Culture

A research team led by Michael Fox, a professor at the Fralin Biomedical Research Institute at VTC, has identified the type of brain cell that produces collagen 19, a protein that is crucial for the formation of inhibitory circuits in the brain.

The study, published in the Journal of Neuroscience, depicts a previously unknown molecular mechanism underlying healthy brain development.

Neurons and glia are the most abundant types of brain cells. Glia, in particular star-shaped glia called astrocytes, release signaling molecules that support the growth and maintenance of healthy synapses, the chemical communication structures between neurons.

Yet in this study, Fox's team discovered that a type of interneuron, a cell type that interprets and relays information sent from other neurons, produces the majority of brain-derived collagen 19 to stimulate synapse formation.

"At a time when many studies are identifying interneuron-like roles for astrocytes, we've identified an unexpected astrocyte-like role for interneurons," said Fox, who is also the director of the School of Neuroscience in Virginia Tech's College of Science.

In previous research, Fox’s team discovered that mice lacking the gene that encodes collagen 19 exhibit a loss of inhibitory synapses surrounding neuronal cell bodies located in the brain's hippocampus and neocortex. In humans, these brain regions are involved in cognitive functions, such as reasoning, language, perception, memory, and learning. They have also been shown to play roles in sensory perception, memory, and learning in mice.

Excessive excitatory connections between neurons in these brain areas could explain why mice with this genetic mutation are more prone to develop seizures and behavioral abnormalities. This gene has also been associated with neuropsychiatric disorders in humans. In particular, it's been suggested that loss of this gene in humans could be associated with familial cases of schizophrenia, a brain disorder that afflicts more than 2 million Americans, according to the National Institute of Mental Health.

But Fox's earlier discovery about the importance of collagen 19 beckoned another question: Where does this protein come from?

In the new study, the scientists used riboprobes - small segments of ribonucleic acids (RNA) that bind to complementary segments of RNA - to look for different cell type markers in normal mice, wild-type, and mice with the genetic mutation. This method revealed that the majority of brain-derived collagen 19 is produced by a type of interneuron.

This interneuron type is one of the first to develop in the neocortex and it plays a role in helping surrounding synaptic circuits mature. In this case, after this type of interneuron releases collagen 19 molecules, the proteins serve as a signal that instructs another abundant type of interneuron to produce inhibitory synapses.

"Initially when we proposed this, some people thought it was far-fetched that one neuron could influence another cell's development when they're not synaptically coupled," Fox said.

Roughly 20 percent of a person's body mass is made of collagens, which form the matrix of connective tissue that wraps around organs, muscles, and cellular structures. Because of the complex molecular structure of collagens, just a small genetic variation alters the protein's shape, rendering the collagen molecule useless waste that cells destroy and recycle for parts.

Collagen genetic mutations are linked to a litany of connective tissue disorders, but Fox says they're still underexplored in the brain.

"What keeps me interested in this project is that we know so little about the role that extracellular matrix proteins like collagen 19 play in mediating healthy circuit formation," Fox said. "When you're a student taking a neuroscience class, you'll often learn that the brain doesn't have a lot of connective tissue in it, but we're finding more and more that the presence of these extracellular matrix proteins actually seems to lay the foundation for healthy brain development."

Fox's lab plans to build on this discovery by working to develop new ways to restimulate inhibitory synapse growth in diseased or injured brains. The team previously found that a small peptide derived from this collagen, matricyptin, is sufficient to promote the growth of inhibitory synapses in cells lacking collagen 19.

"We want to translate what we're learning about how these circuits develop into therapeutics," Fox said. "We've found a peptide that shows some promise in stimulating inhibitory synapse formation and are studying ways to employ it."

WASHINGTON -- A new method for visualizing breath that is exhaled while someone is speaking or singing could provide important new insights into how diseases such as COVID-19 spread and the effectiveness of face masks.

"Scientists believe the SARS-CoV-2 virus is primarily spread through respiratory droplets that can be carried in the breath or expelled through coughing or sneezing," said Thomas Moore from Rollins College, who performed the research. "But it is also transmitted by airborne aerosols, which are small particles that remain in the air longer than the larger droplets. The system I developed provides a way to estimate how far the breath travels before being dispersed into the surrounding air and can provide visual evidence that masks significantly limit the distance the breath travels in the air."

In The Optical Society (OSA) journal Applied Optics, Moore describes how he used a variation of electronic speckle pattern interferometry to image temperature differences between exhaled breath and the surrounding air. The new technique can also be used to study the details of how breath flows from the mouth while speaking or singing, which could be useful for music instruction and speech therapy.

From musical instruments to people

Moore originally developed the imaging technology to study the flow of air through musical instruments such as organ pipes. "In response to the COVID-19 pandemic, I began imaging the breath of people speaking and singing," he said. "I realized that by scaling up my existing system, I could likely determine how far the breath extends and how effective masks may be in limiting the extent of the breath."

Most existing approaches used to image exhaled breath require expensive equipment and can image only a relatively small area. Moore designed a system that uses common commercially available optical components to overcome these limitations.

"I used a variation of electronic speckle pattern interferometry, which has been used for many years to study the vibrational patterns of solid objects," said Moore. "The innovation was to change the system in such a way that it can be used to image transparent things, such as the breath, instead of solid vibrating objects."

The imaging system uses the fact that the speed of light will change depending on the temperature of air it passes through. Because the breath is warmer than the surrounding air, the light transmitted through the breath arrives at the camera slightly sooner than light that did not pass through it. This slight difference in the speed of light can be used to create images of exhaled breath.

Moore tested the new system by imaging the breath of two professional vocalists singing and a professional musician playing a flute, one of the few instruments where the musician blows directly into the surrounding air. "The work with the musicians immediately confirmed that the system worked well and could be used to study a variety of problems," he said.

Changing the air flow

Moore is currently using the method to study how effective masks are at reducing the distance that exhaled aerosols travel. He is especially interested studying singing because research indicates that more aerosol is exhaled while singing or speaking loudly than when speaking normally. He is also working to make the system more stable against vibrations and to further increase the size of the system to image larger areas.

Moore says that the technique has already revealed new information that may affect how we approach distancing and masking requirements, especially when outdoors. He expects to submit these results for publication soon.

"The pandemic has caused an economic catastrophe for many musicians, and any information we can give them that will help them get back to work is important," said Moore. "We have had a lot of interest from the musical community, and I expect the healthcare community will also be interested once we begin to publish our results."

DETROIT (December 21, 2020) - With the Michigan high school and collegiate sports season influx due to the COVID-19 pandemic, a study by Sports Medicine researchers at Henry Ford Health System provides a new perspective on performance levels of female professional athletes after they return from anterior cruciate ligament (ACL) injury and reconstructive surgery.

The study published in the Orthopaedic Journal of Sports Medicine found that players in the Women's National Basketball Association didn't regain their elite performance level for at least two years after injury. That's about a year longer than players in the National Basketball Association who suffered the same injury. Additionally, WNBA players had significantly lower performance numbers in games played, games started, minutes played, points scored, rebounds, assists and blocked shots during the season in which they returned to play.

The Henry Ford Sports Medicine research team that included Lafi Khalil, M.D., and lead author Joseph Tramer, M.D., noted that the findings are important for both players and coaches to set reasonable expectations for returning , not only at the professional level but also at collegiate and high school levels.. Numerous studies have identified many causes that contribute to high rates of ACL injuries in female athletes including differences in lower extremity muscle activation, joint laxity, neuromuscular control, knee anatomy and hormonal factors.

"The data on WNBA players' ACL tears and reconstruction has been previously studied, but what previous investigations did not evaluate is the performance levels after returning from these injuries," said Kelechi Okoroha, M.D., the study's senior author. "The players we studied were back playing after seven months, but the statistical data revealed that they didn't return to their previous performance numbers on the court until their second or third year back on the court."

Orthopedic studies confirm that female athletes are 2 to 10 times more likely to sustain an ACL tear than male athletes, depending on the sport. With basketball players, females are at 2 to 7 times greater risk.

The ACL is an important ligament in stabilizing the knee and many professional athletes' season have come to a sudden end thanks to this very common injury. In the U.S., approximately between 100,00 and 200,000 ACL ruptures occur annually. ACL reconstructions are among the most common sports medicine procedures performed, numbering about 100,000 each year.

In this retrospective study, researchers evaluated ACL injuries in 59 WNBA players from 1997-2018 and their impact on their return to sport and performance level. Data was collected for each player before and after injury to assess changes in playing time and statistical performance. Players who returned to play after ACL reconstruction were compared with their uninjured counterparts.

Key performance findings on average in the first year after surgery:

Games played decreased from 69.6 to 57

Minutes played decreased from 23.4 to 18.4

Points per game decreased from 10.2 to 6.5

Dr. Okoroha has led similar respective performance studies of NBA, NFL and MLB male athletes and thinks this research of female athletes is important in comparing the information and accurately counseling athletes returning from ACL injury.

"In comparison, the WNBA players returned to competition at a lower rate (69.5%) than NBA players with similar injuries (88.9%) and their performance numbers were measuredly lower once they returned," said Dr. Okoroha.

As a former college basketball player and team captain at Xavier University of Louisiana, Dr. Okoroha also brings a player's perspective on the implications of ACL injuries, "Some of my teammates suffered ACL ruptures. These are devastating injuries that not only impact a player's morale and outlook but also require a great deal of mental and physical work to return to previous performance levels," said Dr. Okoroha.

WHAT:

Reston ebolavirus (RESTV) should be considered a livestock pathogen with potential to affect other mammals, including people, according to National Institutes of Health scientists. The caution comes from a study published in Proceedings of the National Academy of Sciences in which the scientists found that experimental piglets infected with RESTV developed severe respiratory disease and shed the virus from the upper respiratory tract. RESTV can infect humans but is not known to cause disease. Now the scientists express concern that pigs could serve as an "interim or amplifying host for ebolaviruses."

"The emergence of RESTV in pigs is a wake-up call as transmission into humans through direct contact with pigs or the food chain is a possibility," they state in their study report. Scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) conducted the work at Rocky Mountain Laboratories in Hamilton, Montana.

Scientists first identified RESTV in 1989 in research monkeys shipped from the Philippines to Reston, Virginia. The virus also gained attention in 2008 when an outbreak swept through pigs in the Philippines. That outbreak led to the first association of pig-to-human RESTV transmission, prompting the World Health Organization to issue a global alert in February 2009. RESTV sequences also have been identified in pigs in China, and the scientists suggest officials monitor pigs for disease throughout the Philippines and Southeast Asia.

The NIAID scientists conducted their study to answer two key questions: could they cause disease in young pigs--mimicking natural infection with RESTV isolated from the 2008 swine outbreak--and if so, would those pigs shed virus through their respiratory tract? Their work confirmed that in fact the pigs developed severe pneumonia with virus shedding from the upper respiratory tract. They also determined that the age of the piglets at the time of infection--they used animals between three and seven weeks old--did not change the course of disease. Their work involved Yorkshire cross-bred pigs, which frequently are used in commercial pig production systems. RESTV has not been found in commercial pigs in the United States.

Continued studies in this project will examine whether co-infection with other swine viruses affects the ability of RESTV to cause severe disease in pigs and whether pigs have a broad role in hosting ebolaviruses.

Cleveland - Child care programs can be safe within the context of low community transmission of COVID-19, according to new research from Case Western Reserve University, based on data from child care programs throughout Ohio.

The study took place from Aug. 15 to Nov. 20, during a timeframe of relatively low community transmission of COVID-19. The team found COVID-19 infection rates at child care programs have been low as a result of:

clear and comprehensive state guidelines for mitigating transmission within child care settings;

streamlined reporting of cases to monitor trends;

resources to support adherence to state guidelines; and

high compliance with these guidelines by child care workers and families.

The Case Western Reserve study was funded by the Ohio Bureau of Workers' Compensation (BWC) and supported by the Ohio Department of Job and Family Services (ODJFS). The study relied on a sample of child care facilities that mirrors a mix of urban, suburban, and rural settings found across the country, offering insight into child care experiences nationally.

Additional findings from the ongoing study will provide another look as community transmission rates rise, with data collection continuing until the end of December. These new findings will be released in early 2021.

"We all have seen reports from across the country of vast numbers of parents--mostly women--dropping out of the workforce during the pandemic to care for their children as schools and child care facilities closed," said Darcy Freedman, professor of Population and Quantitative Health Sciences at the Case Western Reserve School of Medicine and director of the Mary Ann Swetland Center for Environmental Health, who served as the principal investigator of the study. "How to reopen and stay open safely is important to tens of thousands of families across the state and hundreds of thousands of families across the country."

The findings show that child care programs in Ohio may have had higher readiness to handle COVID-19 than other sectors of the economy because of already-existing standards designed to promote safe and healthy environments, Freedman said. These, combined with statewide infection control guidelines adopted with high compliance by child care workers and families, resulted in lower levels of COVID-19 transmission within child care settings during the study's initial phase through early November.

But Freedman cautioned that additional supports, such as steady access to affordable personal protective equipment (PPE) and sanitizing materials, may be needed for child care programs to remain vigilant as the COVID-19 epidemic continues.

Case Western Reserve researchers note that public health officials anticipate that even with the distribution of a vaccine, communities across the country may continue to see consistent low to moderate community transmission rates through 2021.

From the start of the pandemic in March 2020 until Nov. 13, less than 1% of all COVID-19 cases in Ohio were among child care workers and children affiliated with child care programs, based on incident reporting from child care programs to ODJFS. During most of the study's timeframe, COVID-19 positivity rates in Ohio were below the 5% threshold used to establish low risk of community transmission. COVID-19 positivity rates in Ohio began rising above 5% starting Oct. 20.

"Maintaining safety within child care programs requires capacity for staff and families to fully adhere to mitigation strategies, both within child care programs and outside in the community," Freedman said.

More than 6,000 child care programs are licensed in the state. Pre-pandemic, these facilities cared for more than 500,000 children each day. The Case Western Reserve survey of parents participating in this study noted that shuttering child care programs due to COVID-19 transmission would have the following results:

Nearly 75% of families would have to reduce their work hours.

More than half of families--59%--would need one person in the household to leave the workforce to stay home with children.

Key recommendations based on the study findings:

Maintain child care capacity to fully comply with COVID-19 mitigation strategies;

Develop a supply chain for affordable personal protective equipment and cleaning materials, allowing child care programs to uphold rigorous hygiene and sanitizing procedures;

Standardize communication about COVID-19 disseminated through child care programs;

Expand workforce pipeline for child care staffing during the pandemic.

New Rochelle, NY, December 21, 2020--The 2020 Nobel Prize in Physiology or Medicine went to three researchers for their discovery of hepatitis C virus (HCV). The undying perseverance that it took to find and cure this elusive virus is eloquently detailed in the peer-reviewed journal Viral Immunology. Click here to read the article now.

Rodney S. Russell, PhD, Editor-in-Chief of Viral Immunology, from Memorial University of Newfoundland, St. John's, recounts his own research experience with HCV and tells the story of how the virus was discovered.

"The strongest theme I see in the field of HCV research is perseverance," says Dr. Russell. "Finding HCV was not easy, working with HCV was not easy, curing HCV was not easy, and even now, making an effective vaccine against HCV is proving not to be easy. What impresses me most about the thousands of scientists around the world who contributed to the study of this virus, even before it was discovered, was, and still is, their absolute unwillingness to quit."

In order to survive, flourish and successfully reproduce, organisms rely on a high degree of genetic stability. Mutagenic agents, which can threaten the integrity of the genetic code by causing mutations in DNA, pose a serious risk to human health. They have long been implicated in a range of genetically inherited afflictions, as well as cancer, aging and neurodegenerative diseases like Alzheimer's.

It now appears that mutagenic threats to a cell's subtle machinery may be far more widespread than previously appreciated. In a new study, Michael Lynch and his colleagues demonstrate that DNA mutation itself may represent only a fraction the health-related havoc caused by mutagens.

The study highlights the ability of mutagenic compounds to also affect the process of transcription, during which a DNA sequence is converted (or transcribed) to mRNA, an intermediary stage preceding translation into protein.

The research findings, (which highlight mutagenic transcription errors in yeast, worms, flies and mice), suggest that the harmful effects of mutagens on transcription are likely much more pervasive than previously appreciated--a fact that may have momentous implications for human health.

"Our results have the potential to completely transform the way we think about the consequences of environmental mutagens," Lynch says.

Professor Lynch is the director of the Biodesign Center for Mechanisms in Evolution and a researcher in ASU's School of Life Sciences.

The research results appear in the current issue of the journal PNAS.

Cells under threat

Due to their important role in disease processes, mutagenic compounds have long been a topic of intensive scientific study. Such agents include sunlight and other sources of radiation, chemotherapeutics, toxic byproducts of cellular metabolism, or chemicals present in food and water.

Mutagens can inflict damage to the DNA, which can later snowball when cells divide, and DNA replication multiplies these errors. Such mutations, if not corrected through DNA proofreading mechanisms, can be passed to subsequent generations and depending on the location at which they appear along the human DNA strand's three billion letter code may seriously impact health, in some cases, with lethal results.

But even if repaired prior to replication, transiently damaged DNA can also interfere with transcription--the process of producing RNA from a DNA sequence. This can happen when RNA polymerase, an enzyme that moves along a single strand of DNA, producing a complementary RNA strand, reads a mutated sequence of DNA, causing an error in the resulting RNA transcript.

Because RNA transcripts are the templates for producing proteins, transcription errors can produce aberrant proteins harmful to health or terminate protein synthesis altogether. It is already known that even under the best of conditions, transcript error rates are orders of magnitude higher than those at the DNA level.

RNA: a string of errors?

While the existence of transcription errors has long been recognized, their quantification has been challenging. The new study describes a clever technique for ferreting out transcription errors caused by mutagens and separating these from experimental artifacts--mutations caused during library preparation of RNA transcripts through processes of reverse-transcription and sequencing.

The method described involves the use of massively parallel sequencing technology to identify only those errors in RNA sequence directly caused by the activity of a mutagen. The results demonstrate that at least some mutagenic compounds are potent sources of both genomic mutations and abundant transcription errors.

The circular sequencing assay outlined in the study creates redundancies in the reverse-transcribed message, providing a means of proofreading the resultant linear DNA. In this way, researchers can confirm that the transcription errors observed are a result of the mutagen's effects on transcription and not an artifact of sample preparation.

The DNA molecule has been shown to be particularly vulnerable to a class of mutagens known as alkylating agents. One of these, known as MNNG, was used to inflict transcriptional errors on the four study organisms. The effects observed were dose-dependent, with higher levels of mutagen causing a corresponding increase in transcriptional errors.

Hidden mistakes may be costly to health

Transcription errors differ from mutations in the genome in at least one vital respect. While DNA replication during cell division acts to amplify mutations to the genome, transcription errors can accumulate in non-dividing cells, with a single mutated DNA template giving rise to multiple abnormal RNA transcripts.

The full effects of these transcription errors on human health remain largely speculative because they have not been amenable to study until now. Using the new technique, researchers can mine the transcriptome--the full library of a living cell's RNA transcripts, searching for errors caused by mutagens.

While the new research offers hope for a more thorough understanding of the relationship between various mutagens and human health, it is also a cautionary tale. A preoccupation with mutational defects in DNA sequence may have blinded science to the potential effects of agents that result in transcription errors without leaving permanent traces in the genome.

This fact raises the possibility that a broad range of environmental factors as well as chemicals and foods deemed safe for human consumption are in need of careful reevaluation based on their potential for producing transcriptional mutagenesis. Further, transcriptional errors in both dividing and non-dividing cell types are likely key players in the complex processes of physical aging and mental decline.

Conditions causing arrhythmia are among the most common cardiac conditions. A study headed by Prof. Georg Schmidt of the Technical University of Munich (TUM) has demonstrated for the first time that the nocturnal respiratory rate can help with an important prediction: It is an indicator of whether a defibrillator will help to extend the life of patients with arrhythmia.

Sudden cardiac death is one of the leading causes of mortality in western industrialized countries. It can be prevented by an implantable cardioverter defibrillator (ICD). This automatically detects life-threatening heart rhythms and emits electrical signals to stop them. The guidelines recommend the implantation of ICDs in patients with a significantly weakened pump function of the left ventricle. According to the German Heart Surgery Report, more than 42,000 defibrillators were implanted in Germany in 2018.

However, the effectiveness of implanting ICDs is sometimes questionable. The latest Heart Surgery Report by the German Heart Foundation also notes that the benefits of defibrillator therapy are not as clear-cut as previously believed. Moreover, they are often offset by relatively common complications arising both during and after the implantation procedure.

Predictive value of the nocturnal respiratory rate

Researchers at TUM have now demonstrated that the nocturnal respiratory rate of heart patients - which has hitherto received little attention - can help to predict the success of ICD treatment. Between May 2014 and September 2018 they monitored 1,971 heart patients at 44 European heart centers. 1,363 of the patients received an ICD, while the control group was treated conservatively. The different treatment options were dictated by the varying availability of ICD therapy at the participating European centers. Consequently, the study was non-randomized. However, the resulting distortions were compensated for through sophisticated statistical analysis. The study has now been published in eClinicalMedicine, an open-access journal produced by the renowned journal The Lancet.

In both groups the scientists measured the average nocturnal respiratory rate between midnight and 6 am based on an ECG protocol. The ICD patients had a survival advantage of 31.3 percent over the control group. At the same time, a significant link was seen between a low nocturnal respiratory rate and reduced mortality: ICD patients with a rate below 18 breaths per minute had a 50 percent survival advantage as compared to the control group, while those with a higher nocturnal respiratory rate gained no survival advantage through the defibrillator.

A biosignal hitherto neglected by cardiologists

"The breathing rate has been largely ignored as a biosignal in the field of cardiology," says Prof. Georg Schmidt, the last author of the study, who heads the working group for biosignal processing at TUM's university hospital Klinikum rechts der Isar. "Our conclusions will now place a greater focus on this parameter," says Prof. Schmidt, noting that the study demonstrates the predictive value of breathing frequency for therapeutic efficacy. "Especially in borderline cases, checking the patient's breathing rate can help to decide on the right therapy."

Randomized study needed

Against this backdrop, Schmidt, who also chairs the TUM Ethics Commission, believes that it would be reasonable to aim for a randomized study versus the established guidelines. "This would involve dividing the patients observed to gain no advantage from the ICD in our study into two groups, with one having an ICD implanted and the other receiving conservative treatment. If a randomized study of this kind reveals that heart patients with a higher nocturnal breathing rate do not benefit from the ICD implant, they could be spared this invasive treatment in the future."

RIVERSIDE, Calif. -- A research team at the University of California, Riverside School of Medicine has identified a pathway involving astrocytes, a class of central nervous system support cells, that could shed light on why seizures happen in a subset of multiple sclerosis, or MS, patients.

Study results, available in ASN Neuro, improve scientific understanding of how seizures arise in MS and could provide the foundation for better therapies to manage treatment-resistant seizures in MS and other brain diseases.

Characterized by progressive episodic decline in neurological function, MS affects more than 900,000 people in the United States. This autoimmune disease damages the fatty sheath -- myelin -- that protects nerve fibers, which hinders the speed of signals in the central nervous system. While not classically considered a defining symptom of the disease, seizures occur three-times more often in MS patients than healthy individuals and may portend a flare-up of symptoms. MS patients that experience seizures also have a decreased quality of life and higher mortality rate. The mechanisms that cause seizures in MS patients remains poorly understood.

"During a seizure, there is a dysfunction between inhibition and excitation and a bunch of neurons fire together without control," said Seema Tiwari-Woodruff, a professor of biomedical sciences and senior author on the paper.

Neurons are cells in the central nervous system that transmit information between the body or other neurons to allow us to move, feel, and think. Astrocytes provide the fastidiously maintained environment that the neurons need to perform by controlling the molecular signals present in the brain. Seizures can occur when astrocytes are unable to keep up with this task.

Tiwari-Woodruff and her colleagues examined postmortem brain tissue obtained from MS patients who experienced seizures (7 samples) and MS patients that did not (21 samples). The team found that astrocytes in the hippocampal samples taken from MS patients with seizure showed signs of being less able to regulate the kinds of signals likely to cause a seizure. They observed reduced synaptic glutamate (EEAT2), impaired water and potassium ion buffering (AQP4) and altered gap junction coupling between astrocytes (CX43) in MS patients with seizures. In addition, connections between astrocytes were altered in MS patients with seizures, a finding also noted in epileptic brains but never observed before in MS patients.

"The most exciting aspect of the study was discovering that astrocytes in the brains of MS patients with seizures looked a lot like astrocytes in epileptic brains," said Andrew S. Lapato, a postdoctoral fellow at the University of Colorado, Anschutz Medical Campus who as first author conducted the work as part of his graduate studies in Tiwari-Woodruff's lab. "Researchers might be able to enhance the support roles of astrocytes or compensate for their dysfunction to prevent or treat seizures in MS patients."

EAAT2 is the most widely distributed glutamate transporter in mammalian brains. A reduction in EAAT2 allows the neurons to fire more frequently, resulting in increased seizure activity. The reduction in this transporter has been observed in both patients with MS and temporal lobe epilepsy.

AQP4 maintains the extracellular space volume that allows for ion movement across the connective tissue of the nervous system. A reduction in AQP4 allows the concentration of extracellular potassium ions to increase, which may depolarize neurons and lead to hyperexcitability and protracted stimulation-evoked seizures. The researchers found these results are analogous to epilepsy, suggesting a similar process in MS patients with seizures.

Previous studies found CX43, the major connexin isoform expressed by astrocytes, is altered in response to inflammation or demyelination. Increased CX43 expression is also common in patients with epilepsy. While this study was unable to draw a more definitive link between CX43 and seizure activity, it opens another pathway to explore in future studies.

For this study, the team obtained 28 brain tissue samples from the National Institute of Health NeuroBioBank/Human Brain & Spinal Fluid Resource Center brain bank at the University of California, Los Angeles. The samples in the study were 57% female and 43% male patients. The samples for MS with seizures represent male and female patients almost equally.

"One of the treasures of having post-mortem brain tissues for our study is that we can use them to see how expressed proteins differ among MS patients," Tiwari-Woodruff said. "If we don't know what the disease looks like, then we don't know what we can do to treat it."

NEWPORT, Ore. - Poop samples are an effective, non-invasive tool for monitoring gray whale reproduction, stress and other physiological responses, a new study from Oregon State University shows.

Researchers from OSU's Geospatial Ecology of Marine Megafauna Laboratory collected 158 fecal, commonly known as poop, samples from Eastern North Pacific gray whales off the coast of Oregon between 2016 and 2018 and used the samples to assess endocrine levels and establish hormone baselines for stress and reproduction in the animals.

The study is believed to be the first to use fecal samples as an endocrine assessment tool in Eastern North Pacific gray whales. Fecal samples can provide a wide range of important information about whale health in a noninvasive way, said Leigh Torres, an associate professor in OSU's Marine Mammal Institute and director of the GEMM Lab.

"Understanding whale physiology is really important to evaluate how human, activities impact whales," Torres said. "But it is really, really hard to study whale physiology. You can't observe most physiological responses. And you can't just ask a whale: Are you stressed out? So we have to get creative."

The findings were published this month in the journal Conservation Physiology. The paper's lead author is Leila Soledade Lemos, who recently completed her doctorate in Oregon State's Department of Fisheries and Wildlife and worked with Torres in the GEMM Lab. Lemos is now a postdoctoral associate at Florida International University.

Most gray whales migrate from breeding grounds in Mexico to feeding grounds in the Bering and Chukchi seas between Alaska and Russia, where they spend the summer. Torres and her team study a distinct population of gray whales known as the Pacific Coast Feeding Group, which spend the summer months feeding in coastal waters of Oregon, as well as northern California, Washington and southern Canada.

Torres and her research team have been observing and conducting annual "health check-ups" on this population since 2016. When they spot a defecating whale from a boat or via a drone, they follow in the animal's wake and use nets to capture samples. The drones are also used to capture images of the whales, allowing researchers to monitor the animals' body condition and behavior.

Researchers used the collected fecal samples to analyze four hormone metabolites: two reproductive hormones; a stress hormone; and thyroid, which can indicate nutrition-related stress.

With this data, the researchers were able to see how hormones fluctuated with a whale's age and sex and establish baseline hormone levels for different cycles of a whale's life, including during pregnancy.

"This was a first step to understanding how hormones vary through a whale's life cycle and in times of stress," Lemos said. "It helps us establish baselines and ranges of hormone levels."

The researchers also were able to document a stressful event in a specific whale. They collected a fecal sample from a whale within 24 hours of a documented injury from a propeller or vessel strike. The fecal sample collected after the injury showed a spike in stress hormone levels, almost three times higher than this whale's stress levels on previous days without the injury.

The researchers also captured a fecal sample from a mature male who was engaged in competitive reproductive behavior with another male whale. That whale's testosterone level was very high and may reflect the typical hormone levels of adult breeding males. The researchers' ability to connect fecal samples to specific individual whales adds important context to the data to help understand what drives hormone variation, Torres said.

Researchers have continued to collect fecal samples over the last two summers and will continue to analyze hormones as part of their broader work on whale health.

The researchers' ultimate goal is to understand how variations in human-generated ocean noise impacts whale health, Torres said. Analysis of fecal samples is emerging as an important new tool for understanding how different stressors impact whale physiology. They also hope to use the endocrine information to better understand the role of nutrition and changes in diet on overall whale health.

"Our ability to link hormone variation to an individual's condition is really a significant advance for the study of whale physiology," Torres said. "All of our future work on impacts of disturbance events will build on this foundation. It's super exciting to be able to use these tools to think about whale life in a holistic way."

CHICAGO (December 21, 2020): A virtual telehealth platform is allowing the surgery program at the Medical University of South Carolina (MUSC) to evaluate and wait-list patients for kidney transplantation despite reductions in direct, in-person health care visits brought about by the Coronavirus Disease 2019 (COVID-19) pandemic. Between April and September, surgical teams have been able to perform more transplant evaluations and add the same number of patients to the wait list as they did in the same period last year, according researchers whose study was selected for the 2020 Southern Surgical Association Program and published online as an "article in press" by the Journal of the American College of Surgeons in advance of print.

"Because of the platform, we can give continuous access to patients in the kidney transplantation program even in the midst of a pandemic that has restricted access to the hospital. We can provide access to kidney transplantation even for patients who have difficulty getting to the transplant center because of where they live or who have difficulties due to their socioeconomic status," said Vinayak S. Rohan, MD, FACS, an assistant professor of surgery and lead study author. Patients in the virtual telehealth program lived, on average, 130 miles from the transplant center, and 65 percent were African American.

Before being considered for kidney transplantation, patients with end-stage renal disease must undergo a comprehensive evaluation that includes a medical and surgical history, physical and psychosocial exam, and blood testing for compatibility with an eventual donated organ.

Depending on a patient's condition, other testing may be ordered, including blood testing for the overall function of the heart, kidneys, liver, thyroid, and immune system, as well as targeted studies of the lungs and heart, cancer screening, colonoscopy, gynecologic or prostate examination, and dental workup to be sure there is no sign of infection or gum disease that could affect the immune system.1

This evaluation is routinely done in one or more in-person visits to the transplantation center or to primary or other physicians' offices. However, the onset of COVID-19 severely limited patient access to non-urgent care and closed ambulatory clinics that conduct kidney transplant evaluation.

An operational team from MUSC's division of transplant surgery quickly moved to reduce the need for in-person visits by implementing a virtual kidney transplant evaluation. The team included transplant surgeons, nephrologists, advanced practice practitioners, social workers, and other members of the surgical quality improvement program.

The research team stratified patients who had recently been referred by their doctors or dialysis units for possible transplantation and were in the process of pre-transplant review by providers and insurance carriers. After an initial review of their medical records, patients were stratified into one of three groups.

The first, or "red," group included patients whose age or medical condition made it unlikely they would end up being candidates for transplantation and therefore require a full presurgical evaluation. Patients in this group were over age 70 and had a history of stroke, significant cardiac or peripheral vascular disease, or poor functional status.

The second, or "green," group included patients who were likely to be candidates for transplantation and placed on the wait list for a donated organ. Patients in this group were under 45 years of age and had no history of diabetes.

The third group, or "yellow," group included "fast track" patients as well as all other patients. "Fast track" patients were on the wait list at another transplantation center and required minimum further workup.

Patients were scheduled and evaluated by the virtual platform based on this stratification. "Fast-track" patients were expedited through the virtual evaluation. These patients were followed by individuals in the red and green groups.

After an initial call to determine if a patient or a family member could use a smart phone or tablet and verify insurance, the patient was scheduled for check-in, a link to the doxy.me virtual platform was sent, and the telehealth visit was completed. The doxy.me virtual platform was chosen because it is easy to use, complies with HIPAA privacy, and does not require additional software to complete the visit.

Between April and September, 176 transplantations were performed. Of the 1,148 patients who were referred for transplantation, 930 underwent virtual evaluation and 282 were placed on the wait list. In the same period in 2019, 177 transplantations were performed. Of 1,639 patients referred, 880 were evaluated and 308 were wait-listed.

Dr. Rohan believes this type of platform can be used by any medical specialty even after the pandemic. "However, we need new regulations to achieve this goal," he pointed out.

Provisions in the national COVID-19 aid and relief legislation, the CARES Act, made the shift to the virtual evaluation platform possible by expanding Medicare coverage for telehealth during the pandemic.2,3

"We need to continue this practice in the future, even after the CARES Act expires, and expand care across state lines so that patients can continue having access to medical care across all specialties," he said.

BEER-SHEVA, Israel...December 21, 2020 - The identification of people wearing masks has often presented a unique challenge during the pandemic. A new study by researchers from Ben-Gurion University of the Negev (BGU) in Israel and York University in Canada reveals the impact of this predicament and its potentially significant repercussions.

The findings were just published in the journal Scientific Reports.

"For those of you who don't always recognize a friend or acquaintance wearing a mask, you are not alone," according to the researchers Prof. Tzvi Ganel, head of the Laboratory for Visual Perception and Action at the BGU Department of Psychology, and Prof. Erez Freud, who earned his Ph.D. at BGU and is now a faculty member at York University in Toronto, Ontario.

"Faces are among the most informative and significant visual stimuli in human perception and play a unique role in communicative, social daily interactions," the researchers note. "The unprecedented effort to minimize COVID-19 transmission has created a new dimension in facial recognition due to mask wearing."

To examine the effects of wearing masks, Prof. Ganel and Prof. Freud used a modified version of the Cambridge Face Memory Test, the standard for assessing facial perception, which included masked and unmasked faces. The study was conducted online with a large group of nearly 500 people.

The researchers found that the success rate of identifying someone wearing a mask was reduced by 15%. “This could lead to many errors in correctly recognizing people we know, or alternatively, accidently recognizing faces of unfamiliar people as people we know,” says Prof. Galia Avidan who is a member of the BGU Department of Psychology and the Department of Cognitive and Brain Sciences, and an expert on facial recognition and perception. "Face masks could be even more challenging to people whose face recognition skills are not ideal to begin with and cause greater impairment."

The research team also found that masks specifically interfered with extracting a holistic impression of faces and led to feature-by-feature processing which is a less accurate and more time-consuming strategy.

"Instead of looking at the entire face, we're now forced to look at eyes, nose, cheeks, and other visible elements separately to construct an entire facial face percept - which we used to do instantly," the researchers say.

These changes in performance, along with the alteration along the processing style of faces, could have significant effects on activities of daily living, including social interactions, as well as other situations involving personal interactions, such as education.

"Given that mask wearing has rapidly become an important norm in countries around the globe, future research should explore the social and psychological implications of wearing masks on human behavior," Ganel says. "The magnitude of the effect of masks that we report in the current study is probably an underestimation of the actual degree in performance dropdown for masked faces."

A prehistoric croc measuring more than five metres long - dubbed the 'swamp king' - ruled south eastern Queensland waterways only a few million years ago.

University of Queensland researchers identified the new species of prehistoric croc - which they named Paludirex vincenti - from fossils first unearthed in the 1980s.

UQ PhD candidate Jorgo Ristevski, from UQ's School of Biological Sciences, said they named the species after Geoff Vincent who discovered the giant fossilised skull near the town of Chinchilla.

"In Latin, 'Paludirex' means 'swamp king', and 'vincenti' honours the late Mr Vincent," he said.

"For several years the fossilised skull was on display in the Queensland Museum, before it was donated to the Chinchilla Museum in 2011.

"The 'swamp king' was one intimidating croc.

"Its fossilised skull measures around 65 centimetres, so we estimate Paludirex vincenti was at least five metres long.

"The largest crocodylian today is the Indo-Pacific crocodile, Crocodylus porosus, which grows to about the same size.

"But Paludirex had a broader, more heavy-set skull so it would've resembled an Indo-Pacific crocodile on steroids."

Paludirex was one of the top predators in Australia a few million years ago, capable of preying on giant prehistoric marsupials.

"The waterways of the Darling Downs would once have been a very dangerous place because of it," Mr Ristevski said.

Mr Ristevski's supervisor, Dr Steve Salisbury, said various species of prehistoric crocodylians had existed in Australia.

"Crocs have been an important component of Australia's fauna for millions of years," Dr Salisbury said.

"But the two species we have today -- Crocodylus porosus and Crocodylus johnstoni -- are only recent arrivals, and were not part of the endemic croc fauna that existed here from about 55 million years ago.

"Whether Paludirex vincenti went extinct as a result of competition with species like Crocodylus porosus is hard to say.

"The alternative is that it went extinct as the climate dried, and the river systems it once inhabited contracted - we're currently investigating both scenarios."

The research has been published in the open access journal PeerJ (DOI: 10.7717/peerj.10466).

The research group led by Dr Sjoerd van Wijk from the Institute of Experimental Cancer Research in Paediatrics at Goethe University already two years ago found evidence indicating that the anti-diarrhoea drug loperamide could be used to induce cell death in glioblastoma cell lines. They have now deciphered its mechanism of action and, in doing so, are opening new avenues for the development of novel treatment strategies.

When cells digest themselves

In certain types of tumour cells, administration of loperamide leads to a stress response in the endoplasmic reticulum (ER), the cell organelle responsible for key steps in protein synthesis in the body. The stress in the ER triggers its degradation, followed by self-destruction of the cells. This mechanism, known as autophagy-dependent cell death occurs when cells undergo hyperactivated autophagy. Normally, autophagy regulates normal metabolic processes and breaks down and recycles the valuable parts of damaged or superfluous cell components thus ensuring the cell's survival, for example in the case of nutrient deficiency. In certain tumour cells, however, hyperactivation of autophagy destroys so much cell material that they are no longer capable of surviving.

"Our experiments with cell lines show that autophagy could support the treatment of glioblastoma brain tumours," says van Wijk. Glioblastoma is a very aggressive and lethal type of cancer in children and adults that shows only a poor response to chemotherapy. New therapeutic approaches are therefore urgently required. The research group led by van Wijk has now identified an important factor that links the ER stress response with the degradation of the ER (reticulophagy): The "Activating Transcription Factor" ATF4 is produced in increased amounts both during ER stress and under the influence of loperamide. It triggers the destruction of the ER membranes and thus of the ER.

Anti-diarrhoea drug triggers cell death in glioblastoma cells

"Conversely, if we block ATF4, far fewer cells in a tumour cell culture die after adding loperamide," says van Wijk, describing the control results. In addition, the research group was able to detect ER debris in loperamide-treated cells under the electron microscope. "ER degradation, that is, reticulophagy, visibly contributes to the demise of glioblastoma cells," says van Wijk. The team also showed that loperamide triggers only autophagy but not cell death in other cells, such as embryonic mouse fibroblasts. "Normally, loperamide, when taken as a remedy against diarrhoea, binds to particular binding sites in the intestine and is not taken up by the bowel and is therefore harmless".

Mechanism of action also applicable to other diseases

The loperamide-induced death of glioblastoma cells could help in the development of new therapeutic approaches for the treatment of this severe form of cancer. "However, our findings also open up exciting new possibilities for the treatment of other diseases where ER degradation is disrupted, such as neurological disorders or dementia as well as other types of tumour," says van Wijk. However, further studies are necessary before loperamide can actually be used in the treatment of glioblastoma or other diseases. In future studies it has to be explored, for example, how loperamide can be transported into the brain and cross the blood-brain barrier. Nanoparticles might be a feasible option. The research team in Frankfurt now wants to identify other substances that trigger reticulophagy and examine how the effect of loperamide can be increased and better understood.

Philadelphia, December 21, 2020 - Controlling inflammation after transplantation of organs, cells, or tissues is critical for graft survival; however, it can be difficult. Continuing injuries due to chronic rejection can be particularly problematic. Now, a team of researchers from Albert Einstein College of Medicine report that neutralizing the cell signaling molecule, tumor necrosis factor (TNF), can prevent cascades of injurious molecules and signals after cell transplantation in The American Journal of Pathology, published by Elsevier.

"New insights into immune inflammatory mediators indicate that rejection and tissue injury can be avoided with available drugs," explained director of the research team Sanjeev Gupta, MD, Department of Medicine and of Pathology, and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA. "The ability to prevent and/or control tissue injury will improve graft survival for transplantation medicine, advance use of cells and tissues for regenerative medicine, and offer insights for controlling inflammation-related tissue injury in other circumstances."

Transplanting organs from unrelated or mismatched donors into individuals triggers immunological defenses against "foreign" material. Development of immunosuppressive drugs to block lymphocyte responses has delivered success in the short term, but chronic rejection and tissue injury over long periods due to unidentified mechanisms and processes can lead to the loss of transplanted organs.

To understand the factors at work in tissue rejection, the researchers at Albert Einstein College of Medicine developed liver cell transplantation models in laboratory rats with or without immunosuppression, using drugs routinely given to humans. The state of inflammation was studied using gene expression arrays to query the activation of soluble signals associated with various cell types. The analysis was guided by recent advances in mapping gene expression differences and the networks affected during complex interactions using commercially available computer software. The software queries the scientific literature to suggest relationships and negative or positive reactions in genes.

The studies identified differences in the expression of 40-50 soluble networks. In particular, the activation of TNF, a major inflammatory mediator, and its cellular receptors is prominent, persisting over the long term.

Blocking TNF stopped the activation of most other inflammatory signals, revealing that it is a "master switch" for orchestrating cytokines, chemokines, and receptors arising from the body's innate or inbuilt systems defending against foreign material, e.g., microbes, viruses, and mismatched transplants. To further understand the role of TNF, the researchers neutralized it with the well-established drugs etanercept or thalidomide to improve cell transplant outcomes alongside conventional immunosuppression with tacrolimus and mycophenolate mofetil.

Computer mapping of gene expression showed that blocking TNF markedly decreases the recruitment and activity of inflammatory cells. Other studies provided direct evidence that blocking TNF led to superior survival and proliferation of transplanted cells, regenerating the liver far more effectively.

Lead author Fadi-Luc Jaber, PhD, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA, commented "The efficacy of this anti-inflammatory mechanism for liver regeneration surprised me. These mechanisms will provide further means to treat liver conditions."

"The translational potential of these findings is exciting because the additional inflammatory markers and genes offer further means for diagnosing the pathology of organ rejection in individuals. This type of inflammatory interference will decrease tissue injury, promote graft survival, and survival of transplanted cells and engineered tissues, and help advance organ regeneration," observed Dr. Gupta. "The inflammatory cascades orchestrated through TNF also hold lessons for the pathology in other less well understood conditions, such as COVID-19."