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Cancer is a group of diseases characterised by uncontrolled cell growth caused by mutations, and other alterations in the genome of cells. A tumour can present from hundreds to thousands of mutations, but only a few are vital for its tumorigenic capacity. These key mutations affect the function of cancer driver genes. Finding the genes that harbour this cancer driver mutations is one of the main goals in cancer research.

Researchers from IRB Barcelona's Biomedical Genomics Lab, led by ICREA researcher Nuria Lopez-Bigas, have performed an extensive computational analysis of around 28,000 tumours from 66 types of cancer and have identified 568 cancer driver genes. These pivotal genes play specific roles in the regulation of cell growth, the cell cycle and DNA replication, among others. Mutations in these genes, confer malignant cells the capacity to reproduce rapidly and endlessly, evade the immune system and other defence systems, spread and invade other tissues, and modify the environment to their benefit, among other capabilities.

"The compendium of driver genes provides cancer researchers, both in the clinical and basic research setting, with crucial knowledge and it has an important impact on clinical decision-making," says López-Bigas. "For instance, if we know that the tumorigenic capacity of a tumour relies on a specific protein, an approved targeted therapy -i.e., antibodies or other inhibitors hindering its function- may be employed by oncologists to treat the patient", she adds.

Most cancer driver genes are highly specific

With the identification of the 568 cancer driver genes, the researchers have observed that most are highly specific and with their mutations capable of triggering only a few tumour types. However, there is a small group, accounting for less than 2% of those identified, that is very versatile and can drive more than 20 different types of cancer. "Although it's been known that cancer driver genes have different degree of specificity since they were first identified, having this snapshot of the compendium has allowed us to address this question it in an unbiased way," says Abel González Perez, Research Associate in the Biomedical Genomics Lab, who also led the study.

Previous studies by other groups have shown that cancers are caused by an average of 4 key mutations in cancer driver genes. Some types of cancer, characterised by a low number of mutations, present only one mutation in these genes, while others that typically present many mutations, such as colorectal and uterus tumours, hold up to 10. Other genomic alterations, such as structural variants, changes in the number of copies of genes, and mutations affecting non-coding areas of the genome also contribute to tumorigenesis.

Positive selection as an indicator

Surprising mutational patterns in a gene, different from the expected under neutrality, constitute signals that they are under positive selection in tumorigenesis. IRB Barcelona researchers use these signals of positive selection to identify mutational driver genes. To compute these signals, the accumulation of mutations under neutrality needs to be accurately modelled for all genes, so that deviations of any gene from the expected pattern may be readily spotted.

Signals of positive selection that are exploited to identify mutational driver genes are, for example, the abnormally high number of mutations in a gene or an unexpected distribution of mutations along the sequence of a gene. In this latest article, published in the journal Nature Reviews Cancer, the researchers present an update of the open-access IntOGen platform, including the values computed for these signals across all mutational driver genes. "The IntOGen platform provides the ideal infrastructure for the systematic update of the compendium, as more tumour sequencing data are released into the public domain," says first author Francisco Martínez-Jiménez, postdoctoral researcher in the Biomedical Genomics Lab.

Enriching the Cancer Genome Interpreter

The Biomedical Genomics Lab previously developed a platform called the Cancer Genome Interpreter, aimed at supporting clinical decision-making in oncology. The recently published compendium of driver genes in each cancer type, as well as their mutational patterns across tumours, will feed the new version of Cancer Genome Interpreter, under development, thus refining its capability of identifying mutations that may be key for an individual's tumour, and which constitute therapeutic targets. The snapshot of the compendium of driver genes, and the computational system used to produce it are freely available to clinical and basic cancer researchers for exploration and download.

Remarkable progress in our understanding of phosphate metabolism has been made over the last two decades, and this in turn has led to significant advances in the knowledge and management of diseases such as hypo- and hyperphosphatemia and tumour-induced osteomalacia, among other related disorders.

A special issue of Calcified Tissue International now features 10 invited reviews that elucidate the latest knowledge and noteworthy progress on phosphate metabolism. The issue has been curated by guest editors, Professors S. Minisola and ML Brandi, renowned experts in rare skeletal diseases.

Professors René Rizzoli and Stuart Ralston, Editors of Calcified Tissue International, noted: "These state-of-the-art reviews give insights into the physiology and pathology of phosphate metabolism as well as the important advances that have been made to date at the translational and clinical level. Importantly, they point to new directions for future research which are expected to benefit patients who suffer from phosphate wasting and related disorders. We sincerely thank the authors of these outstanding reviews for providing important and timely updates."

The prevalence of the highly infectious coronavirus disease, COVID-19, has caused massive health and socio-economic upheavals worldwide. Major slumps in industrial production due to stringent lockdown measures and export restrictions have led to severe logistical challenges and drastic disruptions to the global supply chains. Rising to the challenges and unprecedented demands, the 3D printing technology has demonstrated operational resilience with timely and innovative responses to help in the global supply efforts.

In an article published in Nature Reviews Materials, researchers from the Singapore University of Technology and Design (SUTD), Nanyang Technological University, Cedars-Sinai Medical Center and HP Inc examined how the digital versatility and quick prototyping of 3D printing has enabled the swift mobilization of the technology and a rapid response to emergencies in a closed loop economy.

The researchers explained how 3D printing has enabled product customization, complex designs and on-demand manufacturing using any decentralized 3D printing facility in the world by leveraging designs shared online. This has led to the broad spectrum of 3D printing applications in the fight against COVID-19 including the printing of personal protective equipment (PPE), medical and testing devices, personal accessories, visualization aids, and emergency dwellings.

For instance, due to severe shortages of ventilator machines, continuous positive airways pressure (CPAP) machines were used as substitutes for COVID-19 patients who require sub-intensive therapy. A 3D printable mask connector design, the Charlotte valve, was produced and it was specially designed to fit and connect Decathlon's Easybreath snorkelling masks to CPAP machines.

3D printing also served as an alternative and more efficient manufacturing option to keep up with the demand for nasopharyngeal (NP) swabs. The 3D printed NP swabs were fabricated with complex tip structures for enhanced sample collection efficacy, hence eliminating the need to apply flocks at the tips. Separately, 3D printing has even been used to fabricate temporary emergency dwellings to isolate those under quarantine, relieving the overloaded medical infrastructures.

The article additionally discussed technological suitability, accountability of new approved designs, copyright infringements as well as regulations and guidelines that 3D print manufacturers need to abide by to ensure safe and effective performance of 3D-printed medical devices and translate the good intentions of individuals into meaningful contributions.

"The agility and precision of 3D printing has allowed for innovative solutions amidst the supply chain pressures that we are facing globally. This has resulted in rapidly deployable built environment, healthcare medical devices and training tools which have been crucial in the fight to save lives and contain this virus," said corresponding author Professor Chua Chee Kai from SUTD.

Stroke, Parkinson's disease and depression - these medical illnesses have one thing in common: they are caused by changes in brain functions. For a long time, research has therefore been conducted into ways of influencing individual brain functions without surgery in order to compensate for these conditions.

Scientists at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, have taken a decisive step. They have succeeded in precisely influencing the functioning of a single area of the brain. For a few minutes, they inhibited exactly the area that processes the sense of touch by specifically intervening in its rhythm. As a result, the area that was less networked with other brain regions, its so-called functional connectivity, decreased, and thus also the exchange of information with other brain networks.

This was possible because the researchers had previously determined each participant's individual brain rhythm that occurs when perceiving touch. With the personal frequency, they were able to modulate the targeted areas of the brain one at a time in a very precise manner using what is known as transcranial alternating current stimulation. "This is an enormous advance," explains Christopher Gundlach, first author of the underlying study. "In previous studies, connectivity fluctuated extensively when the current was distributed in different areas of the brain. The electrical current randomly sought its own path in the brain and thus affected different brain areas simultaneously in a rather imprecise manner.

In a preliminary study, the neuroscientists had already observed that this form of stimulation not only reduces the exchange of the targeted brain networks with other networks, it also affects the brain's ability to process information, in this case the sense of touch. When the researchers inhibited the responsible somatosensory network, the perception threshold increased. The study participants only perceived stimuli when they were correspondingly strong. When, on the other hand, they stimulated the region, the threshold value dropped and the study participants already felt very gentle electrical stimuli.

"The deliberate change in brain rhythm lasted only briefly. As soon as the stimulation is switched off, the effect disappears again," explains study leader Bernhard Sehm. "Nevertheless, the results are an important step towards a targeted therapy for diseases or disorders caused by disturbed brain functions". Targeted brain stimulation could help to improve, direct and, if necessary, attenuate the flow of information.

The development of chemotherapeutic agents with selective anti-cancer activities is increasingly unattractive due to the emergence of resistance, poor targeting of cancer tissues, and subsequent metastasis. Among tumor characteristic cell types, cancer stem cells are increasingly associated with cancer progression and metastasis, reflecting self-renewal and their propensity to enter the circulation.

Scientists at Japan Advanced Institute of Science and Technology (JAIST) have created a regulation technology of fatal cancer stemness using the combination of nanotechnology and genetic engineering called as "photothermogenetics" that allows for effective cancer elimination.

Developed by Associate Professor Eijiro Miyako and his team from JAIST, photo-active functional nanocarbon complexes, which made of polyethylene glycol (PEG)-modified carbon nanohorns (CNH) with an antibody against the receptor potential vanilloid family type 2 (TRPV2), showed high potential as a targeting cancer chemotherapeutic agent.

In fact, the nanocomplexes are effectively heated by biologically permeable near-infrared light. After application to cancer cells and mice tumor models, these complexes photo-thermally triggered calcium influx into target cells overexpressing TRPV2 (temperature-responsive membrane protein), resulting in increased cancer cell death and effective regulation of cancer stemness. The present experiments warrant further consideration of this novel chemotherapeutic approach using the best combination of nanotechnology and genetic engineering for the treatment of refractory cancers and control of fatal cancer stemness.

Tropical Storm Josephine weakened on Aug. 16 in the North Atlantic Ocean and satellite imagery showed the storm had become elongated and stretched out into a trough of low pressure a couple of hundred miles north of Puerto Rico.

Early on Sunday, Aug. 16, the Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard NASA's Aqua satellite provided infrared temperatures of the storm's cloud tops and revealed the storm had become more disorganized over the last day. Coldest cloud top temperatures were near minus 70 degrees Fahrenheit and were displaced from the center. At the time, the National Hurricane Center said, "Josephine's low-level center has raced out over 100 nautical miles to the west of a remnant area of deep convection, which itself is shrinking and becoming more disorganized."

Later in the day, at 1:30 p.m. EDT, the MODIS instrument aboard NASA's Terra satellite provided a visible image of Josephine as it was degenerating into a trough (elongated area) of low pressure about 175 miles (280 km) north of San Juan, Puerto Rico. The MODIS image showed a low-level swirl that became less defined later in the day. Wind data on the afternoon of Aug. 16 indicated Josephine had degenerated into a trough of low pressure.

Josephine's Final Advisory

The NHC posted its final advisory on Josephine on Sunday, Aug. 16 at 5 p.m. EDT (2100 UTC). At that time, the remnants of Josephine were located near latitude 20.9 degrees north and longitude 65.8 degrees west. The remnants were moving toward the west-northwest near 12 mph (19 kph), and is expected to turn toward the northwest.

Maximum sustained winds are near 35 mph (55 kph) with higher gusts. The maximum winds associated with the remnants are forecast to continue to decrease over the next day or two. The remnants are forecast to recurve toward the north and northeast Tuesday and Tuesday night.

About NASA's Worldview and Terra Satellite

NASA's Earth Observing System Data and Information System (EOSDIS) Worldview application provides the capability to interactively browse over 700 global, full-resolution satellite imagery layers and then download the underlying data. Many of the available imagery layers are updated within three hours of observation, essentially showing the entire Earth as it looks "right now." One of the satellites providing data is NASA's Terra Satellite. Terra is one in a fleet of NASA satellites that provide data for hurricane research.

Tropical cyclones/hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For updated forecasts, visit: http://www.nhc.noaa.gov

By Rob Gutro
NASA's Goddard Space Flight Center

KANSAS CITY, MO - It can be hard to dispute the common adage 'survival of the fittest'. After all, "most of the genes in the genome are there because they're doing something good," says Sarah Zanders, PhD, assistant investigator at the Stowers Institute for Medical Research. But, she says, "others are just there because they've figured out a way to be there."

The conventional understanding of evolution is that genes encoding a beneficial function are the most frequently transmitted, which ensures that the fittest organisms - the ones that have traits most favorable for their environment - survive. Less known is the fact that there exist parasitic gene elements within an organism that are doing just the opposite.

"The way one could think of it is that the genome is like a society," explains Zanders. "Within that society, there are individuals who derive their living from doing good things and making valuable contributions. But there are others who don't contribute in beneficial ways and are actually harmful to society," explains Zanders.

The Zanders Lab studies parasitic genes in Schizosaccharomyces pombe, a species of fission yeast sometimes found in the popular fermented tea drink kombucha. Because of its simplicity and fast generation times, S. pombe is a highly tractable system for studying parasitic gene elements, particularly a class known as meiotic drivers. Instead of conferring a benefit to their host, meiotic drivers confer distinct disadvantages to their host, in order to bias their own perpetuation. One method of doing so, employed by the wtf meiotic drive genes, is through selective poisoning of cells in meiosis.

Meiosis is the process of cell division through which sexually-reproducing organisms form gametes - such as egg and sperm cells in humans, or spores in yeast - to propagate the next generation. Normally, this process results in gametes that inherit one of two copies of each chromosome carried by the parent cell, and each copy is transmitted to gametes at an equal rate. Meiotic drivers, however, short-circuit this law of Mendelian segregation.

"Usually all the alleles - or variants of a particular gene - get a fair chance, and natural selection can pick the best ones," explains Zanders. "But alleles that are meiotic drivers select themselves even if they're not the best option. And they're never the best option."

In a paper published online August 13, 2020, in eLife, members of the Zanders lab explain how it could be possible that meiotic drivers persist in the population, even as they kill off many would-be hosts. It turns out that S. pombe can employ variants of other genes to help suppress the negative effect of meiotic drivers, albeit at a cost to fitness.

Usually, to propagate laboratory strains of S. pombe, they are inbred. "When you outcross two isolates that are almost identical, they produce almost no progeny," explains first author María Angélica Bravo Núñez, PhD, who was involved in the identification of the wtf genes, and who did this work in the Zanders Lab as a predoctoral researcher at the Graduate School of the Stowers Institute. "This suggested there might be some type of competition at play." Bravo Núñez and colleagues used this reasoning to seek out genes that could be in conflict in similar, but non-identical, genomes of S. pombe. The central experimental design of the current work involved outcrossing of S. pombe isolates that are over 99% identical.

"Outcrossing can have many advantages," says Bravo Núñez, such as providing a normal allele of a gene to rescue the effect of a mutant allele. "But the meiotic drive genes that we study actually exert their deleterious effect in the heterozygous scenario, where the alleles of a gene are not the same."

One illuminating experiment they did was to compare outcomes of inbred and outcrossed S. pombe isolates in a genetic background containing a mutation in rec12, which is a gene that promotes proper chromosome segregation.

"Rec12 usually promotes fertility," says Bravo Núñez. "When we removed rec12 function, the numbers of viable spores decreased, but only in the inbred scenario. The relative numbers of viable spores didn't really decrease in the outcrossed scenario." Moreover, of the viable spores, they found that survival was biased towards atypical gamete products, resulting from mis-segregation and unequal crossover of paired chromosomes. In other words, surviving spores contained the maximal number of meiotic drivers, sometimes due to inheriting an extra chromosome. This finding was surprising because extra chromosomes are usually considered very harmful. In humans, for instance, extra or missing chromosomes can lead to inviable gametes, severe birth defects, or infertility.

"When you have heterozygosity of wtf genes, making a mutation in the rec12 gene is relatively good for the organism, because that's just what has to happen in order to not kill all the progeny," says Bravo Núñez.

"We think of rec12 as this gene that's really important for fertility," explains Zanders. "But the situation is totally different when there is outcrossing. Having rec12 doesn't actually help at all, because the yeast is better off making gametes that do not result from proper chromosome segregation. This is just one example of the power of meiotic drivers to change the landscape of meiosis. Fundamentally, what is 'good' for the organism has changed."

"Having that extra chromosome is not good, and the yeast colonies look unusual, small, and irregular. But after they continue to grow for a while, the cells lose that extra chromosome and then they can thrive as haploids. So, this step is actually just temporary," says Bravo Núñez.

Precisely because meiotic drivers exert their influence in a heterozygous scenario, they are easy to miss. "There are many flavors of meiotic drive. Some forms of meiotic drive are hard to measure experimentally because the bias is so subtle," says Zanders. "We're not the first to study meiotic drivers in depth. We just have a better model system now, so we can make more progress faster."

"Drive systems tend to be repetitive, and you can usually find them in various copies in genomes," says Bravo Núñez. "They have, in many cases, already been found in other systems, such as fungi, mice, and fruit flies, but are not yet fully characterized." The study of meiotic drivers in S. pombe "will hopefully guide future research to understand other drive systems."

"Humans certainly have meiotic drive genes. Whether or not they have meiotic drive genes of the gamete-killing type is unclear," says Zanders. "Meiotic drive has likely affected the evolution of human centromeres, which are regions of chromosomes that are very important for proper chromosome segregation. Certain chromosome fusions exhibit meiotic drive in humans, as do sequences that are involved in DNA recombination. We're going to continue focusing on these and other parasitic gene elements, their strategies, and their effects."

Other coauthors of this work include Ibrahim M. Sabbarini and Lauren E. Eide from the Stowers Institute and Robert L. Unckless, PhD, from the University of Kansas.

This work was funded in part by the Stowers Institute for Medical Research, March of Dimes Foundation Basil O'Connor Starter Scholar Research Award (5-FY18-58 to SEZ), Searle Scholar Award (to SEZ), and National Institutes of Health (National Institute of General Medical Sciences awards R00GM114436 and DP2GM132936 to SEZ and National Cancer Institute award F99CA234523 to MABN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Lay Summary of Findings

A new study published online August 13, 2020, in eLife from the laboratory of Sarah Zanders, PhD, at the Stowers Institute for Medical Research describes a strategy that the S. pombe fission yeast genome can use to mitigate some of the worst effects conferred by parasitic gene elements known as meiotic drivers.

The meiotic drivers analyzed in the study are able to short-circuit the conventional law of Mendelian segregation, which usually ensures that each gamete (reproductive cell) receives one of two copies of each chromosome from the parent cell with equal transmission. Meiotic drivers instead can poison gametes that do not contain their genetic sequence, thereby swinging the transmission rate in their favor.

As a way of enabling the survival of some gametes that would otherwise die, the S. pombegenome can employ variants of other genes to create a situation that "protects" them, even if it comes at a cost to fitness. For example, a mutation in rec12, a gene responsible for proper chromosome segregation, can lead to gametes having extra chromosomes. While extra chromosomes are usually undesirable, in this scenario they actually enable more gametes to survive. This surprising insight into meiotic drivers and how they can be suppressed could help researchers better understand the forces that shape the evolution of gamete formation, as well as those underlying human infertility.

Although Live Oak trees are common in South Florida today, Ken Feeley, a University of Miami biology professor, said their time here may be fleeting. With climate change pushing up temperatures, the oaks, which favor cooler conditions, could soon decline in the region and be replaced with more tropical, heat-loving species such as Gumbo Limbo or Mahogany trees.

"Live Oaks occur throughout the southeast and all the way up to coastal Virginia, so down here we are in one of the very hottest places in its range," said Feeley, who is also the University's Smathers Chair of Tropical Tree Biology. "As temperatures increase, it may simply get too hot in Miami for oaks and other temperate species."

Likewise, in Canada, as temperatures increase, sugar maple trees--which are used to produce maple syrup--are losing their habitats. And in New York City, trees that are more typical of the balmy South, such as Magnolias, are increasing in abundance and blooming earlier each year, news reports indicate.

These are just a few examples of a larger trend happening across the Americas--from Hudson Bay to Tierra del Fuego--as plant communities shift their ranges and respond to changing climates, Feeley pointed out. In his newest study, published in Nature Climate Change, Feeley, along with three of his graduate students and a visiting graduate student from the Nacional University of Colombia, analyzed more than 20 million records of more than 17,000 plant species from throughout the Western Hemisphere. They found that since the 1970s, entire plant ecosystems have changed directionally over time to include more and more of the species that prefer warmer climates. This process is called thermophilization.

"Almost anywhere you go, the types of species that you encounter now are different than what you would have found in that same spot 40 years ago, and we believe that this pattern is the direct result of rising temperatures and climate change," Feeley said.

The research of Feeley and his students demonstrates that entire ecosystems are consistently losing the plant species that favor cold temperatures, and that those plants are being replaced by more heat-tolerant species that can withstand the warming climate. Plants favoring cool temperatures are either moving to higher elevations and latitudes, or some species may even be going locally extinct. Feeley and his students are now exploring key focal species that may offer more insight into these processes.

"Some of these changes can be so dramatic that we are shifting entire habitat types from forests to grasslands or vice versa--by looking at all types of plants over long periods of time and over huge areas, we were able to observe those changes," he explained.

In addition to the effects of rising temperatures, the researchers also looked at how plant communities are being affected by changes in rainfall during the past four decades. Feeley and his team observed shifts in the amounts of drought-tolerant versus drought-sensitive plant species. But in many cases, the observed changes were not connected to the changes in rainfall. In fact, in many areas that are getting drier, the drought-sensitive species have become more common during the past decades. According to Feeley, this may be because of a connection between the species' heat tolerances and their water demands. Heat tolerant species are typically less drought-tolerant, so as rising temperatures favor the increase of heat-tolerant species, it may also indirectly prompt a rise in water-demanding species. Feeley stressed that this can create dangerous situations in some areas where the plant communities are pushed out of equilibrium with their climate.

"When drought hits, it will be doubly bad for these ecosystems that have lost their tolerance to drought," he said, adding that "for places where droughts are becoming more severe and frequent--like in California--this could make things a lot worse."

But the implications of thermophilization go far beyond just the loss of certain plants, according to Feeley. Plants are at the base of the food chain and provide sustenance and habitat for wildlife--so if the plant communities transform, so will the animals that need them.

"All animals--including humans--depend on the plants around them," Feeley said. "If we lose some plants, we may also lose the insects, birds, and many other forms of wildlife that we are used to seeing in our communities and that are critical to our ways of life. When people think of climate change, they need to realize that it's not just about losing ice in Antarctica or rising sea levels--climate change affects almost every natural system in every part of the planet."

CLEVELAND--Researchers at Case Western Reserve University have added to the growing body of understanding about how hydroxychloroquine (HCQ) is not a possible defense against COVID-19.

Specifically, they found that HCQ is not effective in preventing COVID-19 in patients with lupus and rheumatoid arthritis (RA), suggesting a broader interpretation of HCQ as ineffective preventive medicine for the general population. Their findings were recently published in the Annals of the Rheumatic Diseases.

Many researchers have focused on patients with systemic lupus erythematosus (SLE) and RA because HCQ is frequently taken by these patients. Anecdotal reports in the early stages of the pandemic showed these patients were not getting COVID-19. Earlier researchers then explored HCQ in the lab and found it effective against the virus, in addition to its already established anti-inflammatory properties, so testing in people for prevention or treatment at first held some promise. Since those early tests, various more recent studies have shown that HCQ is not effective in treating moderate-to-severe hospitalized cases. Treatment with HCQ early in the disease or for mild cases is still under review.

"Our study shows, with a large degree of confidence, that HCQ is ineffective as a preventive antiviral in people with SLE and/or RA taking drugs that suppress their immune system, putting them at greater risk," said Mendel Singer, PhD, MPH, lead author and associate professor and vice chair for education in the Department of Population & Quantitative Health Sciences at the Case Western Reserve School of Medicine. "Given how the study was structured, one can make an educated extension that it is not effective in preventing COVID-19 in people without those conditions. It is not uncommon for something to show promise in the lab, and then prove ineffective in the more complex biological landscape of humans."

The Case Western Reserve team drew on a large national database, pulling de-identified patient data from 36 health systems, to compile a much larger study than previous work, looking at patients with SLE and/or RA and their health outcomes related to their use of HCQ. Prior studies had fewer than 20 COVID-19 patients with SLE and/or RA; this study had 159. This study showed that patients with SLE and/or RA who contracted COVID-19 were just as likely to be taking HCQ as SLE and/or RA patients who did not get COVID-19.

"By drawing on data from a relatively large patient population with lupus and/or RA, we can offer a higher level of confidence in our findings," said Singer. "We see from this large retrospective review that this drug is ineffective in preventing COVID-19 in these patients who have been taking HCQ. If HCQ were effective in prevention, we would have seen fewer HCQ-taking SLE/RA patients with COVID-19, but did not. This likely means that HCQ is not active against the SARS-CoV-2 virus in humans--versus in the lab--and is unlikely to be an effective preventive antiviral for anyone."

ORLANDO, Aug. 17, 2020 - An international team of researchers using data from Arecibo Observatory and the Fermi Space Telescope have discovered what they call a "gamma-ray heartbeat" coming from a cosmic gas cloud.

The cloud is in the constellation Aquilla and "beats" in rhythm with a black hole 100 light years away in a microquasar system known as SS 433. The results were published today in the journal Nature Astronomy.

"This result challenges obvious interpretations and is unexpected from previously published theoretical models," says Jian Li, a Humboldt Fellow with the Deutsches Elektronen-Synchrotron in Zeuthen, Germany, and study co-author. "It provides us with a chance to unveil the particle transport from SS 433 and to probe the structure of the magnetic field in its vicinity."

In the SS 433 system, a black hole orbits a giant star, 30 times the mass of Earth's sun. The black hole sucks matter from the giant star while orbiting it, forming a swirling accretion disc that drains into the black hole, like water into a bathtub drain.

Some of the matter doesn't fall into the hole though, but rather jets out in high speed spirals from the disc's center in both directions, top and bottom, like pegs on a wheel.

The researchers made the discovery by analyzing more than a decade of data from NASA's Fermi Large Area Space Telescope and from Galactic ALFA HI survey data collected with the Arecibo Observatory's 1,000-foot-wide radio telescope. The observatory was recently damaged and is currently offline, but scientists continue to have access to data previously collected. Engineers are assessing what caused a cable to break and plans for repairs.

The researchers found that the precession, or wobble, of the black hole's jets matched with a gamma-ray signal emitted from a gas cloud. The researchers have labeled the position in the gas cloud Fermi J1913+0515. The position was revealed using Arecibo Observatory's telescope, and Fermi provided data about the SS 433 system.

"The consistent periods indicate the gas cloud's emission is powered by the micro quasar," Li says.

Scientists still do not fully know how the jets overcome the black hole's pull and are emitted from the disc, and the current study presents a new question - How does the black hole power the gas cloud's heartbeat?

The study's researchers say further observations and theoretical work are needed, but one suggestion is that the cloud's gamma-ray emissions are caused by the injection of the nuclei of hydrogen atoms, known as fast protons, that are produced at the end of the jets, or near the black hole.

"SS 433 continues to amaze observers at all frequencies and theoreticians alike," Li says. "And it is certain to provide a testbed for our ideas on cosmic-ray production and propagation near microquasars for years to come."

Study co-authors also included Diego Torres with the Institute of Space Sciences, Barcelona, Spain, the Institució Catalana de Recerca i Estudis Avançats in Barcelona, and the Institut d'Estudis Espacials de Catalunya in Barcelona; Ruo-Yu Liu with the School of Astronomy and Space Science, at Nanjing University in China and the Key Laboratory of Modern Astronomy and Astrophysics at Nanjing University, Ministry of Education, in China; Matthew Kerr with the Space Science Division of the Naval Research Laboratory in Washington, D.C.; Emma de Oña Wilhelmi with Deutsches Elektronen-Synchrotron in Zeuthen, Germany, and the Institute of Space Sciences in Barcelona, Spain; and Yang Su with Purple Mountain Observatory and Key Laboratory of Radio Astronomy in the Chinese Academy of Sciences in Nanjing, China.

UCF manages the National Science Foundation's Arecibo Observatory under a cooperative agreement with Universidad Ana G. Méndez and Yang Enterprises Inc. The facility, which is home to one of the most powerful telescopes on the planet, is used by scientists around the world to conduct research in the areas of atmospheric sciences, space weather research, planetary sciences, radio astronomy and radar astronomy.

Adolescents transitioning into high school encounter a large number of unfamiliar peers, who they quickly label into groups by using an individual's appearance as their guide.

But how do visible queues of high school cliques correlate with what youth say about themselves?

Are adolescents that are stereotyped by peers as jocks actually more sports-oriented, populars more well-liked, and loners more lonely than the average high schooler?

A new study led by University of Illinois Chicago researcher Rachel Gordon, in collaboration with colleagues from the University of Texas at Austin, examines the accuracy of these peer group classifications based on similar values, behaviors, and interests.

The study, which is published in Social Psychology Quarterly, shows that peer crowd classification predicts aspects of unknown peers' mental health, academic achievement, extracurricular involvement, social status, and risk-taking behaviors.

"This study offers insights into the link between perceptions and reality and the social-psychological shortcuts that can, on the one hand, make youths' lives easier and, on the other hand, pigeonhole others into categories different from their true selves," said Gordon, professor of sociology and a fellow of the Institute for Health Research and Policy at UIC.

The researchers, who build on their earlier work on modern-day adolescent experiences, used video and survey data from a subgroup of U.S. youth who were born in 1991 and attended high school in the mid- to late- 2000s. These children were recruited at birth for the National Institute of Child Health and Human Development's Study of Early Child Care and Youth Development.

To determine relevant peer crowds, the researchers assembled 10 focus groups totaling 61 approximate same-age peers as the youth in the previous study. Participants were asked to describe crowds they encountered in high school and their feedback led to the identification of nine peer crowds used in the study - "populars," "jocks," "smarts," "fine arts," druggies/stoners," "emo/goths," "anime/mangas," "troublemakers," and "loners."

Participants were also asked to view seven-second video clips of 15-year-olds and classify them into one of the groups. Ratings based on the short video clips were compared to what the depicted youth actually said about themselves.

For each outcome of the students' self-assessment, the researchers placed crowds into sets predicted by the focus group members to fall into low, middle, and high levels. The hypothesized low mental health group reported more depressive symptoms and loneliness than the middle group, as predicted. In terms of sports participation, the hypothesized high group was more involved in sports than both the middle and low groups. Lastly, the hypothesized high risk-taking group reported engaging in a higher average number of risks compared to the middle group.

"In many cases, these associations were consistent with expectations, based on what same-age focus groups predicted would be the hallmarks of various crowds," said Gordon, who chairs the Institute of Government and Public Affairs' working group on education and learning.

Other notable findings include:

-Focus groups did not consider "smarts" to be part of the low mental health group, despite "smarts" reporting greater loneliness than other crowds.

-Both the "fine arts and "anime/mangas" were assumed by focus groups as having middle levels of achievement. Members of the "fine arts" group had relatively high achievement in terms of their GPAs and advanced English enrollment. "Anime/mangas" had high GPAs but were among the crowds with the lowest enrollment in advanced English courses.

-"Smarts" had unexpectedly low sports participation compared to other crowds although focus group members viewed them as all-around engaged in extra-curricular activities.

-Despite being placed by focus groups in the middle, "jocks" had lower arts participation than almost all other crowds.

-"Smarts and "anime/mangas" engaged in less risk-taking than other crowd members, although focus groups expected them to fall in the middle.

Mild cases of coronavirus disease 2019 (COVID-19) can trigger robust memory T cell responses, even in the absence of detectable virus-specific antibody responses, researchers report August 14 in the journal Cell. The authors say that memory T cell responses generated by natural exposure to or infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--the virus that causes COVID-19--may be a significant immune component to prevent recurrent episodes of severe disease.

"We are currently facing the biggest global health emergency in decades," says senior author Marcus Buggert (@marcus_buggert) of the Karolinska Institutet. "In the absence of a protective vaccine, it is critical to determine if exposed or infected people, especially those with asymptomatic or very mild forms of the disease who likely act inadvertently as the major transmitters, develop robust adaptive immune responses against SARS-CoV-2."

To date, there is limited evidence of reinfection in humans with previously documented COVID-19. Most studies of immune protection against SARS-CoV-2 in humans have focused on the induction of neutralizing antibodies. But antibody responses tend to wane and are not detectable in all patients, especially those with less severe forms of COVID-19. Research in mice has shown that vaccine-induced memory T cell responses, which can persist for many years, protect against the related virus SARS-CoV-1, even in the absence of detectable antibodies. Until now, it was not clear how SARS-CoV-2-specific T cell responses relate to antibody responses or to the clinical course of COVID-19 in humans.

To address this gap in knowledge, Buggert and his collaborators assessed SARS-CoV-2-specific T cell and antibody responses in more than 200 individuals from Sweden across the full spectrum of exposure, infection, and disease. During the acute phase of infection, the T cell responses were associated with various clinical markers of disease severity. After recovery from COVID-19, SARS-CoV-2-specific memory T cell responses were detectable. The strongest T cell responses were present in individuals who recovered from severe COVID-19. Meanwhile, progressively lower T cell responses were observed in individuals who recovered from very mild COVID-19, and family members exposed to the virus.

In line with expectations, all 23 individuals who recovered from severe COVID-19 developed both SARS-CoV-2-specific antibody and T cell responses. But surprisingly, SARS-CoV-2-specific memory T cell responses were detected months after infection in exposed family members and in most individuals with a history of very mild COVID-19, sometimes in the absence of SARS-CoV-2-specific antibodies. Among the 28 exposed family members, only 17 (a few more than half) had detectable antibody responses, whereas nearly all (26/28) showed T cell responses. Among the 31 individuals who recovered from mild COVID-19, almost all had detectable antibody responses (27/31) and developed T cell responses (30/31).

"Our findings suggest that the reliance on antibody responses may underestimate the extent of population-level immunity against SARS-CoV-2," Buggert says. "The obvious next step is to determine whether robust memory T cell responses in the absence of detectable antibodies can protect against COVID-19 in the long-term."

In her role as the American Association of Critical-Care Nurses (AACN) 2020 Distinguished Research Lecturer, Karen Giuliano, a University of Massachusetts Amherst associate professor, has examined her "unconventional journey" from caring for patients at the bedside to challenging precedent in critical care to medical device design and innovation.

Giuliano's paper, published in the American Journal of Critical Care, describes her 35-year nursing career, leading to her current joint position with the College of Nursing and the Institute for Applied Life Sciences (IALS), where she heads up a product development laboratory.

"My goal is to share lessons learned and to help participants to see the many different ways that critical care nursing knowledge can be used to improve patient care," Giuliano writes.

In addition to publishing her paper, the journal posted a video interview with Giuliano discussing her experiences and perspective in critical-care nursing.

She writes, "My nursing practice has always included a propensity to play with ideas and do things differently, and my practice and clinical research interests are largely driven by a passionate desire to improve the delivery of care for nurses and the experience of care for patients and their families."

Giuliano emphasizes the importance of developing medical products in cooperation with bedside caregivers. "Nurses, especially critical care nurses, are in a unique position to identify and address everyday health care issues, challenge assumptions and the status quo, address unrecognized and unarticulated needs, and ensure that clinical outcomes research serves as the foundation for validating the effectiveness of medical product innovation," she writes.

After 15 years as a critical care nurse, Giuliano spent 13 years with Philips Healthcare, focusing on developing multiparameter patient monitors. In her academic role at UMass Amherst, "My hope is to cultivate productive and fun interdisciplinary collaborations, especially with business and engineering colleagues, deepen and share my passion and ability to contribute to person-centered, humanistic patient care, and expand my capacity to develop and mentor the next generation of nurses."

Giuliano is also collaborating with an Indiana-based startup, Recovery Force, to lead the clinical testing of a portable active-compression system designed to improve patient mobility and prevent deep vein thrombosis. The research is funded by a $1.8 million National Institutes of Health Phase 2 Small Business Innovation Research grant.

HOUSTON -- (Aug. 17, 2020) -- Meals are typically family affairs for zebras, gazelles, cape buffalo and other grazing species in the African Serengeti, but in one of the first studies of its kind, ecologists have found grazing species can be more willing to share meals in areas frequented by lions.

The study, which is available online this week in the journal Ecology, was conducted by a team from Rice University, Princeton University, Wake Forest University and the University of Minnesota. They analyzed more than 115,000 camera-trap photos to see where, when and how often six of the Serengeti's most abundant grazing species -- cape buffalo, gazelle, hartebeest, topi, wildebeest and zebra -- formed mixed-species groups.

"The mixed-species groups occur near places where lions like to hunt, which suggests the grazers are trying to reduce their chances of being killed by predators," said Rice lead-author Lydia Beaudrot.

Mixed-species groups of grazers were found in 1.9% of the camera-trap photos, which were collected between 2010-2015 in Tanzania's Serengeti National Park and processed by volunteers for the citizen science website snapshotserengeti.org. Camera-trap findings were combined with information from long-term GPS collar monitoring by the Serengeti Lion Project and satellite imagery that showed both the location of hunting areas favored by lions and where and when food was plentiful or scarce for grazers.

"Mixed-species groups were most likely in 'risky' places, like woodland habitats and near rocky outcroppings that lions use as viewsheds," said Beaudrot, an assistant professor of biosciences.

But the threat from lions apparently isn't the only thing grazers have to consider.

"One of the most interesting results is that grazers in mixed-species groups appear to be making a tradeoff between the risk of being eaten and the need to eat," Beaudrot said.

Mixed-species groups were less likely to form when plant productivity was low, she said, which suggests there is a foraging cost associated with mixed-species grazing, said study co-author Meredith Palmer, a behavioral ecologist and postdoctoral fellow at Princeton.

"These animals face a trade-off," Palmer said. "When different species group together, each individual is less likely to be eaten by a lion than it would be if it were alone or even possibly with its own species. But each individual is also foraging, and if they get further apart they don't have to compete as much for food. As forage becomes more scarce, these animals have to decide whether the extra food they would get from grazing alone is worth the increased danger from lions."

The study focuses on a longstanding idea in ecology called the 'stress gradient hypothesis,' which holds that species are more likely to compete with one another when times are good and more likely to benefit each other when they're under stress, Beaudrot said.

"The hypothesis is supported by the findings from more than 700 plant studies, but it's rarely been applied to animals because mixed-species behavior is rare and there typically aren't enough data about it to draw statistically significant conclusions," she said.

The collaboration began when Beaudrot heard Palmer describe the Snapshot Serengeti database in a talk at the 2018 Gordon Research Conference on Predator-Prey Interactions. While mixed-species groups had previously been documented in animals, including primates, cetaceans, ungulates, fish and birds, Palmer and Beaudrot realized that the size of the Snapshot Serengeti camera-trap database would allow them a rare opportunity to not simply observe mixed-species groups but to examine the ecological context within which they occur.

"Our findings partially support the hypothesis," Beaudrot said. "On the one hand, we found mixed-species groups were more likely to occur when stress was high because of predators, but we also found that mixed-species groups were less likely to form when stress from food scarcity was high, which suggests that stress can also lead to increased competition."

She and Palmer said there are also plenty of questions to address with follow-up research, including how mixed-species groups better protects grazers from lions.

"The larger groups could provide more warning of lions because there are more eyes for vigilance, or that individual species in the group benefit from the behavior of other species in a way that they wouldn't if they had grazed on their own," Palmer said. "Or it could simply be that the odds of any one individual being eaten go down if it's part of a larger group. Our study can't differentiate between any of those mechanisms."

Opioid use, particularly in high doses, can cause deafness, according to Rutgers researchers.

The study, published in The Journal of Medical Toxicology, reviewed records from the New Jersey Poison Control Center, based at Rutgers New Jersey Medical School, from 1999 to 2018 to determine the association between opioid use and degrees of hearing loss.

Researchers identified 41 people with opioid exposure who experienced full or partial hearing loss or tinnitus, likely caused by toxicity to the ear. More than half had used heroin, followed by oxycodone, methadone and tramadol; 88 percent had only one known exposure.
Most people reported the condition affecting both ears, with 12 people experiencing deafness, 15 partial or total loss of hearing acuity, 10 tinnitus and four a mix of symptoms.

While some people may regain their hearing, the loss could be permanent with others -- 21 percent of those reporting the condition had no improvement in hearing when they were discharged from the hospital.
"The delicate structures of the inner ear are very susceptible to injury if oxygen supply is insufficient, as well as to the direct effect of toxins like opioids," said co-author Lewis Nelson, chair of the Department of Emergency Medicine.

"Although the study found a link with heroin, toxicity to the ear can occur with every opioid," said Diane Calello, executive and medical director of the New Jersey Poison Control Center. "This study supports what has been found in animal studies, which is that any opioid can cause hearing loss," she said. "This might be because we already have built-in opioid receptors, or binding sites, in the inner ear. Activating them may trigger this injury in some patients."

The researchers said health care providers should be aware of the association with opioid use when evaluating a patient with hearing loss.