Culture

RESEARCH TRIANGLE PARK, N.C. -- A new machine learning algorithm, developed with Army funding, can isolate patterns in brain signals that relate to a specific behavior and then decode it, potentially providing Soldiers with behavioral-based feedback.

"The impact of this work is of great importance to Army and DOD in general, as it pursues a framework for decoding behaviors from brain signals that generate them," said Dr. Hamid Krim, program manager, Army Research Office, an element of the U.S. Army Combat Capabilities Develop Command, now known as DEVCOM, Army Research Laboratory. "As an example future application, the algorithms could provide Soldiers with needed feedback to take corrective action as a result of fatigue or stress."

Brain signals contain dynamic neural patterns that reflect a combination of activities simultaneously. For example, the brain can type a message on a keyboard and acknowledge if a person is thirsty at that same time. A standing challenge has been isolating those patterns in brain signals that relate to a specific behavior, such as finger movements.

Doing so, is the first step in developing brain-machine interfaces that help restore lost function for people with neurological and mental disorders, which requires the translation of brain signals into a specific behavior, called decoding.

As part of a Multidisciplinary University Research Initiative grant awarded by ARO and led by Maryam Shanechi, assistant professor at the University Of Southern California Viterbi School Of Engineering, researchers have developed a new machine learning algorithm to address the brain modeling and decoding challenge. The research is published in Nature Neuroscience.

"Our algorithm can, for the first time, dissociate the dynamic patterns in brain signals that relate to specific behaviors and is much better at decoding these behaviors," said Shanechi, the lead senior author of the study.

The researchers tested the algorithm on standard brain datasets during the performance of various arm and eye movements. They showed that their algorithm discovered neural patterns in brain signals that directed these movements but were missed with standard algorithms.

They also showed that the decoding of these movements from brain signals - predicting what the movement kinematics are by just looking at brain signals that generate the movement - was much better with their algorithm.

"The algorithm has significant implications for basic science discoveries," Krim said. "The algorithm can discover shared dynamic patterns between any signals beyond brain signals, which is widely applicable for the military and many other medical and commercial applications."

Shanechi said the reason for the new algorithm's success was its ability to consider both brain signals and behavioral signals such as movement kinematics together, and then find the dynamic patterns that were common to these signals.

This decoding also depends on our ability to isolate neural patterns related to the specific behavior. These neural patterns can be masked by patterns related to other activities and can be missed by standard algorithms.

In the future, the new algorithm could also enhance future brain-machine interfaces by decoding behaviors better. For example, the algorithm could help allow paralyzed patients to directly control prosthetics by thinking about the movement.

In a mouse study aimed at modeling human exposure to the toxic metal cadmium, researchers from North Carolina State University found that female offspring of mice exposed to cadmium during pregnancy became obese in adulthood, developed fatty livers and could not process glucose normally. Male offspring were not affected in the same way. The study also sheds light on how cadmium exposure could affect mitochondrial function and developmental signaling pathways in the liver.

Cadmium is a toxic heavy metal. Environmental exposure commonly occurs from fossil fuel emissions, smoking, and some food and water sources. It is an accumulative toxin, meaning that at normal exposure levels, exposure must occur over years to produce toxic effects. However, there is compelling evidence in humans that relatively short-term developmental exposure to cadmium may increase risk for obesity and obesity-related conditions such as cardiovascular disease and type 2 diabetes.

To explore the hypothesis that developmental cadmium exposure increases risk of obesity later in life, Scott Belcher, associate professor of biology at NC State, conducted a mouse study that modeled cadmium exposure during human gestational development.

Adult female mice were given cadmium at 500 parts per billion daily via drinking water from two weeks prior to conception through 10 days after giving birth. The dose and duration represented a developmental exposure period equivalent to human gestational development. There were no observed impacts from cadmium exposure on the pregnant mice.

There were 224 male and female offspring analyzed from the cadmium-exposed mothers. At the end of the study, the adult female offspring weighed 27% more and had seven times more fat than unexposed female offspring raised in identical conditions. Additionally, female offspring of exposed mothers had elevated triglycerides, fatty livers with increases in precancerous lesions, and altered responses to glucose. The livers of male offspring were unaffected by the cadmium exposure.

Using RNA sequencing analysis, Belcher and his team found that cadmium was altering mitochondrial functions and causing disruption of retinoid and insulin signaling in the livers of females, affecting pathways that are vital to normal glucose response.

"Essentially the cadmium is knocking out mechanisms that protect the liver from oxidative stress in females," Belcher says. "I was shocked at the extent of the difference in effects on female versus male offspring. We don't know why, but the response to maternal cadmium exposure is absolutely sexually dimorphic in the liver.

"To the best of our knowledge, this work is the first demonstration of an environmental compound acting as both a retinoid disruptor and as a sex-specific delayed obesogen," Belcher says.

Military and law-enforcement personnel repeatedly exposed to low-level blasts have significant brain changes - including an increased level of brain injury and inflammation - compared with a control group, a new study has found.

Led by University of Virginia School of Medicine researcher James Stone, MD, PhD, the study compared the brains of 20 "breachers" - specialists who use explosives to enter buildings and other structures - with a 14-person, age-matched control group. The breachers had been exposed to an average of 4,628 blasts, while the control group had been exposed to an average of three.

Blood measurements and neuropsychological assessments suggest that the breachers have increased levels of brain injury and inflammation, which the researchers wrote is "consistent with the theory that exposure to breaching-related blasts leads to system-wide effects in the brain."

The study also found that the breachers had statistically significant differences in blood flow, brain structure and brain activity.

"This study is the first to comprehensively assess military and law enforcement personnel to better understand whether repetitive blast exposure over a career can lead to changes within the brain," Stone said. "This is an area of high importance to military and law enforcement communities, as it is becoming increasingly clear there may be occupational health considerations related to repetitive low-level blast exposure in training and operations over the career of an exposed individual."

Investigating Brain Injury

The researchers wrote that further studies will be needed to determine more precisely what level and frequency of blast exposure may result in the observed brain changes.

Stone and his colleagues have two additional studies underway to further examine the effects of blasts on the brains of military personnel. The first - backed by a three-year, $2.1 million grant from the U.S. Department of Defense - is researching the effects of regular exposure to artillery blasts. The second is examining whether special operations forces are at risk for brain injury over their career.

"These additional studies will allow us to better understand whether the observations made in breachers are also seen in other blast-exposed populations, such as those that operate heavy weapons," Stone said. "We also hope to be able to shed light on how the brain responds to repetitive blasts on a molecular level."

The SARS-CoV-1 coronavirus pandemic has left a significant footprint on the global economy. For this reason, it had a substantial impact on the behaviour of all financial instruments, including cryptocurrencies. It turns out that the fluctuations experienced by the virtual currency market during this period reflect changes in other capital and commodity markets. This market has also shown relative stability during this difficult time. It is another proof that cryptocurrencies can be treated as a mature and full-fledged financial instrument.

Social systems are characterized by a vast network of connections and factors that can influence their structure and dynamics. Among these systems, the entire economic sphere of human activity seems to be the most interconnected and complex. All financial markets belong to this sphere, including the youngest of them - cryptocurrencies.

The first cryptocurrency - bitcoin - appeared in 2008 at the height of the global financial crisis. Its creators intended to provide a tool for carrying out transactions via the Internet without the participation of a central unit managing the issue of money. From this perspective, cryptocurrencies can be considered as an independent financial instrument. However, has the cryptocurrency market lived up to the hopes placed in it? How did it react to the situation caused by the emergence of crisis conditions? And have cryptocurrencies already reached the maturity and stability required of a full-fledged financial instrument?

Events related to the outbreak and development of the COVID-19 epidemic provided an excellent opportunity to seek answers to these questions. A group of scientists from the IFJ PAN in Krakow lead by Prof. Stanislaw Drozdz decided to study the behaviour of the cryptocurrency market in response to the economic situation caused by the coronavirus.

"Our previous quantitative analyses of the various characteristics of the complexity of the cryptocurrency market and the specifics of its correlation with more traditional world markets, such as stocks, currencies or commodities, showed that this market in these aspects became essentially indistinguishable and independent from them. With the pandemic ahead, however, we seriously considered the possibility that investors would start to get rid of something like bitcoin in the first place. Due to their virtuality, most potential market participants still perceive cryptocurrencies as quite peculiar items. In times of crisis, during violent economic and political turmoil, people resort to financial resources they consider more reliable. But our comparisons showed that solid instruments recorded drops at the most critical moments, while cryptocurrencies behaved much more stable," says Prof. Drozdz.

In the first phase of the pandemic, when it was not known how the whole situation would develop, there was an escape from risky financial instruments to bitcoin. One could observe a positive correlation of bitcoin with financial instruments considered safe, such as the Swiss franc, Japanese yen, gold and silver. Then there was a further increase in the number of infections around the world and the associated sharp drops in global stock markets - especially in the US - due to a total sell-off of all assets, including bitcoin. Investors resorted to cash, mainly the yen and the dollar. During this period, bitcoin lost its safe-haven status, but the same was true of gold and silver. Still, it behaved like a regular, traditional, and reliable financial instrument. Particularly significant is the correlation of bitcoin (BTC) and ethereum (ETH) with conventional financial instruments during the spikes on global stock exchanges as the epidemic slows down during the summer of 2020.

"This is an intriguing effect because there were no such correlations before the pandemic, and they remain at a significant level. It may be proof that bitcoin has become a full-fledged element of the financial market. One can say that the COVID-19 pandemic has positively verified cryptocurrencies. It turned out that investors were not afraid of bitcoin; quite the opposite - they included it in their investment portfolios," Dr. Marcin Watorek describes the research findings.

Scientists from Krakow focused on the dynamic and structural properties of the cryptocurrency market. They analyzed data showing the exchange rates of 129 cryptocurrencies on the Binance platform. The analysis consisted of three parts aimed at examining a different aspect of the market structure.

"We approached the topic from three standpoints: the dynamics of the cryptocurrency exchange rates to other virtual and fiat currencies, coupling and decoupling of cryptocurrencies and traditional assets, and the inner structure of the cryptocurrency market. We used data from January 2019 to June 2020. This period covers the specific time of the COVID-19 pandemic; we paid special attention to this event and examined how strong its impact was on the structure and dynamics of the market. The analyzed data include several other significant events, such as the double bull and bear phase in 2019," Dr. Jaroslaw Kwapien explains the methodology of the work.

The analysis of the cross-correlation between the cryptocurrency market represented by the BTC/USD and ETH/USD exchange rate and the traditional markets of major fiat currencies, major commodities (such as oil and gold) and US stock indices led to the conclusion that the cryptocurrency market was independent of other markets throughout 2019, but temporarily correlated with these markets during several events in the first half of 2020, such as in January, when the first COVID-19 case was reported in the United States, in March during the pandemic outbreak, and from May to July 2020 during the second wave of the pandemic. In the first case, bitcoin showed anti-correlation with major stock indices such as the S&P500 and Nasdaq100, but in the second and third cases, the corresponding correlations were positive. The correlations between bitcoin and several fiat currencies and the commodity market were also positive for these phases.

The lack of statistically significant correlations in 2019, when classic financial instruments experienced no turmoil, was presumably due to market cap asymmetry between the cryptocurrency market and conventional markets to the disadvantage of the former, which is still too small to have any significant impact on other markets. However, traditional markets can easily influence the cryptocurrency market when they become turbulent. This is what happened in March and June 2020.

"The most significant result of our analyses of the dynamics of the world's financial markets during the COVID-19 pandemic is that the cryptocurrency market, and especially bitcoin, turned out to be one of the most resistant to turbulence experienced by all global markets during this period. This observation is in line with and complements our previously published results on the approached stability and maturity of the cryptocurrency market in the past 2-3 years. The COVID-19 period seems to confirm those earlier signals", Prof. Drozdz summarizes the work.

DURHAM, N.C. -- In the orchestra of the brain, the firing of each neuron is controlled by two notes--excitatory and inhibitory-- that come from two distinct forms of a cellular structure called synapses. Synapses are essentially the connections between neurons, transmitting information from one cell to the other. The synaptic harmonies come together to create the most exquisite music--at least most of the time.

When the music becomes discordant and a person is diagnosed with a brain disease, scientists typically look to the synapses between neurons to determine what went wrong. But a new study from Duke University neuroscientists suggests that it would be more useful to look at the white-gloved conductor of the orchestra -- the astrocyte.

Astrocytes are star-shaped cells that form the glue-like framework of the brain. They are one kind of cell called glia, which is Greek for "glue." Previously found to be involved in controlling excitatory synapses, a team of Duke scientists also found that astrocytes are involved in regulating inhibitory synapses by binding to neurons through an adhesion molecule called NrCAM. The astrocytes reach out thin, fine tentacles to the inhibitory synapse, and when they touch, the adhesion is formed by NrCAM. Their findings were published in Nature on November 11.

"We really discovered that the astrocytes are the conductors that orchestrate the notes that make up the music of the brain," said Scott Soderling, PhD, chair of the Department of Cell Biology in the School of Medicine and senior author on the paper.

Excitatory synapses -- the brain's accelerator -- and inhibitory synapses -- the brain's brakes -- were previously thought to be the most important instruments in the brain. Too much excitation can lead to epilepsy, too much inhibition can lead to schizophrenia, and an imbalance either way can lead to autism.

However, this study shows that astrocytes are running the show in overall brain function, and could be important targets for brain therapies, said co-senior author Cagla Eroglu, PhD, associate professor of cell biology and neurobiology in the School of Medicine. Eroglu is a world expert in astrocytes and her lab discovered how astrocytes send their tentacles and connect to synapses in 2017.

"A lot of the time, studies that investigate molecular aspects of brain development and disease study gene function or molecular function in neurons, or they only consider neurons to be the primary cells that are affected," said Eroglu. "However, here we were able to show that by simply changing the interaction between astrocytes and neurons -- specifically by manipulating the astrocytes -- we were able to dramatically alter the wiring of the neurons as well."

Soderling and Eroglu collaborate often scientifically, and they hashed out the plan for the project over coffee and pastries. The plan was to apply a proteomic method developed in Soderling's lab that was further developed by his postdoctoral associate Tetsuya Takano, who is the paper's lead author.

Takano designed a new method that allowed scientists to use a virus to insert an enzyme into the brain of a mouse that labeled the proteins connecting astrocytes and neurons. Once tagged with this label, the scientists could pluck the tagged proteins from the brain tissue and use Duke's mass spectrometry facility to identify the adhesion molecule NrCAM.

Then, Takano teamed up with Katie Baldwin, a postdoctoral associate in Eroglu's lab, to run assays to determine how the adhesion molecule NrCAM plays a role in the connection between astrocyte and inhibitory synapses. Together the labs discovered NrCAM was a missing link that controlled how astrocytes influence inhibitory synapses, demonstrating they influence all of the 'notes' of the brain.

"We were very lucky that we had really cooperative team members," said Eroglu. "They worked very hard and they were open to crazy ideas. I would call this a crazy idea."

STONY BROOK, NY, November 12, 2020 - What happens in our brain that makes us experience the sweet taste of a donut or the bitter taste of tonic water? What are the patterns of neural activity responsible for the perception of taste? A new study from Stony Brook University found that the map of neural responses mediating taste perception does not involve, as previously believed, specialized groups of neurons in the brain, but rather overlapping and spatially distributed populations.

The findings, to be published in Current Biology, counter an influential but controversial theory based on studies suggesting that there is a topographic map in the gustatory cortex that is responsible for our perception of taste. According to this theory, the gustatory cortex has "hot spots" of neurons whose activation leads to the perception of certain tastes. The new study by Stony Brook researchers demonstrates such a simple map of taste does not exist in the cortex of behaving animals.

When we taste food, neural activity propagates from the tongue to the brainstem and up to the cerebral cortex region known as the gustatory cortex. Activation of the gustatory cortex contributes to our perception of taste and flavor. Early imaging experiments provided evidence in favor of the theory of taste coding that postulates the existence of spatially localized clusters of neurons encoding specific tastes. These clusters, also known as "hot spots" form a map of taste on the gustatory cortex, with an hot spot for "sweet," one for "bitter," one for "salty," and one for "savory." According to this model of taste function, the activation of one cluster would correspond to the sensation of a specific taste.

"Our experiments demonstrate there is not a map with hot spots in the gustatory cortex of behaving animals," says Alfredo Fontanini, MD, PhD, lead investigator and Chair of the Department of Neurobiology and Behavior in the College of Arts and Sciences and Renaissance School of Medicine at Stony Brook University. "Instead, each taste is represented by spatially distributed ensembles of neurons sprinkled across the cortex. Neurons can represent one or many taste sensations and form what is called an ensemble code. Basically, neurons act very much like instruments in an orchestra playing different notes forming a chord."

The researchers demonstrated this activation repeatedly in behaving mice sampling different tastes from a spout. They used calcium imaging to determine how taste and task-related variables are represented in alert licking mice. With the experiments they collected data on how various taste stimuli evoke responses from neurons in the gustatory cortex. They found that some neurons respond to a single taste and other to multiple.

An analysis of the distribution of responses over multiple spatial scales demonstrated that taste representations are distributed across the cortex, with no sign of spatial clustering or topography as would be expected with a map of the gustatory cortex corresponding specific taste sensations.

"Our findings are important because they address one of the basic organizing principles of brain function," explains Dr. Fontanini. "Topographical maps are a pervasive feature of brain organization. Demonstrating that the spatial organization of taste responses is not as simple as previously believed makes us re-evaluate the neurobiological processes underlying taste perception and taste-related brain functions."

The researchers conclude that their overall data provides evidence for a distributed neurobiological brain process when it comes to taste, a coding scheme differing from the topographical brain organization of visual, somatosensory and auditory systems and similar to olfaction.

Households need financial support if Covid-19 restrictions are to be successful in Malawi. Furthermore, the authorities issuing the restrictions have an additional bearing on their enforceability. These are findings from a new study examining the relationship between authorities and civil compliance in one of the world's poorest countries.

In April 2020, then-President Peter Mutharika and his government announced plans to impose a 21-day national lockdown of Malawi. The announcement was met with country-wide protests. A coalition of domestic human rights organizations warned of a possible nationwide famine and accused the government of not taking sufficient measures to protect the country's poor. The shutdown decision was appealed to the country's highest court, which followed ruled against the government.

The spring's events highlight the tough challenges governments face when dealing with a pandemic in countries like Malawi. With its 18.6 million inhabitants, Malawi is one of the most densely populated countries in Africa, but also one of the poorest in the world, with 40 per cent of the population living in extreme poverty. Widespread poverty makes restrictive policies too costly for people, while a weak healthcare system exacerbates the adverse health effects of the pandemic. These contradictions have led political scientists to take an interest in authorities' abilities to pass restrictions that could work during a pandemic.

Local adaption of restrictions

The Program on Governance and Local Development (GLD), along with the Institute for Public Opinion and Research in Malawi (IPOR) and other international scholars, have examined factors affecting the population's ability to comply with Covid-19 restrictions, such as bans on larger crowds and social distancing.

They found that decision-makers need to adapt restrictions to local conditions to bring about measures that are the least costly for the individual. Decision-makers are further urged to cooperate with local authorities. The GLD-IPOR study shows that people are most likely to listen to their district health officials when it comes to Covid-19 measures as there is a respect for their medical expertise, according to Professor Ellen Lust, Founding Director of GLD.

The survey included interviews with 4,641 Malawians. Among other questions, respondents were asked what drives their compliance with Covid-19 regulations. For instance, do they comply out of respect for authorities, fear of retaliation, or is compliance with restrictions connected to the economic cost for the individual?

"The cost to the individual was found to be an important factor. Social distancing restrictions and directives to wash hands are easier to comply with as they are less costly for the individual. In a country where a large part of the population already suffers from socioeconomic vulnerability, regulations preventing people from working could have devastating consequences. If such restrictions are to be successful, food supply guarantees and income support are vital for people to survive."

Survey participants were also asked which authority in the local community they trusted the most concerning preventive measures and recommendations during the pandemic - the chief physician at the district hospital, the local religious leader, or a local traditional authority.

"The survey found that, while people have great respect for all three, they see them as authorities in different areas. When it comes to information about Covid-19 risks, people rely most heavily on the chief physician's recommendations in his capacity as a medical expert."

Lust concludes, 'we hope that this research will contribute to the development of sustainable strategies at national and local levels to counter the spread of Covid-19 in Malawi.'

EVANSTON, Ill. -- Long ago and far across the universe, an enormous burst of gamma rays unleashed more energy in a half-second than the sun will produce over its entire 10-billion-year lifetime.

After examining the incredibly bright burst with optical, X-ray, near-infrared and radio wavelengths, a Northwestern University-led astrophysics team believes it potentially spotted the birth of a magnetar.

Researchers believe the magnetar was formed by two neutron stars merging, which has never before been observed. The merger resulted in a brilliant kilonova -- the brightest ever seen -- whose light finally reached Earth on May 22, 2020. The light first came as a blast of gamma-rays, called a short gamma-ray burst.

"When two neutron stars merge, the most common predicted outcome is that they form a heavy neutron star that collapses into a black hole within milliseconds or less," said Northwestern's Wen-fai Fong, who led the study. "Our study shows that it's possible that, for this particular short gamma-ray burst, the heavy object survived. Instead of collapsing into a black hole, it became a magnetar: A rapidly spinning neutron star that has large magnetic fields, dumping energy into its surrounding environment and creating the very bright glow that we see."

The research has been accepted by The Astrophysical Journal and will be published online later this year.

Fong is an assistant professor of physics and astronomy in Northwestern's Weinberg College of Arts and Sciences and a member of CIERA (Center for Interdisciplinary Exploration and Research in Astrophysics). The research involved two undergraduates, three graduate students and three postdoctoral fellows from Fong's laboratory.

'There was a new phenomenon happening'

After the light was first detected by NASA's Neil Gehrels Swift Observatory, scientists quickly enlisted other telescopes -- including NASA's Hubble Space Telescope, the Very Large Array, the W.M. Keck Observatory and the Las Cumbres Observatory Global Telescope network -- to study the explosion's aftermath and its host galaxy.

Fong's team quickly realized that something didn't add up.

Compared to X-ray and radio observations, the near-infrared emission detected with Hubble was much too bright. In fact, it was 10 times brighter than predicted.

"As the data were coming in, we were forming a picture of the mechanism that was producing the light we were seeing," said the study's co-investigator, Tanmoy Laskar of the University of Bath in the United Kingdom. "As we got the Hubble observations, we had to completely change our thought process, because the information that Hubble added made us realize that we had to discard our conventional thinking and that there was a new phenomenon going on. Then we had to figure out about what that meant for the physics behind these extremely energetic explosions."

Magnetic monster

Fong and her team have discussed several possibilities to explain the unusual brightness -- known as a short gamma-ray burst -- that Hubble saw. Researchers think short bursts are caused by the merger of two neutron stars, extremely dense objects about the mass of the sun compressed into the volume of a large city like Chicago. While most short gamma-ray bursts probably result in a black hole, the two neutron stars that merged in this case may have combined to form a magnetar, a supermassive neutron star with a very powerful magnetic field.

"You basically have these magnetic field lines that are anchored to the star that are whipping around at about 1,000 times a second, and this produces a magnetized wind," Laskar explained. "These spinning field lines extract the rotational energy of the neutron star formed in the merger, and deposit that energy into the ejecta from the blast, causing the material to glow even brighter."

"We know that magnetars exist because we see them in our galaxy," Fong said. "We think most of them are formed in the explosive deaths of massive stars, leaving these highly magnetized neutron stars behind. However, it is possible that a small fraction form in neutron star mergers. We have never seen evidence of that before, let alone in infrared light, making this discovery special."

Strangely bright kilonova

Kilonovae, which are typically 1,000 times brighter than a classic nova, are expected to accompany short gamma-ray bursts. Unique to the merger of two compact objects, kilonovae glow from the radioactive decay of heavy elements ejected during the merger, producing coveted elements like gold and uranium.

"We only have one confirmed and well-sampled kilonova to date," said Jillian Rastinejad, a co-author of the paper and graduate student in Fong's laboratory. "So it is especially exciting to find a new potential kilonova that looks so different. This discovery gave us the opportunity to explore the diversity of kilonovae and their remnant objects."

If the unexpected brightness seen by Hubble came from a magnetar that deposited energy into the kilonova material, then, within a few years, the ejected material from the burst will produce light that shows up at radio wavelengths. Follow-up radio observations may ultimately prove that this was a magnetar, leading to an explanation of the origin of such objects.

"Now that we have one very bright candidate kilonova," Rastinejad said, "I'm excited for the new surprises that short gamma-ray bursts and neutron star mergers have in store for us in the future."

CHAPEL HILL, N.C. -- A new study published in Science confirms that SARS-CoV-2 has mutated in a way that's enabled it to spread quickly around the world, but the spike mutation may also make the virus more susceptible to a vaccine.

The new strain of coronavirus, called D614G, emerged in Europe and has become the most common in the world. Research at the University of North Carolina at Chapel Hill and the University of Wisconsin-Madison shows the D614G strain replicates faster and is more transmissible than the virus, originating in China, that spread in the beginning of the pandemic.

There were bright spots in the study findings: While the D614G strain spreads faster, in animal studies it was not associated with more severe disease, and the strain is slightly more sensitive to neutralization by antibody drugs.

The study published Nov. 12 provides some of the first concrete findings about how SARS-CoV-2 is evolving.

"The D614G virus outcompetes and outgrows the ancestral strain by about 10-fold and replicates extremely efficiently in primary nasal epithelial cells, which are a potentially important site for person-to-person transmission," said Ralph Baric, professor of epidemiology at the UNC-Chapel Hill Gillings School of Global Public Health and professor of microbiology and immunology at the UNC School of Medicine.

Baric has studied coronaviruses for more than three decades and was integral in the development of remdesivir, the first FDA-approved treatment for COVID-19.

Researchers believe the D614G strain of coronavirus dominates because it increases the spike protein's ability to open cells for the virus to enter. These crown-like spikes give the coronavirus its name.

The D614G mutation causes a flap on the tip of one spike to pop open, allowing the virus to infect cells more efficiently but also creating a pathway to the virus' vulnerable core.

With one flap open, it's easier for antibodies -- like the ones in the vaccines currently being tested -- to infiltrate and disable the virus.

For the recent study, Baric Lab researchers -- including first author Yixuan J. Hou -- worked in collaboration with Yoshihiro Kawaoka and Peter Halfmann, both virologists on faculty at the University of Wisconsin-Madison.

"The original spike protein had a 'D' at this position, and it was replaced by a 'G,'" Kawaoka said. "Several papers had already described that this mutation makes the protein more functional and more efficient at getting into cells."

That earlier work, however, relied on a pseudotyped virus that included the receptor-binding protein but was not authentic. Using reverse genetics, Baric's team replicated a matched pair of mutant SARS-CoV-2 viruses that encoded D or G at position 614 and compared basic property analysis using cell lines, primary human respiratory cells, and mouse and hamster cells.

Kawaoka and Halfmann contributed their unique coronavirus study model, which uses hamsters. The University of Wisconsin-Madison team -- including Shiho Chiba, who ran the hamster experiments -- performed replication and airborne transmission studies with both the original virus and the mutated version created by Baric and Hou.

They found that the mutated virus not only replicates about 10 times faster -- it's also much more infectious.

Hamsters were inoculated with one virus or the other. The next day, eight uninfected hamsters were placed into cages next to infected hamsters. There was a divider between them so they could not touch, but air could pass between the cages.

Researchers began looking for replication of the virus in the uninfected animals on day two. Both viruses passed between animals via airborne transmission, but the timing was different.

With the mutant virus, the researchers saw transmission to six out of eight hamsters within two days, and to all the hamsters by day four. With the original virus, they saw no transmission on day two, though all of the exposed animals were infected by day four.

"We saw that the mutant virus transmits better airborne than the [original] virus, which may explain why this virus dominated in humans," Kawaoka said.

The researchers also examined the pathology of the two coronavirus strains. Once hamsters were infected, they presented essentially the same viral load and symptoms. (The hamsters with the mutated strain lost slightly more weight while sick.) This suggests that while the mutant virus is much better at infecting hosts, it doesn't cause significantly worse illness.

Researchers caution that the pathology results may not hold true in human studies.

"SARS-CoV-2 is an entirely new human pathogen and its evolution in human populations is hard to predict," Baric said. "New variants are continually emerging, like the recently discovered mink SARS-CoV-2 cluster 5 variant in Denmark that also encodes D614G.

"To maximally protect public health, we must continue to track and understand the consequences of these new mutations on disease severity, transmission, host range and vulnerability to vaccine-induced immunity."

DALLAS - Nov. 12, 2020 - UT Southwestern researchers have discovered a mechanism that cells use to degrade microRNAs (miRNAs), genetic molecules that regulate the amounts of proteins in cells.

The findings, reported online today in Science, not only shed light on the inner workings of cells but could eventually lead to new ways to fight infectious diseases, cancer, and a bevy of other health problems.

Scientists have long known that genes contain the instructions for making every protein in an organism's body. However, various processes regulate whether different proteins are produced and in what amounts. One of these mechanisms involves miRNAs, small pieces of genetic material that break down complementary pieces of messenger RNA (mRNA) in cells, preventing the mRNA sequence from being translated into proteins.

Since the discovery of miRNAs in 1993, researchers have amassed a wealth of knowledge about the hundreds of different miRNA molecules and their targets as well as mechanisms that control their production, maturation, and roles in development, physiology, and disease. However, explains Joshua Mendell, M.D., Ph.D., professor and vice chair of the department of molecular biology at UTSW, and postdoctoral fellow Jaeil Han, Ph.D., very little was known about how cells dispose of miRNAs when they're finished using them.

"As long as miRNA molecules stick around in a cell, they reduce the production of proteins from their target mRNAs," explains Mendell, a Howard Hughes Medical Institute (HHMI) investigator and member of the Harold C. Simmons Comprehensive Cancer Center. "So understanding how cells get rid of miRNAs when they are no longer needed is pivotal for fully appreciating how and when they do their jobs."

To answer this question, Mendell, Han, and their colleagues harnessed CRISPR-Cas9, a gene-editing tool that recently won the 2020 Nobel Prize in Chemistry for two scientists who developed it. By serving as "molecular scissors," Mendell says, this system can cut out individual genes, allowing researchers to explore their functions.

In a human cancer cell line known as K562, the researchers used CRISPR-Cas9 to target most of the 20,000 protein-coding genes in the human genome, looking for any that caused a normally short-lived miRNA known as miR-7 to linger in cells. Their search turned up at least 10 genes that are needed to degrade this miRNA.

The researchers learned that the proteins encoded by these genes come together in cells to form a larger assembly known as a ubiquitin ligase, which functions to tag other proteins for destruction. This particular ubiquitin ligase had never been described before, Mendell says, but like other ubiquitin ligase complexes, it appears to mark proteins destined for degradation. However, rather than tag miR-7 itself, further investigation showed that this complex instead tags a protein called Argonaute, which ferries miRNAs through cells.

Once the Argonaute protein attached to miR-7 is targeted for degradation, this miRNA is left naked in the cell - a state that triggers cells to destroy the miRNA using RNA-degrading enzymes.

The research team found that this ubiquitin ligase complex is key for degrading not only miR-7 in K562 cells, but also a variety of other miRNAs in other cell types and species. These results suggest that this mechanism for miRNA decay acts broadly to control the levels of miRNAs during animal development and across tissues. Because other studies have shown that abnormal levels of various miRNAs are associated with a variety of diseases and infections, finding ways to control miRNA degradation - either to eradicate problematic miRNAs in cells or hold on to beneficial ones - could represent a new way to treat these conditions.

"For over a decade, researchers have been searching for mechanisms through which cells degrade miRNAs," says Han. "Now that we've discovered new cellular machinery that can accomplish this, we will be able to apply this discovery to better understand how miRNAs are regulated and, we hope, eventually develop new therapies."

Philadelphia, November 12, 2020 - Osteoarthritis (OA), a widely acknowledged cause of disability that affects patients' quality of life and has significant economic impact through healthcare costs and loss of earnings. In a novel study researchers have identified cytoplasmic localized histone deacetalyse 6 (HDAC6) as a promising therapeutic target to postpone development of and possibly treat OA using the HDAC6 inhibitor Tubastatin A. They report their results in The American Journal of Pathology, published by Elsevier.

"Because chondrocytes are the only resident cells in articular cartilage, the steady state of these cells is important to maintain joint function," explained lead investigator Weiyang Gao, MD, Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China. "In various OA diseases, chondrocytes undergo a series of pathophysiologic changes, leading to the loss of chondrocytes, which can impair mitochondrial function and extracellular matrix synthesis (ECM) to promote the progression of OA."

Investigators detected the variations in expression level of HDAC6 after destabilization of the medial meniscus (DMM)-induced mouse OA model. They dissected the knee cartilage tissue of two-week-old mice to obtain primary chondrocytes. HDAC6 was up-regulated after OA and peaked at four weeks post-DMM. Thus, they constructed primary chondrocytes overexpressing HDAC6 by transfection of plasmid.

Their results indicate that overexpression of HDAC6 causes mitochondrial dysfunction and promotes reactive oxygen species production, leading to ECM degradation. However, the administration of the selective HDAC6 inhibitor Tubastatin A reversed the effect caused by HDAC6 overexpression in vitro and further postponed the progression of OA in vivo by ameliorating the degradation of cartilage and improving the microenvironment and function of the joint, suggesting that HDAC6 may be a target for delaying and managing OA with Tubastatin A.

"To our knowledge this is the first study to show that the expression level of HDAC6 is up-regulated in chondrocytes during the OA process and that the up-regulated expression of HDAC6 is associated with mitochondrial disfunction and ECM degradation," commented Dr. Gao. "Our results show that HDAC6 is a potential target for treatment of OA and supports the administration of Tubastatin A to treat OA."

OA is an inflammatory disease characterized by increased degradation of cartilage tissue in the joint due to overproduction of enzymes degrading the extracellular matrix. It is the most common joint disorder in the United States and is highly prevalent around the world. Among US adults 60 years of age and older the prevalence of symptomatic knee OA is approximately 10 percent in men and 13 percent in women. Chondrocytes are the only resident cells of articular cartilage, and the steady state of their intracellular environment is of great significance for maintaining the articular cartilage morphology.

Women who experience sexual violence combined with other forms of intimate partner violence suffer greater damage to their health and are much more likely to attempt suicide, according to a study led by researchers at the University of Bristol's Centre for Academic Primary Care published today [12 November] in the International Journal of Epidemiology .

Intimate partner violence - psychological, physical or sexual violence perpetrated by a current or former partner - is the most common form of violence experienced by women worldwide.

The study, conducted in collaboration with the World Health Organization (WHO) and University of Melbourne, found that all types of intimate partner violence were associated with long-lasting damage to health but combinations that included sexual violence were more common and markedly more damaging to women's physical and mental health.

Researchers analysed data from the WHO multi-country study on women's health, which has information from 16 different sites in 11 different countries on over 21,000 women who have ever had a partner. This new analysis assessed different combinations of psychological, physical and sexual intimate partner violence and their impacts on health.

They found that over 15 per cent of ever-partnered women had experienced a combination of intimate partner violence that included sexual violence. Those who had experienced this in the last year were ten times more likely to attempt suicide than those who had not. Women who had experienced multiple forms of abuse were also more likely to experience difficulty walking, difficulty with daily activities, pain or discomfort, poor memory or concentration, dizziness, and vaginal discharge, and to be taking sleeping pills or painkillers.

Study lead, Dr Lucy Potter a GP and NIHR In-Practice Clinical Research Fellow at the University of Bristol's Centre for Academic Primary Care, said: "We know intimate partner violence is damaging to health. What this study adds is the recognition of the profound harm caused by multiple forms of abuse, particularly when it includes sexual violence, and how we do not see this when all forms of abuse are lumped together as one experience. Practitioners and policy makers must appreciate the diversity of experience of intimate partner violence to tailor support appropriately.

"We also found that these health impacts persist over a year after the abuse ends. So, effective prevention and early intervention are vital to the health of individuals and families and health systems."

Senior author, Professor Gene Feder from the University of Bristol's Centre for Academic Primary Care, said: "Violence against women is a violation of human rights that damages their and their children's physical and mental health, with substantial health care and societal costs. It is an important cause of ill health among women globally and an indicator for Goal 5 - Gender Equality and Women and Girls' Empowerment - of the United Nations' Sustainable Development Goals.

"This study, analysing the impact of different types and combinations of intimate partner violence, shows the severe health impact when these include sexual or psychological abuse. These types of abuse are often not recognised by health care providers."

For years, researchers have known through numerous studies that hearing and other sensory systems of adults and children who have autism differ from children or adults without autism.

Now, University of Miami and Harvard Medical School researchers who explored responses to the standard hearing test administered to millions of newborns around the world, are closing in on a way to detect early indicators of autism--perhaps as early as at birth.

Published in the journal Autism Research, the findings could inform additional research and pave the way for evaluations that can better identify newborns with elevated autism risk by using standard hearing tests. The researchers note that such tests are already regularly and widely used to screen newborns for hearing loss. The tests work by measuring auditory brainstem response (ABR), which gauges how well a baby's inner ear and brain respond to sound.

"We're not at the point just yet where we're telling clinicians to use ABR testing as a determinant for autism in babies," said study co-author Elizabeth Simpson, an associate professor in the College of Arts and Sciences' Department of Psychology, whose research focuses on understanding infant social cognitive development. "But we are saying that this study presents a promising direction in how ABR testing can be used as a method for precise autism detection at birth."

"The importance for diagnosing autism early during infant and child development, when interventions can have the most impact, cannot be overstated," said the study's lead author Oren Miron, a research associate in the Department of Biomedical Informatics at Harvard Medical School. "Any additional tool that could clarify diagnostic clues would be invaluable in that regard."

For the study, researchers analyzed large datasets of Florida infants who were screened for hearing impairments with ABR tests. Usually conducted in hospital maternity wards, the tests make computer recordings of the auditory nerve activity of babies who are exposed to sounds transmitted by electrodes placed on their scalps. The test sound is very mild and can be performed while the infants sleep.

The research team analyzed nearly 140,000 auditory recordings from babies born in Florida and matched the data with records from the Florida Department of Education indicating children with developmental disabilities. Ultimately, they found that newborns who were later diagnosed with autism had slower brain responses to sounds during their ABR tests.

"Within the dataset we used from the Department of Education records of children who had autism, we saw how many we could match up from the ABR test screenings," Simpson said. "We located 321 children who had ABR test screenings taken when they were newborns and who were later diagnosed with autism by preschool age."

With additional investigation, researchers hope to add additional layers to the ABR screenings so that doctors can use them not only to better understand a newborn's hearing and risk for autism, but potentially other developmental problems--like speech, language impairment, and Sudden Infant Death Syndrome--that could arise later.

"We know autism spectrum disorder is connected to how children process sound, so even if the child's hearing is normal, it can still be processed differently," Simpson added. "With better understanding of how ABR testing can be used to identify at-risk babies, we can flag children who might be at risk."

An international team including chemists from RUDN University suggested an economically feasible and environmentally friendly method to synthesize surfactants. The new compounds can become an eco-friendly alternative to traditional chemicals used in oil production, skincare products manufacture, and in the pharmaceutical industry to transport drugs to diseased body tissues. The work was published in the Journal of Molecular Liquids.

Surfactants are common both in the industry and in our everyday life. They are used as bases for detergents, added to lubricants and construction materials (concrete mixes, cement, and drilling fluids), and protect equipment from corrosion. The most effective of them are gemini surfactants that contain two hydrophilic (water-attracting) groups. However, there also "pseudo" gemini surfactants that have one hydrophilic and one hydrophobic (water-resistant) group of atoms bound together. An international team of chemists including partners from RUDN University synthesized several new "pseudo" gemini surfactants and confirmed that their performance characteristics were on par with the existing compounds. The new synthesis method is quite cost-efficient, works at room temperature, and does not require expensive reagents.

"The creation of cheap methods for the synthesis of gemini surfactants with satisfactory performance characteristics can be a turning point for the chemistry of detergents. We focused both on the development of synthetic methods and on studying the properties of new compounds," said Fedor Zubkov, a PhD, and an Assistant Professor at the Department of Organic Chemistry, RUDN University.

To create new compounds, the chemists used six common higher fatty acids: capric, lauric, myristic, palmitic, stearic, and oleic acid. The hydrophilic properties of the new surfactants came from amines synthesized based on two affordable reagents--hexamethylenediamine and epoxypropene. To obtain a surfactant, the team dissolved an amine and one one the acids (at the ratio 1:2) in acetone at room temperature and then concentrated the solvent. The final products looked like viscous yellow liquids. The molecules of the surfactants were formed due to electrostatic interaction between oxygen atoms in the carboxylic groups of the acids and amino groups in the amine.

The team at RUDN University conducted a thorough study of the properties of the new compounds and paid special attention to the key characteristic of surfactants--their ability to reduce the superficial tension of solutions and form micelles. It is this property that makes surfactants usable in the skincare industry. The lowest superficial tension values (up to 20 mN/m) were registered for the surfactant based on myristic acid. By this parameter, the new surfactant is almost identical to fluorine-containing ones that are often used in the industry. However, unlike them, the new compound is more environmentally friendly. Weaker chemical bonds make it biodegradable and therefore unlikely to be accumulated in the environment.

Other important characteristics of surfactants are foam formation and foam stability. Five out of six new surfactants formed foam in a water solution, and in the case of two of them (based on lauric and myristic acids), the volume of produced foam exceded the volume of the initial solution 3 to 4 times. The compounds based on palmitic and stearic acids produced less foam, but it was more stable and lasted up to three days. These and other characteristics of the new compounds make them promising for the skincare industry, medicine, anti-corrosion treatment of construction and industrial facilities, and oil recovery increase.

"Gemini surfactants and their synthesis are a burning issue for modern chemistry, as they can potentially replace traditional monomeric surfactants and make the chemical industry move environmentally friendly," added Fedor Zubkov.

The United States may have set itself up for the spread of a pandemic without even knowing it.

According to new research from the McKelvey School of Engineering at Washington University in St. Louis, pollution may bear part of the blame for the rapid proliferation in the United States of SARS-CoV-2, the virus responsible for the spread of COVID-19.

The research, from the lab of Rajan Chakrabarty, associate professor in the Department of Energy, Environmental & Chemical Engineering, was published online ahead of print in the journal Science of The Total Environment.

When it comes to how ill someone gets after contracting COVID-19, medical professionals believe that a person's health -- having certain medical conditions, for example -- can play a vital role. When it comes to how fast the virus can spread through the community, it turns out the health of the environment is directly correlated to the basic reproduction ratio R0, which denotes the expected number of people each sick person can infect.

The reproduction ratio R0 of COVID-19 associates directly with the long-term ambient PM2.5 exposure levels. And the presence of secondary inorganic components in PM2.5 only makes things worse, according to Chakrabarty.

"We checked for more than 40 confounding factors," Chakrabarty said. Of all of those factors, "There was a strong, linear association between long-term PM2.5 exposure and R0."

PM2.5 refers to ambient particles with a diameter of 2.5 micrometers or less; at that size, they can enter a person's lungs and cause damage. For this reason, PM2.5 can be detrimental to respiratory health. But how this relates to the spread of COVID-19 through a population had yet to be explored.

Chakrabarty and his graduate student Payton Beeler, both aerosol researchers who have done previous coronavirus modeling, became interested in the relationship after two papers were published in quick succession. First, a July paper in the journal Science found that levels of susceptibility to COVID-19 is a driving factor for the pandemic; it is more important than temperature, which researchers initially thought might play an outsized role.

Then in August, research published in the Journal of Infection found that the highest number of cases of COVID-19 with severe illness were in places with higher pollution levels.

"I was thinking, why, in the majority of the U.S. states, have we had such a rapid spread of the virus?" Chakrabarty said. Particularly in the earlier stages of the pandemic. "We wanted to confine our study to the point in time when the shutdown was in place. For the most part, people did remain confined from early March until the end of April."

The team decided to look at places where R0 was greater than one -- that's the point at which one person can spread an illness to more than one person, and the illness takes off. In those places, they looked at 43 different factors -- including population density, age distribution, even time delays in states' stay-at-home orders.

Then, using pollution estimates across the U.S. between 2012 and 2017 published by Randall Martin, professor in the Department of Energy, Environmental & Chemical Engineering, the team looked for any relationships.

Modeling revealed an increase of almost 0.25 in R0 corresponding to a 10% increase in sulfate, nitrogen dioxide and ammonium, or SNA composition and an increase of 1 μg/m3 in PM2.5 mass concentrations, respectively.

They found these linear correlations to be strongest in places where pollution levels were well below National Ambient Air Quality Standards (NAAQS), the levels of air pollutants that are considered safe for humans.

"Annual mean PM2.5 national standards are set at or below 12 micrograms per cubic meter, below that you are supposed to be safe," Chakrabarty said. "What we saw, the correlation we're seeing is well below that standard." In fact, they saw a rapid increase in R0 when PM2.5 exposure levels were below 6 micrograms per cubic meter.

Chakrabarty hypothesizes this initial increase in R0, which is followed by a plateau once levels hit 6 micrograms per cubic meter, is a result of initial changes in condition; when the air is free of PM2.5 , an individual is unaffected. The initial exposure is the catalyst for change in lung health resulting in a change from non-susceptibility to susceptibility, which is reflected in the increasing R0.

And although there was no direct correlation between black carbon -- a.k.a. soot -- and R0, researchers did find a connection.

"Our collaborators at Saint Louis University suggested a mediation/moderation statistical approach," a detailed analysis that looks at the way additional variables affect the outcome of the initial relationship. In this case, researchers looked at soot's effect on R0, considering SNA's effect.

"We found black carbon acts as a kind of catalyst. When there is soot present, PM2.5 has more of an acute effect on lung health, and therefore on R0."

The mediation/moderation study was not superfluous -- one of the common ways people are exposed to SNA is through pollution emitted from cars and coal-fired power plants. Both of which also emit soot.

"Although decades of strict air quality regulations in the U.S. have resulted in significant reductions of nitrogen dioxide levels," the authors wrote in the paper's conclusion, "recent reversal of environmental regulations which weaken limits on gaseous emissions from power plants and vehicles threaten the country's future air quality scenario."

"Instead of working to resolve this issue, these reversals may be setting us up for another pandemic," Chakrabarty said.