Culture

SAN FRANCISCO, Calif. - March 25, 2020 - While researchers are certain that coronavirus spreads through mucus and droplets expelled by coughing or sneezing, it is unclear if the virus is spread through other bodily fluids, such as tears. Today's just-published study offers evidence that it is unlikely that infected patients are shedding virus through their tears, with one important caveat. None of the patients in the study had conjunctivitis, also known as pink eye. However, health officials believe pink eye develops in just 1 percent to 3 percent of people with coronavirus. The study's authors conclude that their findings, coupled with the low incidence of pink eye among infected patients, suggests that the risk of virus transmission through tears is low. Their study was published online today in Ophthalmology, the journal of the American Academy of Ophthalmology.

To conduct the study, Ivan Seah, MBBS, and his colleagues at the National University Hospital in Singapore collected tear samples from 17 patients with COVID-19 from the time they showed symptoms until they recovered about 20 days later. Neither viral culture nor reverse transcription polymerase chain reaction (RT-PCR) detected the virus in their tears throughout the two-week course of the disease.

Dr. Seah also took samples from the back of the nose and throat during the same time period. While the patients' tears were clear of virus, their noses and throats were teeming with COVID-19. Dr. Seah said he hopes their work helps to guide more research into preventing virus transmission through more significant routes, such as droplets and fecal-oral spread.

Despite this reassuring news, it's important for people to understand that guarding your eyes -- as well as your hands and mouth -- can slow the spread of respiratory viruses like the coronavirus.

Here's why:

When a sick person coughs or talks, virus particles can spray from their mouth or nose into another person's face. You're most likely to inhale these droplets through your mouth or nose, but they can also enter through your eyes.

You can also become infected by touching something that has the virus on it -- like a table or doorknob -- and then touching your eyes.

Find other ways you can help protect yourself and others on the Academy's EyeSmart website.

WEST LAFAYETTE, Ind. - A 3D camera should be as easy to use as one found on a smartphone.

That is the guiding principle for a Purdue University professor with more than two decades of experience in the 3D imaging field, who has developed new technologies aimed at making 3D cameras easier to use.

Song Zhang, a professor of mechanical engineering in Purdue's College of Engineering, led a team to create technologies to help compress 3D camera files and automate focus and exposure settings.

"We have come a long way with high-end 3D camera technology," Zhang said. "But using the technology still almost always requires a great deal of training. We want to create technologies to make 3D cameras easier to use for everyone from tourists to doctors to video producers."

To obtain the best image with current high-end 3D cameras based on structured light technique, the manufacturer must conduct precise projector and camera focal length and other parameters calibration, and the user must manually adjust the optimal sensor exposure time. This leads to a training requirement for a user to properly operate the camera, and often involves complicated recalibration processes by the manufacturer if the camera is accidentally disturbed.

Zhang's team has automated the process of profilometry by developing algorithms to rapidly determine the optimal exposure after understanding the intrinsic constant response function of the sensor. The researchers also devised a method of generating highly accurate 3D images using an autofocusing feature on electronically tunable lenses.

"I believe 3D camera technology has the ability to have an even greater impact on the field than 2D camera technology ever has, assuming it is easy enough for users," Zhang said.

HOUSTON -- Treating T cells harvested from a patient with a combination of an epigenetic drug and a cytokine while expanding the cells in the lab re-programs them into a stronger T cell type that persists longer than its comrades, researchers at The University of Texas MD Anderson Cancer Center report in Cancer Immunology Research, a journal of the American Association for Cancer Research.

The combination of panobinostat and interleukin-21 converts the less vigorously expanding effector T cells that attack cancer cells to a more proliferative and enduring central memory T cell type capable of self-renewal, the team found.

"Central memory T cells do almost all the things you want - they persist because they have high replicative and proliferative capacity, and they have inducible cell-killing capacity so what they see they kill very well," says senior author Cassian Yee, M.D., professor of Melanoma Medical Oncology.

Lack of persistence is one major reason cellular therapies that involve harvesting, expanding, and in some instances, genetically modifying, a patient's T cells before returning them to attack cancer fail, Yee says.

"Producing more central memory T cells in vitro can address this persistence challenge and increase the effectiveness of cellular therapies," Yee notes. Clinical trials will be required to advance his team's findings in human T cell lines. Both IL-21 and panobinostat are readily available for use.

Present cellular therapies include chimeric antigen receptor T cells - genetically modified to attack a specific target and used to treat B cell blood cancers - and tumor-infiltrating leukocytes harvested from tumors used to treat melanoma. Both techniques are in clinical trials to address other types of cancer. Yee and colleagues are developing another technique, endogenous T cells, which identifies and harvests tumor-attacking T cells in the blood. All three techniques rely on expanding the T cells in the lab before re-infusing them into patients.

Cellular therapies produce mainly effector CD8-positive T cells that are fully differentiated to attack cells bearing specific antigens. Yee, first author Junmei Wang, Ph.D., instructor in Melanoma Medical Oncology, and colleagues showed that the combination therapy re-programs these effector T cells into central memory cells.

Firing up T cell-stimulating CD28

Their research confirmed that IL-21 activates STAT3, a protein that then connects with the promoter region of the gene encoding the T cell stimulatory protein CD28, firing up CD28.

Their team found that in effector T cells, this process is blocked by histone proteins that intertwine with DNA to form chromatin. This "closed" chromatin status covers the promoter regions on CD28 that STAT hits to activate it.

Acetyl groups that connect to histone proteins cause a more "open" status for gene transcription. Drugs called histone deacetylase (HDAC) inhibitors protect the acetyl group connection and allow transcription factors to connect with genes' promoter regions to activate them.

The team treated human T cell lines with the HDAC inhibitor vorinostat and IL-21. With vorinostat relaxing the chromatin, IL-21-generated STAT3 activated CD28, resulting in expansion of T cells bearing the markers for central memory T cells. The main markers are CD28 and CD62L expression.

A second round of experiments using the HDAC inhibitor panobinostat, which is less toxic to T cells than vorinostat, produced even stronger central memory T cell expansion. The combination was given at the start of T cell expansion procedures.

To further confirm the central memory properties of treated cells, the team assessed expression of genes involved in differentiating T cells and found expression of central-memory differentiating genes to be highly expressed on the identified central memory cells generated by the combination.

A patent application has been filed based on this research, which is being managed in accordance with MD Anderson's conflict-of-interest policies

Teeth constitute a permanent and faithful biological archive of the entirety of the individual's life, from tooth formation to death, a team of researchers has found. Its work provides new evidence of the impact that events, such as reproduction and imprisonment, have on an organism.

"Our results make clear that the skeleton is not a static organ, but rather a dynamic one," explains Paola Cerrito, a doctoral candidate in NYU's Department of Anthropology and College of Dentistry and the lead author of the paper, which appears in the journal Scientific Reports.

The paper's other authors include Shara Bailey, a professor in NYU's Department of Anthropology, Bin Hu, an associate research scientist at NYU's College of Dentistry, and Timothy Bromage, a professor at NYU's College of Dentistry.

The research focused on cementum, the dental tissue that covers the tooth's root. It begins to form annual layers--similar to a tree's "rings"--from the time the tooth surfaces in the mouth.

"The discovery that intimate details of a person's life are recorded in this little-studied tissue, promises to bring cementum straight into the center of many current debates concerning the evolution of human life history," says Bromage.

The Scientific Reports study tested the hypothesis that physiologically impactful events--such as reproduction and menopause in females and incarceration and systemic illnesses in both males and females--leave permanent changes in the microstructure of cementum and that such changes can be accurately timed.

"The cementum's microstructure, visible only through microscopic examination, can reveal the underlying organization of the fibers and particles that make up the material of this part of the tooth," notes Cerrito, who obtained her bachelor's degree at Sapienza University of Rome.

In their work, the scientists examined nearly 50 human teeth, aged 25 to 69, drawn from a skeletal collection with known medical history and lifestyle data, such as age, illnesses, and movement (e.g., from urban to rural environments). Much of this information was obtained from the subjects' next of kin. They then used a series of imaging techniques that illuminated cementum bands, or rings, and linked each of these bands to different life stages, revealing connections between tooth formation and other occurrences.

"A tooth is not a static and dead portion of the skeleton," observes Cerrito. "It continuously adjusts and responds to physiological processes.

"Just like tree rings, we can look at 'tooth rings': continuously growing layers of tissue on the dental root surface. These rings are a faithful archive of an individual's physiological experiences and stressors from pregnancies and illnesses to incarcerations and menopause that all leave a distinctive permanent mark."

Unlocking the full potential of cannabis for agriculture and human health will require a co-ordinated scientific effort to assemble and map the cannabis genome, says a just-published international study led by University of Saskatchewan researchers.

In a major statistical analysis of existing data and studies published in the Annual Review of Plant Biology, the authors conclude there are large gaps in the scientific knowledge of this high-demand, multi-purpose crop.

"Considering the importance of genomics in the development of any crop, this analysis underlines the need for a co-ordinated effort to quantify the genetic and biochemical diversity of this species," the authors state.

The team, which includes scientists in The Netherlands, Germany, and the U.S., found that less than 50 per cent of the cannabis genome is accurately mapped, with about 10 per cent of the genome missing and another 10 to 25 per cent unmapped.

"This means that we lack the foundation on which to build a molecular breeding program for cannabis comparable to what exists for other crops," said lead author Tim Sharbel, a plant scientist in the USask College of Agriculture and Bioresources.

"Developing a high-quality genetic blueprint would provide the building blocks for genomics-based breeding and applications to human and animal health, while strengthening university-industry partnerships."

The findings will serve as a cornerstone for various types of research conducted through the USask-led Cannabinoid Research Initiative of Saskatchewan (CRIS), said Sharbel. The multi-disciplinary team also involved USask researchers from the College of Pharmacy and Nutrition, College of Medicine, and the School of Environment and Sustainability.

"These data are crucial for setting up a core collection of genotypes which can be used to study various cannabis traits," he said.

Sharbel noted that recent societal and governmental acceptance of cannabis has spurred growing interest by companies in medical applications of cannabis use. He is seeking medicinal plant industry partners to help fund academic research that will map, compare and make full use of the closely related genomes of cannabis, hemp, and hops.

"This initiative would become part of an industry-driven effort to exchange resources and improve cannabis, hemp and hops for medicinal and industrial properties," he said.

"If we can publish case studies to show that certain compounds can treat human disorders with statistical significance, then getting such information into the medicare system--for example, as a basis for a Drug Identification Number assigned to a drug product before it can be marketed in Canada--would be of great benefit to companies."

Prior to joining USask, Sharbel worked on medicinal plants with both academic and industry partners for 15 years in Europe, studying the effects of the German chamomile herb on digestive disorders and St. John's wort on dementia.

"Medicinal plants are hugely important to society, have long traditional use throughout human history, and represent important reasons to protect biodiversity. The emergence of the cannabis industry is a good driver for a larger goal of bringing traditional medicinal plants into the mainstream," he said.

The authors found, in the limited data that exists, support for the potential health benefits of cannabis, including treatments for pain, spasticity in multiple sclerosis, and opioid use reduction. The analysis also cites negative short-term effects of THC, the main psychoactive compound in cannabis, such as reduced cognitive function, enhanced anxiety and fatigue, and potential long-term consequences such as permanent loss of memory, intelligence, mental focus, and judgment, as well as addiction.

"It is critical to recognize cannabis and cannabinoids as drugs with potential benefits and associated risks, as would be the case for the investigation of any novel drug," the authors state.

The team noted there is also evidence for developing hemp-type cannabis as a highly digestible, protein-rich food source that would be unlikely to cause an allergic reaction.

As the world prioritizes social distancing to stop or slow down the spread of coronavirus (COVID-19), a new study by researchers at Florida Atlantic University demonstrates that mother-infant touch and contact are essential for optimal neurodevelopmental regulation in early infancy. Kangaroo Care, a skin-to-skin, chest-to-chest method of caring for a baby, especially one who is premature, has been associated with promoting neurophysiological development. This method of caring emphasizes the importance of holding the naked or partially dressed baby against the bare skin of a parent, typically the mother. New research is showing that extended use of Kangaroo Care can positively benefit full-term infants and their mothers during the post-partum period.

The longitudinal randomized, controlled trial investigated if Kangaroo Care influences markers of neuro-maturation in healthy, full-term infants. They focused on the potential association between Kangaroo Care and infant brain development, specifically measures of EEG (electroencephalogram) asymmetry/power and coherence.

In addition to EEG patterns in infants, the researchers looked at basal oxytocin - the "cuddle" hormone - and cortisol reactivity - the "stress" hormone - in infants and their mothers. Oxytocin is considered an affiliative hormone associated with caregiving and affectionate behavior whereas cortisol reactivity is implicated in the stress response system. Researchers compared six weeks of Kangaroo Care to standard caring (control group) during the first three months of life.

For the study, mothers assigned to the Kangaroo Care group were given a Kangaroo Care wrap (Nurtured by Design, The Kangaroo Zak) and were taught proper procedures by a certified trainer at the prenatal visit. Mothers were asked to use Kangaroo Care, skin-to-skin, chest-to-chest contact with her infant, for one hour a day for six weeks and were provided with journals to record the frequency of Kangaroo Care use. Mothers in the control group were given infant feeding pillows and journals and were asked to record infant feedings for six weeks. Babies were fitted with a stretch Lycra cap to measure EEG activity during a five-minute quiet-alert state at three-months. Oxytocin was measured by collecting maternal and infant urine, and infant cortisol reactivity was measured by collecting infant saliva samples before and after a mild stressor.

Results of the study, published in the journal Infant Behavior and Development, provide evidence that the physiology of mothers and their full-term infants is influenced by obtaining Kangaroo Care training and utilizing it during the post-partum period.

"We wanted to know if exposure to extended tactile stimulation using the Kangaroo Care method would increase peripheral basal oxytocin and suppress cortisol reactivity in the babies in our study," said Nancy Aaron Jones, Ph.D., senior author, an associate professor, and director of the FAU WAVES Emotion Laboratory in the Department of Psychology in FAU's Charles E. Schmidt College of Science, and a member of the FAU Brain Institute (I-BRAIN). "We also wanted to examine if Kangaroo Care increases oxytocin levels in mothers, which has important implications for post-partum depression."

Findings showed that the infants' left frontal area of the brain (implicated in higher-order cognitive and emotional regulatory skills) appears to be stimulated from the Kangaroo Care method. In addition, mother/infant dyads showed increased oxytocin along with decreases in stress reactivity, suggesting regulatory abilities are prompted by experiences with positive caregiving in infancy.

Results from the study indicate that Kangaroo Care training and level of use by caregivers during infancy can favorably influence both neurodevelopmental trajectories and infant neurobiological functioning.

"Our findings across several studies demonstrate a link between the supportive dimensions of maternal caregiving behavior and left hemisphere neurodevelopment, with maternal warmth and sensitivity predicting greater regulatory abilities and secure attachment," said Jones. "Full-term infants and their mothers likely benefit from the positive interactive experiences inherent in extended Kangaroo Care use."

Study co-authors are Jillian S. Hardin, Ph.D., who conducted the study for her dissertation; Krystal D. Mize, Ph.D.; and Melannie Platt, Ph.D., all with FAU's Charles E. Schmidt College of Science.

The FAU WAVES Emotion Laboratory is focused on understanding the factors that contribute to the development of socio-emotional wellness during infancy and childhood. Funded in part by the National Institute of Mental Health of the National Institutes of Health, research in the laboratory is designed to explore and understand the contributors to optimal infant and child development.

- FAU -

About Florida Atlantic University:
Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University, with an annual economic impact of $6.3 billion, serves more than 30,000 undergraduate and graduate students at sites throughout its six-county service region in southeast Florida. FAU's world-class teaching and research faculty serves students through 10 colleges: the Dorothy F. Schmidt College of Arts and Letters, the College of Business, the College for Design and Social Inquiry, the College of Education, the College of Engineering and Computer Science, the Graduate College, the Harriet L. Wilkes Honors College, the Charles E. Schmidt College of Medicine, the Christine E. Lynn College of Nursing and the Charles E. Schmidt College of Science. FAU is ranked as a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. The University is placing special focus on the rapid development of critical areas that form the basis of its strategic plan: Healthy aging, biotech, coastal and marine issues, neuroscience, regenerative medicine, informatics, lifespan and the environment. These areas provide opportunities for faculty and students to build upon FAU's existing strengths in research and scholarship. For more information, visit fau.edu.

Analysis of human mobility and epidemiological data by a global consortium of researchers, led by the University of Oxford and Northeastern University, shows that human mobility was predictive of the spread of the epidemic in China. Restrictions of travel from Wuhan unfortunately came too late and research showed that the impact of travel restrictions declines as the epidemic grows. Provinces outside Hubei that acted early to test, track and contain imported COVID-19 cases fared the best at preventing or containing local outbreaks.

Mobile geolocation data from Baidu Inc, combined with a rich epidemiological dataset from the Open COVID-19 Data Working Group, showed that local person-to-person transmission happened extensively early on in the coronavirus outbreak and was mitigated by drastic control measures. However, with an average incubation period of 5 days, and up to 14 days in some cases, these mobility restrictions did not begin to positively impact the data on new cases for over a week - with things appearing to get worse in the 5-7 days immediately after the lockdown as local transmission was well under way.

Among cases reported outside Hubei, 515 cases had a known travel history to Wuhan and a symptom onset date before 31st January 2020, compared with only 39 after 31st January, illustrating the effect of travel restrictions in decreasing the spread to other Chinese provinces.

"Our findings show that early in the coronavirus outbreak travel restrictions were effective in preventing the import of infections from a known source," said Dr Moritz Kraemer from the Oxford Martin Programme on Pandemic Genomics and the Department of Zoology at the University of Oxford. "However, once COVID-19 cases begin spreading locally the contribution of new importations was much smaller. This is where a full package of measures including local mobility restrictions, testing, tracing and isolation need to work together to mitigate the epidemic. Chinese provinces and other countries that have successfully halted internal transmission of COVID-19 need to consider carefully how they will manage reinstating travel and mobility to avoid the reintroduction and spread of the disease in their populations."

Professor Samuel V. Scarpino of Network Science Institute (NetSI) at Northeastern University adds, "The political will in many countries is lagging behind the spread of COVID-19. Travel and mobility restrictions are the most useful right at the start, when local transmission has not yet become a factor. After transmission is established, physical distancing and the quarantine of sick individuals will work, but it takes time. "

In 2007, Finnish Airedale Terrier breeders sent puppies that had died only a few days after being born for pathological examinations to the Finnish Food Safety Authority (Evira), the predecessor of the Finnish Food Authority. Some litters had lost several puppies. A research project initiated at Evira under the direction of Professor Marjukka Anttila uncovered a problem in the puppies' lungs.

"There are vacuoles, or specialised membrane-bound organelles, in the epithelial, or superficial cells of the pulmonary alveoli, which are responsible for gas exchange. They are tasked with producing a substance that reduces surface tension on the surface of these cells, essential to breathing. The vacuoles in the lungs of the dead puppies hadn't matured normally, nor were they able to produce this surfactant," explains doctoral candidate Kati Dillard, LVM, from the Faculty of Veterinary Medicine, University of Helsinki, and the Finnish Food Authority.

A look at the dead puppies' pedigrees soon revealed that the cause was an inherited disease. The gene defect underlying the disease was located in the LAMP3 gene in Professor Hannes Lohi's laboratory. Gene discovery fits well with the clinical picture. The gene produces a protein that functions precisely in the membranes of the vacuoles forming the surfactant.

Nearly 7,000 individual dogs representing nearly 300 different breeds were screened for the gene defect, which was only found in the Airedale Terrier breed. One-fifth of Airedale Terriers were found to be carriers of the defect. In future, carriers can be identified with the help of a gene test, thus making it possible to avoid breeding combinations that give birth to sick dogs.

Potential link with certain breathing problems in human newborns

Neonatal respiratory diseases are typical not only to dogs. Similar defects in the formation of surfactant produced by the epithelial cells of pulmonary alveoli also occur in newborn babies.

"As the LAMP3 gene has not previously been associated with diseases, in the future its role in the breathing difficulties afflicting newborn babies should be investigated. This is another example of canine research that identifies a candidate gene for a human disease," says Professor Hannes Lohi, who headed the study at the Faculty of Veterinary Medicine and the Faculty of Medicine, University of Helsinki, and the Folkhälsan Research Center.

The full title of the research is "The study of the mechanisms of effectiveness of T-cells CAR-T towards solid tumors"; it was supported by nonprofit RakFond (Cancer Fund) and CyStoreLab (a resident of Skolkovo).

Immunotherapy with genetically modified lymphocytes, such as CAR-T cells, is one of the most promising branches of modern fundamental and clinical oncology. A CAR-T cell is a T-lymphocyte with a gene encoding a chimeric antigen receptor, or CAR receptor, in its genome.

"To simplify the concept, we can say that a T-cell is a soldier of the regular forces, and a CAR-T cells are special forces performing particularly difficult tasks. At the same time, CAR-T cells can be 'given a command' to destroy almost any type of tumor," explains project lead Emil Bulatov, Associate Professor at the Department of Biochemistry, Biotechnology and Pharmacology, Leading Research Associate at the Gene and Cell Technology Lab.

The process is as follows: tumor cells contain certain "beacon" proteins on their surface, by which CAR-T cells can find them in the human body and destroy them. In the case of hematologic diseases, one of these proteins is CD19, which is located on the surface of B cells. In the case of solid tumors, the HER2, PCSA, ROR1 proteins can serve as such beacons. It is the fight against solid tumors that is one of the most complex and interesting problems in this area.

Currently, there are only two approved biomedical cell preparations based on CAR-T cells for the treatment of hematologic diseases in the world (Kymriah and Yescarta). However, despite the success of CAR-T cell therapy for the treatment of hematologic diseases, the question of its effective use against solid tumors (carcinoma, neuroblastoma, etc.) remains unresolved. This is due to several reasons, such as high heterogeneity of the cell composition of solid tumors, immunosuppressive tumor microenvironment, difficulties in penetrating the tumor stroma, local hypoxia and a lack of nutrients inside the tumor. Given the high prevalence of solid tumors, the search for ways to effectively use CAR-T immunotherapy for their treatment is extremely relevant.

"Together with colleagues, we have already conducted preliminary experiments on xenograft animal models with a seated tumor, and the results are very encouraging. The data obtained on cell models of solid tumors were generally confirmed in subsequent experiments with immunodeficient mice," states Bulatov.

The use of CAR-T cells was non-toxic to mice and resulted in a marked reduction in tumor size.

"We believe that this work will bring us closer to creating domestic CAR-T-cell preparations and to treating cancer patients. The first stages of translating our results into practice will be held at the Center for Precision and Regenerative Medicine of Kazan Federal University," concludes the researcher.

Osaka, Japan - Most tissues of the body have the extraordinary ability to heal themselves upon injury. But sometimes something goes awry during the complex process of wound healing and the tissue forms too much connective tissue, also called fibrosis, around the injured area, which can result in the organ not functioning properly. Now, researchers from Osaka University have identified a novel protein that plays a central role in the development of such excess scar tissue. In a new study published in Immunity, they showed how the protein Rbm7 induces cell death after tissue injury to then result in the recruitment of a specific type of immune cells, which initiate the formation of tissue fibrosis.

While the reasons for tissue injury can be manifold, including infections, trauma and drug side effects, the default response of the tissue is quite the same in all these cases: Forming new tissue to heal and replace the injured tissue. This seemingly straightforward task includes a complex interplay between tissue and immune cells. While a plethora of molecular actors have been described to participate in this crosstalk, a clear understanding of how tissue fibrosis develops and how it could be prevented has been lacking.

"Fibrosis is a serious phenomenon that irrevocably worsens tissue function," says corresponding author of the study Shizuo Akira. "The goal of our study was to further our mechanistic understanding of fibrosis and discover a potential new avenue for medical treatment of tissue fibrosis."

To achieve their goal, the researchers induced lung fibrosis in mice using bleomycin, a chemotherapeutic drug known to cause lung fibrosis. They first found that the production of the Rbm7, a protein with largely unknown function, is increased in the fibrotic lungs. The researchers then investigated clinical specimens from patients with lung fibrosis and found that Rbm7 is also present in larger quantities in humans with lung fibrosis.

"What made the discovery of Rbm7 so intriguing is the fact that mice lacking Rbm7 produced much less lung fibrosis," says lead author of the study Kiyoharu Fukushima. "We wanted to know the molecular basis for the pro-fibrotic actions of Rbm7."

The researchers showed that an interaction between damaged tissue cells and a specific type of immune cells, so called segregated-nucleus-containing atypical monocytes (SatMs), is key to the onset of fibrosis. When tissue is damaged, by for example the drug bleomycin, affected tissue cells ramp up the production of Rbm7, whose downstream actions eventually result in the death of these cells. As a result, molecules that recruit SatMs are released, which then irreversibly replace the damaged area by scar tissue.

"These are striking results that show how a single protein has the ability to cause something as detrimental as fibrosis," says Akira. "Our findings could offer a new opportunity to prevent and treat tissue fibrosis by targeting Rbm7."

Recent research by Rafael C. Bernardi at the University of Illinois, Urbana-Champaign examines why a common tool in biotechnology -- the binding of streptavidin to biotin -- shows different mechanical resilience in different research labs.

"This interaction has been a key tool in nearly 15,000 published manuscripts," said Bernardi, a research scientist at the Beckman Institute for Advanced Science and Technology. "If you don't do it in a specific way, your results might be inconclusive. It is like creating a building - you can use the same material to make something stable or unstable."

The principle of using the binding of two molecules as a research tool is not limited to streptavidin/biotin systems. "This analysis can also be used in other experiments such as therapeutics and cancer treatments where, depending on the position of the antibody, the stability of a complex is affected," Bernardi said. "The technique is also being used in the work that is being done on the new SARS-CoV-2 coronavirus. The technique we are improving is a very common tool used by the labs that are trying to understand the molecular basis of COVID-19."

Bernardi conducted the research in collaboration with Hermann Gaub, a professor at Ludwig Maximilian University of Munich.The paper "Streptavidin/Biotin: Tethering Geometry Defines Unbinding Mechanics" was published in Science Advances.

Researchers have been using the interaction between streptavidin and biotin for the last 25 years to study, for instance, the folding and unfolding of proteins. In single-molecule folding studies, the protein is usually attached to a surface on one end and to biotin on the other. The streptavidin is then attached to the tip of an atomic force microscope, working as a handle to pull on the protein through the streptavidin/biotin interaction. The researchers measure this effect to understand how the protein folds and unfolds.

"Over the years we have noticed that the numbers associated with the strength of the interaction between streptavidin and biotin varies in different research papers," Bernardi said. "If you're measuring just this interaction, why aren't the numbers always the same? Researchers didn't think about it too much because, for most of them, biotinylation is just a tool."

The researchers used computational analysis to show that the several streptavidin's reactive groups, called reactive amines, can influence how streptavidin and biotin interact under mechanical stress. "Even with the controlled environments we used in our experiments, we got completely different results. You're forcing biotin to take on a different path depending on where the streptavidin attachment takes place," Bernardi said.

The biggest challenge the researchers faced was doing the computational analysis. "We need a lot of computer power to get these results. We were only able to do this because of Blue Waters," Bernardi said, referring to the National Center for Supercomputing Applications' supercomputer on the Illinois campus. To analyze the results, Bernardi employed NAMD, a widely used software for Molecular Dynamics, which was developed by the Theoretical and Computational Biophysics Group at the Beckman Institute.

A new global study reveals the extent to which high-yielding rice varieties favored in the decades since the "Green Revolution" have a propensity to go feral, turning a staple food crop into a weedy scourge.

Weedy rice is a de-domesticated form of rice that infests paddies worldwide and aggressively outcompetes cultivated varieties. A new study led by biologists at Washington University in St. Louis shows that weed populations have evolved multiple times from cultivated rice, and a strikingly high proportion of contemporary Asian weed strains can be traced to a few Green Revolution cultivars that were widely grown in the late 20th century.

The scientists believe that a universal process is at work, acting at a genomic and molecular level to allow rapid adaptation to weediness. The new study is published March 26 in the journal Genome Biology.

"One of the hallmarks of the Green Revolution was the use of cross-breeding to create high-yielding cultivars," said Kenneth M. Olsen, professor of biology in Arts & Sciences. "For rice and many other crops, this involved hybridizing traditional varieties to combine their best traits. This type of rice breeding was very different from traditional rice farming, where varieties aren't cross-bred and farmers replant seed from their own harvests."

The Green Revolution was an era of technology transfer that brought high-yield varieties of rice, maize and wheat to the developing world, more than doubling the cereal production in developing countries from 1961 to 1985. Changes in irrigation, fertilizer and seed development brought about remarkable productivity gains.

But there were other less predictable outcomes.

"Once you start hybridizing different varieties, you can wind up with all kinds of new traits, including some that are unexpected and undesirable," Olsen said. "What we learned from our study is that one of those unexpected side effects was a propensity of the elite cultivars to go feral and emerge as agricultural weeds."

Olsen and his collaborators used whole genome sequencing to examine the origin and adaptation of 524 global weedy rice samples representing all major regions of rice cultivation.

Much like a family tree, the new genomic analysis shows relationships among weedy rice strains and demonstrates the extent to which the same genes are involved each time a new weed strain evolves.

This is the first such study to include weedy rice strains from all over the world in a single analysis.

"One of the huge advantages of being able to sequence entire genomes nowadays is that we can achieve very high-level resolution in figuring out who is related to whom," Olsen said. "This same approach is being used now with the novel coronavirus to track the sources of new infections as they show up in new locations."

"For weedy rice, we were able to infer that a lot of the weed strains that are now widespread in Asia are very closely related to rice cultivars that were first developed during the Green Revolution."

Olsen is a national expert in weedy rice. The National Science Foundation recently awarded $2.6 million to Olsen and collaborators to determine what makes weedy rice such a fierce competitor.

"Although the genetic mechanism isn't especially surprising, what did really surprise me was what a high proportion of weedy rice in Asia originated this way," Olsen said. "We estimated that over a third of the weed strains now infesting some regions of China likely evolved from elite cultivars.

"From our previous studies in other regions, we knew that some weedy rice strains have likely been around since the earliest days of agriculture," Olsen said. "What's now clear is that weedy rice has probably been emerging repeatedly throughout the 10,000-year history of rice cultivation -- right up to the present day."

Study suggests extending school and workplace closures in Wuhan until April, rather than March, would likely delay a second wave of cases until later in the year, relieving pressure on health services

New modelling research, published in The Lancet Public Health journal, suggests that school and workplace closures in Wuhan, China have reduced the number of COVID-19 cases and substantially delayed the epidemic peak--giving the health system the time and opportunity to expand and respond.

Using mathematical modelling to simulate the impact of either extending or relaxing current school and workplace closures, researchers estimate that by lifting these control measures in March, a second wave of cases may occur in late August, whereas maintaining these restrictions until April, would likely delay a second peak until October--relieving pressure on the health services in the intervening months.

However, the authors caution that given the large uncertainties around estimates of the reproduction number (how many people an individual with the virus is likely to infect), and how long a person is infected on average, the true impact of relaxing physical distancing measures on the ongoing COVID-19 epidemic cannot be precisely predicted.

"The unprecedented measures the city of Wuhan has put in place to reduce social contacts in school and the workplace have helped to control the outbreak", says Dr Kiesha Prem from the London School of Hygiene & Tropical Medicine, UK, who led the research. "However, the city now needs to be really careful to avoid prematurely lifting physical distancing measures, because that could lead to an earlier secondary peak in cases. But if they relax the restrictions gradually, this is likely to both delay and flatten the peak."

In December 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China. In mid-January 2020, schools and workplace were closed as part of the Lunar New Year holidays. These closures were then extended to reduce person-to-person contact and prevent the spread of SARS-CoV-2.

In the study, researchers developed a transmission model to quantify the impact of school and workplace closures using information about how often people of different ages mix with each other in different locations, and to assess their effects on bringing the outbreak under control.

Using the latest data on the spread of COVID-19 in Wuhan and from the rest of China on the number of contacts per day by age group at school and work, they compared the effect of three scenarios: no interventions and no holidays (a hypothetical scenario); no physical distancing measures but school winter school break and Lunar New Year holidays as normal; and intense control measures with school closed and only about 10% of the workforce--eg, health-care personnel, police, and other essential government staff--working during the control measures (as started in Wuhan in mid-January). They also modelled the impact of lifting control measures in a staggered way, and during different stages of the outbreak (in March and April).

The analyses suggest that the normal school winter break and Lunar New Year holidays would have had little impact on the progression of the outbreak had schools and workplaces opened as usual (figure 3). However, putting extreme measures in place to reduce contacts at school and workplaces, could reduce case numbers and the size of the epidemic peak, whilst also delaying the peak (figure 4). The effects of these distancing measures seem to vary by age, with the greatest reductions in new cases among school children and the elderly, and lowest among working-aged adults (figures 4 and 5). However, once these interventions are relaxed, case numbers are expected to rise.

Further analysis suggests that physical distancing measures are likely to be most effective if the staggered return to work commences at the beginning of April--potentially reducing the median number of new infections by 24% up to the end of 2020, and delaying a second peak until October.

"Our results won't look exactly the same in another country, because the population structure and the way people mix will be different. But we think one thing probably applies everywhere: physical distancing measures are very useful, and we need to carefully adjust their lifting to avoid subsequent waves of infection when workers and school children return to their normal routine. If those waves come too quickly, that could overwhelm health systems", says co-author Dr Yang Liu from London School of Hygiene & Tropical Medicine. [1]

Despite these important findings, the study has some limitations, including that it assumed no difference in susceptibility between children, and that the extreme distancing measures used in Wuhan may have increased the transmission within households. Finally, the model did not capture individual-level differences in contact rates, which could be important in super-spreading events, particularly early on in an epidemic.

Writing in a linked Comment, Dr Tim Colbourn from University College London, UK (who was not involved in the study) says: "The study by Kiesha Prem and colleagues in The Lancet Public Health is crucial for policy makers everywhere, as it indicates the effects of extending or relaxing physical distancing control measures on the coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China."

He continues: "Given many countries with mounting epidemics now potentially face the first phase of lockdown, safe ways out of the situation must be identified... New COVID-19 country-specific models should incorporate testing, contract tracing, and localised quarantine of suspected cases as the main alternative intervention strategy to distancing lockdown measures, either at the start of the epidemic, if it is very small, or after the relaxation of lockdown conditions, if lockdown had to be imposed, to prevent health-care system overload in an already mounting epidemic."

More than 30 significant risk factors have been identified for the development of psychotic disorders in offspring in research led by the NIHR Maudsley BRC. It is the first comprehensive meta-analysis of pre- and perinatal risk factors for psychosis in nearly 20 years.

These prenatal and perinatal environmental risks, meaning risks during pregnancy and seven days after birth, have a significant effect on the likelihood of their child developing psychosis. As a result, researchers suggest women at risk should be screened early on in their pregnancy so that those with these identified risks can be given additional support. The findings have been published today (Tuesday 24 March 2020) in Lancet Psychiatry.

Gathering data from 152 studies published between 1977 and July 2019 and looking at 98 factors, researchers identified 30 significant risk factors and five protective factors.

Psychotic disorders are severe mental illnesses which cause abnormal thoughts, such as hallucinations or delusions, but they can affect each person in different ways. In 2014, a survey found the 6% of people in England said they had experienced at least on symptom of psychosis.

Factors can be split into four categories; parental and familial, pregnancy, labour and delivery, and foetal growth and development. Significant protective factors were mothers being aged between 20 - 29, first time mothers and higher birthweights in babies.

For risk factors, previous mental health conditions in either parents, nutritional deficiencies, low birthweight and giving birth in the colder months were found to increase the probability of a child developing psychosis. Age related risk factors were either parent being under 20, mothers between 30-34 and fathers over 35. Researchers also found that a lack of prenatal care visits poses a risk and marked this as a potential risk factor to combat with outreach campaigns.

This study confirmed the importance of factors during labour and delivery, such as a foetus' brain being deprived of oxygen and ruptured membranes, which are historically among the most consistently implicated risk factors. Conversely, despite previous studies focusing on infections during pregnancy causing psychosis, this study found significant associations only for HSV-2 and maternal infections 'not otherwise specified' and found that influenza had no indication of a significant effect.

This study will help guide future research in the field of psychosis, as well as form the basis for psychosis risk prediction models which could advance preventative strategies.

Dr Paolo Fusar-Poli, Reader in Psychiatry and Youth Mental Health at Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London said: 'This study is confirming that psychotic disorders originate in the early phases of life with the accumulation of several environmental risk factors during the perinatal and prenatal phases. The results of this study will advance our ability to detect individuals at risk of developing psychosis, predict their outcomes and eventually offer them preventive care.'

Whilst this study focused on the environmental factors there may also be genetic or epigenetic risks factors that are implicated in the onset of psychosis.

March 24, 2020-- In a new study of patients with severe COVID-19 (SARS-CoV-2) hospitalized on ventilators, researchers found that lying face down was better for the lungs. The research letter was published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

In "Lung Recruitability in SARS--CoV-2 Associated Acute Respiratory Distress Syndrome: A Single-Center, Observational Study," Haibo Qiu, MD, Chun Pan, MD, and co-authors report on a retrospective study of the treatment of 12 patients in Wuhan Jinyintan Hospital, China, with severe COVID-19 infection-related acute respiratory distress syndrome (ARDS) who were assisted by mechanical ventilation. Drs. Qiu and Pan were in charge of the treatment of these patients, who were transferred from other treatment centers to Jinyintan Hospital.

A majority of patients admitted to the ICU with confirmed COVID-19 developed ARDS.

The observational study took place during a six-day period the week of Feb. 18, 2020.

"This study is the first description of the behavior of the lungs in patients with severe COVID-19 requiring mechanical ventilation and receiving positive pressure," said Dr. Qiu, professor, Department of Critical Care Medicine, Zhangda Hospital, School of Medicine, Southeast University, Nanjing, China. "It indicates that some patients do not respond well to high positive pressure and respond better to prone positioning in bed (facing downward)."

The clinicians in Wuhan used an index, the Recruitment-to-Inflation ratio, that measures the response of lungs to pressure (lung recruitability). Members of the research team, Lu Chen, PhD, and Laurent Brochard, PhD, HDR, from the University of Toronto, developed this index prior to this study.

The researchers assessed the effect of body positioning. Prone positioning was performed for 24-hour periods in which patients had persistently low levels of blood oxygenation. Oxygen flow, lung volume and airway pressure were measured by devices on patients' ventilators. Other measurements were taken, including the aeration of their airway passages and calculations were done to measure recruitability.

Seven patients received at least one session of prone positioning. Three patients received both prone positioning and ECMO (life support, replacing the function of heart and lungs). Three patients died.

Patients who did not receive prone positioning had poor lung recruitability, while alternating supine (face upward) and prone positioning was associated with increased lung recruitability.

"It is only a small number of patients, but our study shows that many patients did not re-open their lungs under high positive pressure and may be exposed to more harm than benefit in trying to increase the pressure," said Chun Pan, MD, also a professor with Zhongda Hospital, School of Medicine, Southeast University. "By contrast, the lung improves when the patient is in the prone position.

Considering this can be done, it is important for the management of patients with severe COVID-19 requiring mechanical ventilation."

The team consisted of scientists and clinicians affiliated with four Chinese and two Canadian hospitals, medical schools and universities.