Culture

Researchers from the Institute of Biomedicine of Seville (IBIS) have presented a study carried out in the Clinical Biochemistry Service of the Virgen del Rocío University Hospital which identifies the values for six biochemical biomarkers that indicate a patient may be infected with SARS-COV-2 (COVID-19). The key novelty of this study, led by Dr. Juan Miguel Guerrero, head of service and IR of the IBiS Molecular NeuroImmunoendocrinology group, lies in the fact that it was carried out using a blood test and can provide a determination in about 60 minutes.

The Coronavirus continues to concern society and occupy researchers and health professionals. Research remains key to achieving not only a vaccine but also a rapid diagnosis of the disease. The Laboratory of the Virgen del Rocío University Hospital in Seville has identified the values of six biochemical biomarkers which indicate the patient may be infected with the Coronavirus.

This was possible thanks to their cooperation with the specialists at the Clinical Biochemistry service, who evaluated the routine blood tests of more than 200 people conducted in the ED to detect infection. Specifically, they analysed the accuracy of each biomarker to differentiate between patients infected with COVID-19 and those who aren't. The researchers behind the study have established six criteria linked to suspected COVID-19 infection using the blood lymphocyte and eosinophil count, and the levels of ferritin, lactate dehydrogenase, C-reactive protein and d-dimer in plasma. Ninety-one percent of patients infected with COVID-19 met one or more of these biomarker criteria. It is thus possible to rule out a Coronavirus infection with a high degree of probability in patients who meet none of these criteria.

All hospitals have the facilities to test for these biomarkers using quick, automated analysers (in less than 60 minutes). These laboratory criteria, combined with medical history and imaging tests, can be very useful to screen patients with suspected COVID-19.

For this study, the researchers collaborated with the company Blueberry Diagnostics, creating an algorithm that uses artificial intelligence to identify patients infected with COVID-19 with a sensitivity of 100% and a specificity of 100%. A second algorithm has been developed that can detect those patients with a more serious prognosis from the disease, thus making it possible to prioritise their treatment and reduce the mortality rate. The algorithms have since been turned into decision trees which are to be released through a public license so that any hospital can analyse them in its own laboratory.

Neutrinos are chargeless particles with about a mass about a millionth that of an electron that are created by the nuclear processes that occur in the Sun and other stars. These particles are often colourfully described as the 'ghosts' of the particle zoo because they interact so weakly with matter. A paper published in EPJ C by the Borexino collaboration - including XueFeng Ding, Postdoc Associate of Physics at Princeton University, United States - documents the attempts of the Borexino experiment to measure low-energy neutrinos from the Sun's carbon-nitrogen-oxygen (CNO) cycle for the first time.

"This giant instrument, buried beneath the Gran Sasso mountains in the Gran Sasso National Laboratory in Italy, is capturing ghost-like neutrinos from a so-called CNO process in the very centre of the Sun," Ding explains. "We made tens of thousands of simulations and predicted that we would be able to prove these 'CNO' ghosts exist for the first time in human history ever."

The Sun produces energy by converting four hydrogen nuclei to one helium nucleus through two mechanisms. The majority of energy produced by the Sun is initiated by the direct fusion of two protons into a deuteron, starting the pp chain, the other mechanism is catalysed by heavier nuclei, such as carbon, nitrogen and oxygen, known as the CNO cycle - which produces about 1% of our star's energy output. As well as this small energy contribution, the CNO cycle should also produce about 1% of the neutrinos that stream from the Sun.

"Neutrinos from the CNO cycle process in the Sun had remained essentially hypothetical until the recent report of Borexino on the Neutrino 2020 conference," Ding says. "Borexino has been looking for CNO neutrinos since 2016 after the thermal insulation system and active temperature control system were installed. This paper reports a quantitative study on the Borexino sensitivity in searching for CNO neutrinos and explains the methodology."

Since the Sun itself only has a 1% CNO branch, and since neutrinos are already incredibly difficult to detect, there has been essentially no measurement yet of the CNO process itself, even though it is believed to be the dominate energy production avenue in stars much more massive than the Sun. Detecting neutrinos from the CNO cycle will teach researchers much more about it, in turn revealing the secrets locked beneath the surface of the Universe's most massive stars.

New Orleans, LA - A study by researchers at LSU Health New Orleans School of Public Health, believed to be the first study to investigate the role of neighborhood deprivation on COVID-19 in Louisiana, found that the more a neighborhood is deprived, the higher the risk for cases of COVID-19. They report that people living in the most deprived neighborhoods had an almost 40% higher risk of COVID-19 compared to those residing in the least deprived neighborhoods. Their findings are published online in PLOS ONE, available here.

Led by Edward S. Peters, DMD, SM, ScD, FACE, the team at LSU Health New Orleans School of Public Health sought to find more definitive answers about what contributed to the nation's highest per capita rate of COVID-19 cases in New Orleans during the summer of 2020 and the disproportionate number of African Americans affected. Few studies in the US had assessed the role of social determinants of health on COVID-19 disease. The studies that existed examined only a couple of specific risk factors, such as overcrowding and income. The LSU Health New Orleans team took a much more comprehensive approach to examine the relationship between neighborhood deprivation and COVID-19 in Louisiana.

The authors explain, "Risk factors leading to COVID-19 disease, hospitalization, and mortality exist not only at the individual or biological level; neighborhood-level factors and their interactions with individual-level factors are also responsible for the observed disparities. Lack of access to health care, unemployment, less education, and poor housing conditions significantly increase the risk of COVID-19 infection. These determinants of health can be studied collectively as neighborhood or area deprivation."

"We used a measurement called the Area Deprivation Index (ADI) to look at how relative deprivation of Louisiana neighborhoods is associated with the rate of COVID-19 cases," notes Dr. Peters, Professor and Chair of Epidemiology at LSU Health New Orleans School of Public Health. "The ADI uses 17 census-derived measures of poverty, education, housing, and employment indicators at the census tract level to classify neighborhoods. It is a robust metric measuring many relevant social determinants of health that may help explain the socio-biologic mechanisms of disease. We obtained the cumulative number of Louisiana COVID-19 case counts from the Louisiana Department of Health on July 31, 2020. We estimated COVID-19 risk for five categories of deprivation, ranging from least to most deprived neighborhoods."

The authors noted that non-Hispanic African Americans are more likely to have vulnerable and low-paying jobs that do not allow remote work, are more likely to rely on public transportation and to live in crowded housing or work in crowded worksites that place them an increased risk for COVID-19. African Americans exhibit a greater burden of chronic medical conditions such as hypertension, diabetes, heart disease, chronic disease, and obesity that increase the severity of COVID-19 illness. In Louisiana, 2.9 million people have at least one chronic condition, and 68% of Louisiana adults are overweight or obese. Furthermore, the poverty rate is much higher among African Americans compared to Non-Hispanic Whites, and African Americans tend to live in neighborhoods with high poverty. Neighborhood socioeconomic status is linked to access to health care services, and people residing in low socioeconomic status neighborhoods are less likely to have access to health care services, which further increases the risk of adverse health outcomes related to COVID-19, such as a higher rate of hospitalizations and mortality.

"We observed a great disparity in deprivation among Louisiana neighborhoods," Peters says. "We also found an association between neighborhood deprivation and cumulative COVID-19 cases per 1,000 persons in Louisiana. Neighborhoods with greater deprivation should be especially targeted with public health prevention measures such as wearing a mask while in public, social distancing, and considered as a priority for COVID-19 vaccine delivery."

The research team also included Drs. Evrim Oral, Susanne Straif-Bourgeois, and Ariane L. Rung, along with PhD student Madhav KC, all at LSU Health New Orleans School of Public Health.

The world's largest solar observatory, the U.S. National Science Foundation's Daniel K. Inouye Solar Telescope, just released its first image of a sunspot. Although the telescope is still in the final phases of completion, the image is an indication of how the telescope's advanced optics and four-meter primary mirror will give scientists the best view of the Sun from Earth throughout the next solar cycle.

The image, taken January 28, 2020, is not the same naked eye sunspot currently visible on the Sun. This sunspot image accompanies a new paper by Dr. Thomas Rimmele and his team. Rimmele is the associate director at NSF's National Solar Observatory (NSO), the organization responsible for building and operating the Inouye Solar Telescope. The paper is the first in a series of Inouye-related articles featured in Solar Physics. The paper details the optics, mechanical systems, instruments, operational plans and scientific objectives of the Inouye Solar Telescope. Solar Physics will publish the remaining papers in early 2021.

Read Daniel K. Inouye Solar Telescope - Observatory Overview, by Thomas R. Rimmele et al. - Solar Physics volume 295, issue 12, 2020

"The sunspot image achieves a spatial resolution about 2.5 times higher than ever previously achieved, showing magnetic structures as small as 20 kilometers on the surface of the sun," said Rimmele.

The image reveals striking details of the sunspot's structure as seen at the Sun's surface. The streaky appearance of hot and cool gas spidering out from the darker center is the result of sculpting by a convergence of intense magnetic fields and hot gasses boiling up from below.

The concentration of magnetic fields in this dark region suppresses heat within the Sun from reaching the surface. Although the dark area of the sunspot is cooler than the surrounding area of the Sun, it is still extremely hot with a temperature of more than 7,500 degrees Fahrenheit.

This sunspot image, measuring about 10,000 miles across, is just a tiny part of the Sun. However, the sunspot is large enough that Earth could comfortably fit inside.

Sunspots are the most visible representation of solar activity. Scientists know that the more sunspots that are visible on the Sun, the more active the Sun is. The Sun reached solar minimum, the time of fewest sunspots during its 11-year solar cycle, in December 2019. This sunspot was one of the first of the new solar cycle. Solar maximum for the current solar cycle is predicted in mid-2025.

"With this solar cycle just beginning, we also enter the era of the Inouye Solar Telescope," says Dr. Matt Mountain, president of the Association of Universities for Research in Astronomy (AURA), the organization that manages NSO and the Inouye Solar Telescope. "We can now point the world's most advanced solar telescope at the Sun to capture and share incredibly detailed images and add to our scientific insights about the Sun's activity."

Sunspots, and associated solar flares and coronal mass ejections, cause many space weather events, which frequently impact the Earth, a consequence of living inside the extended atmosphere of a star. These events affect technological life on Earth. The magnetic fields associated with solar storms can impact power grids, communications, GPS navigation, air travel, satellites and humans living in space. The Inouye Solar Telescope is poised to add important capabilities to the complement of tools optimized to study solar activity particularly magnetic fields.

NSF's Inouye Solar Telescope is located on the island of Maui in Hawai?i. Construction began in 2013 and is slated to be completed in 2021.

"While the start of telescope operations has been slightly delayed due to the impacts of the COVID-19 global pandemic," said Dr. David Boboltz, NSF Program Director for the Inouye Solar Telescope, "this image represents an early preview of the unprecedented capabilities that the facility will bring to bear on our understanding of the Sun."

The Daniel K. Inouye Solar Telescope is a facility of the National Science Foundation operated by the National Solar Observatory under a cooperative agreement with the Association of Universities for Research in Astronomy, Inc. The Inouye Solar Telescope is located on land of spiritual and cultural significance to Native Hawaiian people. The use of this important site to further scientific knowledge is done so with appreciation and respect.

Vanderbilt University Medical Center researchers have discovered individuals with type 1 and type 2 diabetes infected with COVID-19 are three times more likely to have a severe illness or require hospitalization compared with people without diabetes.

Because of this amplified impact, they are urging policymakers to prioritize these individuals for COVID-19 vaccination. Their findings were published in Diabetes Care, the journal of the American Diabetes Association.

While studies have suggested that those with type 2 diabetes are at higher risk for more serious complications and being hospitalized if they get COVID-19, little is known about the risk for individuals with type 1 diabetes. In the U.S. alone, an estimated 1.6 million individuals have type 1 diabetes.

"I think these data support prioritizing individuals with type 1 or individuals with type 2 diabetes for immunization alongside other high-risk medical conditions that increase the risk of getting very sick with COVID-19, such as heart or lung disease," said Justin Gregory, MD, MSCI, lead investigator for the study.

The team of investigators identified electronic health records (EHRs) of more than 6,000 patients across 137 Vanderbilt Health clinical sites who had a COVID-19 diagnosis during the period from mid-March until the first week of August. The team then closely reviewed the patients' medical records and contacted many individuals by telephone to identify additional risk factors and gather more information on how COVID-19 had impacted their health.

They compared the overall impact of COVID-19 for three populations: individuals with type 1 diabetes, individuals with type 2 diabetes and those who did not have diabetes. The study was a prospective cohort study, meaning researchers identified the study subjects soon after their infection with COVID-19 and followed these individuals as they progressed through the illness. Prospective studies have lower risk of investigator bias as the outcome is not known when study subjects are identified.

"People with type 1 diabetes don't need to live in fear and have undue anxiety, but they need to be really diligent in doing the things we all should be doing," Gregory said. "All of us should be washing our hands and staying 6 feet apart. We should be conscientious about limiting the time spent with people outside our household. I'm not asking people with type 1 diabetes to do anything that all of us shouldn't already be doing. I just think they need to be the most diligent about doing it day in and day out."

Biologists from RUDN University working together with their colleagues from the Institute of Molecular Biology of the Russian Academy of Sciences and the Institute of Flax studied the genes that determine the fatty acid composition in flaxseed oil and identified polymorphisms in six of them. The team also found out what gene variations could extend the shelf life of flaxseed oil. This data can be used to improve the genetic selection of new flax breeds. The results were published in the BMC Plant Biology journal.

Linum usitatissimum or common flax has been known as an oil crop since the early Neolithic Age. Its seeds are used to produce oil, paints, lacquers, biofuel, resins, linseed oil varnish, linoleum, and pet food, while its stocks are a source of fiber for textiles and sealing materials. Breeds and lines of flax differ by fatty acid content and composition. The lines that contain less than 5% of linolenic acid but have a high content of linolic acid are known for long shelf life which is important for the food industry. The synthesis of fatty acids in flax is determined by genes that belong to the SAD and FAD families. A team of biologists including specialists from RUDN University used deep DNA sequencing to study the genome of flax and confirmed that SAD and FAD genes and their polymorphisms directly affect the fatty acid content in flax seeds and the shelf life of flaxseed oil.

"We created a representative set of 84 flax breeds and lines with different fatty acid content in their oil. Using deep sequencing, we identified the sequences of six genes: SAD1, SAD2, FAD2A, FAD2B, FAD3A and FAD3B," said Parfait Kezimana, a postgraduate student at the Agrarian and Technological Institute of RUDN University.

The team studied the genetic material of 50 flax germs from each breed and line to find polymorphisms allowing for intraparietal heterogeneity. Using the Illumina platform (MiSeq sequencer) with 400? coverage, the team managed to accurately identify the sequence of the genes.

Based on the content of fatty acids in flaxseed oil and different polymorphisms in the studied genes, the team found out which genes and their allelic variants determined the quantities of certain acids. All but one breed with low linolenic acid content had a polymorphism that substituted the amino acid histidine in FAD3B with tyrosine and the amino acid tryptophan in FAD3A with a stop codon. Thanks to these mutations, the oil made from these breeds of flax has a longer shelf life and is better preserved.

"We have evaluated the polymorphisms of SAD and FAD genes in a set of flax breeds and lines with different oil compositions and identified the polymorphisms that determine the content of fatty acids in them. Our results could be used to develop markers for the genetic selection of new flax breeds. In the future, breeds could be certified based on their DNA sequences," added Parfait Kezimana from RUDN University.

In the last five decades, we've learned a lot about the secret lives of proteins -- how they work, what they interact with, the machinery that makes them function -- and the pace of discovery is accelerating.

The first three-dimensional protein structure began emerging in the 1970s. Today, the Protein Data Bank, a worldwide repository of information about the 3D structures of large biological molecules, has information about hundreds of thousands of proteins. Just this week, the company DeepMind shocked the protein structure world with its accurate, AI-driven predictions.

But the 3D structure is often not enough to truly understand what a protein is up to, explains Ken Dill, director of the Laufer Center for Physical and Quantitative Biology at Stony Brook University and a member of the National Academy of Sciences. "It's like somebody asking how an automobile works, and a mechanic opening the hood of a car and saying, 'see, there's the engine, that's how it works.'"

In the intervening decades, computer simulations have built upon and added to the understanding of protein behavior by setting these 3D molecular machines in motion. Analyzing their energy landscapes, interactions, and dynamics has taught us even more about these prime movers of life.

"We're really trying to ask the question: how does it work? Not just, how does it look?" Dill said. "That's the essence of why you want to know protein structures in the first place, and one of the biggest applications of this is for drug discovery."

Writing in Science magazine in November 2020, Dill and his Stony Brook colleagues Carlos Simmerling and Emiliano Brini shared their perspectives on the evolution of the field.

"Computational Molecular Physics is an increasingly powerful tool for telling the stories of protein molecule actions," they wrote. "Systematic improvements in forcefields, enhanced sampling methods, and accelerators have enabled [computational molecular physics] to reach timescales of important biological actions.... At this rate, in the next quarter century, we'll be telling stories of protein molecules over the whole lifespan, tens of minutes, of a bacterial cell."

SPEEDING SIMULATIONS

Decades after the first dynamic models of proteins, however, computational biophysicists still face major challenges. To be useful, simulations need to be accurate; and to be accurate, simulation needs to progress atom by atom and femtosecond (10^-12 seconds) by femtosecond. To match the timescales that matter, simulations must extend over microseconds or milliseconds -- that is, millions of time-steps.

"Computational molecular physics has developed at a fast clip relatively speaking, but not enough to get us into the time and size and motion range we need to see," he said.

One of the main methods researchers use to understand proteins in this way is called molecular dynamics. Since 2015, with support from the National Institutes of Health and the National Science Foundation, Dill and his team have been working to speed up molecular dynamics simulations. Their method, called MELD, accelerates the process by providing vague but important information about the system being studied.

Dill likens the method to a treasure hunt. Instead of asking someone to find a treasure that could be anywhere, they provide a map with clues, saying: 'it's either near Chicago or Idaho.' In the case of actual proteins, that might mean telling the simulation that one part of a chain of amino acids is near another part of the chain. This narrowing of the search field can speed up simulations significantly -- sometimes more than 1000-times faster -- enabling novel studies and providing new insights.

PROTEIN STRUCTURE PREDICTIONS FOR COVID-19

One of the most important uses of biophysical modeling in our daily lives is drug discovery and development. 3D models of viruses or bacteria help identify weak spots in their defenses, and molecular dynamics simulations determine what small molecules may bind to those attackers and gum up their works without having to test every possibility in the lab.

Dill's Laufer Center team is involved in a number of efforts to find drugs and treatments for COVID-19, with support from the White House-organized COVID-19 HPC Consortium, an effort among Federal government, industry, and academic leaders to provide access to the world's most powerful high-performance computing resources in support of COVID-19 research.

"Everyone dropped other things to work on COVID-19," Dill recalled.

The first step the team took was to use MELD to determine the 3D shape of the coronavirus' unknown proteins. Only three of the 29 of the virus' proteins have been definitively resolved so far. "Most structures are not known, which is not a good beginning for drug discovery," he said. "Can we predict structures that are not known? That's the primary thing that we used Frontera for."

The Frontera supercomputer at the Texas Advanced Computing Center (TACC) -- the fastest at any university in the world -- allowed Dill and his team to make structure predictions for 19 additional proteins. Each of these could serve as an avenue for new drug developments. They have made their structure predictions publicly available and are working with teams to experimentally test their accuracy.

While it seems like the vaccine race is already close to declaring a winner, the first round of vaccines, drugs, and treatments are only the starting point for a recovery. As with HIV, it is likely that the first drugs developed will not work on all people, or will be surpassed by more effective ones with fewer side-effects in the future.

Dill and his Laufer Center team are playing the long game, hoping to find targets and mechanisms that are more promising than those already being developed.

REPURPOSING DRUGS AND EXPLORING NEW APPROACHES

A second project by the Laufer Center group uses Frontera to scan millions of commercially available small molecules for efficacy against COVID-19, in collaboration with Dima Kozakov's group at Stony Brook University.

"By focusing on the repurposing of commercially available molecules it's possible, in principle, to shorten the time it takes to find a new drug," he said. "Kozakov's group has the ability to quickly screen thousands of molecules to identify the best hundred ones. We use our physics modeling to filter this pool of candidates even further, narrowing the options experimentalists need to test."

A third project is studying an interesting cellular protein known as PROTAC that directs the "trash collector proteins" of human cells to pick up specific target proteins that they would not usually remove.

"Our cell has smart ways to identify proteins that needs to be destroyed. It gets next to it, puts a sticker on it, and the proteins who collect trash take it away," he explained. "Initially PROTAC molecules have been used to target cancer related proteins. Now there is a push to transfer this concept to target SARS-CoV-2 proteins."

Collaborating with Stony Brook chemist Peter Tonge, they are working to simulate the interaction of novel PROTACS with the COVID-19 virus. "These are some of our most ambitious simulations, both in term of the size of the systems we are tackling and in terms of the chemical complexity," he said. "Frontera is a crucial resource to give us sufficient turnaround times. For one simulation we need 30 GPUs and four to five days of continuous calculations."

The team is developing and testing their protocols on a non-COVID test system to benchmark their predictions. Once they settle on a protocol, they will apply this design procedure to COVID systems.

Every protein has a story to tell and Dill, Brini and their collaborators are building and applying the tools that help elucidate these stories. "There are some problems in protein science where we believe the real challenge is getting the physics and math right," Dill concluded. "We're testing that hypothesis on COVID-19."

BOSTON - New research from Boston Medical Center finds that the COVID-19 emergency systemic changes made to decrease in-person visits during the pandemic have led to a decrease in hospital-wide Hepatitis C (HCV) testing by 50 percent, and a reduction in new HCV diagnoses by more than 60 percent. Published in the Journal of Primary Care and Community Health, this new research highlights the impact that the COVID-19 pandemic is having on hospital-wide and ambulatory HCV testing, and the ramifications of this decrease in identification of the virus.

The study findings demonstrate a greater impact in primary care clinics where there was a 72 percent decrease in testing and 63 percent decrease in new diagnoses. This is where telemedicine was incorporated into the clinical workflows, showing standard preventive care, including HCV testing, was not routinely performed throughout the pandemic, and telemedicine acting as a barrier to HCV care. The findings that testing for and diagnoses of HCV were decreased during the COVID-19 surge is alarming, due to the effect that undetected disease can have on those who are unknowingly infected. From the public health perspective, HCV is a transmissible infection that can propagate throughout a population if not detected and treated.

"The large decrease in HCV screening demonstrates the tradeoffs that occurred between maintaining safety and delivering preventive care services as a result of the health system responses during this pandemic," says Heather Sperring, MS, a data quality specialist in the Center for Infectious Diseases and Public Health Programs at Boston Medical Center and corresponding author on this study. "Nontraditional methods of preventive healthcare delivery need to be used in order to prevent the detrimental long-term effects of these gaps in patient care. This includes proactive efforts aimed at increasing preventive care and screening, and interventions that reduce health risks, decrease avoidable emergency room visits, and minimize the time necessary for patients to be in the hospital."

The data for this analysis was collected prospectively from December 1, 2019 to June 30, 2020. Using descriptive statistics, the analysis was completed by comparing unique patient tests for 3.5-month periods before and after March 16, 2020, analyzing total tests and total new HCV RNA positive results before and after, and mean daily tests. Effective March 16, 2020, BMC implemented the utilization of telemedicine for outpatient clinics wherever possible; preventive care, including phlebotomy for HCV screening, was not performed during this time. HCV test results for patients were collected each day and comparisons were made for all testing across the hospital, as well as exclusively for the primary care sites that have been the most heavily affected by the introduction of telemedicine. Since 2016, BMC has been utilizing an HCV screening program to better identify and treat patients with HCV.

"The healthcare impacts of COVID-19 are more widespread than the effects of the disease itself. The pandemic has had substantial implications for our patients, and not just those who contracted COVID-19," says Elissa Schechter-Perkins, MD, MPH, an emergency medicine physician at Boston Medical Center, an associate professor of emergency medicine at Boston University School of Medicine and co-author on this study. "Hepatitis C virus is likely just one example of many chronic diseases whose cascade of care was affected by COVID-19."

As an urban safety-net hospital, the patient population at BMC has four times more cases of HCV than the national average and are consistently screened for HCV in the emergency department and other clinics throughout the hospital, per current CDC recommendations. Other public health initiatives need to be monitored in the context of telemedicine workflows in order to improve access to HCV testing, and for healthcare professionals to continue to monitor HCV screening trends.

First came their pioneering research a few years ago linking burnout and depression. Now City College of New York psychologist Irvin Sam Schonfeld and his University of Neuchâtel collaborator Renzo Bianchi present the Occupational Depression Inventory [ODI], a measure designed to quantify the severity of work-attributed depressive symptoms and establish provisional diagnoses of job-ascribed depression.

Touted by the duo as the first such measure of its kind, the ODI comprises nine symptom items and a subsidiary question assessing turnover intention. A total of 2254 employed individuals in the United States, New Zealand and France participated in the study.

"We examined the psychometric and structural properties of the ODI as well as the nomological network of work-attributed depressive symptoms," said Schonfeld, describing the methodology.

They adopted an approach centered on exploratory structural equation modeling (ESEM) bifactor analysis and developed a diagnostic algorithm for identifying likely cases of job-ascribed depression. Work-attributed depressive symptoms correlated in the expected direction with other variables of interest?e.g., job satisfaction, general health status?and were markedly associated with turnover intention. Of the 2254 participants, 7.6% (n = 172) met the criteria for a provisional diagnosis of job-ascribed depression.

According to Schonfeld, their study suggests that the ODI constitutes a sound measure of work-attributed depressive symptoms. "It may help occupational health researchers and practitioners identify, track and treat job-ascribed depression more effectively," he said, adding: "ODI-based research may contribute to informing occupational health policies and regulations in the future."

Schonfeld said unlike other researchers who charge researchers to use instruments they develop; he and Bianchi would make the ODI available to colleagues worldwide at no cost. Entitled "The Occupational Depression Inventory: A new tool for clinicians and epidemiologists," their study appears in the Journal of
Psychosomatic Research.

LA JOLLA--Researchers at La Jolla Institute for Immunology (LJI) have found that people with sepsis have never-before-seen particles in their blood. The scientists are the first to show that these particles, called elongated neutrophil-derived structures (ENDS), break off of immune cells and change their shape as they course through the body.

"We actually found a new particle in the human body that had never been described before," explains LJI Instructor Alex Marki, M.D., who served as first author of the study. "That's not something that happens every day."

The research, published December 4, 2020 in the Journal of Experimental Medicine shows the importance of understanding how immune cells change over the course of a disease.

"ENDS are not normal--they are not detectable in healthy people or mice," says LJI Professor Klaus Ley, M.D., who served as senior author of the study. "But ENDS are very high in sepsis, and I would not be surprised if they were high in other inflammatory diseases."

The beginning of the ENDS

The discovery of ENDS started with an odd observation.

Marki was studying neutrophils, a kind of immune cell that moves through the bloodstream and slips into tissues to fight infections. At the time, he was studying living mice to confirm the presence of tubes called tethers. These tethers are attached to neutrophils as they roll on the blood vessel wall.

During these experiments Marki noticed long, thin objects of neutrophil origin sticking to the vessel wall. Since no such structure was described in the scientific literature, the team had to come up with a name for them. The initial lab slang name "sausages" was eventually replaced by the elongated neutrophil-derived structures or ENDS.

Desperate for learning more about these new objects, the LJI team developed a series of new techniques to study how ENDS form and degrade--and to detect them in human and mouse blood plasma.

Thanks to sophisticated imaging techniques, the LJI team figured out that tethers become ENDS. As the neutrophils flop and roll along, their tethers get longer and longer. Eventually the tethers become too thin--just 150 nanometers (around 1/500th the width of a human hair). Then they break in the middle. Part of the tether stays with the neutrophil, but the broken fragment flies away in the bloodstream, off to form an ENDS.

The researchers showed that these ENDS curl against the vessel wall until they get a rounded shape. It's likely that the ENDS stay intact for a while, but not for long. Without any life-sustaining organelles inside, the ENDS begin to die. In fact, the researchers found that the ENDS secrete tell-tale signaling molecules that promote inflammation.

Compared with healthy subjects, the researchers showed that ENDS are around 100-fold more detectable in septic patients.

What this means for sepsis

Sepsis can occur when the immune system overreacts to an infection by flooding the body with dangerous chemicals. Instead of just fighting the infection, these chemicals trigger organ damage as they course through the bloodstream. The mortality rate for septic "shock" is 30 percent.

"Once you're in the hospital, sepsis is the most common cause of death," Ley says.

Ley and Marki are still not sure why ENDS form in patients with sepsis. To learn more, Marki hopes to collect more patient samples to track ENDS formation and frequency over time. "I'd like to study blood from several time points from each patient--to see the dynamics of how ENDS change," he says.

Ley says it is theoretically possible that ENDS could one day serve as a biomarker for early sepsis detection, but it is currently impossible to detect them in a clinical setting. "Right now, the assay is not practical because it takes specialized instrumentation," says Ley.

Rather than serving as a diagnostic, Ley thinks studying ENDS could reveal secrets to how the immune system evolved. He's curious to learn how the process to form ENDS evolved--and why.

"Neutrophils are very soft cells that can deform to reach almost any place in the body," says Ley. "So one hypothesis I have is that ENDS might be the price you pay for having such a soft cell--that if you pull too hard, it falls apart."

Boston, Mass. - Since the novel coronavirus emerged at the end of last year, scientists around the world -- including Beth Israel Deaconess Medical Center (BIDMC) immunologist Dan Barouch, MD, PhD -- have been developing vaccines to protect against COVID-19 and to put an end to the global pandemic. As of November 2020, three pharmaceutical companies released early data showing high rates of protection in Phase 3 human trials for their vaccines, but questions remain about how the body develops and maintains immunity after vaccination or infection.

In a new paper in the journal Nature, Barouch, Director of BIDMC's Center for Virology and Vaccine Research, and colleagues shed light on the role of antibodies and immune cells in protection against SARS-CoV-2, the virus that causes COVID-19, in rhesus macaques. "In this study, we define the role of antibodies versus T cells in protection against COVID-19 in monkeys. We report that a relatively low antibody titer (the concentration of antibodies in the blood) is needed for protection," said Barouch. "Such knowledge will be important in the development of next generation vaccines, antibody-based therapeutics, and public health strategies for COVID-19."

Building on previous findings that SARS-CoV-2 infection protects rhesus monkeys from re-exposure, Barouch and colleagues purified and collected antibodies from animals that had recovered from infection. They administered the antibodies at various concentrations to 12 uninfected macaques and observed that protection against SARS-CoV-2 challenge was dose dependent. Animals that received higher amounts of antibodies were protected more completely, while animals that received lower amounts of antibodies were protected less well. Similarly, when the researchers administered various concentrations of the purified antibodies to 6 macaques with active SARS-CoV-2 infection, those given higher doses demonstrated more rapid viral control.

In a second set of experiments, Barouch and colleagues evaluated the role of specific immune cells -- CD8+ T cells -- in contributing to protection against the virus by removing these cells from animals that had recovered from SARS-CoV-2 infection. Removal of these immune cells left the animals vulnerable to infection after re-exposure to SARS-CoV-2.

"Our data define the role of antibodies and T cells in protection against COVID-19 in monkeys. Antibodies alone can protect, including at relatively low levels, but T cells are also helpful if antibody levels are insufficient," said Barouch, who is also Professor of Medicine at Harvard Medical School, and a member of the Ragon Institute of MGH, MIT, and Harvard. "Such correlates of protection are important given the recent successful vaccine results from human trials, and the likelihood that these and other vaccines will become widely available in the spring; as a result future vaccines may need to be licensed based on immune correlates rather than clinical efficacy."

HOUSTON - (Dec. 4, 2020) - In his first year of graduate school, Rice University biochemist Zachary Wright discovered something hidden inside a common piece of cellular machinery that's essential for all higher order life from yeast to humans.

What Wright saw in 2015 -- subcompartments inside organelles called peroxisomes -- is described in a study published today in Nature Communications.

"This is, without a doubt, the most unexpected thing our lab has ever discovered," said study co-author Bonnie Bartel, Wright's Ph.D. advisor and a member of the National Academy of Sciences. "This requires us to rethink everything we thought we knew about peroxisomes."

Peroxisomes are compartments where cells turn fatty molecules into energy and useful materials, like the myelin sheaths that protect nerve cells. In humans, peroxisome dysfunction has been linked to severe metabolic disorders, and peroxisomes may have wider significance for neurodegeneration, obesity, cancer and age-related disorders.

Much is still unknown about peroxisomes, but their basic structure -- a granular matrix surrounded by a sacklike membrane -- wasn't in question in 2015. Bartel said that's one reason Wright's discovery was surprising.

"We're geneticists, so we're used to unexpected things. But usually they don't come in Technicolor," she said, referring to another surprising thing about Wright's find: beautiful color images that show both the walls of the peroxisome subcompartments and their interiors. The images were possible because of bright fluorescent reporters, glowing protein tags that Wright employed for the experiments. Biochemists modify the genes of model organisms -- Bartel's lab uses Arabidopsis plants -- to tag them with fluorescent proteins in a controlled way that can reveal clues about the function and dysfunction of specific genes, including some that cause diseases in people, animals and plants.

Wright, now a postdoctoral research associate in Bartel's lab, was testing a new reporter in 2015 when he spotted the peroxisome subcompartments.

"I never thought Zach did anything wrong, but I didn't think it was real," Bartel said. She thought the images must be the result of some sort of artifact, a feature that didn't really exist inside the cell but was instead created by the experiment.

"If this was really happening, somebody would have already noticed it," she recalled thinking.

"Basically, from that point on, I was trying to understand them," Wright said. He checked his instruments, replicated his experiments and found no evidence of an artifact. He gathered more evidence of the mysterious subcompartments, and eventually wound up at Fondren Library, combing through old studies.

"I revisited the really old literature about peroxisomes from the '60s, and saw that they had observed similar things and just didn't understand them," he said. "And that idea was just lost."

There were a number of references to these inner compartments in studies from the '60s and early '70s. In each case, the investigators were focused on something else and mentioned the observation in passing. And all the observations were made with transmission electron microscopes, which fell out of favor when confocal microscopy became widely available in the 1980s.

"It's just much easier than electron microscopy," Bartel said. "The whole field started doing confocal microscopy. And in the early days of confocal microscopy, the proteins just weren't that bright."

Wright was also using confocal microscopy in 2015, but with brighter reporters that made it easier to resolve small features. Another key: He was looking at peroxisomes from Arabidopsis seedlings.

"One reason this was forgotten is because peroxisomes in yeast and mammalian cells are smaller than the resolution of light," Wright said. "With fluorescence microscopy, you could only ever see a dot. That's just the limit that light can do."

The peroxisomes he was viewing were up to 100 times larger. Scientists aren't certain why peroxisomes get so large in Arabidopsis seedlings, but they do know that germinating Arabidopsis seeds get all of their energy from stored fat, until the seedling leaves can start producing energy from photosynthesis. During germination, they are sustained by countless tiny droplets of oil, and their peroxisomes must work overtime to process the oil. When they do, they grow several times larger than normal.

"Bright fluorescent proteins, in combination with much bigger peroxisomes in Arabidopsis, made it extremely apparent, and much easier, to see this," Wright said.

But peroxisomes are also highly conserved, from plants to yeast to humans, and Bartel said there are hints that these structures may be general features of peroxisomes.

"Peroxisomes are a basic organelle that has been with eukaryotes for a very long time, and there have been observations across eukaryotes, often in particular mutants, where the peroxisomes are either bigger or less packed with proteins, and thus easier to visualize," she said. But people didn't necessarily pay attention to those observations because the enlarged peroxisomes resulted from known mutations.

The researchers aren't sure what purpose is served by the subcompartments, but Wright has a hypothesis.

"When you're talking about things like beta-oxidation, or metabolism of fats, you get to the point that the molecules don't want to be in water anymore," Wright said. "When you think of a traditional kind of biochemical reaction, we just have a substrate floating around in the water environment of a cell -- the lumen -- and interacting with enzymes; that doesn't work so well if you've got something that doesn't want to hang around in the water."

"So, if you're using these membranes to solubilize the water-insoluble metabolites, and allow better access to lumenal enzymes, it may represent a general strategy to more efficiently deal with that kind of metabolism," he said.

Bartel said the discovery also provides a new context for understanding peroxisomal disorders.

"This work could give us a way to understand some of the symptoms, and potentially to investigate the biochemistry that's causing them," she said.

Organic-inorganic hybrid lead iodide perovskites are universally recognized as very promising photovoltaic (PV) materials. While outstanding PV performance is continuously reported, manipulating these hybrid perovskites for extraordinary optoelectronic properties with a greater intrinsic structural stability becomes a growing attention. The soft nature of organic-inorganic halide perovskites renders their lattice particularly tunable to external stimuli such as pressure, undoubtedly offering an effective way to modify their structure for extraordinary optoelectronic properties. However, these soft materials meanwhile feature a general characteristic that even a very mild pressure will lead to detrimental lattice distortion and weaken the critical light-matter interaction, thereby triggering the performance degradation.

Herein, an international research team led by scientists from Center for high pressure science and technology advanced research (HPSTAR) reported a comprehensive high-pressure isotope research on hybrid perovskites. To their surprise, it is observed that the pressure-driven lattice disorder can be significantly suppressed via hydrogen isotope effect, which is crucial for better optical and mechanical properties previously unattainable. By in situ neutron/synchrotron-based analysis and optical characterizations, a remarkable photoluminescence (PL) enhancement by threefold is convinced in deuterated CD3ND3PbI3, which also shows much greater structural robustness with retainable PL after high peak-pressure compression-decompression cycle.

The researchers also proposed an atomic level understanding of the strong correlation among the organic sublattice and lead iodide octahedral framework and structural photonics, where the less dynamic CD3ND3+ cations are vital to maintain the long-range crystalline order through steric and Coulombic interactions. In addition, the result of device-related investigations shows CD3ND3PbI3-based solar cell has comparable photovoltaic performance as CH3NH3PbI3-based device but exhibits considerably slower degradation behavior, thus representing a paradigm by suggesting isotope-functionalized perovskite materials for better materials-by-design and more stable photovoltaic application.

AMHERST, MASS. - If you find yourself in a car with someone outside your household during the COVID-19 pandemic, your instinct may be to roll down your window, whether you're the driver or a back-seat passenger. But a University of Massachusetts Amherst physicist has shown in a new study that opening the car window closest to you isn't always the best option to protect yourself from coronavirus or any airborne infection.

In a paper published Dec. 4 in the journal Science Advances, researchers have revealed certain surprising ways in which the airflow patterns within a car's interior could either heighten or suppress the risk of airborne infection during everyday commutes.

"One might imagine that people instinctively open windows right beside them while riding with a co-passenger during the pandemic. That may not be optimal - though it's better than opening no window," says lead author Varghese Mathai, an assistant professor of physics at UMass Amherst.

He explains, "We designed this research with ride-sharing in mind, from a traditional taxi or Uber and Lyft to noncommercial commutes, assuming a driver and one passenger, seated in the back on the passenger side to provide the best possible spacing between the occupants."

Briefly, the research suggests that opening the windows farthest from the driver and the back-seat passenger might offer some benefits. The findings may provide COVID-19 risk reduction measures for the hundreds of millions of people driving in passenger cars or taking a taxi worldwide.

The most and least risky scenarios for airborne pathogen transmission in a car are understood by scientists: Opening all the windows, along with bringing in fresh air through the vents, is thought to create the best in-cabin environment to reduce the risk of transmission by increasing ventilation. Keeping all the windows up and using only the recirculating air mode is likely the riskiest option.

Realizing the impracticalities of keeping all car windows open in winter or rainy weather, Mathai wanted to examine what happens to aerosolized particles exhaled by occupants inside the car's cabin under various configurations of open and closed windows. "These tiny, potentially pathogenic particles remain in the air for long durations without settling down, so if they are not flushed out of the cabin, they can build up over time posing an increased risk of infection," he explains.

Generally, the air flowing around a car creates a lower pressure on the front windows as compared to the back windows, Mathai says. "We had this idea that if you open the rear and front windows on opposite sides, then you might create an air current from the rear to the front of the cabin, and crossing through the middle."

The study was conducted with colleagues Asimanshu Das, Jeffrey Bailey and Kenneth Breuer at Brown University, where Mathai worked previously and started the study. The researchers hypothesized that if all windows can't be left open, opening the front window on the right side and the rear window on the left side might best protect the driver and passenger from the hundreds of aerosol particles released in every human breath.

"To our surprise, the simulations showed an air current that acts like a barrier between the driver and the passenger," says Mathai, who likened this phenomenon to the air curtain created by a draft blown down vertically at some supermarket entrances, which prevents outdoor air from mixing with indoor air, even if the entrance door is open.

"While these measures are no substitute for wearing a face mask while inside a car, they can help reduce the pathogen load inside the very confined space of a car cabin," he points out.

Like many other researchers during the pandemic, Mathai -- an experimental physicist -- decided to shift his focus toward computer simulations while working from home. He later backed up his findings using smoke visualization and field tests that identified low-speed and high-speed zones inside the car.

The research describes the driver-to-passenger and passenger-to-driver transmission for different ventilation options, and used passive scalar transport as a proxy for infectious particles. Heat maps illustrate the scalar concentration fields originating from either the driver or passenger.

The researchers used a simplified, time-averaged model for the turbulent air flow, and study implications are limited to airborne mode of transmission, the authors stress. The computer model was based roughly on the exterior of a Toyota Prius driven at around 50 mph and the field tests of smoke and flow wand were recorded in the cabin of a Kia Optima.

An analysis of lung tissues from patients with different types of pulmonary fibrosis - including cases triggered by COVID-19 - has revealed a promising molecular target to ameliorate the chronic and irreversible disease. Experiments in mouse models of lung fibrosis showed that administering blockers of an epigenetic regulator called MBD2 via intratracheal inhalation protected the mice against fibrotic lung injury, highlighting a potential viable therapy. A poor understanding of what causes pulmonary fibrosis has greatly hindered the development of treatments, and to this day, no effective therapy is available other than lung transplantation. To tackle this limitation, Yi Wang and colleagues studied lung samples from patients with pulmonary fibrosis triggered by one of three causes: SARS-CoV-2 infection, systemic sclerosis-associated interstitial lung disease, or an unknown factor. The researchers also studied mouse models of pulmonary fibrosis, which they induced in the animals by administering the compound bleomycin. All cases of pulmonary fibrosis, they found, were characterized by overexpression of MBD2. This activity localized in areas occupied by macrophages - known contributors to the development of pulmonary fibrosis. To investigate this further, the scientists depleted the Mbd2 gene in macrophages of mice, which protected the animals against pulmonary fibrosis, characterized by markedly reduced macrophage accumulation in the lung following administration of bleomycin. As well, direct administration of liposomes - established carriers of inhaled drugs - loaded with Mbd2 silencer RNA into the trachea of mice protected them from lung injuries and fibrosis. Since MBD2 itself does not affect the essential epigenetic process of DNA methylation, inhibiting the molecule could prove to be a safe way to treat pulmonary fibrosis. However, future studies will first need to assess the impact of altered MBD2 expression in other types of cells relevant to pulmonary fibrosis, the authors say.