Culture

One of the grand quests in neuroscience is to build a precise map of the brain, charting all its neurons and the connections between them. Such a wiring diagram, called a connectome, promises to help shed light on how a collection of cells can together give rise to thoughts, memories, behaviors and myriad other functions.

Now, researchers at Harvard Medical School, Boston Children's Hospital and the European Synchrotron Radiation Facility (ESRF) have demonstrated that a new x-ray microscopy technique could help accelerate efforts to map neural circuits and ultimately the brain itself.

Reporting in Nature Neuroscience on Sept. 14, the team describes how x-ray holographic nano-tomography (XNH) can be used to image relatively large volumes of mouse brain and fruit fly nervous tissue at high resolutions.

Combined with artificial intelligence-driven image analysis, they reconstructed dense neural circuits in 3D, comprehensively cataloging neurons and even tracing individual neurons from muscles to the central nervous system in fruit flies.

"We think this is going to open new avenues for understanding the brain, both in how it's organized and the circuitry that underlies its function," said co-corresponding author Wei-Chung Allen Lee, HMS assistant professor of neurology at Boston Children's. "This type of knowledge can give us foundational insights into neurological disorders, diseases that affect the structure of the brain and much more."

For biological questions like neural circuit discovery, x-ray microscopy holds several advantages over current approaches based on electron microscopy (EM), according to the authors.

"We think XNH can bring a lot of value to neuroscience, because we can now access much larger volumes in shorter times," said co-corresponding author Alexandra Pacureanu, a scientist at the ESRF. "This is the beginning of a new approach for efforts to map neural circuits."

Near-light speed

Studying the connectome is a monumental challenge. The human brain, for example, contains some 100 billion neurons with 100 trillion neural connections, roughly the number of stars within 1,000 galaxies.

In animal models, scientists have made remarkable progress, such as imaging an entire fruit fly brain, primarily by taking serial slices of a brain, each a thousand times thinner than a human hair, imaging the slices with EM and stitching the images together for analysis.

The costs of this method can be prohibitive in terms of time and resources, requiring large numbers of EM images, which have a narrow field of view, and an intense effort to reconstruct even small neural circuits. There is a need for new imaging modalities to accelerate such efforts, the study authors said.

To do so, Lee's lab, which studies the organization and function of neural circuits, collaborated with Pacureanu, who specializes in x-ray microscopy and neuroimaging. Spearheaded by co-first authors Aaron Kuan, research fellow in neurobiology at HMS, and Jasper Phelps, graduate student in the Harvard Program in Neuroscience, the team focused on applying XNH to neural tissue.

The technique works analogously to a CT scan, which uses a rotating x-ray to create serial cross-sectional images of a body. In contrast, XNH exposes a rotating tissue sample to high-energy x-rays at the ESRF's synchrotron, which accelerates electrons to near-light speed around an 844-meter ring.

Unlike standard x-ray imaging, which relies on differences in x-ray attenuation as the beam passes through a tissue, XNH creates images based on variations of subtle phase shifts of the beam induced by the sample. This latter approach increases sensitivity and, combined with imaging in cryogenic conditions, helps preserve and protect the specimen from being damaged by x-ray energy.

Images generated by XNH must be interpreted to identify which structures are neurons. The team tackled this by applying deep learning, an artificial intelligence technique increasingly used for applications such as face or object recognition.

As proof of principle, the researchers scanned millimeter-sized volumes of mouse and fruit fly neural tissue and reconstructed 3D images, achieving resolutions around 87 nanometers. This was enough to comprehensively visualize neurons and trace individual neurites, the projections from neurons that form the wiring of neural circuits.

Importantly, these reconstructions took a few days to achieve, compared to the months to years it can take to reconstruct similar volumes using serial EM sections.

Form to function

In the mouse brain, the team looked at an area of the cortex involved in integrating sensory stimuli and perceptual decision making. Previous EM studies have noted interesting structural characteristics of so-called pyramidal neurons in this area, but have been limited to sample sizes of around 20 neurons per dataset due to limitations in field of view.

Using XNH, the researchers scanned over 3,200 cells in this area. Combined with aligned EM data, the team characterized the structure and connectivity of hundreds of pyramidal neurons, which revealed distinct structural properties--such as strong and spatially compressed inhibitory inputs on certain neurite areas--that suggest unique and previously undescribed functional properties.

"Being able to visualize neurons helps us to understand the organizational principles of the brain and how different circuits or networks can perform computations that are required for behavior," said Lee, who is an investigator at the Kirby Neurobiology Center at Boston Children's. "We can then do further experiments to link structural data with functional experiments to try to address this question directly."

They also imaged the neurons contained within a fruit fly leg, a structure difficult to section and study with EM. With XNH, they were able to map all of the motor neurons extending from the fly equivalent of a spinal cord into a leg, as well as the sensory neurons that relay signals to the central nervous system.

"This technique has been applied to neural tissue before, but never with this level of quality and resolution," said Pacureanu, who is a former a visiting scientist in the Department of Neurobiology in the Blavatnik Institute at HMS. "We've shown that we can achieve sufficient resolution to trace neurites and move studies toward the direction of connectomes."

The researchers are now working to improve and further optimize XNH for imaging biological tissue.

The current resolution achieved by the technique is not yet high enough to visualize synapses, which currently requires aligned EM data to study. However, the physical limits of the technique are far from being reached, the authors said, and efforts to push the resolution will be aided by a next-generation x-ray source recently operational at the ESRF.

"X-ray microscopy has particular strengths and one of our goals is to apply it to larger networks of neural connections at higher resolutions," Lee said. "The hope is we could someday help address questions like can we understand neural circuits that underlie complex behaviors like decision making? Can we get inspiration for more efficient computer algorithms and artificial intelligence? Can we reverse engineer the algorithms of the brain?"

Additional authors on the study include Logan Thomas, Tri Nguyen, Julie Han, Chiao-Lin Chen, Anthony Azevedo, John Tuthill, Jan Funke and Peter Cloetens.

The work was supported by the National Institutes of Health (grant R01NS108410), the Edward R. and Anne G. Lefler Center for the Study of Neurodegenerative Disorders and the Goldenson Family and the European Research Council (grant 852455).

A planet observed crossing in front of, or transiting, a low-mass star has been determined to be about the size of Jupiter. While hundreds of Jupiter-sized planets have been discovered orbiting larger sun-like stars, it is rare to see these planets orbiting low-mass host stars and the discovery could help astronomers to better understand how these giant planets form.

"This is only the fifth Jupiter-sized planet transiting a low-mass star that has been observed and the first with such a long orbital period, which makes this discovery really exciting", said Caleb Cañas, lead author of the paper and a Ph.D. student at Penn State and NASA Earth and Space Science Fellow.

Originally detected by NASA's Transiting Exoplanet Survey Satellite (TESS) spacecraft, astronomers characterized the planet's mass, radius, and its orbital period using the Habitable-zone Planet Finder (HPF), an astronomical spectrograph built by a Penn State team and installed on the 10m Hobby-Eberly Telescope at McDonald Observatory in Texas. A paper describing the research appears in the September 2020 issue of the Astronomical Journal and is publicly accessible on arXiv.

"A transiting Jupiter-sized planet is amenable to further observations to see how well the orbit is aligned with the spin-axis of the host star and to constrain how it could have formed," said Cañas. "Furthermore, the low mass of the host star and the long orbital period result in a Jupiter with a moderate temperature compared to similar planets detected with NASA's Kepler space telescope."

The host star, TOI-1899, is a low-mass (M dwarf) star about 419 light years away from Earth. The planet, TOI-1899 b, is two-thirds the mass of Jupiter, ten percent larger in radius than Jupiter, and is 0.16 astronomical units (AU)--a measure defined as the distance between the Earth and the sun--from its host star such that a full year on TOI-1899 takes only 29 Earth days. For comparison, the four other transiting Jupiter-size planets around comparable stars complete their orbits in less than 4 days.

The planet was detected by TESS using the transit method, which searches for stars showing periodic dips in their brightness as a telltale sign of an orbiting object crossing in front of the star and blocking a portion of its light. The signal was later confirmed as a planet using precision observations from the HPF spectrograph that measure the planet's mass by analyzing how it causes its host start to the wobble.

From a formation and orbital evolution perspective, there is not a clear dividing line between warm Jupiters and the large planets even closer to their host stars, the more commonly discovered hot Jupiters.

"Warm Jupiters like TOI-1899 b orbit surprisingly close to their star," said Rebekah Dawson, assistant professor of astronomy and astrophysics at Penn State and an author of the paper. "Even though the planet's orbital period is long compared to many other giant planets detected and characterized through the transit method, it still places the giant planet much closer to its star than we'd expect from classical formation theories. Detailed characterization of their physical and orbital properties, system architecture, and host stars--as the HPF team has done for TOI-1899 b--allow us test theories for how giant planets can form or be displaced so close to their star."

The Habitable-zone Planet Finder was delivered to the 10m Hobby Eberly Telescope at McDonald Observatory in late 2017, and started full science operations in late 2018. HPF is designed to detect and characterize planets in the Habitable-zone--the region around the star where a planet could sustain liquid water on its surface--around nearby M-dwarf stars, but is also capable of making sensitive measurements for planets outside the habitable zone.

"This warm Jupiter is a compelling target for atmospheric characterization with upcoming missions like the James Webb Space Telescope," said Suvrath Mahadevan, professor of astronomy and astrophysics at Penn State, the principal investigator of the HPF spectrograph, and an author of the paper. "HPF was critical in helping us to confirm this, but detecting a second transit is important to very precisely pin down its period."

In addition to data from HPF, additional data were obtained with the 3.5m Telescope at the Kitt Peak National Observatory (KPNO) in Arizona and the 3m Shane Telescope at Lick Observatory for high contrast imaging and photometric observations with the 0.9m WIYN Telescope at KPNO, 0.5 m ARCSAT telescope at Apache Point Observatory, and the 0.43 m telescope at the Richard S. Perkin Observatory in New York.

A major new international study has provided a first worldwide insight into how soil erosion may be affecting the longevity of our soils.

The study, led by Lancaster University in collaboration with researchers from Chang'an University in China, and KU Leuven in Belgium, brought together soil erosion data from around the globe, spanning 255 locations across 38 countries on six continents.

This data was used to calculate how long it would take for the top 30 cm of soil to erode at each location - the soil lifespan. The top layer of soil is often rich in nutrients and organic matter, making it important for growing food, fibres, feed and fuel. Soil erosion is a serious threat to global sustainability, endangering food security, driving desertification and biodiversity loss, and degrading ecosystems

The study included soils that are conventionally farmed, as well as those managed using soil conservation techniques, to find out how changes to land use and management practices can extend the lifespans of soils.

Researchers found more than 90 per cent of the conventionally farmed soils in the study were thinning, and 16 per cent had lifespans of less than a century. These rapidly thinning soils were found all over the world, including countries such as Australia, China, the UK, and the USA.

"Our soils are critically important and we rely on them in many ways, not least to grow our food", says lead author Dr Dan Evans of Lancaster University. "There have been many headlines in recent years suggesting that the world's topsoil could be gone in 60 years, but these claims have not been supported with evidence. This study provides the first evidence-backed, globally relevant estimates of soil lifespans.

"Our study shows that soil erosion is a critical threat to global soil sustainability, and we need urgent action to prevent further rapid loss of soils and their delivery of vital ecosystem services."

However, there are causes for optimism. In the data, soils managed with conservation strategies tended to have longer lifespans, and in some cases these practices promoted soil thickening. Only seven per cent of soil under conservation management had lifespans shorter than a century, and nearly half exceeded 5,000 years.

Co-author, Professor Jess Davies, also of Lancaster University, said: "Whilst 16 per cent of soils with lifespans shorter than 100 years is a more optimistic estimate than '60 harvests left', soil is a precious resource and we can't afford to lose that much over a human lifetime.

"But importantly what our study also shows is that we have the tools and practices to make a difference - employing the appropriate conservation methods in the right place can really help protect and enhance our soil resource and the future of food and farming."

Converting arable land to forest was found to be the best way to lengthen soil lifespans. However, other approaches that allow farming to continue, such as cover cropping, where plants are grown between cropping seasons to protect the soil, were also shown to be highly effective. The ploughing of land along contours rather than down slope, and hillslope terracing were similarly suggested as beneficial for lengthening soil lifespans.

Professor John Quinton, of Lancaster University and co-author of the study, said: "It is clear that we have a conservation toolbox that can slow erosion and even grow soil. Action is needed to promote the adoption of these measures so that we can protect and enhance our soil resource for future generations."

A National Institutes of Health-funded study found that people with substance use disorders (SUDs) are more susceptible to COVID-19 and its complications. The research, published today in Molecular Psychiatry, was co-authored by Nora D. Volkow, M.D., director of the National Institute on Drug Abuse (NIDA). The findings suggest that health care providers should closely monitor patients with SUDs and develop action plans to help shield them from infection and severe outcomes.

By analyzing the non-identifiable electronic health records (EHR) of millions of patients in the United States, the team of investigators revealed that while individuals with an SUD constituted 10.3% of the total study population, they represented 15.6% of the COVID-19 cases. The analysis revealed that those with a recent SUD diagnosis on record were more likely than those without to develop COVID-19, an effect that was strongest for opioid use disorder, followed by tobacco use disorder. Individuals with an SUD diagnosis were also more likely to experience worse COVID-19 outcomes (hospitalization, death), than people without an SUD.

"The lungs and cardiovascular system are often compromised in people with SUD, which may partially explain their heightened susceptibility to COVID-19," said Dr. Volkow. "Another contributing factor is the marginalization of people with addiction, which makes it harder for them to access health care services. It is incumbent upon clinicians to meet the unique challenges of caring for this vulnerable population, just as they would any other high-risk group."

NIDA's Dr. Volkow and Rong Xu, Ph.D., of Case Western Reserve University in Cleveland, Ohio, analyzed EHR data collected until June 15, 2020, from 360 hospitals nationwide. The EHRs were de-identified to ensure privacy.

The study population consisted of over 73 million patients, of which over 7.5 million had been diagnosed with an SUD at some point in their lives. Slightly more than 12,000 were diagnosed with COVID-19, and about 1,880 had both an SUD and a COVID-19 diagnosis on record. The types of SUDs investigated in the study were tobacco, alcohol, opioid, cannabis, and cocaine.

The complicating effects of SUD were visible in increased adverse consequences of COVID-19. Hospitalizations and death rates of COVID-19 patients were all elevated in people with recorded SUDs compared to those without (41.0% versus 30.1% and 9.6% versus 6.6%, respectively).

Additionally, African Americans with a recent opioid use disorder diagnosis were over four times more likely to develop COVID-19, compared to whites. Results showed that hypertension, diabetes, cardiovascular diseases, and renal diseases, which are risk factors for COVID-19, were more prevalent among African Americans than whites with opioid use disorder.

According to the authors, the study findings underscore the need to screen for, and treat, SUDs as part of the strategy for controlling the pandemic. Additional research needs to be done to better understand how best to treat those with SUDs who are at risk for COVID-19 and counsel on how to avoid the risk of infection.

New research at Washington University School of Medicine in St. Louis helps illuminate a surprising mind-body connection. In mice, the researchers found that immune cells surrounding the brain produce a molecule that is then absorbed by neurons in the brain, where it appears to be necessary for normal behavior.

The findings, published Sept. 14 in Nature Immunology, indicate that elements of the immune system affect both mind and body, and that the immune molecule IL-17 may be a key link between the two.

"The brain and the body are not as separate as people think," said senior author Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology and a professor of neurosurgery, of neurology and of neuroscience. "What we've found here is that an immune molecule -- IL-17 -- is produced by immune cells residing in areas around the brain, and it could affect brain function through interactions with neurons to influence anxiety-like behaviors in mice. We are now looking into whether too much or too little of IL-17 could be linked to anxiety in people."

IL-17 is a cytokine, a signaling molecule that orchestrates the immune response to infection by activating and directing immune cells. IL-17 also has been linked to autism in animal studies and depression in people.

How an immune molecule like IL-17 might influence brain disorders, however, is something of a mystery since there isn't much of an immune system in the brain and the few immune cells that do reside there don't produce IL-17. But Kipnis, along with first author and postdoctoral researcher Kalil Alves de Lima, PhD, realized that the tissues that surround the brain are teeming with immune cells, among them, a small population known as gamma delta T cells that produce IL-17. They set out to determine whether gamma-delta T cells near the brain have an impact on behavior. Kipnis and Alves de Lima conducted the research while at the University of Virginia School of Medicine; both are now at Washington University.

Using mice, they discovered that the meninges are rich in gamma-delta T cells and that such cells, under normal conditions, continually produce IL-17, filling the tissues surrounding the brain with IL-17.

To determine whether gamma-delta T cells or IL-17 affect behavior, Alves de Lima put mice through established tests of memory, social behavior, foraging and anxiety. Mice that lacked gamma-delta T cells or IL-17 were indistinguishable from mice with normal immune systems on all measures but anxiety. In the wild, open fields leave mice exposed to predators such as owls and hawks, so they've evolved a fear of open spaces. The researchers conducted two separate tests that involved giving mice the option of entering exposed areas. While the mice with normal amounts of gamma-delta T cells and levels of IL-17 kept themselves mostly to the more protective edges and enclosed areas during the tests, mice without gamma-delta T cells or IL-17 ventured into the open areas, a lapse of vigilance that the researchers interpreted as decreased anxiety.

Moreover, the scientists discovered that neurons in the brain have receptors on their surfaces that respond to IL-17. When the scientists removed those receptors so that the neurons could not detect the presence of IL-17, the mice showed less vigilance. The researchers say the findings suggest that behavioral changes are not a byproduct but an integral part of neuro-immune communication.

Although the researchers did not expose mice to bacteria or viruses to study the effects of infection directly, they injected the animals with lipopolysaccharide, a bacterial product that elicits a strong immune response. Gamma-delta T cells in the tissues around the mice's brains produced more IL-17 in response to the injection. When the animals were treated with antibiotics, however, the amount of IL-17 was reduced, suggesting gamma-delta T cells could sense the presence of normal bacteria such as those that make up the gut microbiome, as well as invading bacterial species, and respond appropriately to regulate behavior.

The researchers speculate that the link between the immune system and the brain could have evolved as part of a multipronged survival strategy. Increased alertness and vigilance could help rodents survive an infection by discouraging behaviors that increase the risk of further infection or predation while in a weakened state, Alves de Lima said.

"The immune system and the brain have most likely co-evolved," Alves de Lima said. "Selecting special molecules to protect us immunologically and behaviorally at the same time is a smart way to protect against infection. This is a good example of how cytokines, which basically evolved to fight against pathogens, also are acting on the brain and modulating behavior."

The researchers now are studying how gamma-delta T cells in the meninges detect bacterial signals from other parts of the body. They also are investigating how IL-17 signaling in neurons translates into behavioral changes.

Botox injections to manage jaw and facial pain do not result in clinically significant changes in jaw bone when used short term and in low doses, according to researchers at NYU College of Dentistry. However, they found evidence of bone loss when higher doses were used.

The researchers, whose findings are published in the Journal of Oral Rehabilitation,, call for further clinical studies to track bone- and muscle-related changes with long-term use of Botox for TMJD, or temporomandibular muscle and joint disorders.

TMJDs are a group of common pain conditions that occur in the jaw joint and surrounding muscles, with the most common type involving the muscles responsible for chewing. While many individuals manage their TMJD symptoms with conservative treatments such as jaw exercises, oral appliances, dietary changes, and pain medication, some do not respond to these treatments.

Botox (or botulinum toxin), an FDA-approved injectable drug known for its wrinkle-reducing capabilities, is approved to treat certain muscle and pain disorders, including migraines. It works in part by temporarily paralyzing or weakening muscles. In the U.S., a Phase 3 clinical trial is currently underway to study the use of Botox to treat TMJD, but in the meantime, it is increasingly being used off-label.

Thus far, small studies using Botox to treat TMJD in humans have had mixed results. In animal studies, Botox injections in jaw muscles have led to major bone loss in the jaw. This is thought to be due to the muscles not being used to exert force needed for bone remodeling, but Botox may also have a direct effect on bone resorption, the process of breaking down bone tissue.

"Given these concerning findings from animal studies, and the limited findings from clinical studies, more research on the safety of Botox for jaw muscles and bones is critically important," said Karen Raphael, professor in the Department of Oral and Maxillofacial Pathology, Radiology and Medicine at NYU College of Dentistry and the study's lead author.

The NYU study included 79 women with TMJD affecting their facial muscles: 35 of whom received Botox injections (between two and five rounds in the past year) and 44 who were not treated with Botox but may have used other TMJD treatments. Using specialized CT scans, the researchers measured participants' jaw bone density and volume.

The researchers found that jaw bone density and volume were similar between women who had Botox injections to treat their TMJD and those who did not. While most study participants were given relatively low doses of Botox--smaller than in most clinical trials for TMJD--individuals who received higher doses of Botox were more likely to have lower bone density.

Raphael and her colleagues recommend that more human studies be conducted to better understand the impact of the long-term use of Botox on jaw muscles and bones--and whether it just reduces muscle force on bone or also plays a direct role in altering bone resorption.

"Should Botox receive regulatory approval for the treatment of TMJD, we would recommend that a phase IV study be done using low-radiation CT and MRI to track bone- and muscle-related changes with Botox use, examining both dose and long-term use," said Raphael. "Unless specialized imaging of muscle and bone are conducted among patients who receive Botox treatment over long periods, true cumulative effects will remain unknown."

When states turn to private prisons, the number of criminals incarcerated rises and the length of sentences increases.

That's the finding of a new paper from Washington State University researchers just published in the journal Labour Economics, entitled "Do privately-owned prisons increase incarceration rates?"

The study found that private prisons lead to an average increase of 178 new prisoners per million population per year. At an average cost of $60 per day per prisoner, that costs states between $1.9 to $10.6 million per year, if all those additional prisoners are in private prisons.

The length of sentences also increases when private prisons come into a state, especially in nonviolent crimes that have more leeway in sentencing guidelines.

"Not all crimes are created equally," said Gregmar Galinato, a co-author and professor in WSU's School of Economic Sciences. "For crimes like property damage, fraud, or non-violent drug crimes - crimes where judges have more leeway in sentencing - states saw higher sentencing rates and significant increases in sentence lengths when private prisons were established."

The number of new sentences and sentencing lengths weren't affected in violent crime sentences, where judges have less leeway in sentencing, he said.

Galinato wrote the paper with Ryne Rohla, who earned a Ph.D. in Economics from WSU and now works in the Office of the Attorney General for Washington State.

The authors found two potential reasons for the effect of private prisons. The first is corruption, where judges or legislators may be influenced to give out harsher sentences or write laws with harsher penalties.

The most prominent corruption example is the 'kids for cash' scandal in Pennsylvania, where two judges were bribed by a private prison company to give harsher sentences to juvenile offenders instead of probation to increase occupancy at for-profit detention centers.

The other potential reason for the findings is increased capacity.

"If a judge knows prisons are at or over capacity, he or she is likely more hesitant to send marginal criminals to prison," Galinato said. "But when you have private prisons that don't have capacity concerns, that induces more people to be incarcerated."

Galinato doesn't normally study prisons, but has studied corruption in previous research. In 2015, he was watching Elementary, a television show re-imagining Sherlock Holmes stories, and saw an episode about private prison corruption. That inspired him to do some basic research, which is when he learned about the 'kids for cash' scandal.

"I saw the corruption angle and thought 'I can model this,'" he said.

Galinato hopes the paper influences government officials to consider the costs and the benefits when thinking about expanding private prisons.

"We aren't saying private prisons are bad," he said. "But states need to be careful with them. If your state has previous and regular issues with corruption, I wouldn't be surprised to see laws being more skewed to give longer sentences, for example. If the goal is to reduce the number of incarcerated individuals, increasing the number of private prisons may not be the way to go. One can study sentencing reform and even anti-corruption policies that improve the efficacy and fairness of judicial outcomes."

Although people have been questioning the role of private prisons in mass incarceration in the U.S. for many years, Galinato saw no published research that rigorously estimates the causal effect between such prisons and incarceration rates.

That's because comparing the growth of private prisons to increases in incarceration rates could be related in a different way: increased crime could mean more private prisons are necessary to hold them. Although Galinato and Rohla started working on the paper in 2015, it took them several years to account for that possible bias in the research.

Once they factored that in, while going through thousands of papers about privatization, the data still showed private prisons led to more prisoners and longer sentences.

"It was very hard work, and we found out why nobody has done this work before," Galinato said. "But we hope this has an impact and gives lawmakers something to think about when considering bringing in or adding private prisons."

DETROIT - Patients on immunosuppressive therapy for common skin and rheumatic diseases like psoriasis and rheumatoid arthritis are not at increased risk for contracting COVID-19 and should continue taking their medicine as prescribed, say Henry Ford Health System dermatology researchers in a study published in the Journal of the American Academy of Dermatology.

Most of these patients are not at any greater risk for COVID-19 than the general population, despite their weakened immune system, says Jesse Veenstra, M.D., Ph.D., a Henry Ford dermatologist and the study's lead author. He says the findings should reassure patients and doctors alike.

"If you require an immune suppressant medication for your condition to be well controlled, you should not be afraid to continue that medication during the pandemic," Dr. Veenstra says.

The study is one of the first to analyze the association between immunosuppressive medications for skin diseases and the risk of COVID-19 infection and outcomes. Until recently, little was known about managing patients on these medications in the pandemic and whether they may be at increased risk for infection with COVID-19 or related complications because of their weakened immune system.

Dr. Veenstra and his research colleagues conducted a retrospective analysis of 213 patients who were taking immunosuppressive medication for an immune-mediated inflammatory disease. The patients were tested for COVID-19 between Feb. 1 and April 18 and had been receiving immunosuppressive medication for at least one month prior to being tested for COVID-19.

Key findings from their analysis:

Of the 213 patients, 36% tested COVID-19 positive and had no greater odds of being hospitalized or placed on a ventilator than the general population.

There was no evidence that any single immunosuppressive medication increased a patient's odds for testing positive or developing serious disease.

Race was a predictor for COVID-19 status, with African Americans having greater odds of testing positive.

Patients prescribed a TNF alpha inhibitor had significantly lower odds for hospitalization. TNF alpha inhibitors are part of a class of immunosuppressive biologics used to stop inflammation.

Conversely, Dr. Veenstra says, patients who were on multidrug therapy regimens were at greater odds of being hospitalized than those taking a single medication. Dr. Veenstra says more research is needed to fully explain this finding, but it may suggest that multiple medications further suppress a patient's immune system, thus rendering them more susceptible to COVID-19.

Generally, patients who are immunosuppressed are predisposed to upper respiratory infections like the common cold, which may cause coughing, a runny nose and a sore throat. To date, however, this patient population has not been reported to be at higher risk for COVID-19. Older adults and people with underlying medical conditions like cancer, COPD and diabetes are considered high risk for contracting the coronavirus.

"Physicians who prescribe these medications should feel comfortable either continuing or resuming their patients on these medications," Dr. Veenstra says. "They can counsel their patients that there's data to support the safety profile of these medications during the COVID-19 pandemic."

Henry Ford dermatologists treat one of the largest patient populations in Michigan for inflammatory skin diseases like psoriasis, eczema and lupus, prompting researchers to examine whether the immunosuppressive medications made patients more susceptible to the new, emerging coronavirus.

"Traditionally, you think of these medications putting you at higher risk for infection," Dr. Veenstra says. "With COVID, this is a new type of pathogen, and no one really knows how these medications affect your immune system's ability to deal with the infection. The question is, do these medications put you at greater risk for contracting COVID, and if you did get it, would you be sicker because of these medicaitons."

An Analysis of High School Mission Statements in Massachusetts from 2001 to 2019, research conducted by team from Boston College and Wesleyan University, found that 95 percent of Mass. high schools altered or changed their mission statement during the timeframe. Examined in the context of local, state, and federal educational reform efforts, these results indicate that schools can fluidly add and expand new themes and competencies in response to community needs; however, the results also suggest that most schools had increased their scope and purpose without relinquishing any of their past objectives. The rare exception observed by the researchers was a 14-percent drop in school mission statements describing student's physical development.

"This study, the first to examine changes to school mission statements over time, provides tangible, empirical evidence that schools are expecting more of our students and our communities are expecting more from our schools," said study co-author Damian Bebell, assistant research professor at Boston College's Lynch School of Education and Human Development.

Wesleyan University's College of Education Studies Co-chair and study co-author Steven E. Stemler noted: "When school mission statements are systematically coded and analyzed, they reveal important differences in school priorities, reinforcing that today's high schools face considerable challenges in their effort to address an ever-increasing set of themes."

In 2019, the average high school exhibited 6.2 unique and different themes in their mission, a statistically significant increase from 5.1 themes in 2001. Common themes and objectives across school missions were categorized and analyzed to explore shifts and patterns in school purpose over the first decades of the 21st century.

Using a coding rubric that examined 12 of the most common mission statement themes, the researchers found the most prevalent themes in 2019 were students' emotional development (91 percent), cognitive development (86 percent), and civic development (67percent) across their random sample of 45 Massachusetts public high schools. Additionally, the researchers saw an increase in career preparation, rising from 19 percent of school in 2001 to 38 percent in 2019. Another notable change during this 18-year period was schools' increased descriptions of their environment as challenging (38 percent in 2001 to 62 percent in 2019).

Falls are the leading cause of fatal injuries in older adults, causing more than 800,000 hospitalizations and about 30,000 deaths in the U.S. every year. Some risk factors are well-known -- advanced age, problems with vision or balance, muscle weakness -- but an under-recognized factor is early Alzheimer's disease. Older people in the earliest stages of Alzheimer's, before cognitive problems arise, are more likely to suffer a fall than people who are not on track to develop dementia.

Researchers at Washington University School of Medicine in St. Louis have found that, in older people without cognitive problems who experience a fall, the process of neurodegeneration that leads to Alzheimer's dementia already may have begun. The findings, available online in the Journal of Alzheimer's Disease, suggest that older people who have experienced falls should be screened for Alzheimer's and that new strategies may be needed to reduce the risk of falling for people in the disease's early stages.

"In the world of fall research, we generally say that you're at risk of falling if you lose strength and balance," said co-senior author Susan Stark, PhD, an associate professor of occupational therapy, of neurology and of social work. "If you lose strength and balance, the recommended treatment is to work on strength and balance. But if someone is falling for another reason, maybe because his or her brain has begun accumulating Alzheimer's-related damage, that person might need a different treatment entirely. We don't yet know what that treatment might be, but we hope we can use this information to come up with new treatment recommendations that will reduce the risk of falls in this population."

In 1987, John C. Morris, MD, then a trainee at Washington University, discovered that older people with Alzheimer's dementia are more than twice as likely to suffer a traumatic fall than people of the same age without dementia. Morris is now the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology and head of the university's Charles F. and Joanne Knight Alzheimer's Disease Research Center.

Since Morris' discovery more than three decades ago, scientists have learned that the brains of Alzheimer's patients start undergoing changes decades before memory loss and confusion become apparent. First, plaques of amyloid proteins form, then tangles of tau protein. Some brain areas begin to shrink, and communication networks between distant parts of the brain start to decay. Stark and colleagues have shown that the link between Alzheimer's and falling holds true even during the silent phase of the disease: People with so-called preclinical Alzheimer's are at increased risk of falling despite having no apparent cognitive problems.

To better understand why people without cognitive symptoms are at risk of falling, first author Audrey Kelemen, a graduate student in Stark's lab, and colleagues followed 83 people over age 65 for a year. All participants were assessed as cognitively normal by a qualified neurologist at the beginning of the study. Each participant filled out monthly calendars recording any falls and underwent brain scans for amyloid and for signs of atrophy and impaired connectivity.

The researchers discovered that the presence of amyloid in the brain alone did not put people at increased risk of falling but that neurodegeneration did. Participants who fell had smaller hippocampi -- brain regions that are devoted to memory and that shrink in Alzheimer's disease. Their somatomotor networks -- webs of connections that are involved in receiving sensory inputs and controlling movement ­-- also showed signs of decay. The researchers concluded that falling is most likely to occur in the neurodegeneration phase of preclinical Alzheimer's -- the last five years or so before memory loss and confusion arise.

"Since I started working on this project, I've started asking my patients about falls, and I can't tell you how often that has helped me start understanding what is going on with the individual," said co-senior author Beau M. Ances, MD, PhD, the Daniel J. Brennan, MD, Professor of Neurology and a professor of radiology and of biomedical engineering. Ances treats patients who have dementia and other neurological conditions on the Washington University Medical Campus.

"When a person's mobility is being diminished, even though the person looks very normal, that could be a sign that something needs further evaluation," Ances said. "It's actually a really important potential marker that should make us say, 'Wait a minute. Let's dive into this more. Are there other things that go along with it?'"

The researchers have begun further experiments to better understand why brain changes in Alzheimer's put people at risk of falling, so they can develop fall-prevention recommendations. In the meantime, simple changes could go a long way toward protecting older people from devastating falls, Stark said.

"You can prevent a lot of falls just by making the environment safer," Stark said. "Simple changes could help and can't hurt: making sure the tub isn't slippery; making sure you can get up easily off the toilet; balance and strength training; reviewing your prescriptions to see if certain medications or combinations of medications are increasing the risk of falling. Until we have specific fall-prevention treatments for people with preclinical Alzheimer's, there are still plenty of things we can do to make people safer."

HSE University researchers have found microRNA molecules that are potentially capable of repressing the replication of human coronaviruses, including SARS-CoV-2. It turns out that the virus uses miRNA hsa-miR-21-3p to inhibit growth in the first stages of infection in order to delay the active immune response. The results of the research have been published in the journal PeerJ.

After the virus gets inside the cell, it starts actively interacting with various in-cell molecules. One such molecule class is microRNAs (miRNAs), which are small RNAs whose main function is to regulate gene expression. When a virus enters, miRNAs start binding certain parts of its genome RNA, which leads to the destruction of virus RNAs. Such an attack can stop virus replication completely. However, in cases when miRNAs are not very 'aggressive', such interactions do not destroy the virus but rather slow down its replication. This scenario is beneficial for the virus since it helps avoid a fast immune response in the cell. And some of the viruses purposefully accumulate host miRNA binding sites. This becomes their advantage: viruses with more binding sites survive and reproduce better, which leads to their evolutionary domination.

Researchers from the HSE Faculty of Biology and Biotechnology, Stepan Nersisyan and Alexander Tonevitsky, together with first-year students Narek Engibaryan, Aleksandra Gorbonos, Ksenia Kirdey, and Alexey Makhonin, detected cell miRNAs that are able to bind coronavirus genomes.

There are seven types of human coronaviruses in total. Four of them (HCoV-OC43, HCoV-NL63, HCoV-HKU1 and HCoV-229E) are widespread and cause the common cold, while viruses MERS-CoV, SARS-CoV and SARS-CoV-2 can cause dangerous atypical pneumonia. The researchers found four families of human miRNAs with detected binding sites with all the viruses under consideration.

The image shows miRNA binding sites hsa-miR-21-3p and hsa-miR-421, which are mutual for six out of seven human coronaviruses.

To find out how the virus can interact with the detected miRNAs, the researchers analysed the available data on miRNA sequences in lungs of mice infected with SARS-CoV. They discovered that the infection leads to an 8-fold increase in the expression of the previously detected miRNA hsa-miR-21-3p.

'MiRNA hsa-miR-21-3p has big potential for binding all human coronaviruses. But after infection with SARS-CoV, the concentration of this miRNA in the lungs grows a lot. If we assume that this is a mechanism of immune response, it is unclear why the virus does not eliminate the binding sites with cell miRNAs in the process of mutation. On the contrary, we see that the virus 'accumulates' them in its genome during the evolution - our research demonstrates that such sites are present in all human coronaviruses and do not mutate considerably. We suppose that this way the virus uses this miRNA to slow down its replication in the early stages of infection in order to delay the active immune response,' Stepan Nersisyan said.

The next step of the team's research will be experimental verification of their discoveries. The researchers are also planning to investigate the possibility of medicinal effect on the virus that targets the discovered miRNAs. In particular, they plan to determine whether their artificial introduction or elimination is able to prevent virus reproduction.

A new study comprehensively reveals how civil wars impact wildlife in countries affected by conflict.

Researchers at the University of East Anglia (UEA), in the UK, Federal University of Paraíba (UFPB), Brazil, and University of Agostinho Neto (UAN), Angola, found that the main impacts of civil wars on native mammals are often indirect, ultimately arising from institutional and socio-economic changes, rather than from direct military tactics.

Increased access to automatic weapons and suspension of anti-poaching patrols were leading causes of wildlife population collapse, while installation of military bases within core conservation areas, overhunting of large-bodied mammals, and new settlements of displaced refugees also strongly impacted species.

Published today in the journal Nature Scientific Reports, the study suggests that civil wars in low-governance countries can have both positive and negative impacts on native wildlife populations depending on space and time scales, but the overall trend is negative.

The authors warn that even during post-war peace times, wild mammal populations will fail to recover as long as rural people living in war-torn countries remain armed and wildlife management regulations cannot be enforced. They call for robust international policies that can prevent the consequences of warfare, warning that restoring depleted wildlife populations may take many decades and require active intervention efforts.

Civil wars often coincide with global biodiversity hotspots, however little is known about how they affect wildlife. This study drew local ecological knowledge to assess for the first time the main consequences of a prolonged civil war in Southwest Africa on forest and savannah mammals, using Angola as a case study. The country is home to at least 275 species of mammals, many of them historically hunted by the local communities before, during and after the intermittent 27-year Angolan civil war (1975-2002).

In Angola's main protected area, Quiçama National Park and Quiçama Game Reserve, the abundance of 20 out of 26 wild mammal species studied was 77 per cent lower after the war compared to the pre-war baseline, particularly for large-bodied species such as elephants in open-savannah environments. Significantly, this decline was not reversed by the end of the post-war period (2002-2017).

Franciany Braga-Pereira, a Zoology PhD candidate at UFPB, led the study. Ms Braga-Pereira said: "Currently, 36 countries worldwide are experiencing civil wars and most of these conflicts are either fuelled or funded by international interests or began after an external intervention.

"These internationalized conflicts are more prolonged and less likely to find a political resolution. Therefore, considering measures that can reduce the impact of warfare on wildlife, we emphasize the intentional or inadvertent complicity of foreign powers, which should promote policies that mitigate the detrimental environmental impacts of armed conflicts."

Co-author Prof Carlos Peres, from UEA's School of Environmental Sciences, said: "Low-governance developing countries are struggling as it is, even during peacetimes, to protect their wildlife resources, never mind the colossal adverse consequences of breakdown in law-and-order brought about by a civil war. Yet there are no adequate international mechanisms to deploy peace forces to maintain the status quo of vulnerable wildlife populations in troubled parts of the world."

The research involved interviews with expert local hunters, which revealed that large-bodied mammals, such as red buffalo, kudu and red sable, were preferred targets that had been overhunted during the war. As their populations became increasingly depleted, the size structure of prey species gradually shifted towards smaller-bodied species, for example bushpig, bushbuck kewel and blue duilker, during the post-war period. However, once the depletion in forest was lower than in the savannah, hunters operating in forest areas were occasionally able to kill larger species in the post-war period.

In their model of how civil wars impact wildlife, the authors explain that civil war could be a double-edged sword, resulting also in declines in extractive industries such as oil, mining and agribusiness, which can benefit wildlife, and demilitarized and landmine zones, which severely discourage human settlements and game hunters, thereby creating potential game refuges as passive 'no-take' areas.

Research from the University of Kent has found that TRESK, a calcium regulated two-pore potassium channel, regulates the brain's central circadian clock to differentiate behaviour between day and night.

It was previously understood that the brain's circadian clock, otherwise known as the suprachiasmatic nucleus (SCN), depends on multiple mechanisms to ensure rhythmic electrical activity that varies between day and night. Yet, this research has clarified that TRESK plays a crucial role in this system. The mechanism was previously unknown.

The study, led by Dr Gurprit Lall at the Medway School of Pharmacy and colleagues at the University of Oxford, investigated the role of TRESK in the brain's central circadian clock and found that when TRESK levels were reduced the biological rhythm was disrupted.

The brain's circadian clock is usually active during daylight and not during the night. When the absence of TRESK was explored in the study, the clock had lost its day and night association and did not sense light. This further identifies that not only does TRESK affect cell membrane activity, it affects response behaviour and the clock's communication to the body. Humans need this to perform efficiently.

Dr Lall said: 'This research has shown that TRESK is key to SCN function, regulating multiple aspects of SCN neurophysiology. TRESK provides a clear delineation of light responses between the day and night. It maintains the SCN in the appropriate state for nocturnal light-induced behavioural changes. These findings are significant to future research into how the circadian clock responds to environmental stimuli.'

PITTSBURGH, Sept. 14, 2020 - University of Pittsburgh School of Medicine scientists have isolated the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 virus, which is the cause of COVID-19. This antibody component, which is 10 times smaller than a full-sized antibody, has been used to construct a drug--known as Ab8--for potential use as a therapeutic and prophylactic against SARS-CoV-2.

The researchers report today in the journal Cell that Ab8 is highly effective in preventing and treating SARS-CoV-2 infection in mice and hamsters. Its tiny size not only increases its potential for diffusion in tissues to better neutralize the virus, but also makes it possible to administer the drug by alternative routes, including inhalation. Importantly, it does not bind to human cells--a good sign that it won't have negative side-effects in people.

Ab8 was evaluated in conjunction with scientists from the University of North Carolina at Chapel Hill (UNC) and University of Texas Medical Branch (UTMB) at Galveston, as well as the University of British Columbia and University of Saskatchewan.

"Ab8 not only has potential as therapy for COVID-19, but it also could be used to keep people from getting SARS-CoV-2 infections," said co-author John Mellors, M.D., chief of the Division of Infectious Diseases at UPMC and Pitt. "Antibodies of larger size have worked against other infectious diseases and have been well tolerated, giving us hope that it could be an effective treatment for patients with COVID-19 and for protection of those who have never had the infection and are not immune."

The tiny antibody component is the variable, heavy chain (VH) domain of an immunoglobulin, which is a type of antibody found in the blood. It was found by "fishing" in a pool of more than 100 billion potential candidates using the SARS-CoV-2 spike protein as bait. Ab8 is created when the VH domain is fused to part of the immunoglobulin tail region, adding the immune functions of a full-size antibody without the bulk.

Abound Bio, a newly formed UPMC-backed company, has licensed Ab8 for worldwide development.

Dimiter Dimitrov, Ph.D., senior author of the Cell publication and director of Pitt's Center for Antibody Therapeutics, was one of the first to discover neutralizing antibodies for the original SARS coronavirus in 2003. In the ensuing years, his team discovered potent antibodies against many other infectious diseases, including those caused by MERS-CoV, dengue, Hendra and Nipah viruses. The antibody against Hendra and Nipah viruses has been evaluated in humans and approved for clinical use on a compassionate basis in Australia.

Clinical trials are testing convalescent plasma--which contains antibodies from people who already had COVID-19--as a treatment for those battling the infection, but there isn't enough plasma for those who might need it, and it isn't proven to work.

That's why Dimitrov and his team set out to isolate the gene for one or more antibodies that block the SARS-CoV-2 virus, which would allow for mass production. In February, Wei Li, Ph.D., assistant director of Pitt's Center for Therapeutic Antibodies and co-lead author of the research, began sifting through large libraries of antibody components made using human blood samples and found multiple therapeutic antibody candidates, including Ab8, in record time.

Then a team at UTMB's Center for Biodefense and Emerging Diseases and Galveston National Laboratory, led by Chien-Te Kent Tseng, Ph.D., tested Ab8 using live SARS-CoV-2 virus. At very low concentrations, Ab8 completely blocked the virus from entering cells. With those results in hand, Ralph Baric, Ph.D., and his UNC colleagues tested Ab8 at varying concentrations in mice using a modified version of SARS-CoV-2 . Even at the lowest dose, Ab8 decreased by 10-fold the amount of infectious virus in those mice compared to their untreated counterparts. Ab8 also was effective in treating and preventing SARS-CoV-2 infection in hamsters, as evaluated by Darryl Falzarano, Ph.D., and colleagues at the University of Saskatchewan. Sriram Subramaniam, Ph.D., and his colleagues at the University of British Columbia uncovered the unique way Ab8 neutralizes the virus so effectively by using sophisticated electron microscopic techniques.

"The COVID-19 pandemic is a global challenge facing humanity, but biomedical science and human ingenuity are likely to overcome it," said Mellors, also Distinguished Professor of Medicine, who holds the Endowed Chair for Global Elimination of HIV and AIDS at Pitt. "We hope that the antibodies we have discovered will contribute to that triumph."

PULLMAN, Wash. - More political candidates may be shifting primarily to social media to advertise rather than TV, according to a study of advertising trends from the 2018 campaign season. The study, published recently in American Political Science Review, also found that Facebook political ads were more partisan, less negative and less issue-focused than those on TV.

"The 2018 race showed that social media can be helpful to candidates who may not have a lot of resources, including challengers and those who are not already well known," said Travis Ridout, Washington state University political science professor and a corresponding author on the study. "It allows them to get their messages out."

Facebook ads are more practical for many down-ballot candidates who cannot afford the high price of TV advertising, Ridout added. A much broader range of candidates also used Facebook ads than TV.

Ridout along with co-authors from Bowdoin College, and Emory, Stanford and Wesleyan universities, analyzed Facebook and TV advertising data for nearly 7,300 candidates in the 2018 federal and state level races. They found that the vast majority, about 6,000, only advertised on the social media platform. A little more than 1,000 candidates used both Facebook and TV advertising. Only 242 relied on TV ads alone. The study focused on advertising by candidates' campaigns as opposed to advertising by political action committees, also known as PACs, and other outside groups.

While Facebook's affordability was an equalizing factor, the researchers also noted that the platform's ability to target ads often limits the audience--which may explain why Facebook political ads tended to be more partisan and contained less information about actual issues. The candidates appeared to be using Facebook to speak to their supporters. They used TV to reach undecided voters.

"TV political advertising is almost always about persuasion. It's 'vote for me' or 'don't vote for the other candidate'," said Ridout. "There's some of that persuasion on Facebook too, but there are more fundraising ads and acquisition ads that urge voters to 'take this survey' or 'provide your email address'. The other purpose is for mobilization: encouraging supporters to register to vote, attend a campaign rally or find their polling place."

The Facebook ads also tended to avoid the double-edged sword of negative advertising. According to Ridout, negative ads can make people who might have supported an opponent decide to stay home on election day, but they can also make some of those same voters angry, encouraging them to go to the polls. These types of ads still appeared more often on TV than social media in 2018.

Given the "emotional gut punch" TV is able to deliver more effectively than Facebook, and the many older avid voters who still watch television, Ridout doesn't expect TV political ads to go away any time soon. Still, during the 2020 campaign and in the future, the political scientist expects to see campaigns put more money put into social media, and that comes with its own set of problems.

"As more of us are getting messages from politicians online, as opposed to through television, it portrays a world for us in which things are more partisan," Ridout said. "Misinformation policies on social media also don't seem to be equally enforced. Sometimes they are enforced for small fry, but for rich candidates, they will just rewrite the rules. We may be handing a lot of power to Google and to Facebook in particular, to make really big decisions about how Americans are informed prior to election day."