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What The Study Did: Researchers evaluated the proportion of patients who completed COVID-19 testing and the proportion of positive cases using language as a surrogate for immigrant status.

Authors: H. Nina Kim, M.D., M.Sc., and Herbert C. Duber, M.D., M.P.H., of the University of Washington in Seattle, are the corresponding authors.

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

(doi:10.1001/jamanetworkopen.2020.21213)

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

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The first stages of placental development take place days before the embryo starts to form in human pregnancies. The finding highlights the importance of healthy placental development in pregnancy, and could lead to future improvements in fertility treatments such as IVF, and a better understanding of placental-related diseases in pregnancy.

In a study published in the journal Nature, researchers looked at the biological pathways active in human embryos during their first few days of development to understand how cells acquire different fates and functions within the early embryo.*

They observed that shortly after fertilisation as cells start to divide, some cells start to stick together. This triggers a cascade of molecular events that initiate placental development. A subset of cells change shape, or 'polarise', and this drives the change into a placental progenitor cell - the precursor to a specialised placenta cell - that can be distinguished by differences in genes and proteins from other cells in the embryo.

"This study highlights the critical importance of the placenta for healthy human development," said Dr Kathy Niakan, group leader of the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute and Professor of Reproductive Physiology at the University of Cambridge, and senior author of the study.

Niakan added: "If the molecular mechanism we discovered for this first cell decision in humans is not appropriately established, this will have significant negative consequences for the development of the embryo and its ability to successfully implant in the womb."

The team also examined the same developmental pathways in mouse and cow embryos.** They found that while the mechanisms of later stages of development differ between species, the placental progenitor is still the first cell to differentiate.

"We've shown that one of the earliest cell decisions during development is widespread in mammals, and this will help form the basis of future developmental research. Next we must further interrogate these pathways to identify biomarkers and facilitate healthy placental development in people, and also cows or other domestic animals," said Claudia Gerri, lead author of the study and postdoctoral training fellow in the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute.

During IVF, one of the most significant predictors of an embryo implanting in the womb is the appearance of placental progenitor cells under the microscope. If researchers could identify better markers of placental health or find ways to improve it, this could make a difference for people struggling to conceive.

"Understanding the process of early human development in the womb could provide us with insights that may lead to improvements in IVF success rates in the future. It could also allow us to understand early placental dysfunctions that can pose a risk to human health later in pregnancy," said Niakan.

For frontline healthcare workers during the COVID-19 pandemic, wearing personal protective equipment (PPE) like face visors, googles, and respiratory protective equipment is an essential part of working life. More workers are wearing facial PPE now than ever before, often for extended periods of time, to protect them against the SARS-CoV-2 virus.

However, extended PPE use, particularly on the delicate skin of the face, can cause friction and shear injuries like skin tears, blistering, ulcers, and hives.

The effects of friction and shear can be reduced by lubricants, which workers are advised to apply every half hour. Half-hourly applications can be impractical during shift work and may expose workers to the virus, and many typical moisturisers don't last long as they are designed to be absorbed into the skin for a 'non-greasy feel'.

Now, researchers from Imperial College London have investigated which products create the longest-lasting protective layer between PPE and skin. They hope their findings will help healthcare workers and other long-term PPE users like those in hospitality to prevent skin injury and deformity.

They found that the best lubricants to use are those that don't absorb into the skin, creating a long-lasting layer of protection between skin and PPE. They say that non-absorptive creams like coconut oil-cocoa butter beeswax mixtures, and powders like talcum powder, are most likely to provide PPE wearers with long-lasting skin protection.

The findings are published today in PLOS ONE.

Lead author Dr Marc Masen, of Imperial's Department of Mechanical Engineering, said: "We think of moisturisers as good for our skin, but commercial skin creams are often designed to absorb into the skin without leaving any residue. While this is fine for everyday moisturising, our study shows that a greasy residue is precisely what's needed to protect skin from PPE friction."

To identify the best-performing lubricants, the researchers custom-built a tribometer - an instrument that assesses friction between two surfaces - and used it to test the friction between skin and polydimethylsiloxane (PDMS), which is a common component of PPE.

They used the tribometer to test commercially available products to measure how they changed the friction between PDMS and the inner forearm skin of a healthy 44-year-old male participant. They tested friction upon application, and then one, two, and four hours after application.

They found that while most products initially reduced friction by 20 per cent, some silicone-based and water-and-glycerin based lubricants increased friction levels over time by up to 29 per cent compared to dry skin.

However, two products reduced friction as time went on. Talcum powder reduced friction by 49 per cent on application and 59 per cent at four hours, and a commercially available product comprising coconut oil, cocoa butter and beeswax reduced friction by 31 per cent on application and 53 per cent at four hours. A mixture of petrolatum and lanolin reduced friction by 30 per cent throughout testing.

When testing commercial moisturisers, they found that friction on application was low, but increased drastically within ten minutes of application. The researchers say this is because the active ingredients, known as humectants, attract water like magnets from the lower layers of skin to the upper ones, leaving it soft, unlubricated, and breakable.

Co-author Dr Zhengchu Tan, also of the Department of Mechanical Engineering, said: "The products that don't absorb easily into the skin are the ones that provide a protective layer. In fact, for PPE wearers, it's best to actively avoid creams and moisturisers which advertise a 'non-greasy feel'."

Dr Masen said: "Friction can be incredibly damaging for the skin, particularly when applied for an extended period. We hope our study will save healthcare workers and other frontline PPE wearers from suffering with the painful and damaging effects of skin friction."

The researchers say that while their study signposts PPE wearers to the best skin-saving products, they are looking to perform further studies using facial skin and more participants. Due to COVID-19 restrictions during lockdown, they were only able to test the products on one study participant, and used his inner forearm as a surrogate for facial skin.

Family carers for children and adults with intellectual disabilities have reported rates of mental health problems under lockdown that are up to 10 times higher than parents without those responsibilities, a new study has found.

They were five times more likely to report severe anxiety, and between four and ten times more likely to report major depression, compared to parents who did not have caring responsibilities for children with intellectual disability.

The challenges faced by informal carers - usually mothers - of children and adults with intellectual disability have been largely overlooked during the coronavirus crisis.

To address this, a research team carried out an online study aimed at documenting their mental health. Led by Professor Paul Willner from Swansea University, the project involved Swansea researchers and colleagues from the universities of Warwick, Kent and Birmingham, and the Challenging Behaviour Foundation.

The team analysed 244 online surveys, which were completed during the strict lockdown period by carers of adults with intellectual disability, of children with intellectual disability, and a comparison group of carers for children without intellectual disability.

More than 90 per cent of the carers taking part were female. Eleven households had had direct experience of COVID-19.

Key findings were:

Moderate to severe anxiety - 43% of carers of children with intellectual disability reported this, compared with 8% of parents of children without intellectual disability.

Moderate to severe levels of depression were reported by 45% of carers of children with intellectual disability, compared with 11% of parents of children without.

Major depression was found in 31% of carers of children with intellectual disability but only 3% of parents of children without intellectual disability.

Social support - compared to parents of children without intellectual disability, carers of children with intellectual disability received significantly less support from other sources, particularly family and friends - despite their greater needs.

No respite: carers for adults with intellectual disability; the closure of adult day services and respite care meant that this group felt they had significantly less support than carers of children, who could still send their children to school if they wished.

Professor Paul Willner of Swansea University, head of the project, said:

"It is likely from these data that the mental health of carers of children and adults with intellectual disability has been adversely affected by the pandemic. This effect is over and above any pre-existing mental health problems. They are also affected to a greater extent than parents of people without disabilities but are less well supported. Our findings are one illustration of how the pandemic has amplified existing inequalities."

The authors make recommendations on supporting carers better, including:

Long-term consistent support from a named key worker

More nurses trained in learning disabilities, with carers' mental health in their remit

More respite provision, to be continued through any further lockdowns

Services better equipped to offer support to carers remotely via phone or online

Access for carers to specialist mental health support

Peer support groups

Professor Willner added:

"We should acknowledge the essential role played by informal carers and take steps to ensure they are appropriately and proactively supported. There are significant costs for the carers themselves and for society more generally if mental ill health robs them of their ability to continue providing care for their loved ones."

The research was published in the Journal of Applied Research in Intellectual Disabilities.

Mitochondria are the powerhouses of our cells, generating energy that supports life. A giant molecular proton pump, called complex I, is crucial: It sets in motion a chain of reactions, creating a proton gradient that powers the generation of ATP, the cell's fuel. Despite complex I's central role, the mechanism by which it transports protons across the membrane has so far been unknown. Now, Leonid Sazanov and his group at the Institute of Science and Technology Austria (IST Austria) have solved the mystery of how complex I works: Conformational changes in the protein combined with electrostatic waves move protons into the mitochondrial matrix. This is the result of a study published today in Science.

Complex I is the first enzyme in the respiratory chain, a series of protein complexes in the inner mitochondrial membrane. The respiratory chain is responsible for most of the cell's energy production. In this chain, three membrane proteins set up a gradient of protons, moving them from the cell's cytoplasm into the mitochondrial inner space, called the matrix. The energy for this process comes mostly from the electron transfer between NADH molecules, derived from the food we eat, and oxygen that we breathe. ATP synthase, the last protein in the chain, then uses this proton gradient to generate ATP. Complex I is remarkable not only because of its central role in life, but also for its sheer size: with a molecular weight of 1 Megadalton, the eukaryotic complex I is one of the biggest membrane proteins. Its size also makes complex I hard to study. In 2016, Sazanov and his group were the first to solve the structure of mammalian complex I, following on their 2013 structure of a simpler bacterial enzyme. But the mechanism by which complex I moves protons across the membrane has remained controversial. "One idea was that a part of complex I works like a piston, to open and close channels through which protons travel", explains Sazanov. "Another idea was that residues at the center of complex I act as a driver. It turns out that an even more unusual mechanism is at work."

Water wire helps protons to hop across the membrane

Previously, Sazanov and his group have shown that L-shaped complex I consists of hydrophilic and membrane arms. In the hydrophilic arm, electrons tunnel from NADH to quinone, the hydrophobic electron carrier. The membrane arm, where proton translocation happens, has three similar subunits with structures related to antiporters, and one subunit containing a quinone binding cavity. In this cavity, complex I transfers two electrons per catalytic cycle to quinone, which delivers the electrons further to complexes III and IV. But mystery surrounded how the interaction between electrons and quinone can move four protons per cycle across the membrane, since the antiporter-like subunits are far away from quinone cavity. To solve this puzzle, Sazanov and his team performed cryo-EM on sheep complex I. In a tour-de-force effort, PhD student Domen Kampjut solved 23 different structures of complex I, obtained under different conditions. By adding NADH and quinone, the researchers could capture images of complex I at work, changing conformation between the two main states. Due to high-resolution achieved, they could resolve the water molecules inside the protein, which are essential to allow proton transfer. They found that many water molecules in the central axis of the membrane arm provide a way for protons to hop between polar residues and waters, forming pathways along and across the membrane.

But only in one subunit, furthest away from quinone, do protons hop across the membrane. The other two subunits rather provide a coupling between the farthest subunit and quinone. When the binding cavity "waits" for quinone, a helix blocks the water wire in the central axis. When quinone binds in the binding cavity, the protein conformation around this area changes dramatically and this helix rotates. Now, the water wire connects all membrane subunits of complex I and two protons are delivered to quinone, to complete its reduction. This key part of the mechanism creates a charge near the first antiporter and starts an electrostatic wave of interactions between charged residues, which propagates along the antiporters, resulting in the translocation of four protons in total. "We show that a new and unexpected mechanism is at work in complex I. A mixture of both conformational changes and an electrostatic wave pumps protons across the membrane", explains Sazanov. "This mechanism is highly unusual, as it involves the rotation of an entire helix inside the protein. It seems a bit excessive, but probably helps the mechanism to be robust."

The new research complements studies from Sazanov group published in the last two months, on the mechanism of proton pumping in bacterial complex I (Nature Communications) and on the structure of MRP antiporters, from which complex I has evolved (eLife).

NASA-NOAA's Suomi NPP satellite passed over the Eastern North Pacific Ocean and captured a visible image of Tropical Storm Lowell that revealed the storm was dealing with wind shear.

Wind shear is caused by winds outside of a tropical cyclone that are blowing against it at different altitudes and directions. Wind shear weakens tropical cyclones by adversely affecting their circulation. Wind shear can elongate a storm and make it spin more slowly, leading to weakening.

The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP provided a visible image of Lowell on Sept. 23. Around the time of the Suomi NPP image, the National Hurricane Center noted a band of deep convection and thunderstorms had continued over the eastern quadrant of the storm, but the center was exposed and was located west of that band of thunderstorms. Lowell was being affected by moderate northwesterly wind shear which is not expected to abate much.

By 5 p.m. EDT on Sept. 23, Lowell was maintaining strength with a few bands of deep convection and developing thunderstorms located 30 nautical miles or more to the east of the exposed center.

Lowell's Status on Sept. 24

At 5 a.m. EDT (0900 UTC) on Sept.24, the center of Tropical Storm Lowell was located near latitude 21.2 degrees north and longitude 123.7 degrees west. That is about 890 miles (1,435 km) west of the southern tip of Baja California, Mexico.

Lowell was moving toward the west-northwest near 10 mph (17 kph). Maximum sustained winds are near 45 mph (75 kph) with higher gusts. Gradual weakening is forecast to begin by late Thursday.

Lowell's Forecast

NHC said a turn toward the west is expected Thursday morning, with that heading and a gradual increase in forward speed continuing through early next week. Lowell is expected to weaken to a tropical depression by late Friday and become a remnant low by early Saturday.

Experts from the University of Stirling, working closely with the Government of Gabon, have led an international study into the impact of climate change on Central Africa's rainforests and the threat posed to elephant populations in the region.

Dr Emma Bush and Dr Robin Whytock, of the Faculty of Natural Sciences, along with Professors Kate Abernethy and Lee White, are lead authors of 'Long-term collapse in fruit availability threatens Central African forest megafauna' published in renowned journal Science. It reveals that a significant reduction in fruit production by trees in Lopé National Park, Gabon, has coincided with a decline in the physical condition of fruit-eating forest elephants.

The study found an 81% decline in fruit production between 1986 and 2018, alongside an 11% drop in the physical condition of fruit-dependent forest elephants since 2008.

This means that, on average, elephants and other animals would have encountered ripe fruit on one in every 10 trees in the 1980s, but need to search more than 50 trees today.

The region's climate has changed since the 1980s, becoming warmer and drier, and it is believed this may be behind the decline in rainforest fruit production. Mean temperature has increased by almost 1oC during the course of the study. Some tree species in Lopé National Park are dependent on a dip in temperature to trigger flowering but warmer temperatures may mean that this vital cue to producing fruit is being missed.

Dr Emma Bush said: "The massive collapse in fruiting among more than 70 tree species studied at Lopé National Park, Gabon may be due to species missing the environmental cue to bear fruit, because of increased temperatures and less rainfall. Less fruit in the ecosystem will have huge impacts on forest dynamics such as seed dispersal, plant reproduction and food availability for wildlife such as forest elephants, chimpanzees, and gorillas."

The University of Stirling is a pioneer in tropical ecology research, having established the world-renowned Station d'Etudes des Gorilles et Chimpanzes (SEGC - The Gorilla and Chimpanzee Research Station) with the Centre Internationale de Recherches Médicales de Franceville (CIRMF, The International Medical Research Centre in Franceville) in Lopé National Park, central Gabon, in 1983.

This 37-year, on-going collaboration between the University and the Government of Gabon has generated a unique data set that allows researchers to monitor how the rainforests and wildlife of the Congo Basin are responding to climate change.

Dr Robin Whytock said: "Large animals like forest elephants are already under severe pressure in Central Africa due to hunting, habitat loss and habitat degradation. If important protected areas like Lopé National Park in Gabon can no longer support them because there is not enough food, then we may see further population declines, jeopardising their survival in the long-term.

"We know that large bodied animals, like elephants, are disproportionately important for the healthy functioning of ecosystems and their loss could result in broad changes to forest systems and even reduce the amount of carbon stored there."

Functioning tropical ecosystems are important for global climate regulation and global health. This research highlights how global climate change might be affecting plants and animals locally, through decreased forest food production. It also adds to the global body of evidence highlighting the ongoing biodiversity crisis and the consequences of rapid climatic change.

Professor Lee White, Gabon's Minister of Water, Forest, Sea and Environment, and an Honorary Professor at the University of Stirling, said: "Long-term ecological research such as ours is unfortunately extremely rare in the tropics, and it is possible that similar processes are underway, but undetected, throughout the tropical rainforests of our planet.

"It is alarming that climate change may be resulting in forest elephants going hungry, and we need to seriously consider whether this is forcing elephants out of the forests to approach rural villages in search of food, resulting in an increase in crop raiding.

DALLAS - Sept. 24, 2020 - Two studies led by UT Southwestern researchers shed light on the biology and potential vulnerabilities of schistosomes - parasitic flatworms that cause the little-known tropical disease schistosomiasis. The findings, published online today in Science, could change the course of this disease that kills up to 250,000 people a year.

About 240 million people around the world have schistosomiasis - mostly children in Africa, Asia, and South America in populations that represent "the poorest of the poor," says study leader James J. Collins III, Ph.D., associate professor in UTSW's department of pharmacology.

Most of those infected survive, but those who die often suffer organ failure or parasite-induced cancer. Symptoms can be serious enough to keep people from living productive lives, Collins says.

The parasite that causes this disease has a complicated life cycle that involves stages in both freshwater snails and mammals. Dwelling in mammalian hosts' circulatory systems, schistosomes feed on blood and lay copious numbers of eggs, all while causing an array of symptoms including abdominal pain, diarrhea, bloody stool, or blood in the urine. Larval worms are released from snails into water, where the flatworms then may infect humans by penetrating the skin. Schistosomiasis may become a chronic disease that affects the person for years.

Only one drug, praziquantel, is available to treat this condition. However, Collins explains, it is of limited use - it doesn't kill all intramammalian stages of the schistosome life cycle, and it has a variable cure rate in some endemic settings. There's been little interest by pharmaceutical companies in developing new drugs for this disease, he adds, because there is no monetary incentive to do so. Consequently, relatively few studies have been devoted to understanding schistosomes' basic biology, which might reveal inherent weaknesses that could serve as targets for new drugs.

To that end, Collins and his colleagues embarked upon two separate studies - one at the cellular level and another at the molecular level - to better understand these organisms.

In the first study, the researchers delved into the cell types that make up these flatworms. Although the worms are multicellular organisms composed of a variety of unique tissue types, researchers knew little about the different cell populations in these parasites.

With a goal to create an atlas of cell types in Schistosoma mansoni - one of the schistosome species that commonly causes schistosomiasis - Collins and his team used a technique called single-cell RNA sequencing that distinguishes individual cell types based on their unique gene expression patterns. With this method, they identified 68 molecularly unique clusters of cells, including a population of stem cells that form the gut. When the researchers used a targeted approach called RNA interference (RNAi) to shut down the activation of a key gene in these cells, the resulting worms couldn't digest red blood cells - a key to their growth and a pivotal part of the pathology they cause.

In the second study, the researchers used RNAi to sort out the function of about 20 percent of S. mansoni's protein coding genes - 2,216 in total. Previously, only a handful of genes in these organisms had been assessed.

By deactivating the genes one by one, Collins and his colleagues identified more than 250 genes crucial for survival. Using a database of pharmacological compounds, the researchers then searched for drugs that had the potential to act on proteins produced by these genes, identifying several compounds with activity on worms. The team also uncovered two protein kinases - a group of proteins renowned for their ability to be targeted by drugs - that are essential for muscle function. When these kinases were inhibited, the worms became paralyzed and eventually died, suggesting that drugs targeting these proteins could eventually treat people with schistosomiasis. A next step in the research will be to search for inhibitors of these proteins.

Collins notes that these strides in understanding the basic biology of schistosomes could eventually lead to new treatments to save untold lives in places where schistosomiasis is endemic.

"This is a very important disease that most people have never heard of," he says. "We need to invest and invigorate research on these parasites."

Using a NASA satellite rainfall product that incorporates data from satellites and observations, NASA estimated Post-tropical Cyclone Beta's rainfall rates as it moved over Mississippi, Alabama and Tennessee. Beta continues a steady northeast track into Mississippi, bringing heavy rainfall across Mississippi into the Tennessee Valley.

Beta's Status on Sept. 24

NOAA's National Weather Service Weather Prediction Center (WPC) in College Park, Md. noted that at 5 a.m. EDT (0900 UTC) the center of Post-Tropical Cyclone Beta was located near latitude 31.9 degrees north and longitude 91.0 degrees west. The post-tropical cyclone is moving toward the northeast near 12 mph (19 kph). Maximum sustained winds are near 30 mph (45 kph) with higher gusts.

Estimating Beta's Rainfall Rates from Space

NASA's Integrated Multi-satellitE Retrievals for GPM or IMERG, which is a NASA satellite rainfall product, estimated on Sept. 24 at 3:30 a.m. EDT (0730 UTC), Beta was generating as much as 10 to 15 mm (0.40 to 0.60 inches) of rain per hour over Alabama. Lighter rainfall rates were occurring over Mississippi and Tennessee at the time of the image. Rainfall throughout most of the storm was estimated as falling at a rate between 0.2 and 1 mm (0.007 to 0.4 inches) per hour.

At the U.S. Naval Laboratory in Washington, D.C., the IMERG rainfall data was overlaid on infrared imagery from NOAA's GOES-16 satellite to provide a full extent of the storm.

Watches and Warnings

On Sept. 24, Flash Flood Watches were in effect from southwestern Mississippi to parts of northern Alabama, and southern Middle Tennessee.

NOAA's WPC said, "Rainfall totals of 2 to 4 inches are expected through early Friday from central to northern Mississippi, across the Middle Tennessee Valley and into the Southern Appalachians. Isolated flash and urban flooding is possible, as well as isolated minor river flooding on smaller rivers. An isolated tornado or two are possible this afternoon across Southern Alabama."

Beta's Forecast

Beta is expected to continue moving in a northeasterly direction for the next day and a half. Some weakening is forecast for the next 36 hour before weakening into a frontal system.

What Does IMERG Do?

This near-real time rainfall estimate comes from the NASA's IMERG, which combines observations from a fleet of satellites, in near-real time, to provide near-global estimates of precipitation every 30 minutes. By combining NASA precipitation estimates with other data sources, we can gain a greater understanding of major storms that affect our planet.

What the IMERG does is "morph" high-quality satellite observations along the direction of the steering winds to deliver information about rain at times and places where such satellite overflights did not occur. Information morphing is particularly important over the majority of the world's surface that lacks ground-radar coverage. Basically, IMERG fills in the blanks between weather observation stations.

Tel Aviv University researchers suggest that carriers of the genetic mutations PiZ and PiS are at high risk for severe illness and even death from COVID-19. These mutations lead to deficiency in the alpha1-antitrypsin protein, which protects lung tissues from damage in case of severe infections. Other studies have already associated deficiency in this protein with inflammatory damage to lung function in other diseases.

The study was led by Prof. David Gurwitz, Prof. Noam Shomron, and MSc candidate Guy Shapira of TAU's Sackler Faculty of Medicine, and published in The FASEB Journal on September 22, 2020.

The researchers analyzed data from 67 countries on all continents. Comparisons revealed a highly significant positive correlation between the prevalence of the two mutations in the population and COVID-19 mortality rates (adjusted to size of the population) in many countries, such as the USA, the UK, Belgium, Spain, Italy, and more.

Consequently, the researchers suggest that these mutations may be additional risk factors for severe COVID-19. They now propose that their findings should be corroborated by clinical trials, and if validated should lead to population-wide screening for identifying carriers of the PiS and/or PiZ mutations. Such individuals should then be advised to take extra measures of social distancing and later be prioritized for vaccination once vaccines are available. According to the researchers, these steps can be effective in reducing COVID-19 morbidity and fatality rates.

Analysis of databases reveals that in Belgium, where 17 of every 1,000 people carry the PiZ mutation (the more dominant of the two mutations discussed in this study), the COVID-19 mortality rate was 860 per million according to figures for September 2020. In Spain the picture is similar: 17 of every 1,000 citizens carry the PiZ mutation, and the COVID-19 fatality rate is 640 per million. In the USA, where 15 per 1,000 are carriers, 590 of every million died of the coronavirus.

The numbers in the UK are in line with the overall trend: 14 per 1,000 carry the mutation and 60 per million have died of COVID-19. In Italy, where 13 per 1,000 are carriers, the mortality rate is 620 per million. In Sweden, where 13 per 1,000 are carriers, the fatality rate is 570 per million.

On the other hand, the researchers found that in many countries in Africa and South East Asia, where these mutations are relatively rare, COVID-19 mortality rates are correspondingly low as of September 2020. In Japan, where 9 of every million died in the pandemic, the mutations' prevalence is negligible. Similar numbers were also found in China, South Korea, Taiwan, Thailand, Vietnam, and Cambodia.

Prof. Gurwitz, Prof. Shomron, and Shapira conclude, "Our data analysis reveals a strong correlation between these mutations and severe illness and death from COVID-19. We call upon the research community to test our hypothesis against clinical data, and also call upon decision makers in every country to conduct population-wide screening for identifying mutation carriers and prioritize them for vaccination once COVID-19 vaccines have been approved. In the meantime, carriers should be notified that they may belong to a high-risk group and advised to maintain strict social isolation."

Understanding of fibromuscular dysplasia (FMD), a rare blood vessel disease, is making the jump from the laboratory to the clinic with new findings about a genetic variant.

Researchers found the mutation in a gene that is associated with classical Ehlers-Danlos Syndrome as well, in multifocal FMD. That means it could help clinicians understand whether a person inherited the disease from a relative or another mechanism, in affected families.

"We identified four independent families with the same genetic variant in COL5A1 and vascular disease in a pattern of dysplasia-associated arterial disease, including arterial dissections and multifocal FMD," says senior author Santhi Ganesh, M.D., an associate professor of internal medicine and human genetics, and a cardiologist at the Michigan Medicine Frankel Cardiovascular Center. "Notably, the variant appears to have been inherited from a shared ancestral founder."

Ganesh says the implication of this finding is that other carriers of this variant may exist in the population. The pattern of arterial involvement among carriers of the COL5A1 "G514S" variant is unique, providing clinicians with clues for when to suspect its involvement.

"The identified genetic variant meets clinical criteria for pathogenicity - a first for FMD," she says.

Further, additional variants in the COL5A1 gene were associated with a higher rate of arterial dissections among individuals with multifocal FMD.

NASA's Aqua satellite caught a visible image of Dolphin after it passed east central Japan on Sept. 24, where it became an extratropical storm in the Northwestern Pacific Ocean.

At 11 p.m. EDT on Sept. 23 (0300 UTC on Sept. 24) the Joint Typhoon Warning Center (JTWC) noted, "Animated multispectral satellite imagery shows the ragged low level circulation has become quasi-stationary and fully exposed as the rapidly decaying central convection sheared 140 plus nautical miles to the east-northeast. Analysis indicates that tropical cyclone Dolphin now fully embedded in the baroclinic zone and has become extra-tropical."

Strong vertical wind shear from the west-southwest was battering Dolphin and pushing the bulk of clouds to the east-northeast. Wind shear occurs when winds outside of a tropical cyclone blow against it and adversely affect its circulation by displacing clouds and precipitation and weakening the system.

Dolphin on Sept. 24

At 11 p.m. EDT on Sept. 23 (0300 UTC on Sept. 24) the center of Dolphin was located near latitude 33.1 degrees north and longitude 141.8 degrees east. That is about 175 nautical miles southeast of Yokosuka, Japan. Dolphin was barely moving to the south at 1 knot and had maximum sustained winds near 30 knots (35 mph/55 kph).

NASA's Aqua Satellite View

The Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Aqua satellite captured a visible image of Dolphin at 11:35 p.m. EDT on Sept. 23 (0335 UTC on Sept. 24). The image showed the storm appeared more elongated. That is an indication that the storm was weakening and it had become extratropical.

What is an Extra-tropical Storm?

Often, a tropical cyclone will transform into an extra-tropical cyclone as it recurves toward the poles (north or south, depending on the hemisphere the storm is located in). An extra-tropical cyclone is a storm system that primarily gets its energy from the horizontal temperature contrasts that exist in the atmosphere.

Tropical cyclones have their strongest winds near the earth's surface, while extra-tropical cyclones have their strongest winds near the tropopause - about eight miles (12 km) up. Also, tropical cyclones, in contrast, typically have little to no temperature differences across the storm at the surface and their winds are derived from the release of energy due to cloud/rain formation from the warm moist air of the tropics.

Dolphin's Final Forecast  

Forecasters at the JTWC noted, "The remnant storm-force cold-core low [pressure area] will drift slowly poleward [north] and deeper into the cold polar air mass. There is also a distinct possibility that the cyclone will remain quasi-stationary and dissipate."

The consumption of raw carrots triggers allergic reactions in many people. Contrary to popular belief, cooked carrots can also have this effect. This was recently discovered by a research team at the University of Bayreuth. The carrot's allergen, Dau c 1, assumes a structure that is harmless to allergy sufferers when highly heated. However, as soon as the temperature drops, it largely regains its natural structure. The researchers present their study in the journal "Molecular Nutrition & Food Research".

"The results of our research clearly suggest that sufferers who are sensitive to the carrot allergen should generally avoid eating carrots. Heating carrots does not destroy or only incompletely destroys the protein structures that can cause allergic reactions ", says Prof. Dr. Birgitta Wöhrl from the Biochemistry IV research group at the University of Bayreuth. "The risk of allergy patients developing an allergic reaction arises not only when eating freshly cooked carrots or canned carrots. It also arises when carrot extract is added to food," adds Thessa Jacob M.Sc., first author of the study and PhD student at the Biochemistry IV research group.

The natural carrot allergen Dau c 1 is actually a mixture of several, structurally very similar proteins. These so-called isoallergens were produced individually in the laboratory in bacteria. Both the protein mixture of the natural Dau c 1 and the individual isoallergens were examined at temperatures up to 95 degrees Celsius to see how their structures change upon increasing and decreasing the temperature. This analysis showed that the natural mixture and almost all isoallergens are still capable of causing allergies after cooling down to 25 degrees Celsius. Despite the previous heating, antibodies present in the organism of allergy patients will still trigger allergic reactions. Although in some cases this effect is less pronounced than before heating, it is generally maintained.

"This is the first time that the Dau c 1 isoallergens have been subjected to such an extensive series of tests. The separate examination of the structurally similar molecules was particularly important to us in order to determine which of the isoallergens trigger immune reactions under the tested conditions," says Thessa Jacob M.Sc.

The tests clearly showed that the structural stability of the carrot allergen does not depend on temperature alone. Acidity, as expressed by the pH value, is also important. Of particular interest is pH value 3, which typically prevails in the stomach after food intake. At this level of acidity and at normal room temperature, at least some epitopes can continue to exist despite previous heating. Epitopes are those molecular substructures by which the immune system of allergy sufferers recognises the respective allergen, allowing an allergic reaction to occur.

In their structural investigations of the Dau c 1 isoallergens, the researchers mainly used magnetic resonance spectroscopy (NMR) and CD spectroscopy in laboratories on the Bayreuth campus. For other analytical procedures, they received support from the Paul Ehrlich Institute in Langen and from Nano Temper Technologies in Munich.

Earthquakes can be abrupt bursts of home-crumbling, ground-buckling energy when slices of the planet's crust long held in place by friction suddenly slip and lurch.

"We typically think of the plates on either side of a fault moving, deforming, building up stresses and then: Boom, an earthquake happens," said Stanford University geophysicist Eric Dunham.

But deeper down, these blocks of rock can slide steadily past one another, creeping along cracks in Earth's crust at about the rate that your fingernails grow.

A boundary exists between the lower, creeping part of the fault, and the upper portion that may stand locked for centuries at a stretch. For decades, scientists have puzzled over what controls this boundary, its movements and its relationship with big earthquakes. Chief among the unknowns is how fluid and pressure migrate along faults, and how that causes faults to slip.

A new physics-based fault simulator developed by Dunham and colleagues provides some answers. The model shows how fluids ascending by fits and starts gradually weaken the fault. In the decades leading up to big earthquakes, they seem to propel the boundary, or locking depth, a mile or two upward.

Migrating swarms

The research, published Sept. 24 in Nature Communications, also suggests that as pulses of high-pressure fluids draw closer to the surface, they can trigger earthquake swarms - strings of quakes clustered in a local area, usually over a week or so. Shaking from these seismic swarms is often too subtle for people to notice, but not always: A swarm near the southern end of the San Andreas Fault in California in August 2020, for example, produced a magnitude-4.6 quake strong enough to rattle surrounding cities.

Each of the earthquakes in a swarm has its own aftershock sequence, as opposed to one large mainshock followed by many aftershocks. "An earthquake swarm often involves migration of these events along a fault in some direction, horizontally or vertically," explained Dunham, senior author of the paper and an associate professor of geophysics at Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth).

The simulator maps out how this migration works. Whereas much of the advanced earthquake modeling of the last 20 years has focused on the role of friction in unlocking faults, the new work accounts for interactions between fluid and pressure in the fault zone using a simplified, two-dimensional model of a fault that cuts vertically through Earth's entire crust, similar to the San Andreas Fault in California.

"Through computational modeling, we were able to tease out some of the root causes for fault behavior," said lead author Weiqiang Zhu, a graduate student in geophysics at Stanford. "We found the ebb and flow of pressure around a fault may play an even bigger role than friction in dictating its strength."

Underground valves

Faults in Earth's crust are always saturated with fluids - mostly water, but water in a state that blurs distinctions between liquid and gas. Some of these fluids originate in Earth's belly and migrate upwards; some come from above when rainfall seeps in or energy developers inject fluids as part of oil, gas or geothermal projects. "Increases in the pressure of that fluid can push out on the walls of the fault, and make it easier for the fault to slide," Dunham said. "Or, if the pressure decreases, that creates a suction that pulls the walls together and inhibits sliding."

For decades, studies of rocks unearthed from fault zones have revealed telltale cracks, mineral-filled veins and other signs that pressure can fluctuate wildly during and between big quakes, leading geologists to theorize that water and other fluids play an important role in triggering earthquakes and influencing when the biggest temblors strike. "The rocks themselves are telling us this is an important process," Dunham said.

More recently, scientists have documented that fluid injection related to energy operations can lead to earthquake swarms. Seismologists have linked oil and gas wastewater disposal wells, for example, to a dramatic increase in earthquakes in parts of Oklahoma starting around 2009. And they've found that earthquake swarms migrate along faults faster or slower in different environments, whether it's underneath a volcano, around a geothermal operation or within oil and gas reservoirs, possibly because of wide variation in fluid production rates, Dunham explained. But modeling had yet to untangle the web of physical mechanisms behind the observed patterns.

Dunham and Zhu's work builds on a concept of faults as valves, which geologists first put forth in the 1990s. "The idea is that fluids ascend along faults intermittently, even if those fluids are being released or injected at a steady, constant rate," Dunham explained. In the decades to thousands of years between large earthquakes, mineral deposition and other chemical processes seal the fault zone.

With the fault valve closed, fluid accumulates and pressure builds, weakening the fault and forcing it to slip. Sometimes this movement is too slight to generate ground shaking, but it's enough to fracture the rock and open the valve, allowing fluids to resume their ascent.

The new modeling shows for the first time that as these pulses travel upward along the fault, they can create earthquake swarms. "The concept of a fault valve, and intermittent release of fluids, is an old idea," Dunham said. "But the occurrence of earthquake swarms in our simulations of fault valving was completely unexpected."

Predictions, and their limits

The model makes quantitative predictions about how quickly a pulse of high-pressure fluids migrates along the fault, opens up pores, causes the fault to slip and triggers certain phenomena: changes in the locking depth, in some cases, and imperceptibly slow fault movements or clusters of small earthquakes in others. Those predictions can then be tested against the actual seismicity along a fault - in other words, when and where small or slow-motion earthquakes end up occurring.

For instance, one set of simulations, in which the fault was set to seal up and halt fluid migration within three or four months, predicted a little more than an inch of slip along the fault right around the locking depth over the course of a year, with the cycle repeating every few years. This particular simulation closely matches patterns of so-called slow-slip events observed in New Zealand and Japan - a sign that the underlying processes and mathematical relationships built into the algorithm are on target. Meanwhile, simulations with sealing dragged out over years caused the locking depth to rise as pressure pulses climbed upward.

Changes in the locking depth can be estimated from GPS measurements of the deformation of Earth's surface. Yet the technology is not an earthquake predictor, Dunham said. That would require more complete knowledge of the processes that influence fault slip, as well as information about the particular fault's geometry, stress, rock composition and fluid pressure, he explained, "at a level of detail that is simply impossible, given that most of the action is happening many miles underground."

Rather, the model offers a way to understand processes: how changes in fluid pressure cause faults to slip; how sliding and slip of a fault breaks up the rock and makes it more permeable; and how that increased porosity allows fluids to flow more easily.

In the future, this understanding could help to inform assessments of risk related to injecting fluids into the Earth. According to Dunham, "The lessons that we learn about how fluid flow couples with frictional sliding are applicable to naturally occurring earthquakes as well as induced earthquakes that are happening in oil and gas reservoirs."

Conducting studies in vitro -- a Latin term that literally means "in the glass"--is essential in the fields of medicine and biology. Working with in vitro cultures is a relatively cost-effective and easily repeatable way of gaining insight into the interactions between cells or microorganisms and specific chemical compounds, such as drugs, nutrients, and toxins. However, to properly assess the toxicity of a compound, a reliable and efficient way to distinguish live cells from cells killed due to toxicity is necessary.

Researchers have elucidated several methods to tell live and dead cells apart, and one popular approach is the "dye exclusion test (DET)" using synthetic dyes. In conventional DET, a dye such as trypan blue or methylene blue selectively permeates and stains dead cells, distinguishing them from live cells. This seems simple enough, but these synthetic dyes have been known to damage living cells in the culture as well. This renders them unusable for long-term studies with a single culture.

Fortunately, as is described in their study published in MDPI Biology, a team of scientists from the Tokyo University of Science, Japan―comprising Assistant Professor Ryoma Tagawa, Professor Yoshikazu Higami, Professor Eiji Tokunaga, and Assistant Professor Kyohei Yamashita―recently discovered an alternative to DET with synthetic dyes: DET using a natural pigment made from Monascus purpureus (MP), a mold species traditionally used in Asia for the production of fermented foods. According to Dr Yamashita, lead author of this and two other studies on MP, its discovery as a tool for distinguishing dead cells was a case of serendipity.

Dr Yamashita and a colleague were working alongside Dr Koji Yamada and Dr Kengo Suzuki from euglena Co., Ltd. to find effective ways of culturing Euglena gracilis, a type of single-cell algae, in foods, when they stumbled upon the usefulness of MP and another natural dye called anthocyanin pigment for studying cell health over time. The results of their study are published in PeerJ in the world's first report on the application of natural food pigments in cell viability assays.

Dr Yamashita then went on to lead another study demonstrating the applicability of MP in DET for another single-cell organism species with a vastly different structure, Paramecium.

In their most recent study, the one published in MDPI Biology, Dr Yamashita and colleagues proved that MP can be used to ascertain the viability of breast cancer cells. They found that, unlike trypan blue, MP does not damage living cells and is robust against a typical chemotherapy drug cisplatin. Moreover, MP took only ten minutes to stain dead cells and costs a tenth of what trypan blue does. Considering all this, Dr Yamashita remarks: "The proposed natural pigment enables the long-term monitoring of the life and death of cells, which may bring about improvements in the efficiency of biomass production, basic research on metabolic mechanisms, and applied research in fields such as breeding."

In addition to its use as a reagent to monitor the life and death of cells, Dr Yamashita notes that the pigment is also nutritious to living cells and has antioxidative characteristics, which is useful for boosting culture efficiency and performing quality control in the food industry, where safe fermentation is critical. It is also safe to humans and the environment.

This applicability of MP to completely different kinds of cells--breast cancer, Euglena, and Paramecium--has made Dr Yamashita very optimistic about its potential. He states: "Our natural pigment could be the tool that opens up new research fields involving the determination of the causes behind the death of cells. Moreover, natural pigments are highly likely to have useful properties that have not yet been found, and there is much room for exploration."

There is certainly a bright and colorful future ahead for this promising natural dye!