Culture

New study confirms high prevalence of depression during the menopause transition

CLEVELAND, Ohio (July 1, 2020)--Depression has been shown to be prevalent during menopause, affecting as many as 70% of women transitioning into menopause. A new study not only confirms the high prevalence of depression but also the greatest risk factors for it in postmenopausal women, as well as any relationships with anxiety and fear of death. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

With the decrease in hormone production during menopause, women are more prone to a number of psychological problems, including depression, anxiety, irritability, nervousness, sadness, restlessness, memory problems, lack of confidence and concentration, and a loss of libido. At the same time, as women age, the fear of death becomes more pronounced. Depression and anxiety, which are the most common psychological problems that occur during the menopause transition, likely increase that fear.

In this new study involving 485 postmenopausal Turkish women aged between 35 and 78 years, researchers sought to determine the frequency of depressive symptoms in postmenopausal women, the variables affecting it, and the levels of anxiety and fear of death. They then evaluated the relationship between all these variables and postmenopausal depression. They found that depression in postmenopausal women is a common and important health problem that requires further study. In this specific study, 41% of the participants were confirmed to experience some form of depression, although it is theorized that this rate was lower than in some previous studies because of the somewhat lower age of participants (average age, 56.3 y).

In addition, the researchers identified those risk factors that most affected depression in postmenopause. These included being a widow or separated from one's spouse, alcohol consumption, any medical history requiring continuous medication, the presence of any physical disability, physician-diagnosed mental illness, and having four or more living children. They did not, however, confirm any relationship between depression and the fear of death, although the somewhat younger age of the study group may have influenced this lack of association.

Study results appear in the article "Depression, anxiety and fear of death in postmenopausal women."

"The findings of this study involving postmenopausal Turkish women are consistent with existing literature and emphasize the high prevalence of depressive symptoms in midlife women, particularly those with a history of depression or anxiety, chronic health conditions, and psychosocial factors such as major stressful life events. Women and the clinicians who care for them need to be aware that the menopause transition is a period of vulnerability in terms of mood," says Dr. Stephanie Faubion, NAMS medical director.

Credit: 
The Menopause Society

Indices of health under our feet

IMAGE: Wastewater gathered at treatment plants contains a wealth of information relevant to human and environmental health. A new technique known as wastewater-based epidemiology can extract this vital information and use...

Image: 
Biodesign Institute

A treasure trove of information relevant to human and environmental health is hiding in an unexpected place. Samples of wastewater from homes, institutions, towns and cities around the world can now be probed for valuable data concerning community well-being, antibiotic use and resistance, recreational substance consumption and abuse, biomarkers of disease as well as environmental hazards and degradation.

This rapidly emerging health surveillance technique, termed wastewater-based epidemiology (WBE), is an economical and powerful tool. It can teach us much about large populations contributing into a centralized­­ sewerage system during the course of a full 24-hour cycle.

In a pair of new studies, Rolf Halden, director of the ASU Biodesign Center for Environmental Health Engineering and author for the 2020 Book Environment, describes the process and highlights important new findings extracted from the municipal wastewater most of us contribute to on a daily basis. Halden is also a professor at ASU's School of Sustainable Engineering and the Built Environment.

"After being around for more than 15 years, wastewater-based epidemiology is finally getting the attention it deserves, thanks in no small part to the challenges brought about by the COVID-19 pandemic," says Halden, a pioneer and champion of WBE whose team has built the largest single monitoring network and sample archiv­­­­e in the U.S. and around the world.

Data-rich waste

Advances in WBE technologies and applications are progressing rapidly. The method offers a low-cost strategy for obtaining health and environmental data on a local, regional, national and even continental scale. It can provide valuable information with acute spatial and temporal resolution. Because the method aggregates community-wide data, it is non-invasive and ensures the privacy of the population under study.

In addition to its ability to measure ingestion rates of drugs including cocaine and opioids, WBE has been proposed as a means of identifying exposure to agents including pesticides, personal care products, infectious pathogens, persistent organic pollutants, as well as for tracking community-wide incidence of illnesses including diabetes, allergies, stress-induced disorders and cancer.

In the first of two current studies, with Biodesign Institute research scientist Erin Driver as lead author, wastewater samples from a large university in the American Southwest were analyzed for the presence of caffeine, tobacco and alcohol. This study monitored the presence of these substances during the 2017-18 academic year. It is the first U.S. study to focus on these common psychotropic compounds, aimed at comparing data output from WBE to that of conventional methods, namely the use of questionnaires.

Alcohol, nicotine and caffeine use are significant public health concerns, claiming some 550,000 lives annually. Data suggest college-aged students are particularly vulnerable to overconsumption of these substances, often resulting in behaviors that last their lifetimes, which create poorer health outcomes. This work shows the utility of monitoring this particular subset of a population and illustrates the prospective benefit of long-term monitoring networks on college campuses to improve student health and promote future success.

Efficient, near real-time monitoring

WBE represents an attractive alternative to community-wide monitoring through self-reported surveys, which may introduce sampling and reporting biases and are often comparatively costly to administer; how much more expensive, was one of the questions investigated in the study.

In addition to measurements of the quantities of stimulants consumed, the study revealed strong positive correlations for the consumption of alcohol and nicotine as well as between nicotine and caffeine, but not between alcohol and caffeine.

Temporal information was also tracked, indicating that caffeine consumption was highest during the week, while nicotine and alcohol consumption peaked on the weekends, as anticipated. The study demonstrated the practicality and reliability of campus-wide longitudinal tracking of some 60,000 students directly and inexpensively.

In addition to monitoring health indices related to behavior, WBE could ultimately provide a low-cost means of carrying out infectious disease surveillance across populations, providing an early-warning system to alert researchers to disease outbreaks in near real time, within as little as 24 hours.

Halden hopes to leverage the power of WBE technology, ultimately combining a broad range of human health indicators present in wastewater into a comprehensive system he calls the Human Health Observatory (HHO). Currently, ASU's HHO gathers data from over 350 cities representing around 32 million people or roughly 10% of the U.S. population and a quarter billion people globally.

Data streams

Strategies for extracting information on particular target substances vary, often using sophisticated methods such as liquid chromatography tandem mass spectroscopy, which can fingerprint chemical traces based on their differing molecular weights and characteristic ionization and fragmentation behavior. But the basic process used for WBE is simple.

Samples of raw wastewater--sewage entering a water reclamation facility, are typically collected over a 24-hour period and then shipped to the laboratory to determine the average concentration of chemicals or their biological metabolites. The concentration value is then multiplied with the flow volume of sewage during the sampling period, to provide a more meaningful unit of a quantity of a substance per 1,000 people per day. Combining this information with estimates of average excretion rates of target metabolites permits researchers to determine the quantity of consumption of a given substance, be it cups of coffee, number of alcoholic beverages or cigarettes smoked.

The final data in the university study showed levels of alcohol consumption to be consistent with quantities observed in self-reported surveys. But whereas both study methods were shown to yield similar findings, Driver summed up the big news as follows: "In this study, use of WBE was over 200-times cheaper than conventional methods, yielding data at more frequent intervals throughout the academic year. Costs were reduced from an estimated $127 to only $0.58 per person when using wastewater analytics."

The researchers are now measuring how the COVID-19 epidemic and the associated stay-at-home orders are impacting substance use in the university's home city.

Health surveillance refined

In the other new study, lead authors Professors Olga Hart and Rolf Halden of the Biodesign Center for Environmental Health Engineering report on a modeling study that considered all 13,940 major sewage treatment plants in the U.S. and demographic information collected by the U.S. Census during the 2017 American Community Survey.

The aim of the study was to investigate and understand potential biases in WBE studies by examining variations in data collected due to temperature, seasonal variations and rates of biomarker decay. To do this, the researchers assumed stable consumption in the population over one calendar year and computed how the community contributing to the chemical signal detectable at a given wastewater treatment plant would change as a function of the changes induced by seasonally variable temperatures and biomarker decay rates.

The study also found intriguing correlations between seasonal temperatures and the size and distance a population can be observed by wastewater analytics. In general, during the colder months of the year the "visibility down the pipe" is better, leading to a larger population captured that resides farther away from the plant, and a more even representation of all people served by the treatment plant.

In contrast, in-sewer degradation during the summer months reduced the observable population and the detectable chemistry was composed primarily of communities closer to the treatment. This finding gained great significance when census data showed considerable differences in demographic indicators exist as a function of the distance of residence from a plant. Compared to the cold winter season, observations in the summer were more likely to capture households with lower income, less educational attainment, more prevalent military service, higher unemployment, and greater lack of health insurance. Hart summed up the findings:

"If not taken into account, this uneven distribution of populations within urban environments could lead to skewed data from wastewater sampling, or to attributing to seasonal change, patterns that are actually of demographic origin. Just like in traditional human subject studies, whether we are trying to better understand the health status of communities by passive monitoring or testing the impact of proactive interventions, it's critical to understand if our study population significantly changes from observation to observation."

Halden agreed and added: "This study challenges WBE researchers to reassess their data in the context of temperature changes. Regardless of whether we are monitoring chemicals or biological agents in wastewater, our research community will have to pay more attention to ambient air temperatures in order to get the most robust information from wastewater analysis."

Credit: 
Arizona State University

Respiratory droplet motion, evaporation and spread of COVID-19-type pandemics

image: Flow diagram outlining the interconnections of the model developed.

Image: 
Swetaprovo Chaudhuri, Saptarshi Basu, Prasenjit Kabi, Vishnu R Unni and Abhishek Saha

WASHINGTON, June 30, 2020 -- It is well established that the SARS-CoV-2 virus responsible for the COVID-19 disease is transmitted via respiratory droplets that infected people eject when they cough, sneeze or talk. Consequently, much research targets better understanding droplet motion and evaporation to understand transmission more deeply.

In a paper in Physics of Fluids, by AIP Publishing, researchers developed a mathematical model, proceeding from first principles, for the early phases of a COVID-19-like pandemic using the aerodynamics and evaporation characteristics of respiratory droplets.

The researchers modeled the pandemic dynamics with a reaction mechanism, where each reaction has a rate constant obtained by calculating the frequency of collisions between the infectious droplet cloud ejected by an infected person and a healthy person.

"The size of the droplet cloud, the distance it travels, and the droplet lifetimes are, therefore, all important factors that we calculated using conservation of mass, momentum, energy and species," said Swetaprovo Chaudhuri, one of the authors.

The model could be used to estimate approximately how long droplets can survive, how far they can travel, and which size of droplet survives for how long. Though, as Chaudhuri adds, "The actual situation could be complicated by wind, turbulence, air-recirculation or many other effects."

"Without wind and depending on the ambient condition, we found droplets travel between 8 to 13 feet before they evaporate or escape," said Abhishek Saha, a co-author.

This finding implies that social distancing at perhaps greater than 6 feet is essential.

Furthermore, the initial size of the longest surviving droplets is in the range of 18-50 microns, meaning masks can indeed help. These findings could help inform reopening measures for schools and offices looking at student or employee density.

"This model is not claiming to predict the exact spread of COVID-19," said Saptarshi Basu, another author. "But, our work shows that droplet evaporation or desiccation time is highly sensitive to the ambient temperature and relative humidity."

More broadly, this multiscale model and the firm theoretical underpinning that connects the two scales -- macroscale pandemic dynamics and the microscale droplet physics -- could emerge as a powerful tool in clarifying the role of environment on infection spread through respiratory droplets.

Credit: 
American Institute of Physics

To find giant black holes, start with Jupiter

image: On a quest to find the Universe's largest black holes, Vanderbilt researcher identifies the center of the solar system within 100 meters.

Image: 
David Champion

The revolution in our understanding of the night sky and our place in the universe began when we transitioned from using the naked eye to a telescope in 1609. Four centuries later, scientists are experiencing a similar transition in their knowledge of black holes by searching for gravitational waves.

In the search for previously undetected black holes that are billions of times more massive than the sun, Stephen Taylor, assistant professor of physics and astronomy and former astronomer at NASA's Jet Propulsion Laboratory (JPL) together with the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) collaboration has moved the field of research forward by finding the precise location - the center of gravity of our solar system - with which to measure the gravitational waves that signal the existence of these black holes.

The potential presented by this advancement, co-authored by Taylor, was published in the journal the Astrophysical Journal in April 2020.

Black holes are regions of pure gravity formed from extremely warped spacetime. Finding the most titanic black holes in the Universe that lurk at the heart of galaxies will help us understand how such galaxies (including our own) have grown and evolved over the billions of years since their formation. These black holes are also unrivaled laboratories for testing fundamental assumptions about physics.

Gravitational waves are ripples in spacetime predicted by Einstein's general theory of relativity. When black holes orbit each other in pairs, they radiate gravitational waves that deform spacetime, stretching and squeezing space. Gravitational waves were first detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015, opening new vistas on the most extreme objects in the universe. Whereas LIGO observes relatively short gravitational waves by looking for changes in the shape of a 4-km long detector, NANOGrav, a National Science Foundation (NSF) Physics Frontiers Center, looks for changes in the shape of our entire galaxy.

Taylor and his team are searching for changes to the arrival rate of regular flashes of radio waves from pulsars. These pulsars are rapidly spinning neutron stars, some going as fast as a kitchen blender. They also send out beams of radio waves, appearing like interstellar lighthouses when these beams sweep over Earth. Over 15 years of data have shown that these pulsars are extremely reliable in their pulse arrival rates, acting as outstanding galactic clocks. Any timing deviations that are correlated across lots of these pulsars could signal the influence of gravitational waves warping our galaxy.

"Using the pulsars we observe across the Milky Way galaxy, we are trying to be like a spider sitting in stillness in the middle of her web," explains Taylor. "How well we understand the solar system barycenter is critical as we attempt to sense even the smallest tingle to the web." The solar system barycenter, its center of gravity, is the location where the masses of all planets, moons, and asteroids balance out.

Where is the center of our web, the location of absolute stillness in our solar system? Not in the center of the sun as many might assume, rather it is closer to the surface of the star. This is due to Jupiter's mass and our imperfect knowledge of its orbit. It takes 12 years for Jupiter to orbit the sun, just shy of the 15 years that NANOGrav has been collecting data. JPL's Galileo probe (named for the famed scientist that used a telescope to observe the moons of Jupiter) studied Jupiter between 1995 and 2003, but experienced technical maladies that impacted the quality of the measurements taken during the mission.

Identifying the center of the solar system's gravity has long been calculated with data from Doppler tracking to get an estimate of the location and trajectories of bodies orbiting the sun. "The catch is that errors in the masses and orbits will translate to pulsar-timing artifacts that may well look like gravitational waves," explains JPL astronomer and co-author Joe Simon.

Taylor and his collaborators were finding that working with existing solar system models to analyze NANOGrav data gave inconsistent results. "We weren't detecting anything significant in our gravitational wave searches between solar system models, but we were getting large systematic differences in our calculations," notes JPL astronomer and the paper's lead author Michele Vallisneri. "Typically, more data delivers a more precise result, but there was always an offset in our calculations."

The group decided to search for the center of gravity of the solar system at the same time as sleuthing for gravitational waves. The researchers got more robust answers to finding gravitational waves and were able to more accurately localize the center of the solar system's gravity to within 100 meters. To understand that scale, if the sun were the size of a football field, 100 meters would be the diameter of a strand of hair. "Our precise observation of pulsars scattered across the galaxy has localized ourselves in the cosmos better than we ever could before," said Taylor. "By finding gravitational waves this way, in addition to other experiments, we gain a more holistic overview of all different kinds of black holes in the Universe."

As NANOGrav continues to collect ever more abundant and precise pulsar timing data, astronomers are confident that massive black holes will show up soon and unequivocally in the data.

Credit: 
Vanderbilt University

Is a 'cytokine storm' relevant to COVID-19?

What The Editorial Says: The term "cytokine storm" and its relevance to COVID-19 are examined in this editorial.

Authors: Pratik Sinha, M.B., Ch.B., of the University of California, San Francisco, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.3313)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

#  #  #

Media advisory: The full editorial is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.3313?guestAccessKey=35141c51-8b85-4048-baf6-4159be1c6091&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=063020

Credit: 
JAMA Network

Researchers have found a promising therapy for cardiac regeneration

Ischemic heart disease (IHD) has maintained its rank as one of the worldwide leading causes of mortality outweighing the burden from all malignancies combined.

When IHD develops, chronic myocardial ischemia, aggravated in some instances by periods of acute ischemia in the form of myocardial infarction, ensue. Damaged myocardium is replaced with a fibrotic scar that over-activates physiologic compensatory mechanisms with challenging sequalae, such as myocardial rigidity and eventually, over time, heart failure.

A research collaboration team at University of Helsinki together with a State Key Laboratory of Cardiovascular Disease (FuWai Hospital, Beijing, China) has investigated in a mouse model of artificial myocardial infarction, the molecular mechanisms underlying novel, easily clinically implementable tissue-engineered approach for stimulating the myocardial regeneration.

The tissue-engineered approach relies on a local transplantation of minute pieces of autologous atrial appendage tissue, termed atrial appendage micrografts (AAMs), to the surface of the ischaemically stressed myocardium.

Results of the investigation are published in the Journal of Heart and Lung Transplantation.

"We were able to get a comprehensive view on how the heart's functional, structural and metabolic aspects of healing are influenced by AAMs patch transplantation following acute ischemia," says Docent Esko Kankuri from University of Helsinki.

Heart's pumping function preserved, also improved functional recovery

The research group ulitized complementary tools, including systematic postoperative functional echocardiographic follow-up, histomorphometric analyses and finally site-selective proteomics in tandem with functional bioinformatics.

"We demonstrated not only preservation of heart's pumping function following critical ischemic insult but also improved functional recovery following AAMs transplantation during follow-up," says Docent Maciej Lalowski from University of Helsinki.

"We identified 1 005 proteins from the myocardium, of which 216 were differentially expressed immediately below the AAMs patch in 'subtransplant' area and 43 in the interventricular septum remote to the AAMs transplantation site," Lalowski continues.

The therapy is currently undergoing clinical safety and feasibility evaluation as an adjuvant to the coronary artery bypass grafting operation.

Credit: 
University of Helsinki

Discovery of new step in how brain cells work could lead to new therapies for epilepsy

image: Dr Tobias Engel, FutureNeuro Investigator and Senior Lecturer in the School of Physiology and Medical Physics at RCSI University of Medicine and Health Sciences

Image: 
Lafayette Photography

Dublin, Tuesday, 30 June 2020: Researchers have identified a critical new step in how brain cells function in people with one of the most common forms of epilepsy. This could lead to new treatment approaches for people with drug-resistant epilepsy.

The study was led by researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, hosted by RCSI University of Medicine and Health Sciences with colleagues at Severo Ochoa-Centre for Molecular Biology (CBMSO) of Madrid and Institute for Research in Biomedicine (IRB) of Barcelona. The research is published in Brain.

Changes in gene activity are known to be important in the development of epilepsy. Normally, a molecule called messenger RNA is produced when a gene is active. This becomes the template for the production of the proteins that brain cells use to function. A critical step is the addition of a short sequence called a poly(A) tail. This has never been studied before in epilepsy. The team discovered that this tailing process (polyadenylation) is dramatically altered for about one third of the genes of someone with epilepsy, changing protein production in the brain.

"Our discovery adds another piece to the puzzle to help us understand why gene activity is different in someone with epilepsy," said Dr Tobias Engel, FutureNeuro Investigator and Senior Lecturer in the School of Physiology and Medical Physics at RCSI. "It is remarkable that so many active genes in the brain show a change in this polyadenylation process. We believe that this could ultimately lead us to new targeted treatments, allowing us to investigate if we could stop a person from developing epilepsy."

Epilepsy is one of the most common chronic brain diseases, affecting over 65 million people worldwide. While current drug treatments are usually effective in suppressing seizures, they do not work in one third of people with epilepsy and have no effect on the underlying causes of the disease.

"Regulated poly(A) tailing of messenger RNAs is a step in gene expression regulation barely explored in brain diseases, and our study should foster its investigation in other brain conditions in which gene expression alteration is suspected," said Dr José Lucas, Research Professor at Severo Ochoa-Centre for Molecular Biology of Madrid.

Prof. David Henshall, Director of FutureNeuro and Professor of Physiology in the School of Physiology and Medical Physics at RCSI, said, "Our aim in FutureNeuro is to provide faster diagnostics, precision therapeutics and eHealth enabled solutions for those with chronic and rare neurological diseases. This research is a great example of how understanding basic mechanisms of a disease can guide us to new targets for treatment."

Credit: 
RCSI

Auditory hallucinations rooted in aberrant brain connectivity

image: Depiction of a working theory on the thalamic circuitry that is involved in psychotic symptoms in individuals with the genetic disorder, 22q11 deletion syndrome.

Image: 
Elsevier, 2020 (Creative Commons license, CC-BY)

Philadelphia, June 30, 2020 - Auditory hallucinations, a phenomenon in which people hear voices or other sounds in the absence of external stimuli, are a feature of schizophrenia and some other neuropsychiatric disorders. How they arise in the brain has been unclear, but new research indicates that altered brain connectivity between sensory and cognitive processing areas may be responsible.

The study from researchers led by Stephan Eliez, MD, PhD, at Geneva University, Switzerland, appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

"Our results demonstrate aberrant development of the thalamic nuclei involved in sensory processing and [an] immature pattern of thalamo-cortical connectivity to the brain's auditory regions," said lead author Valentina Mancini, MD.

Using magnetic resonance imaging (MRI), the researchers compared brain structures and their connectivity in 110 healthy control subjects and in 120 subjects with a genetic disorder, named 22q11.2 deletion syndrome, or DS. People with 22q11.2 DS are at far higher risk than the general public to develop schizophrenia and to experience sensory hallucinations. An estimated one percent of people with schizophrenia have this disorder.

Abnormalities in the thalamus, a brain region recognized as the "gateway" for sensory information coming into the brain, had already been implicated in schizophrenia and hallucinations. In the current study, the authors sought to parse more specifically how the thalamus and its connections to other brain areas differed in people with 22q11.2 DS - with and without auditory hallucinations (AH) - from the control group. For this longitudinal study, the researchers collected brain scans every three years from subjects aged 8 to 35, with each receiving between 1 and 4 scans.

While neither the total volume of the thalamus nor its developmental growth trajectory differed between 22q11.2 DS and control subjects, the researchers found differences in specific thalamic sub-nuclei. The medial and lateral geniculate nuclei (MGN, LGN), which are involved in relaying auditory and visual sensory information, were smaller in people with 22q11.2 DS. In contrast, thalamic nuclei that communicate with the frontal cortex, which is involved in higher cognitive functions, were larger in 22q11.2 DS subjects than in healthy controls. In addition, other thalamic nuclei developed differently in the two groups.

When comparing 22q11.2 DS subjects with and without AH, those with AH had a smaller volume of MGN and a different developmental trajectory.

Upon assessing functional connectivity within the brain, the authors also found that subjects with AH had greater connectivity between MGN with the auditory cortex and other language-processing areas. They postulate that such hyper-connectivity might underlie the activation of such auditory areas at rest, leading to hallucinations.

"These findings provide a mechanistic explanation to the extreme likelihood of hallucinatory phenomena in youths prone to psychosis due to 22q11.2 deletion syndrome," Dr. Mancini added. "Further, the investigation of the developmental interactions between the thalamus and the cortex may help to identify new targets for intervention aimed at preventing the emergence of psychotic symptoms in individuals at-risk due to genetic conditions or clinical ultra-high-risk status."

Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging added: "This study of individuals with 22q11 may provide a unique window into the alterations in brain development that underlie the development of psychotic symptoms, as well as other developmental and cognitive problems in these young people."

Credit: 
Elsevier

Lab-grown 'mini-brains' suggest COVID-19 virus can infect human brain cells

image: 'Mini-brain' bioengineered from human stem cells. The ball is about one third of a millimeter and contains about 30,000 cells. The cell nuclei are blue. The SARS-CoV-2 virus is stained red, indicating that a small fraction of brain cells carries a large number of virus particles. This means that virus has multiplied in infected cells.

Image: 
Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health

A multidisciplinary team from two Johns Hopkins University institutions, including neurotoxicologists and virologists from the Bloomberg School of Public Health and infectious disease specialists from the school of medicine, has found that organoids (tiny tissue cultures made from human cells that simulate whole organs) known as "mini-brains" can be infected by the SARS-CoV-2 virus that causes COVID-19.

The results, which suggest that the virus can infect human brain cells, were published online June 26, 2020, in the journal ALTEX: Alternatives to Animal Experimentation.

Early reports from Wuhan, China, the origin of the COVID-19 pandemic, have suggested that 36% of patients with the disease show neurological symptoms, but it has been unclear whether or not the virus infects human brain cells. In their study, the Johns Hopkins researchers demonstrated that certain human neurons express a receptor, ACE2, which is the same one that the SARS-CoV-2 virus uses to enter the lungs. Therefore, they surmised, ACE2 also might provide access to the brain.

When the researchers introduced SARS-CoV-2 virus particles into a human mini-brain model, the team found -- for what is believed to be the first time -- evidence of infection by and replication of the pathogen.

The human brain is well-shielded against many viruses, bacteria and chemical agents by the blood-brain barrier, which in turn, often prevents infections of the brain. "Whether or not the SARS-CoV-2 virus passes this barrier has yet to be shown," notes senior author Thomas Hartung, M.D., Ph.D., chair for evidence-based toxicology at the Bloomberg School of Public Health. "However, it is known that severe inflammations, such as those observed in COVID-19 patients, make the barrier disintegrate."

The impermeability of the blood-brain barrier, he adds, also can present a problem for drug developers targeting the brain.

The impact of SARS-CoV-2 on the developing brain is another concern raised by the study. Previous research from Paris-Saclay University has shown that the virus crosses the placenta, and embryos lack the blood-brain barrier during early development. "To be very clear," Hartung says, "we have no evidence that the virus produces developmental disorders."

However, the mini-brains -- which model the growing human brain -- contain the ACE2 receptor from their earliest stages of development. Therefore, Hartung says, the findings suggest that extra caution should be taken during pregnancy.

"This study is another important step in our understanding of how infection leads to symptoms, and where we might tackle the COVID-19 disease with drug treatment," says William Bishai, M.D., Ph.D., professor of medicine at the Johns Hopkins University School of Medicine, and leader of the infectious disease team for the study.

The human stem cell-derived mini-brain models -- known as BrainSpheres -- were developed at the Bloomberg School of Public Health four years ago. They were the first mass-produced, highly standardized organoids of their kind, and have been used to model a number of diseases, including infections by viruses such as Zika, dengue and HIV.

Credit: 
Johns Hopkins Medicine

Ohio University professor, alum publish paper on record warming of the South Pole

image: Ohio University Professor Ryan Fogt at the South Pole.

Image: 
Courtesy of Ryan Fogt

ATHENS, Ohio (June 30, 2020) - The South Pole has been warming at more than three times the global average over the past 30 years, according to research led by Ohio University professor Ryan Fogt and OHIO alumnus Kyle Clem.

Fogt, professor of meteorology and director of the Scalia Laboratory for Atmospheric Analysis, and Clem coauthored a paper with an international team of scientists published in the journal Nature Climate Change on the findings. According to the study, this warming period was mainly driven by natural tropical climate variability and was likely intensified by increases in greenhouse gas.

Clem, a current postdoctoral research fellow in climate science at Victoria University of Wellington in New Zealand, is the lead author of the study and studied under Fogt for both his bachelor's and master's degrees at Ohio University.

"I've had a passion for understanding the weather and fascination of its power and unpredictability as far back as I can remember," Clem said. "Working with Ryan I learned all about Antarctic and Southern Hemisphere climate, specifically how West Antarctica was warming and its ice sheet was thinning and contributing to global sea level rise. I also learned that Antarctica experiences some of the most extreme weather and variability on the planet, and due to its remote location we actually know very little about the continent, so there are constant surprises and new things to learn about Antarctica every year."

The Antarctic climate exhibits some of the largest ranges in temperature during the course of the year, and some of the largest temperature trends on the planet, with strong regional contrasts. Most of West Antarctica and the Antarctic Peninsula experienced warming and ice-sheet thinning during the late 20th century. By contrast, the South Pole -- located in the remote and high-altitude continental interior -- cooled until the 1980s and has since warmed substantially. These trends are affected by natural and anthropogenic climate change, but the individual contribution of each factor is not well understood.

Clem and his team analyzed weather station data at the South Pole, as well as climate models to examine the warming in the Antarctic interior. They found that between 1989 and 2018, the South Pole had warmed by about 1.8 degrees Celsius over the past 30 years at a rate of +0.6 degrees Celcius per decade - three times the global average.

The study also found that the strong warming over the Antarctic interior in the last 30 years was mainly driven by the tropics, especially warm ocean temperatures in the western tropical Pacific Ocean that changed the winds in the South Atlantic near Antarctica and increased the delivery of warm air to the South Pole. They suggest these atmospheric changes along Antarctica's coast are an important mechanism driving climate anomalies in its interior.

Clem and Fogt argue that these warming trends were unlikely the result of natural climate change alone, emphasizing the effects of added anthropogenic warming on top of the large tropical climate signal on Antarctic climate have worked in tandem to make this one of the strongest warming trends worldwide.

"From the very beginning, Kyle and I worked very well together and were able to accomplish more as a team than we were individually," Fogt said. "We have published every year together since 2013, with one of our continuing collaborations being the annual State of the Climate reports. Our work on this project together each year ultimately led to this publication documenting the warming at the South Pole, however, most importantly for me, apart from being a fantastic scientist and collaborator, my family and I are both honored to consider Kyle one of our closest friends."

Credit: 
Ohio University

Chanterelle mushrooms as a taste enhancer

image: Dr. Verena Mittermeier from the Chair of Food Chemistry and Molecular Sensory Science and Andreas Dunkel from the Leibniz-Institute for Food Systems Biology in front of their institute.

Image: 
Leibniz-LSB@TUM

Chanterelles (Cantharellus cibarius) are one of the most popular mushrooms in Germany. Depending on the weather, chanterelle season starts in early July. Connoisseurs value the mushroom's delicate fruity aroma, which is reminiscent of apricots, and its aromatic and slightly bitter taste profile. Not only do chanterelles have a unique flavor profile, they also function as taste enhancers, lending dishes a well-rounded mouthfeel and a lingering, rich flavor.

Key substances for the kokumi sensation

"Using the ultra-high-performance liquid chromatography-mass spectrometry method developed by our team, we are now the first to accurately quantify the key substances in chanterelles that are responsible for the kokumi effect", says Dr. Verena Mittermeier from the TUM Chair of Food Chemistry and Molecular Sensory Science. Dr. Verena Mittermeier already contributed significantly to the study during her time as a PhD student under Prof. Thomas Hofmann, who now serves as the President of TUM.

As the research team's findings show, the effect is caused by natural substances derived from fatty acids. Storage conditions, such as duration of storage and temperature, affect the composition and concentration of these fatty acid derivatives in the mushrooms. Whether the mushrooms are stored whole or chopped also plays a role.

New quality control marker

According to food chemist Andreas Dunkel from the Leibniz-Institute for Food Systems Biology at the Technical University of Munich, some of these derivatives are specific to chanterelles and can therefore be used as markers to control the quality of mushroom products. These findings could also be used to systematically improve the flavor profile of mushroom dishes or other savoury dishes using natural substances.

Andreas Dunkel explains: "Kokumi is a Japanese word that does not refer to a specific flavor quality such as salty or sweet." Instead, the fatty acid derivatives modulate the sensory characteristics of other ingredients.

Credit: 
Technical University of Munich (TUM)

A data treasure for gait analysis

image: The St. Pölten UAS and the Austrian general accident insurance institution AUVA have made one of the biggest data records for automated gait analysis worldwide openly accessible. Researchers are free to use the data in order to improve automated gait analysis with the help of methods such as machine learning. The dataset and the accompanying description were recently published in the magazine Scientific Data of the renowned publishing house Nature.

Image: 
FH St. Pölten / Florian Kibler

The database comprises information on the so-called "ground reaction force" (GRF) which is the force between the foot and the ground that is generated during movement. It is an important standard parameter used in clinical practice and in research. The figures form the basis for diagnosis and for the assessment of therapeutic success.

"Gait analysis provides a huge amount of data. Their interpretation is challenging and there is a great deal of interest in supporting medical decision-making processes with machine learning methods. The more data we have, the better the results", explains Brian Horsak, head of the research focus Motor Rehabilitation at the St. Pölten UAS.

Anonymised Data of More than 2,000 Patients

In order to facilitate research, therapy and diagnosis, Brian Horsak and his colleagues at the St. Pölten UAS and the AUVA have now published one of the biggest data records worldwide on this topic in anonymised form. The data include anonymised information on more than 2,000 patients after joint transplantations, fractures and ligament injuries as well as associated impairments of the hips, knees, ankles and heel bones.

The data come from several years of clinical gait analysis practice and can be used to improve analysis procedures and models. The database called "GAITREC" is available online free of charge.

"We have processed and published the data together with the AUVA. In times of the coronavirus, this dataset is even more interesting as many experts are unable to collect data in the lab and therefore have to rely on existing data records. Our dataset can be of assistance here, in terms of both teaching and research", emphasises Djordje Slijepčevi?, co-author of "GaitRec" and machine learning expert at the St. Pölten UAS.

Research Focus Motor Rehabilitation

The research focus Motor Rehabilitation at the St. Pölten UAS develops technology-assisted approaches to physical rehabilitation and promotes their widespread application in clinical practice through collaborations with partners. Within the framework of this research focus, the St. Pölten UAS and the AUVA have been carrying out joint research projects for years.

These last couple of years, the St. Pölten UAS has expanded its competencies in the fields of motor rehabilitation, instrumented 3D gait and movement analysis, machine learning, visual analytics, and augmented & virtual reality, and anchored them on location in the Center for Digital Health Innovation (CDHI). With the Digital Health Lab, the UAS has one of the most modern research labs in Austria in these fields.

The technical advancements in the aforementioned areas open up new and innovative treatment options in physical rehabilitation far beyond the existing approaches. The described works on the GAITREC database were partly funded by NÖ Forschungs- und Bildungsges.m.b.H. (NFB) and the department of science and research of the Lower Austrian state government.

Credit: 
St. Poelten University of Applied Sciences

Kessler survey shows education paves the way to employment for youth with disabilities

image: The 2020 survey collected a wealth of information, including details of college majors and occupations, finding that students with disabilities were more likely to pursue career paths focused on helping people, and less likely to choose STEM majors, or to work in STEM disciplines. "Preparing for STEM careers will help people with disabilities take advantage of this growth sector in our economy," said Dr. O'Neill. "Research shows that this is a disparity that can be addressed with the right support system," he added.

Image: 
Kessler Foundation

EAST HANOVER, NJ - June 30, 2020 - On a June 24 webinar, titled, "The ADA Generation: A Dialogue with Recent College Graduates with Disabilities," experts in employment and disability engaged with three young professionals to relate the results of a new national survey to the real-world experiences of recent college graduates with disabilities. The survey, commissioned by Kessler Foundation and implemented by the University of New Hampshire Institute on Disability (UNH-IOD), commemorates the 30th anniversary of the Americans with Disabilities Act (ADA) of 1990, and explores its impact on the first generation to come of age since the ADA's passage in 1990.

The panel focused on the topline findings of the 2020 Kessler Foundation National Employment and Disability Survey: Recent College Graduates, the third in a series of surveys that are changing perceptions about disability and work, and establishing new pathways for greater inclusion of people with disabilities in the workplace. The overall results of the 2020 survey were presented nationally on June 3, 2020 via a Zoom webinar, titled, "The ADA Generation: New Perspectives on Employment and College Graduates with Disabilities," and via a EurekAlert release. The experts reported that college students with disabilities were taking advantages of career services during college, and were transitioning from college to work at the same rate as their peers without disabilities - 90%.

Economist Andrew Houtenville, PhD, of UNH-IOD chaired the June 24 webinar, which featured John O'Neill, PhD, director of the Center for Employment and Disability at Kessler Foundation, Kimberly Phillips, PhD, of UNH-IOD, and psychologist Elizabeth Cardoso, PhD, chair of the Educational Foundations and Counseling Programs at Hunter College-City University of New York. Dr. Cardoso related the survey's new findings to the outcomes of the MIND Alliance grant she received from the National Science Foundation. MIND Alliance fosters careers in Science, Technology, Engineering, and Mathematics (STEM) among minority students with disabilities in high school, community college and college.

The college graduates with disabilities who shared their experiences were Hieu Duc Dang, AA, BA, MS, benefits counselor at the Center for Independence of the Disabled (CIDNY), Bryce Stanley, BA, MS, PhD candidate, research assistant at the University of New Hampshire, and Annemarie Veira, BA, MS, CRC, coordinator of the Office of Disability Resources at of the School of Visual Arts in New York City.

The 2020 survey collected a wealth of information, including details of college majors and occupations, finding that students with disabilities were more likely to pursue career paths focused on helping people, and less likely to choose STEM majors, or to work in STEM disciplines. "Preparing for STEM careers will help people with disabilities take advantage of this growth sector in our economy," said Dr. O'Neill. "Research shows that this is a disparity that can be addressed with the right support system," he added.

Providing comprehensive support beginning in high school can increase the participation of minorities with disabilities in STEM careers, according to Dr. Cardoso. "More than 700 students received the services of the MIND Alliance," she reported, "including role modeling, tutoring, and mentoring, as well as exposure to internships, exposure to careers in STEM, and exposure to individuals with disabilities in STEM careers. These MIND Alliance students excelled in terms of their graduation rates at every level, in transitioning to higher education, and in choosing STEM careers."

During the webinar, Dang, Stanley and Veira shared how their college experiences compared with the survey's main findings, in terms of disability and career services, accommodations, and preparation for transitioning to the workplace. They were encouraged when the survey showed that peers with disabilities were striving to work and transitioning to jobs as they had, but cautioned that there are still disparities in job quality (e.g., earnings, hours working) between college graduates with and without disabilities.

"We've learned a great deal from the survey and our panelists," Dr. O'Neill acknowledged. "We plan to look deeper into our results to find better ways to support and advise youth with disabilities, their families, and educators. Looking at the impact of the type of disability and the type of college, for example, will yield useful information," he predicted. It's clear that we can build on the gains that individuals with disabilities have made since the ADA, and improve their educational experience and employment outcomes."

Credit: 
Kessler Foundation

Brain receptor pulls open electrical gate like a puppet master

image: The NMDA receptor (in green and magenta) is embedded in the neuronal cell membrane (black lollipop-like structures arranged in two rows). The top part of the receptor is outside the neuron and binds neurotransmitters glutamate (green) and glycine (white) in its ligand-binding domains.

Image: 
Furukawa lab/CSHL, 2020

For the first time, researchers in the lab of CSHL Professor Hiro Furukawa have been able to track each atom in the NMDA receptor, an important brain protein, as it transmits or inhibits neural signals. Critical for brain development and function, the receptor converts chemical messages between cells into electrical signals within a neuron. The key to transmitting that information is opening the receptor's built-in ion channel, a hollow pore that allows electrically charged ions to flow. Unlocking the receptor's ion channel is like working a stringed puppet--rock one part of the receptor and slender filaments pull open the channel's gate. Rock it a little differently, the filaments loosen, and the gate snaps shut. Understanding how the receptor works could lead to better treatments for Alzheimer's disease, depression, epilepsy, stroke, or schizophrenia.

Using high resolution electron cryo-microscopy (cryo-EM) and a series of specially constructed receptors, the scientists were able to follow every twist and turn of receptor parts as they bind natural and synthetic compounds, rock open the gate, and let it shut again.

The NMDA receptor is embedded in the neuronal membrane with the receptor binding portion on the outside of the cell and the ion channel spanning the cell membrane. When activating molecules glycine and glutamic acid bind to the ligand-binding domain (LBD) in the right way, the LBD rocks, pulling a loop or filament attached to the ion channel gate to open it. But if an antagonist binds, the loop loosens so much that the LBD cannot pull open the gate. Furukawa says:

"This is all happening because the subunit arrangement changes quite dramatically upon binding to the inhibitor. It all comes down to the stretching and non-stretching of the loop between the ligand-binding domain and the ion channel. They're really a series of conformations or events that are happening outside [the cell], and it eventually gets translated to the ion channel activity,"

Formerly, the stretching of the loops and their effect on the opening and closing of the ion channel were pure speculation on Furukawa's part. Now he has the data to prove what before he could only imagine.

Watch "How does the NMDA receptor work?": https://www.youtube.com/watch?v=5zqBsPmH8ck

There are multiple conformations when glycine and glutamate are bound to NMDA receptor's Ligand Binding Domain (LBD). In going from non-active to active state, there is going to be a rolling motion--I'm going to go back again--there's going to be a rolling motion of Ligand Binding Domain. Here is the loop that tethers Ligand Binding Domain and a transmembrane domain. And the transmembrane domain forms the ion channel pore. When this rolling motion happens, it is that the loop that tethers that transmembrane domain would be stretched. When the loop is stretched, what happens is that the residues, or amino acids, that are forming the ion channel pore is stretched apart.

This discovery will enable researchers to develop better drugs to control the NMDA receptor's activity, which can be involved in Alzheimer's disease, depression, schizophrenia, stroke, and epilepsy. The insights gained in this study may also be applicable to other receptor-mediated ion channels.

Credit: 
Cold Spring Harbor Laboratory

NASA's TESS delivers new insights into an ultrahot world

video: Explore KELT-9 b, one of the hottest planets known. Observations from NASA's Transiting Exoplanet Survey Satellite (TESS) have revealed new details about the planet's environment. The planet follows a close, polar orbit around a squashed star with different surface temperatures, factors that make peculiar seasons for KELT-9 b.

Watch on YouTube: https://youtu.be/bLMIo9Q5mDA

Download in HD: https://svs.gsfc.nasa.gov/13635

Image: 
NASA's Goddard Space Flight Center

Measurements from NASA's Transiting Exoplanet Survey Satellite (TESS) have enabled astronomers to greatly improve their understanding of the bizarre environment of KELT-9 b, one of the hottest planets known.

"The weirdness factor is high with KELT-9 b," said John Ahlers, an astronomer at Universities Space Research Association in Columbia, Maryland, and NASA's Goddard Space Flight Center in Greenbelt, Maryland. "It's a giant planet in a very close, nearly polar orbit around a rapidly rotating star, and these features complicate our ability to understand the star and its effects on the planet."

The new findings appear in a paper led by Ahlers published on June 5 in The Astronomical Journal.

Located about 670 light-years away in the constellation Cygnus, KELT-9 b was discovered in 2017 because the planet passed in front of its star for a part of each orbit, an event called a transit. Transits regularly dim the star's light by a small but detectable amount. The transits of KELT-9 b were first observed by the KELT transit survey, a project that collected observations from two robotic telescopes located in Arizona and South Africa.

Between July 18 and Sept. 11, 2019, as part of the mission's yearlong campaign to observe the northern sky, TESS observed 27 transits of KELT-9 b, taking measurements every two minutes. These observations allowed the team to model the system's unusual star and its impact on the planet.

KELT-9 b is a gas giant world about 1.8 times bigger than Jupiter, with 2.9 times its mass. Tidal forces have locked its rotation so the same side always faces its star. The planet swings around its star in just 36 hours on an orbit that carries it almost directly above both of the star's poles.

KELT-9 b receives 44,000 times more energy from its star than Earth does from the Sun. This makes the planet's dayside temperature around 7,800 degrees Fahrenheit (4,300 C), hotter than the surfaces of some stars. This intense heating also causes the planet's atmosphere to stream away into space.

Its host star is an oddity, too. It's about twice the size of the Sun and averages about 56 percent hotter. But it spins 38 times faster than the Sun, completing a full rotation in just 16 hours. Its rapid spin distorts the star's shape, flattening it at the poles and widening its midsection. This causes the star's poles to heat up and brighten while its equatorial region cools and dims -- a phenomenon called gravity darkening. The result is a temperature difference across the star's surface of almost 1,500 F (800 C).

With each orbit, KELT-9 b twice experiences the full range of stellar temperatures, producing what amounts to a peculiar seasonal sequence. The planet experiences "summer" when it swings over each hot pole and "winter" when it passes over the star's cooler midsection. So KELT-9 b experiences two summers and two winters every year, with each season about nine hours.

"It's really intriguing to think about how the star's temperature gradient impacts the planet," said Goddard's Knicole Colón, a co-author of the paper. "The varying levels of energy received from its star likely produce an extremely dynamic atmosphere."

KELT-9 b's polar orbit around its flattened star produces distinctly lopsided transits. The planet begins its transit near the star's bright poles and then blocks less and less light as it travels over the star's dimmer equator. This asymmetry provides clues to the temperature and brightness changes across the star's surface, and they permitted the team to reconstruct the star's out-of-round shape, how it's oriented in space, its range of surface temperatures, and other factors impacting the planet.

"Of the planetary systems that we've studied via gravity darkening, the effects on KELT-9 b are by far the most spectacular," said Jason Barnes, a professor of physics at the University of Idaho and a co-author of the paper. "This work goes a long way toward unifying gravity darkening with other techniques that measure planetary alignment, which in the end we hope will tease out secrets about the formation and evolutionary history of planets around high-mass stars."

Credit: 
NASA/Goddard Space Flight Center