First Structure of Key COVID Enzyme at Human Body Temperature

Scientists used x-rays to decipher the three-dimensional structure of the main protease of the virus that causes COVID-19 at different temperatures. The background image shows the full structure at 240 Kelvin (-28°F, cyan stick figure) and 100 K (-280°F, dark blue). The red and green blobs represent differences in the structure at these distinct temperatures. The study allowed the scientists to zero in on subtle shifts that occur in the structure as the temperature changes (inset), potentially pointing to areas of the enzyme that could be targeted with inhibitor drugs to impair its function.
 Source/Credit: Brookhaven National Laboratory

Daniel Keedy, City University of New York

Scientists studying a COVID-19 coronavirus enzyme at temperatures ranging from frosty to human-body warm discovered subtle structural shifts that offer clues about how the enzyme works. The findings, published in IUCrJ, the journal of the International Union of Crystallography, may inspire the design of new drugs to counteract COVID-19—and possibly help head off future coronavirus pandemics.

“No previous study has looked at this important coronavirus enzyme at physiological (or body) temperature,” said Daniel Keedy, a structural biologist at the City University of New York (CUNY), who conducted the study in collaboration with scientists at the U.S. Department of Energy’s Brookhaven National Laboratory.

Most structures to date come from frozen samples—far from the temperatures at which the molecules operate within living cells. “If you are working at physiological temperature, you should get a more realistic picture of what’s happening during an actual infection, because that’s where biology happens,” Keedy said.

In addition, he added, the team used temperature as a tool. “By turning that knob and seeing how the protein reacts, we can learn about its mechanics—how it physically works."

Machine learning meets medicine in the fight against superbugs

Scanning electron micrograph of a human neutrophil ingesting MRSA.
Image: National Institute of Allergy and Infectious Diseases, National Institutes of Health on Flickr, CC BY-NC 2.0

MRSA is an antibiotic-resistant staph infection that can be deadly for those in hospital care or with weakened immune systems. Staphylococcus aureus bacteria live in the nose without necessarily producing any symptoms but can also spread to other parts of the body, leading to persistent infections. Management of MRSA is long-term and laborious, so any steps to optimize treatments and reduce re-infections will benefit patients. This new research can predict how effective different treatments will be by combining patient data with estimates of how MRSA moves between different parts of the body. The study was published in the Journal of the Royal Society Interface.

The researchers compared data from 2000 patients with MRSA after hospital visits. In one group, patients were given standard information about how to treat MRSA and prevent its spread. The second group followed a more intensive ‘decolonization’ protocol to eliminate MRSA through wound disinfection, cleaning the armpits and groin, and using nasal spray. Both groups were tested for MRSA on different body parts at various time points over nine months.

The current state-of-the-art in medical research often involves comparing two groups in this way, to see if an intervention or treatment could be effective. The new study added another element: a mathematical model that looked at the interactions between treatments and body parts. 'The model shows how MRSA moves between body parts,' says senior author Pekka Marttinen, professor at Aalto University and the Finnish Center for Artificial Intelligence FCAI. 'It can help us optimize the combination of treatments and even predict how new treatments would work before they have been tested on patients.'

Researchers reprogram human skin cells to aged neurons to study neurodegenerative disorders

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Researchers at Lund University in Sweden have developed a new method for studying age-related brain disorders. The researchers have focused on the neurodegenerative disorder Huntington’s disease and the results have now been published in the journal Brain.

Basic medical research often faces the challenge of developing disease models that correspond to specific disease mechanisms or the disease to be studied. This is a challenge that needs to be solved in order to produce new effective treatments. One example of a disease that is difficult to model for an understanding of the underlying mechanisms is Huntington’s disease. In part, this is due to the difficulty in recreating adequate animal or cellular models.

By reprogramming skin cells into neurons, Johan Jakobsson and his research group have been able to study Huntington’s disease in an innovative way that he believes could be significant for successful studies of several age-related brain disorders.

“We took skin biopsies from patients living with Huntington’s disease and reprogrammed the skin biopsies into neurons. We then compared these neurons with reprogrammed neurons from healthy people. The results are very interesting. We have found several defects that explain some of the disease mechanisms in neurons from patients with Huntington’s disease. Among other things, we observed that neurons from patients with Huntington’s disease show problems in breaking down and recycling a particular kind of protein – which can lead to a lack of energy in these cells”, says Johan Jakobsson, professor of neuroscience at Lund University.

Scientists Create a DNA Test That Identifies Lyme Disease in Horses

Photo credit: Christine Mendoza on Unsplash

A Rutgers scientist aiming to help heal a sick horse created an ultra-sensitive DNA test that could have applications for difficult-to-detect illnesses in humans such as Lyme disease.

As described in a study published in the Journal of Veterinary Diagnostic Investigation, a special DNA test devised by Steven Schutzer, a professor of medicine at Rutgers New Jersey Medical School, helped a Cornell University School of Veterinary Medicine team identify Neurologic Lyme disease in a sick 11-year-old Swedish Warmblood mare.

Although Lyme disease was suspected, a standard PCR test didn’t detect the disease agent, the corkscrew-shaped bacterium Borrelia burgdorferi.

As with the treatment of most diseases, early detection is essential with Lyme.

“Early diagnosis leads to immediate treatment,” Schutzer said. “And, naturally, that gives the best chance for a cure.”

The Schutzer team’s “genomic hybrid capture assay,” a highly sensitive test the team has been developing, identified the pathogen in a sample of the horse’s spinal fluid, allowing it to be diagnosed and successfully treated. The test works by first selectively isolating DNA from the microorganism causing the disease.

“The method is like having a special, specific ‘fishhook’ that only grabs Borrelia DNA and not the DNA of other microbes, nor the DNA of the host (animal or human),” Schutzer said. “Detecting DNA of the disease is a direct test, meaning we know you have active disease if it’s circulating in the blood or spinal fluid.”

Premiere for super­con­duct­ing diode with­out exter­nal mag­netic field

Trilayer graphene is a promising platform for the superconducting diode effect.
Credit: Mathias Scheurer

Superconductors are the key to lossless current flow. However, the realization of superconducting diodes has only recently become an important topic of fundamental research. An international research team involving the theoretical physicist Mathias Scheurer has now succeeded in reaching a milestone: the realization of a superconducting diode effect without an external magnetic field. They report on this in Nature Physics.

One speaks of a superconducting diode effect when a material behaves like a superconductor in one direction of current flow and like a resistor in the other. In contrast to a conventional diode, such a superconducting diode exhibits a completely vanishing resistance and thus no losses in the forward direction. This could form the basis for future lossless quantum electronics. Physicists first succeeded in creating the diode effect about two years ago, but with some fundamental limitations. "At that time, the effect was very weak and it was generated by an external magnetic field, which is very disadvantageous in potential technological applications," explains Mathias Scheurer from the Institute of Theoretical Physics at the University of Innsbruck. The new experiments carried out by experimental physicists at the renowned U.S. Brown University, described in the current issue of Nature Physics, does not require an external magnetic field. 

How hepatitis E outwits the immune system

Daniel Todt, Eike Steinmann and Toni Meister (from left) look at the image of a cell infected with the hepatitis E virus. The capsid protein can be seen in green, the cell nucleus in blue.
Credit: Department of Molecular and Medical Virology

Faulty virus particles could be a deception to distract the immune system from fighting infectious viruses.

Over three million people become infected with the hepatitis E virus every year. So far there is no specifically effective drug. An international research team has examined which factors are important for the virus in the course of its reproductive cycle and how it manages to maintain the infection. The researchers analyzed various mutations in the virus and found changes that may allow the virus to outsmart the immune system. The team from the Molecular and Medical Virology Department of the Ruhr University Bochum around Dr. Toni Meister, Dr. Daniel Todt and Prof. Dr. Eike Steinmann reports in the journal PNAS.

Advantages and disadvantages of mutations

An important defense mechanism against viral infections in our body are special proteins, the antibodies. These usually bind specifically to surface proteins of the virus in order to make it harmless. But viruses have developed strategies to avoid this identification. During infection with the hepatitis E virus, random mutations often result in virus variants that can coexist within an infected person. The antiviral agent ribavirin, which many chronically infected people receive, can even increase the formation of such viral variants.

Improved precision in biological age measurement

Schematic picture of how the reliability of the epigenetic clock (Y-axis: change in methylation) is improved in the new PC clock in longitudinal data (X-axis: year from baseline) from the research study "the Swedish Adoption Twin Study of Aging" (SATSA).
Credit: Sara Hägg 

Epigenetic clocks based on DNA methylation data are a type of biomarker that is useful for estimating biological age in population-based cohorts. However, usability has been limited by partially unreliable estimates due to this. noise in data. In a new study, we present a solution by introducing a method that reduces the noise in the epigenetic clocks for improved precision in longitudinal analyzes and clinical studies.

Biomarkers for aging can be obtained from cellular, molecular, functional and physiological measurements and used to study biological aging in humans. Many studies use the so-called "epigenetic clocks" based on DNA methylation data to analyze the relationship between biological aging and morbidity and mortality. Although these watches are currently considered to be the best predictors of biological age, they still include technical noise, leading to great variation in the measurements.

In order to make the clocks more useful for longitudinal analyzes and clinical studies, improved precision in the measurements is important. Here we present a method where principal component analysis (PCA) is used to separate noise from age-related signals. In this way, only biologically relevant signals are prioritized and the reliability of the PC watches is much higher compared to the original watches.

UF research shows a step toward restoring sea urchins: ‘The lawnmowers of reefs’

Sea urchin
Credit: Josh Patterson 

Coral reef ecosystems are severely threatened by pollution, disease, overharvesting and other factors. For thousands of years, long-spined sea urchins helped keep reefs intact. They eat seaweed, which can kill or seriously damage coral. Without coral, reefs suffer severe consequences, including diminished ability to support fish.

In the mid-1980s, more than 90% of the urchins that crawled the coral reefs in the western Atlantic and Caribbean died for reasons scientists have yet to determine. The population of the long-spined sea urchin – known scientifically as Diadema antillarum -- has been slow to recover on its own. That’s why scientists, including Josh Patterson, are stepping up their efforts to enhance urchin populations.

“You could call these urchins the lawn mowers of the reefs,” said Patterson, a UF/IFAS associate professor of fisheries and aquatic sciences. “They eat fleshy seaweeds that grow out of control on coral reefs and ultimately smother the corals.”

The UF/IFAS restoration ecologist is trying to return more of the urchin to an area that roughly includes the seas off the Florida Keys, Bermuda, the Yucatan Peninsula, Aruba and the Virgin Islands. He’s taken a small step toward the overarching goal of revitalizing the population of the vital echinoderm.

New Technology Sharpens Images of Black Holes

The emission from M87 has now been resolved into a bright, thin ring (orange colormap), arising from the infinite sequence of additional images of the emission region, and the more diffuse primary image, produced by the photons that come directly toward Earth (in blue contours). When viewed at the imaging resolution of the Event Horizon Telescope, the two components blur together. However, by separately searching for the thin ring, it is possible to sharpen the view of M87, isolating the fingerprint of strong gravity.
Credit: Broderick et al. 2022, ApJ, 935, 61

When scientists unveiled humanity’s historic first image of a black hole in 2019 — depicting a dark core encircled by a fiery aura of material falling toward it — they believed even richer imagery and insights were waiting to be teased out of the data.

Simulations predict that, obscured by that bright orange glow, there should exist a thin, bright ring of light created by photons flung around the back of the black hole by its intense gravity.

Now, a team of researchers has combined theoretical predictions and sophisticated imaging algorithms to “remaster” the original imagery of the supermassive black hole at the center of the galaxy M87*, first captured by the Event Horizon Telescope (EHT) in 2019. Their findings, published today in The Astrophysical Journal, are consistent with theoretical predictions and offer new ways to explore these mysterious objects, which are believed to reside at the hearts of most galaxies.

"The approach we took involved leveraging our theoretical understanding of how these black holes look to build a customized model for the EHT data," says Dominic Pesce, a study co-author based at the Center for Astrophysics | Harvard & Smithsonian and member of the EHT collaboration. "Our model decomposes the reconstructed image into the two pieces that we care most about, so that we can study both pieces individually rather than blended together."

Scientists Take Another Theoretical Step to Uncovering the Mystery of Dark Matter, Black Holes

A star (orange) that gets close to a supermassive black hole (black) can be tidally disrupted by the black hole’s strong gravitational pull. According to a new study, if ultra-light bosons exist (purple), they can affect the spin of the black hole, which in turn affects the rate at which tidal disruption events occur.
 Credit: Peizhi Du

Much of the matter in the universe remains unknown and undefined, yet theoretical physicists continue to gain clues to the properties of dark matter and black holes. A study by a team of scientists including three from Stony Brook University proposes a novel method to search for new particles not currently contained in the standard model of particle physics. Their method, published in Nature Communications, could shed light on the nature of dark matter.

The three Stony Brook authors include Rouven Essig, PhD, Professor in the C. N. Yang Institute for Theoretical Physics (YITP); Rosalba Perna, PhD, Professor in the Department of Physics and Astronomy, and Peizhi Du, PhD, postdoctoral researcher at the YITP.

Stars that pass close to the supermassive black holes located in the center of galaxies can be disrupted by tidal forces, leading to flares that are observed as bright transient events in sky surveys. The rate for these events to occur depends on the black hole spins, which in turn can be affected by ultra-light bosons (hypothetical particles with minute masses) due to superradiance. The research team performed a detailed analysis of these effects, and they discovered that searches for stellar tidal-disruptions have the potential to uncover the existence of ultra-light bosons.

A gold inflatable Martian House designed to withstand life on Mars has landed in Bristol

The exterior of the Martian House
Credit: Luke O’Donovan

A two-story house designed for future life on Mars has landed on M Shed Square in Bristol, UK as part of an ongoing public art project, Building a Martian House.

The brainchild of local artists and Watershed Pervasive Media Studio residents Ella Good and Nicki Kent, the project has been designed over several years and brought together space scientists, world renowned architects, engineers, designers, school children and the public, to explore how considering future life on Mars, a planet with low power, zero emissions and zero waste, can inspire us to think creatively about how we can live more sustainably on earth and reassess our relationship with consumerism.

A team led by Hugh Broughton Architects, world experts in creating buildings for extreme environments including the Halley VI British Antarctic Research Station, working in partnership with design studio Pearce+, developed the design of the house.

The design team worked alongside space science and engineering experts Professor Lucy Berthoud, Dr Robert Myhill and Professor James Norman from the University of Bristol. A cohort of construction companies led by Southern Construction Framework generously donated their time and expertise to bring the project to life and funding has been provided by the Edward Marshall Trust.

Male spiders maximize sperm transfer to counter female cannibalism

A male Nephila pilipes spider copulating with a female mate.
Resized Image using AI by SFLORG
Photo credit: Li Daiqin

When sexual conflict results in reproductive strategies that only benefit one of the sexes, it may result in evolutionary arms races. Male spiders have evolved behavioral mating strategies to improve their chances of mating despite the risk of being cannibalized by their mates.

Researchers from the National University of Singapore (NUS) have discovered that male spiders make choices on maximizing their mating success when they are at risk of being cannibalized by their female mates. Led by Associate Professor Li Daiqin from the NUS Department of Biological Sciences, the researchers found that a male chooses one of its paired sexual organs with more sperm for the first copulation with a cannibalistic female. Also, a male transfer significantly more sperm if a female is cannibalistic or when the female is of a much larger physical size.

The study was published in Communications Biology.

Increasing sperm transfer in the face of sexual cannibalism

The theory of the male mating syndrome posits that male spiders are under sexual conflict pressure in sexually cannibalistic situations, as they may only have a single chance to mate. In this study, the researchers explored whether male spiders use additional cannibalism countering strategies by focusing on two male mating tactics. One of which is the “better charged palp” hypothesis which predicts that male spiders selectively make use of one of its paired sexual organs, known as pedipalps or palps, containing more sperm for their first copulation. The other, referred to as the “fast sperm transfer” hypothesis, predicts accelerated insemination when the risk of female cannibalism is high.

Extreme events stress the oceans

Sea snails - the picture shows a pteropod - play an important role in the marine food web. They are especially sensitive to ocean warming and acidification.
Source: Universität Bern Credit: Charlotte Havermans

When marine heatwaves and ocean acidity extreme events co-occur, it can have severe impacts on marine ecosystems. Researchers at the Oeschger Center for Climate Change Research at the University of Bern have determined for the first time the frequency and drivers of these compound events and have projected them into the future.

It's not just the land that is groaning under the heat – the ocean is also suffering from heatwaves. In the Mediterranean Sea along the Italian and Spanish coasts, for example, water temperatures are currently up to 5 °C higher than the long-term average at this time of year. Scientists have investigated marine heatwaves for a few years now – for example at the University of Bern. However, relatively little is known about how marine heatwaves co-occur with other extreme events in the ocean. Such events are known as compound events and considered to be a major risk of climate change. While the processes that lead to extreme events on land, such as floods, forest fires, heatwaves, or droughts and how they interact with each other have been intensively studied in the past, the finding that ocean weather and climate extreme events can also occur in combination is relatively new.

A group of researchers at the Oeschger Center for Climate Change Research, led by Thomas Frölicher, has now investigated whether marine heatwaves co-occur in combination with extreme events in other potential marine ecosystem stressors. In addition to heat, potential stressors also include high acidity levels in the ocean. "For the first time, we have quantified the frequency of compound events in which marine heatwaves happen together with extreme acidity", says Friedrich Burger, postdoctoral researcher and first author of the study just published in the journal Nature Communications. Extreme events of high ocean acidity are occurrences where the proton concentration in seawater is higher than normal.

Detecting diabetes among people at risk

When diabetes starts to develop but no symptoms are yet detectable, part of the beta cells of the pancreas (in green) disappear (right image) compared to a healthy individual (left image). This previously undetectable decrease could be identified by measuring the level of 1,5-anhydroglucitol in the blood.
Credit: UNIGE - Laboratory of Prof. Pierre Maechler

A team from the UNIGE in collaboration with the HUG has discovered a molecule that can identify the development of diabetes before the first symptoms appear.

Diabetes is a severe and growing metabolic disorder. It already affects hundreds of thousands of people in Switzerland. A sedentary lifestyle and an excessively rich diet damage the beta cells of the pancreas, promoting the onset of this disease. If detected early enough, its progression could be reversed, but diagnostic tools that allow for early detection are lacking. A team from the University of Geneva (UNIGE) in collaboration with several other scientists, including teams from the HUG, has discovered that a low level of the sugar 1,5-anhydroglucitol in the blood is a sign of a loss in functional beta cells. This molecule, easily identified by a blood test, could be used to identify the development of diabetes in people at risk, before the situation becomes irreversible. These results can be found in the Journal of Clinical Endocrinology & Metabolism.

In Switzerland, almost 500,000 people suffer from diabetes. This serious metabolic disorder is constantly increasing due to the combined effect of a lack of physical activity and an unbalanced diet. If detected early enough at the pre-diabetes stage, progression to an established diabetes can be counteracted by adopting an appropriate lifestyle. Unfortunately, one third of patients already have cardiovascular, renal or neuronal complications at the time of diagnosis, which impacts their life expectancy.

Scientists develop gel made from spider silk proteins for biomedical applications

The hydrogels stained with a fluorescent dye that binds to amyloid structures and the corresponding brightfield image.
Microscope photo credit: Tina Arndt.

Researchers at KI and SLU have discovered that spider silk proteins can be fused to biologically active proteins and be converted into a gel at body temperature. One of the goals is to develop an injectable protein solution that forms a gel inside the body, which could be used in tissue engineering and for drug release, but also make gels that can streamline chemical processes where enzymes are used. The study is published in Nature Communications.

“We have developed a completely new method for creating a three-dimensional gel from spider silk that can be designed to deliver different functional proteins,” says Anna Rising, research group leader at the Department of Biosciences and Nutrition, Karolinska Institutet (KI) and professor at the Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences (SLU). “The proteins in the gel are very close together and the method is so mild that it can be used even for sensitive proteins.”