Culture

JUPITER, FL--Making memories involves more than seeing friends or taking photos. The brain constantly adapts to new information and stores memories by building connections among neurons, called synapses. How neurons do this--reaching out arm-like dendrites to communicate with other neurons--requires a ballet of genes, signaling molecules, cellular scaffolding and protein-building machinery.

A new study from scientists at Scripps Research and the Max Planck Florida Institute for Neuroscience finds a central role for one signaling molecule, a long, noncoding RNA that the scientists named ADEPTR.

Using a variety of technologies, including confocal and two-photon microscopy, they track ADEPTR's moves, watching as it forms, travels, amasses at the synapse and activates other proteins upon a neuron's stimulation.

Its journey to the far reaches of a brain cell is made possible by a cellular carrier that that tiptoes along a dendrite's microtubule scaffolding. Called a kinesin motor, it deposits ADEPTR near the synapse junction, where it activates other proteins.

The team also found that if ADEPTR is silenced, new synapses don't form during stimulation.

The study, "Activity regulated synaptic targeting of lncRNA ADEPTR mediates structural plasticity by localizing Sptn1 and AnkB in dendrites," is published online April 16 in the journal Science Advances.

Long noncoding RNAs have often been described as "genomic dark matter," because their role in cells has yet to be fully characterized, especially in neurons, says the study's lead author, Scripps Research neuroscientist Sathyanarayanan Puthanveettil, PhD. Puthanveettil's team is finding that they play a signaling role in neural plasticity--how neurons adapt and change with experience.

"Here we report activity-dependent dendritic targeting of a newly transcribed long noncoding RNA for modulating synapse function, and describe its underlying mechanisms," Puthanveettil says. "These studies bring novel insights into the functions of long noncoding RNAs at the synapse."

The first author is Eddie Grinman, a graduate student in Puthanveettil's lab.

A long noncoding RNA is a type of RNA that exceeds 200 nucleotides, and does not get translated into protein. There are thousands of these long noncoding RNA in our cells, but in most cases, their function isn't yet known. What is known is that usually, they tend to stay within the cell nucleus. Some regulate the transcription of genes.

"It was surprising to see a long noncoding RNA move from nucleus to the synapse so rapidly and robustly," Grinman says.

The hippocampus is the part of the brain where learning, memory and emotions reside. Working in hippocampal neurons from mice, the team stimulated the neurons with pharmacological activators of learning-related signaling. They found through molecular and high-resolution imaging techniques that the ADEPTR long noncoding RNA was rapidly expressed and transported to the outer arms of the cell. There, the ADEPTR molecules interact with proteins that play a role in structural organization of synapses, proteins called spectrin 1 and ankyrin B.

They found that ADEPTR became downregulated if exposed to an inhibitory neurotransmitter, GABA.

"These findings add another layer of complexity in synapse modulation and plasticity," Puthanveettil says. "Synaptically localized long noncoding RNA are important regulators of adaptive neuronal function."

Going forward, the team intends to continue characterizing how stimulation affects neuronal plasticity. Also, the authors hope to learn more about the role of ADEPTR in vivo.

"It would be interesting to learn what role ADEPTR plays in forming new memories in living organisms," says Grinman.

The work is revealing one of the most fundamental processes of learning and memory, adaptation to changing information and circumstances.

"Neural plasticity is what allows us to learn, respond to stimuli, and lay down long-term memories," Puthanveettil says. "There is still much to learn about the magnificent complexity of this fundamental biological process."

Research shows that a new telescope could detect a potential signature of life on other planets in as little as 60 hours.

"What really surprised me about the results is that we may realistically find signs of life on other planets in the next 5 to 10 years," said Caprice Phillips, a graduate student at The Ohio State University, who will share preliminary findings at a press conference during the 2021 APS April Meeting.

Gas dwarf planets have the potential to foster life. But because none of these super-Earths or mini-Neptunes exist within our solar system, scientists struggle to determine whether their atmospheres contain ammonia and other potential signs of living things.

Phillips calculated that when the James Webb Space Telescope launches this October, it could feasibly detect ammonia around six gas dwarf planets after just a few orbits.

She and her team modeled how JWST instruments would respond to varying clouds and atmospheric conditions, then produced a ranked list of where the telescope should search for life.

"Humankind has contemplated the questions, 'Are we alone? What is life? Is life elsewhere similar to us?'" said Phillips. "My research suggests that for the first time, we have the scientific knowledge and technological capabilities to realistically begin to find the answers to these questions."

FEATURED TALK

Detecting Biosignatures in the Atmospheres of Gas Dwarfs With JWST (K05.2)
2:06 p.m. - 2:42 p.m. CDT, Sunday, April 18, 2021
Caprice Phillips, phillips.1622@buckeyemail.osu.edu
Livestream: Access here
Abstract: https://meetings.aps.org/Meeting/APR21/Session/K05.2

PRESS CONFERENCE

Register for the press conference to be held on Zoom at 12:00 p.m. CDT, Sunday, April 18, 2021.

Speaker:

Caprice Phillips (Ohio State)

From engineered pandemics to city-toppling cyber attacks to nuclear annihilation, life on Earth could radically change, and soon. Scientists will forecast the fate of the planet at a press conference during the 2021 APS April Meeting.

"Our Earth is 45 million centuries old. But this century is the first when one species--ours--can determine the biosphere's fate," said Martin Rees, the United Kingdom's Astronomer Royal and a founder of the Centre for the Study of Existential Risks at Cambridge University.

"Our globally-linked society is vulnerable to the unintended consequences of powerful new technologies--not only nuclear, but (even more) biotech, cyber, advanced AI, space technology," he added.

Royal astronomer predicts the world in 2050 and beyond

Rees thinks biohackers pose a particularly underappreciated threat to humanity. In the near future, simple equipment will enable people to reengineer the human genome irrevocably or build a superspreading influenza. Like drug laws, regulations could never prevent all such actions--and in a world more interconnected than ever before, the consequences would spread globally.

He will discuss other dangers: population rise leading to plummeting biodiversity, disastrous climate change, uncontrollable cybercriminals, plans for artificial intelligence that erodes privacy, security, and freedom.

But Rees is an optimist. He will offer a path toward avoiding these risks and achieving a sustainable future better than the world we live in today.

"If all of us passengers on 'spaceship Earth' want to ensure that we leave it in better shape for future generations we need to promote wise deployment of new technologies, while minimizing the risk of pandemics, cyberthreats, and other global catastrophes," he said.

Scaling back missile defense could prevent a nuclear attack

A single nuclear weapon could kill millions and destroy a city instantaneously. Hundreds of weapons could wipe out functioning society in a large nation. Even a limited nuclear war could cause a climate catastrophe, leading to the starvation of hundreds of millions of people.

Recently, Russia, China, and North Korea have deployed new types of nearly unstoppable missiles.

"Missile defense is an idea that can sound appealing at first--doesn't defense sound like the right thing to do?" said Frederick Lamb, astrophysicist at the University of Illinois at Urbana-Champaign, cochair of the 2003 APS Study of Boost-Phase Missile Defense, and chair of the current APS Panel on Public Affairs Study of Missile Defense and National Security.

"But when the technical challenges and arms race implications are considered, one can see that deploying a system that is intended to defend against intercontinental ballistic missiles is unlikely to improve the security of the United States," he said.

Lamb points to the United Kingdom's decision to increase its nuclear arsenal by 44%, possibly motivated by Russia's new missile defense system around Moscow. He sees the move as yet another sign that existing limits on nuclear weapons are unraveling. Even missile defenses that would never work in practice can catalyze the development of new nuclear weapons and increase global risk.

Lamb will share what may happen if the United States ramps up new missile defense systems.

"What is done about nuclear weapons and missile defenses by the United States and other countries affects the safety and survival of every person on the planet," he said.

FEATURED TALKS

The World in 2050--and Beyond (X06.1)

10:45 a.m. - 11:21 a.m. CDT, Tuesday, April 20, 2021
Martin Rees, mjr36@cam.ac.uk
Livestream: Access here
Abstract: http://meetings.aps.org/Meeting/APR21/Session/X06.1

Nuclear Weapons and Missile Defense (Y05.2)

2:06 p.m. - 2:42 p.m. CDT, Tuesday, April 20, 2021
Frederick Lamb, fkl@illinois.edu
Livestream: Access here
Abstract: http://meetings.aps.org/Meeting/APR21/Session/Y05.2

PRESS CONFERENCE

Register for the press conference to be held on Zoom at 11:00 a.m. CDT, Monday, April 19, 2021.

Speakers:

Martin Rees (Cambridge)

Frederick Lamb (University of Illinois at Urbana-Champaign)

The composition of the street drugs heroin and cocaine has dramatically changed at alarming speeds across the globe. No longer are these street drugs cut with benign materials such as lactose but now cut with up to 17 or more pharmaceutically active and potentially toxic adulterants.

A drug user may buy cocaine today but may end up with a drug cocktail more dangerous then what was bought and assumed was cocaine. This has a profound effect on public health and safety as well as on the individual street drug users during the COVID-19 pandemic.

Selected by the Editor-in-Chief, Dr. Kenneth Blum as the Editor's Choice in the May 2021 issue of Current Psychopharmacology (CPSP), this work examined the alarming addition of multiple pharmaceutically active substances collectively referred to as "toxic adulterants" and their pathophysiological effects, especially on street drug using patients, in light of the COVID-19 pandemic

Additional pharmaceutically active and potentially toxic compounds have been found in routine street drug seizures at startling amounts. These toxic adulterants include, but are not limited to, ethical pharmaceuticals such as cardiac medications, veterinary pharmaceuticals such as levamisole, industrial chemicals, fungicides, new psychoactive substances all of which have profound effects on the substance user health and COVID-19 risk.

"Never before in the history of addiction medicine have there been so many combinations of drugs and pharmacologically active compounds in a single dose of cocaine or heroin" Stated Dr. David M. Martin, Science Team Director of the project, he continued "Although the reason for this is unclear, it may be to create new product lines for an increasingly overcrowded street drug market and this trend seems to be continuing."

The report concluded that this dangerous new trend in world street drug supply is unprecedented and maybe the undetected cause of many psychostimulant and opioid overdose deaths. This is because many toxic adulterants are not routinely tested in post-mortem or street drug seizure cases. Public health and treatment officials need to know of this new dangerous trend evaluating and treating patients.

To get the full-text article, please visit: https://www.eurekaselect.com/node/190669/article/the-rapidly-changing-composition-of-the-global-street-drug-supply-and-its-effects-on-high-risk-groups-for-covid-19

WASHINGTON, April 16, 2021 -- Early in the COVID-19 pandemic, doctors recognized that patients who developed a "cytokine storm" -- a surge of pro-inflammatory immune proteins -- were often the sickest and at highest risk of dying. But a cytokine storm can also occur in other illnesses, such as influenza. Today, scientists report preliminary results on a sweat sensor that acts as an early warning system for an impending cytokine storm, which could help doctors more effectively treat patients.

The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2021 is being held online April 5-30. Live sessions will be hosted April 5-16, and on-demand and networking content will continue through April 30. The meeting features nearly 9,000 presentations on a wide range of science topics.

A video on the research is available at http://www.acs.org/acsspring2021cytokinesensor.

"Especially now in the context of COVID-19, if you could monitor pro-inflammatory cytokines and see them trending upwards, you could treat patients early, even before they develop symptoms," says Shalini Prasad, Ph.D., the project's principal investigator, who is presenting the work at the meeting.

Early detection is important because once a cytokine storm has been unleashed, the excessive inflammation can damage organs, causing severe illness and death. In contrast, if doctors could administer steroidal or other therapies as soon as cytokine levels begin to rise, hospitalizations and deaths could be reduced.

Although blood tests can measure cytokines, they are difficult to perform at home, and they can't continuously monitor the proteins' levels. Cytokines are excreted in sweat at lower levels than in blood. To collect enough sweat for testing, scientists have asked patients to exercise, or they have applied a small electrical current to patients' skin. However, these procedures can themselves alter cytokine levels, Prasad notes. "When it comes to cytokines, we found that you have to measure them in passive sweat. But the big challenge is that we don't sweat much, especially in air-conditioned environments," she says. Prasad, who is at the University of Texas at Dallas, estimates that most people produce only about 5 microliters, or one-tenth of a drop, of passive sweat in a 0.5-inch square of skin in 10 minutes.

So the researchers wanted to develop an extremely sensitive method to measure cytokine levels in tiny amounts of passive sweat. They drew on their previous work on a wearable sweat sensor to monitor markers of inflammatory bowel disease (IBD). The wristwatch-like device, which is being commercialized by EnLiSense LLC (a company co-founded by Prasad), measures the levels of two proteins that spike during IBD flare-ups. When the device is worn on the arm, passive sweat diffuses onto a disposable sensor strip that is attached to an electronic reader. The sensor strip, which contains two electrodes, is coated with antibodies that bind to the two proteins. Binding of the proteins to their antibodies changes the electrical current flowing through the e-reader. The reader then wirelessly transfers these data to a smartphone app that converts electrical measurements to protein concentrations. After a few minutes, the old sweat diffuses out, and newly excreted sweat enters the strip for analysis.

For their new cytokine sensor (called the SWEATSENSER Dx), the researchers made sensor strips with antibodies against seven pro-inflammatory proteins: interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), TNF-related apoptosis-inducing ligand, IL-10, interferon-γ-induced protein-10 and C-reactive protein. They inserted the strips into their device and, in a small observational study, they tested them on six healthy people and five people with influenza. Two of the sick people showed elevated cytokine levels, and in all participants, cytokines in passive sweat correlated with levels of the same proteins in serum.

The SWEATSENSER Dx was even sensitive enough to measure cytokines in patients taking anti-inflammatory drugs, who excrete cytokines in the low-picogram-per-milliliter concentration range. The device tracked cytokine levels for up to 168 hours before the sensor strip needed to be replaced.

EnLiSense, in partnership with the researchers, is now planning clinical trials of the cytokine sensor in people with respiratory infections. "Access to COVID-19 patients has been a challenge because healthcare workers are overwhelmed and don't have time to test investigational devices," Prasad says. "But we're going to continue to test it for all respiratory infections because the disease trigger itself doesn't matter -- it's what's happening with the cytokines that we're interested in monitoring."

Vitamin D deficiency may impair muscle function due to a reduction in energy production in the muscles, according to a mouse study published in the Journal of Endocrinology. Vitamin D deficient mice were found to have impaired muscle mitochondrial function, which may have implications for muscle function, performance and recovery. This may suggest that preventing vitamin D deficiency in older adults could help maintain better muscle strength and function and reduce age related muscle deterioration, but further studies are needed to confirm this.

Vitamin D is a hormone well known to be important for maintaining bone health and preventing rickets and osteoporosis. In recent years, vitamin D deficiency has been reported to be as prevalent as 40% in European populations and linked to increased risk for several conditions, including COVID-19, cancer and diabetes. Although these studies report association rather than causation, the benefits of vitamin D supplementation are now a major subject of health debate. Multiple studies have also linked low vitamin D levels to poor muscle strength, particularly in older people. Skeletal muscle enables us to move voluntarily and perform everyday activities. It is essential that they have enough energy to power these movements. Specialised organs in cells, called mitochondria, convert nutrients in to energy to meet this demand. Previous studies indicate that impaired muscle strength in people with vitamin D deficiency may be linked to impaired muscle mitochondrial function. Determining the role of vitamin D in muscle performance of older people is also difficult, as they may suffer from a number of pre-existing health conditions that can also affect their vitamin D status. Therefore, previous studies have been unable to determine how vitamin D may directly affect muscle performance.

Dr Andrew Philp and his team at the Garvan Institute of Medical Research in Australia, and collaborating universities, used a mouse model to determine the effects of diet-induced vitamin D deficiency on skeletal muscle mitochondrial function in young, male mice. Mice were either fed a diet with normal quantities of vitamin D, or with no vitamin D to induce deficiency, for a period of 3 months. A typical vitamin D level for humans is 40-50 nmol.L-1, and acute vitamin D deficiency is diagnosed when levels drop below 12 nmol.L-1. On average, the mice in this study had vitamin D levels of 30 nmol.L1, with diet-induced vitamin D deficiency leading to levels of just 3 nmol.L-1. Although this level was more extreme than typically observed in people, it is still within the clinically-recognised range. Tissue and blood samples were collected monthly to quantify vitamin D and calcium concentrations and to assess markers of muscle mitochondrial function and number. After 3 months of diet-induced vitamin D deficiency skeletal muscle mitochondrial function was found to be impaired by up to 37%. This was not due to a reduced number of mitochondria or a reduction in muscle mass.

"Our results show there is a clear link between vitamin D deficiency and oxidative capacity in skeletal muscle. They suggest that vitamin D deficiency decreases mitochondrial function, as opposed to reducing the number of mitochondria in skeletal muscle." Dr Philp comments. "We are particularly interested to examine whether this reduction in mitochondrial function may be a cause of age related loss in skeletal muscle mass and function."

These findings suggest that vitamin D deficiency may impair mitochondrial function and reduce the amount of energy produced in the muscles, which may lead to poor muscle function. Therefore, preventing vitamin D deficiency in older people may help maintain muscle performance and reduce the risk of muscle related diseases, such as sarcopenia. However, further studies that investigate the direct effect of vitamin D deficiency on muscle function and strength are necessary to confirm this.

Whilst this study indicates that vitamin D deficiency can alter mitochondrial function in skeletal muscle, Dr Philp and his team were unable to determine precisely how this process occurred. Therefore, their future work aims to establish how vitamin D deficiency alters mitochondrial control and function in skeletal muscle.

CHAPEL HILL, NC - A study published today in JAMA Internal Medicine shows that wearing two face coverings can nearly double the effectiveness of filtering out SARS-CoV-2-sized particles, preventing them from reaching the wearer's nose and mouth and causing COVID-19. The reason for the enhanced filtration isn't so much adding layers of cloth, but eliminating any gaps or poor-fitting areas of a mask.

"The medical procedure masks are designed to have very good filtration potential based on their material, but the way they fit our faces isn't perfect," said Emily Sickbert-Bennett, PhD, associate professor of infectious diseases at the UNC School of Medicine and lead author of the study.

To test the fitted filtration efficiency (FFE) of a range of masks, UNC researchers worked with James Samet, PhD, and colleagues in the USEPA Human Studies Facility on the campus of UNC-Chapel Hill. There they filled a 10-foot by 10-foot stainless-steel exposure chamber with small salt particle aerosols, and had researchers don combinations of masks to test how effective they were at keeping particles out of their breathing space.

Each individual mask or layered mask combination was fitted with a metal sample port, which was attached to tubing in the exposure chamber that measured the concentration of particles entering the breathing space underneath the researcher's mask. A second tube measured the ambient concentration of particles in the chamber. By measuring particle concentration in the breathing space underneath the mask compared to that in the chamber, researchers determined the FFE.

"We also had the researchers in the chamber undergo a series of range-of-motion activities to simulate the typical motions a person may do throughout their day - bending at the waist, talking, and looking left, right, up and down," said Phillip Clapp, PhD, an inhalation toxicologist in the UNC School of Medicine who has been testing mask FFE with Sickbert-Bennett since the pandemic began.

According to their findings, the baseline fitted filtration efficiency (FFE) of a mask differs person to person, due to each person's unique face and mask fit. But generally, a procedure mask without altering the fit, is about 40-60% effective at keeping COVID-19-sized particles out. A cloth mask is about 40% effective.

Their recent findings on doubling of face masks, shows that when a cloth mask is placed over a surgical mask, the FFE improved by about 20%, and improved even more with a snug-fitting, sleeve-type mask, such as a gaiter. When layered over procedure masks, cloth masks improve fit by eliminating gaps and holding the procedure mask closer to the face, consistently covering the nose and mouth. When a procedure mask is worn over a cloth mask, FFE improved by 16%.

"We've found that wearing two loosely fitted masks will not give you the filtration benefit that one, snug-fitting procedure mask will," Sickbert-Bennett said. "And with the current data supporting how effective mask-wearing is at preventing the spread of COVID-19, the best kind of double-masking is when you and the person you are interacting with are each correctly wearing a very snug-fitting mask."

Douglas Wilbur '14, a visiting Ph.D. scholar in the Department of Communication at UTSA, has published a study that shows how researchers can craft message campaigns to protect individuals from adopting extremist views.

According to his research, when people are explicitly told that they are free to accept or reject propagandistic claims, the likelihood of choosing a moderate view increases. This was a result of a survey of attitudes that tested counter-propaganda strategies, which stressed a person's autonomy, and then measured sentiments after exposure.

The study was recently published in Social Influence with collaborators at the University of Missouri.

"It's ironic, if you think about it. Empowering individuals to make choices when they encounter extremist messaging appears to help people resist such claims," Wilbur said. "What this research showed is consistent with other findings. You tend to see a trend where people will make the right choice."

The Pew Research Center found that two out of every three Americans say social media has a negative impact on what occurs within the U.S. The primary reasons listed in that same survey were misinformation and hate speech.

To combat propaganda in the past, strategists have relied on attitude inoculation theory. Analogous to how physical vaccines inoculate people against a virus, communication messages use psychological inoculation through exposure to both negative messages but also techniques to resist such attacks. As a result, people train and build their psychological immunity to resist future persuasion attempts. The shortcoming of this approach, however, is that it's difficult to apply to large groups.

With that limitation in mind, Wilbur tested two counter-propaganda strategies for boosting peoples' resistance to extremist propaganda. One is based on self-determination theory, or DPT, which argues that people are curious, active, and health-seeking as long as their psychological needs are met. Primarily, in this approach, the individual needs to have agency and control over their actions. Similarly, the other strategy tested relies on psychological reactance theory, or PRT, which assumes that people have strong negative reactions when they feel their freedom is threatened.

Wilbur recruited close to 400 participants online and told them they would read extremist messages. Respondents were randomly assigned to either a neutral control condition, a DPT approach ('it is your choice to agree or not'), or the PRT condition ('don't let them manipulate you'). They then read and rated their agreement of two anti-immigrant extremist messages. After exposure, both campaigns produced lower agreement to the extremist messages when compared to the control condition--regardless of political affiliation.

Wilbur elaborated that the benefits of these agency-based campaigns is that they can be built beforehand and are not message-specific. These proactive strategies and the resulting advantages are a departure from previous approaches that Wilbur himself used during his military tour in Afghanistan. There, he served as a communications officer and was tasked with blocking Al-Qaeda recruiting efforts, yet the existing communications methods at his disposal were slow and reactive.

"Al-Qaeda would put out a video to recruit. Then we would have to discredit it, but this would take time to get a counter-product (opposing argument via pamphlets or videos) out there," Wilbur recalled.

His approach aims to disrupt the radicalization process among vulnerable population groups.

"If we could prime people to think they have autonomy, then yes, they would be more likely to resist propagandist messages," Wilbur said. "We can even build messages about the COVID-19 vaccine--campaigns that tell people that they can chose whether to take the vaccine or not. You want to stress freedom."

NEW YORK, NY (April 16, 2021)--SARS-CoV-2, the virus that causes COVID-19, likely does not directly infect the brain but can still inflict significant neurological damage, according to a new study from neuropathologists, neurologists, and neuroradiologists at Columbia University Vagelos College of Physicians and Surgeons.

"There's been considerable debate about whether this virus infects the brain, but we were unable to find any signs of virus inside brain cells of more than 40 COVID-19 patients," says James E. Goldman, MD, PhD, professor of pathology & cell biology (in psychiatry), who led the study with Peter D. Canoll, MD, PhD, professor of pathology & cell biology, and Kiran T. Thakur, MD, the Winifred Mercer Pitkin Assistant Professor of Neurology.

"At the same time, we observed many pathological changes in these brains, which could explain why severely ill patients experience confusion and delirium and other serious neurological effects--and why those with mild cases may experience 'brain fog' for weeks and months."

The study, published in the journal Brain, is the largest and most detailed COVID-19 brain autopsy report published to date, suggests that the neurological changes often seen in these patients may result from inflammation triggered by the virus in other parts of the body or in the brain's blood vessels.

No Virus in Brain Cells

The study examined the brains of 41 patients with COVID-19 who succumbed to the disease during their hospitalization. The patients ranged in age from 38 to 97; about half had been intubated and all had lung damage caused by the virus. Many of the patients were of Hispanic ethnicity. There was a wide range of hospital length with some patients dying soon after arrival to the emergency room while others remained in the hospital for months. All of the patients had extensive clinical and laboratory investigations, and some had brain MRI and CT scans.

To detect any virus in the neurons and glia cells of the brain, the researchers used multiple methods including RNA in situ hybridization, which can detect viral RNA within intact cells; antibodies that can detect viral proteins within cells; and RT-PCR, a sensitive technique for detecting viral RNA.

Despite their intensive search, the researchers found no evidence of the virus in the patients' brain cells. Though they did detect very low levels of viral RNA by RT-PCR, this was likely due to virus in blood vessels or leptomeninges covering the brain.

"We've looked at more brains than other studies, and we've used more techniques to search for the virus. The bottom line is that we find no evidence of viral RNA or protein in brain cells," Goldman says. "Though there are some papers that claim to have found virus in neurons or glia, we think that those result from contamination, and any virus in the brain is contained within the brain's blood vessels."
"If there's any virus present in the brain tissue, it has to be in very small amounts and does not correlate with the distribution or abundance of neuropathological findings," Canoll says.

The tests were conducted on more than two dozen brain regions, including the olfactory bulb, which was searched because some reports have speculated that the coronavirus can travel from the nasal cavity into the brain via the olfactory nerve. "Even there, we didn't find any viral protein or RNA," Goldman says, "though we found viral RNA and protein in the patients' nasal mucosa and in the olfactory mucosa high in the nasal cavity." (The latter finding appears in an unpublished study, currently on BioRxiv, led by Jonathan Overdevest, MD, PhD, assistant professor of otolaryngology, and Stavros Lomvardas, PhD, professor of biochemistry & molecular biophysics and neuroscience.)

Hypoxic Damage and Signs of Neuronal Death

Despite the absence of virus in the brain, in every patient the researchers found significant brain pathology, which mostly fell into two categories.

"The first thing we noticed was a lot of areas with damage from a lack of oxygen," Goldman says. "They all had severe lung disease, so it's not surprising that there's hypoxic damage in the brain."

Some of these were large areas caused by strokes, but most were very small and only detectable with a microscope. Based on other features, the researchers believe these small areas of hypoxic damage were caused by blood clots, common in patients with severe COVID-19, that temporarily stopped the supply of oxygen to that area.

A more surprising finding, Goldman says, was the large number of activated microglia they found in the brains of most patients. Microglia are immune cells that reside in the brain and can be activated by pathogens.

"We found clusters of microglia attacking neurons, a process called 'neuronophagia,'" says Canoll. Since no virus was found in the brain, it's possible the microglia may have been activated by inflammatory cytokines, such as Interleukin-6, associated with SARS-CoV-2 infection.

"At the same time, hypoxia can induce the expression of 'eat me' signals on the surface of neurons, making hypoxic neurons more vulnerable to activated microglia," Canoll says, "so even without directly infecting brain cells, COVID-19 can cause damage to the brain."

The group found this pattern of pathology in one of their first autopsies, described by Osama Al-Dalahmah, MD, PhD, instructor in pathology & cell biology, in a case report published last March in Acta Neuropathologica Communications. Over the next few months, as the neuropathologists did many more COVID brain autopsies, they saw similar findings over and over again and realized that this is a prominent and common neuropathological finding in patients who die of COVID.

The activated microglia were found predominantly in the lower brain stem, which regulates heart and breathing rhythms, as well as levels of consciousness, and in the hippocampus, which is involved in memory and mood.

"We know the microglia activity will lead to loss of neurons, and that loss is permanent," Goldman says. "Is there enough loss of neurons in the hippocampus to cause memory problems? Or in other parts of the brain that help direct our attention? It's possible, but we really don't know at this point."

Persistent Neurological Problems in Survivors

Goldman says that more research is needed to understand the reasons why some post-COVID-19 patients continue to experience symptoms.

The researchers are now examining autopsies on patients who died several months after recovering from COVID-19 to learn more.

They are also examining the brains from patients who were critically ill with acute respiratory distress syndrome (ARDS) before the COVID-19 pandemic to see how much of COVID-19 brain pathology is a result of the severe lung disease.

"It is machination, it is deception," said the Director General of the Berlin Royal Museums in his defence when criticized for buying a fake. Wilhelm Bode did not budge an inch: the sculpture he acquired in 1909 was an as yet unknown production of the great Renaissance master, Leonardo da Vinci. After one hundred years and numerous controversies, a group of scientists led by a CNRS researcher* has just proven him wrong once and for all. The Flora wax bust, conserved at the Bode Museum in Berlin, recently underwent radiocarbon (14C) dating, which provided both a precise date and an incontrovertible result: it was made in the nineteenth century, nearly 300 years after da Vinci's death. As the sculpture was made primarily from spermaceti, a kind of wax extracted from whales, the researchers had to develop a new calibration method to accurately date the work of art. Their results, which were published on 15 April 2021 in Scientific Reports, show how 14C dating can be applied to unusual materials.

*- The researchers involved work at the Chemistry Research Institute of Paris (CNRS/Chimie ParisTech), the Centre for Research and Restoration of Museums of France (Ministry of Culture), and the Carbon-14 Measurement Laboratory (CEA/CNRS/IRD/IRSN/Ministry of Culture), a national platform managed by the Laboratory for Sciences of Climate and Environment (CNRS/CEA/Université de Versailles Saint-Quentin-en-Yvelines).

In a new publication from Opto-Electronic Advances; DOI https://doi.org/10.29026/oea.2021.200031, Researchers led by Professor Baohua Jia at Swinburne University of Technology, Victoria, Australia, Professor Cheng-Wei Qiu at National University of Singapore, Singapore and Professor Tian Lan at Beijing Institute of Technology, Beijing, China considered the generation of super-resolved optical needle and multifocal array using graphene oxide metalenses.

Ultrathin and lightweight, metalenses are becoming increasingly significant for their use in photonic chips, biosensors and micro imaging systems such as smart phone cameras.

Compared to conventional lenses, metalenses can improve the image quality of current cameras, by enhancing resolution and removing spherical and chromatic aberrations. A single ultrathin (less than the thickness of 1/100 of a human hair) metalens element can be used instead of the multiple element imaging systems required by conventional lenses. Due to the unique light-matter interaction in a confined 2D plane, 2D materials are ideal for use with metalenses, further reducing the required thickness of the lens. 2D Graphene family materials, for example graphene oxides, are air-stable, have many applications and are low-cost and easy to fabricate in large scale. They remain stable in extreme environments, for example lower earth orbit in aerospace, so have potential use in satellites replacing the current bulky lenses and improving imaging quality and lowering launch costs.

The authors of this article developed 200 nm thick graphene oxide metalenses to generate specialized focal intensity distributions. The graphene oxide metalenses have the capability of controlling light amplitude (i.e., transparency of the lens) and phase (refractive index and thickness of the lens) simultaneously. This differs from other metalenses, which introduce the modulations through multi-step nanofabrication or multilevel of nano-elements, the modulations of graphene oxide lenses are locally introduced by the laser photo-reduction process, which converts graphene oxide to graphene material. During the reduction process, the material becomes thinner and has a higher refractive index and absorption. Based on the simultaneous phase and amplitude modulations, the authors demonstrate precise control of the focal intensity distributions by creating a super-resolved ultra-long optical needle and an axial multifocal array, which are extremely challenging for other metalenses.

Graphene oxide metalenses will find broad applications in integrated photonics and compact photonic systems, including microscopic imaging, optical manipulation and photonic chips, and can be integrated on microfluidic chips to form lab-on-a-chip biophotonic devices. This research forms a basis for the development of graphene-based ultrathin integratable photonic devices and paves the way for broader applications, such as replacing current cell phone camera lens potentially allowing a reduction in the thickness of current cell phones.

If you are exposed to silica (quartz) dust at work - e.g. from working with concrete and granite - you have a greater risk of certain types of rheumatic disease. This is shown by results from Aarhus University and Aarhus University Hospital, which have just been published in the International Journal of Epidemiology.

Exposure to silica dust at work, which is the case especially at workplaces within construction and industry, may lead to autoimmune rheumatic diseases. Photo: Unsplash.

Exposure to silica dust at work, which is the case especially at workplaces within construction and industry, may lead to autoimmune rheumatic diseases. Photo: Unsplash.

As the research results from Aarhus University show, exposure to silica dust comes at a cost.

"Exposure to silica dust at work, which is the case especially at workplaces within construction and industry, may lead to autoimmune rheumatic diseases - even at low levels of exposure," says one of the researchers behind the largest study of its kind, Medical Doctor and PhD Signe Hjuler Boudigaard from Aarhus University and Aarhus University Hospital.

Silica dust is formed when flint, sandstone, granite and concrete are grinded or processed in other ways. Some of the dust consists of small particles which - when you inhale them - are carried right down into the smallest parts of the lungs. This so-called respirable dust accumulates in the lungs, where it causes an inflammatory reaction and activates the immune system.

The risk of rheumatic diseases increases

The researchers examined the association between exposure to silica dust and the rheumatic diseases systemic sclerosis, rheumatoid arthritis, lupus erythematosus and small vessel vasculitis, which is a chronic inflammation of the small blood vessels.

They found that the risk of autoimmune rheumatic diseases increased with increasing exposure levels of silica dust. The risk for persons with the highest exposure was one-and-a-half times greater compared to non-exposed people.

The survey comprised 1,541,505 men and 1,470,769 women from the Danish labour force from 1979 to 2015. A total of 17,000 were diagnosed with one of these autoimmune diseases,

and of these, 1,490 had been exposed to silica dust at work. The study shows a clear association between level of exposure to silica dust at work and autoimmune rheumatic disorders, most clearly for systemic sclerosis and rheumatoid arthritis.

"The most important competing factor is tobacco smoking. We accounted for smoking and there was still an association between silica exposure and autoimmune rheumatic diseases. We know that smoking is not randomly distributed in the population, so it was important to take this into account," says Henrik Kolstad, professor at Aarhus University and Aarhus University Hospital and continues:

"In Denmark and Europe, the occupational exposure limit for silica dust is twice the limit in the USA. It's therefore clearly relevant to include our findings when reviewing the current Danish occupational exposure limit"

The next step is to examine whether exposure to silica dust leads to increased levels of antibodies specific for autoimmune rheumatic diseases. According to Henrik Kolstad, the purpose of these studies is to substantiate the causal relationship and gain insight into the possible causal mechanisms.

The leading newspapers in two nuclear waste management forerunner countries, Finland and France, fulfil their "watchdog" roles in highly distinct ways. The Finnish Helsingin Sanomat (HS) tends to reproduce government and industry framings, whereas Le Monde cherishes its role as an independent critic of the powers that be. These differences reflect distinct cultural, political and media traditions in the two countries.

"The critical watchdog model works in a liberal democracy such as the French, based on mistrust towards the governing elites. But would it backfire in Finland by undermining the very institutional trust that the Nordic democracies have been built upon throughout history?" asks the first author of the article, Research Fellow Markku Lehtonen from the Department of Humanities at the Pompeu Fabra University in Barcelona. Lehtonen continues: "Or perhaps the near-absence of criticism reflects weaknesses in the Finnish democracy?"

During the analysis period, from 2005 to 2018, both countries' deep geological disposal projects were advancing towards implementation.

The study, published in the journal Risk, Hazards, & Crisis in Public Policy, examined nuclear waste reporting - in particular related to risks and safety - in Helsingin Sanomat and Le Monde. During the analysis period, from 2005 to 2018, both countries' deep geological disposal projects were advancing towards implementation.

In its reporting on the final disposal of nuclear waste, Helsingin Sanomat focused on "performance?relevant information", exhibiting strong confidence in the safety and viability of the repository and trust in the actors behind the project. Le Monde, in turn, prioritised "morality-relevant information", highlighting the challenges of trust and mistrust between the involved parties, and, to a lesser extent, scepticism in relation to the viability and safety of the project.

Where Helsingin Sanomat underlined the consistent advancement towards a reliably operating repository, Le Monde evoked the numerous uncertainties and obstacles still facing the repository project, including the multiple conflicts and controversies among the involved actors.

"Le Monde constantly reminded of the ambiguous legacy of the French nuclear sector, as a symbol of modernisation, technological prowess, and economic prosperity on the one hand, and as an incarnation of failed promises on the other. Helsingin Sanomat, in turn, underlined continuity, predictability, and certainty. It described the Finnish repository project as a success story essential for the national interest," Lehtonen points out.

In addressing intergenerational equity, Helsingin Sanomat echoed the government and industry argument that a deep geological repository spares future generations from having to tackle the waste problem. By contrast, Le Monde pointed out a major dilemma: burying waste in a repository would deprive future generations of the freedom to decide what to do with the waste, including the possibility that thanks to technological development the waste could be turned into a resource.

"The findings help to understand why the nuclear waste disposal project has advanced in such an unproblematic manner in Finland," notes Research Fellow Matti Kojo from Tampere University, a co-author of the article.

A comprehensive analysis of leading newspapers over fourteen years

The now published study examined nuclear waste reporting - in particular related to risks and safety - in Helsingin Sanomat and Le Monde. The authors underline that the final set of material included only those articles in which the country's own repository project was a central topic (135 articles in HS and 210 in Le Monde).

Finland expects to become the first country in the world to have solved its problem of high-level radioactive waste, with its ONKALO repository expected to become operational by the mid-2020s. France's "Cigéo" facility is to start operating in the early 2030s.

The authors underline that the final set of material included only those articles in which the country's own repository project was a central topic.

The research group has previously compared, among other things, the processes of citizens participation, the role of host communities, and press reporting on nuclear waste management in Finland and Sweden.

Since fast radio bursts (FRBs) were first discovered over a decade ago, scientists have puzzled over what could be generating these intense flashes of radio waves from outside of our galaxy. In a gradual process of elimination, the field of possible explanations has narrowed as new pieces of information are gathered about FRBs - how long they last, the frequencies of the radio waves detected, and so on.

Now, a team led by McGill University researchers and members of Canada's CHIME Fast Radio Burst collaboration has established that FRBs include radio waves at frequencies lower than ever detected before, a discovery that redraws the boundaries for theoretical astrophysicists trying to put their finger on the source of FRBs.

"We detected fast radio bursts down to 110 MHz where before these bursts were only known to exist down to 300 MHz," explained Ziggy Pleunis, a postdoctoral researcher in McGill's Department of Physics and lead author of the research recently published in the Astrophysical Journal Letters. "This tells us that the region around the source of the bursts must be transparent to low-frequency emission, whereas some theories suggested that all low-frequency emission would be absorbed right away and could never be detected."

The study focussed on an FRB source first detected in 2018 by the CHIME radio telescope in British Columbia. Known as FRB 20180916B, the source has attracted particular attention because of its relative proximity to Earth and the fact that it emits FRBs at regular intervals.

The research team combined the capacities of CHIME with those of another radio telescope, LOFAR, or Low Frequency Array, in the Netherlands. The joint effort not only enabled the detection of the remarkably low FRB frequencies, but also revealed a consistent delay of around three days between the higher frequencies being picked up by CHIME and the lower ones reaching LOFAR.

"This systematic delay rules out explanations for the periodic activity that do not allow for the frequency dependence and thus brings us a few steps closer to understanding the origin of these mysterious bursts," adds co-author Daniele Michilli, also a postdoctoral researcher in the Department of Physics at McGill.

WHAT:
The experimental antiviral drug MK-4482 significantly decreased levels of virus and disease damage in the lungs of hamsters treated for SARS-CoV-2 infection, according to a new study from National Institutes of Health scientists. SARS-CoV-2 is the virus that causes COVID-19. MK-4482, delivered orally, is now in human clinical trials. Remdesivir, an antiviral drug already approved by the U.S. Food and Drug Administration for use against COVID-19, must be provided intravenously, making its use primarily limited to clinical settings.

In their study, published in the journal Nature Communications, the scientists found MK-4482 treatment effective when provided up to 12 hours before or 12 hours after infecting the hamsters with SARS-CoV-2. These data suggest that MK-4482 treatment potentially could mitigate high-risk exposures to SARS-CoV-2, and might be used to treat established SARS-CoV-2 infection alone or possibly in combination with other agents.

The same research group, located at Rocky Mountain Laboratories, part of NIH's National Institute of Allergy and Infectious Diseases in Hamilton, Montana, developed the hamster model last year to mimic SARS-CoV-2 infection and mild disease in people. The University of Plymouth in the United Kingdom collaborated on these most recent studies.

The project involved three groups of hamsters: a pre-infection treatment group; a post-infection treatment group; and an untreated control group. For the two treatment groups, scientists administered MK-4482 orally every 12 hours for three days. At the conclusion of the study, the animals in each of the treatment groups had 100 times less infectious virus in their lungs than the control group. Animals in the two treatment groups also had significantly fewer lesions in the lungs than the control group.

The scientists determined the MK-4482 treatment doses for this study based on previous experiments performed in mouse models of SARS-CoV-1 and MERS-CoV. In those studies, MK-4482 was effective at stopping the viruses from replicating.

With funding support from NIAID, Emory University's Drug Innovation Ventures group in Atlanta developed MK-4482 (also known as molnupiravir and EIDD-2801) to treat influenza. Merck and Ridgeback Biotherapeutics are now jointly developing and evaluating MK-4482 as a potential COVID-19 treatment. The drug is in Phase 2 and 3 human clinical studies.