process is warranted.

"When the lungs end up with an excess of hyaluronic acid in them, it's like trying to breathe through Jell-O," Jacobson said. "It reaches a point where regardless of how much oxygen you pump in, it doesn't matter, because the alveoli in the lungs are filled with this hydrogel. With this excess of hyaluronic acid, any water leaking out of the blood vessels due to bradykinin will soak up this structure and the lungs become like a water balloon."

The team also used the Compute and Data Environment for Science, or CADES, at ORNL to determine which genes in the RAS-bradykinin pathways have vitamin D binding sites. The results of their analyses might help scientists determine through experimentation which parts of these pathways could potentially be influenced by vitamin D. Because vitamin D helps regulate the RAS and vitamin D deficiencies have already been associated with more severe illness in COVID-19 patients, Jacobson said it's another molecule worth further study.

WASHINGTON, D.C.--The signs of physical abuse among elderly people can be challenging for health care professionals to recognize, resulting in as few as one in 24 cases being reported to authorities. However, a new study in Annals of Emergency Medicine explores injury patterns and characteristics to help experts spot key differences between abuse and unintentional injury.

"The first place that many vulnerable older patients turn for care is the emergency department," said lead study author Tony Rosen, MD, MPH, FACEP, assistant professor of emergency medicine at Weill Cornell Medicine and director of the Vulnerable Elder Protection Team based at New York-Presbyterian/Weill Cornell Medical Center's emergency department. "Emergency physicians have a unique opportunity to identify the 'red flags' for elder abuse. Improving the ability to recognize, treat, and prevent these incidents can improve the lives of millions of older patients."

The study, "Identifying Injury Patterns Associated with Physical Elder Abuse: Analysis of Legally Adjudicated Cases," compares 78 physical abuse cases with visible injuries among patients aged 60 or older with 78 patients of similar age and sex who visited a New York City emergency department for an unintentional fall between 2001-2014.

Abuse-related injuries are frequently attributed to an unintentional fall, the authors note. By comparing a group of patients injured by an unintentional fall with medical and legal records of prosecuted abuse cases, the study reveals several distinct injury patterns:

Victims of abuse often have head or neck injuries without visible harm to other parts of the body. Abuse victims are more likely than patients who fall to have injuries on the face, head and neck area (67 percent versus 28 percent).

Abuse victims are less likely than patients who fall to have scrapes, fractures or injuries below the waist (8 percent versus 50 percent).

Facial injuries to the left cheek are frequent (22 percent) in abuse cases; a finding that confirms that abusers tend to be right-handed, the authors note.

Neck injuries raise suspicions of abuse because the neck is often protected by the head or the face during an unintentional fall. Among more than 800 examined injuries, researchers found neck injuries and ear injuries resulted from abuse rather than a fall (15 percent versus 0 percent for neck injuries and 6 percent versus 0 percent for ear injuries).

According to the study, 22 percent of cases identified and prosecuted had no visible injury recorded. In many of these cases, victims indicated pain in the arms, chest, abdomen, back, face and jaw, which can inform how to approach patients without visible injury when abuse is suspected.

"Identifying the victims of elder abuse is an important skill set for professionals working in emergency departments caring for older adults," said Dr. Rosen. "Recognizing injury patterns helps encourage an environment where more of these troubling cases of harm against some of the most vulnerable, at-risk older adult patients can be reported and addressed."