Culture

Scientists at Weill Cornell Medicine have developed a computational technique that greatly increases the resolution of atomic force microscopy, a specialized type of microscope that "feels" the atoms at a surface. The method reveals atomic-level details on proteins and other biological structures under normal physiological conditions, opening a new window on cell biology, virology and other microscopic processes.

In a study, published June 16 in Nature, the investigators describe the new technique, which is based on a strategy used to improve resolution in light microscopy.

To study proteins and other biomolecules at high resolution, investigators have long relied on two techniques: X-ray crystallography and cryo-electron microscopy. While both methods can determine molecular structures down to the resolution of individual atoms, they do so on molecules that are either scaffolded into crystals or frozen at ultra-cold temperatures, possibly altering them from their normal physiological shapes. Atomic force microscopy (AFM) can analyze biological molecules under normal physiological conditions, but the resulting images have been blurry and low resolution.

"Atomic force microscopy can easily resolve atoms in physics, on solid surfaces of silicates and on semiconductors, so it means that in principle the machine has the precision to do that," said senior author Dr. Simon Scheuring, professor of physiology and biophysics in anesthesiology at Weill Cornell Medicine. "The technique is a bit like if you were to take a pen and scan over the Rocky Mountains, so that you get a topographic map of the object. In reality, our pen is a needle that is sharp down to a few atoms and the objects are single protein molecules."

However, biological molecules have many small parts that wiggle, blurring their AFM images. To address that problem, Dr. Scheuring and his colleagues adapted a concept from light microscopy called super-resolution microscopy. "Theoretically it wasn't possible by optical microscopy to resolve two fluorescent molecules that were closer together than half the wavelength of the light," he said. However, by stimulating the adjacent molecules to fluoresce at different times, microscopists can analyze the spread of each molecule and pinpoint their locations with high precision.

Instead of stimulating fluorescence, Dr. Scheuring's team noted that the natural fluctuations of biological molecules recorded over the course of AFM scans yield similar spreads of positional data. First author Dr. George Heath, who was a postdoctoral associate at Weill Cornell Medicine at the time of the study and is now a faculty member at the University of Leeds, engaged in cycles of experiments and computational simulations to understand the AFM imaging process in greater detail and extract the maximum of information from the atomic interactions between tip and sample.

Using a method like super-resolution analysis, they were able to extract much higher resolution images of the moving molecules. Continuing the topographic analogy, Dr. Scheuring explained that "if the rocks (i.e., atoms) wiggle a little bit up and down, you can detect this one, then that one, and then you average all detections over time and you receive high-resolution information."

Because previous AFM studies have routinely collected the necessary data, the new technique can be applied retroactively to the blurry images the field has generated for decades. As an example, the new paper includes an analysis of an AFM scan of an aquaporin membrane protein, originally acquired during Dr. Scheuring's doctoral thesis. The reanalysis generated a much sharper image that matches X-ray crystallography structures of the molecule closely. "You basically get quasi-atomic resolution on these surfaces now," said Dr. Scheuring. To showcase the power of the method, the authors provide new high-resolution data on annexin, a protein involved in cell membrane repair, and on a proton-chloride antiporter of which they also report structural changes related to its functional.

Besides allowing researchers to study biological molecules under physiologically relevant conditions, the new method has other advantages. For example, X-ray crystallography and cryo-electron microscopy rely on averaging data from large numbers of molecules, but AFM can generate images of single molecules. "Instead of having observations of hundreds of molecules, we observe one molecule a hundred times and calculate a high-resolution map," said Dr. Scheuring.

Imaging individual molecules as they carry out their functions could open entirely new types of analysis. "Let's say you have a [viral] spike protein that's in one conformation and then it gets activated and goes into another conformation," said Dr. Scheuring. "You would in principle be able to calculate a high-resolution map from that same molecule as it transits from one conformation to the next, not from thousands of molecules in one or the other conformation." Such high-resolution single molecule data could provide more detailed information and avoid the potentially misleading results that can occur when averaging data from many molecules. Furthermore, the map might reveal new strategies for precisely redirecting or interrupting such processes.

While crop yield has achieved a substantial boost from nanotechnology in recent years, alarms over the health risks posed by nanoparticles within fresh produce and grains have also increased. In particular, nanoparticles entering the soil through irrigation, fertilizers and other sources have raised concerns about whether plants absorb these minute particles enough to cause toxicity.

In a new study published online in the journal Environmental Science and Technology, researchers at Texas A&M University have used machine learning to evaluate the salient properties of metallic nanoparticles that make them more susceptible for plant uptake. The researchers said their algorithm could indicate how much plants accumulate nanoparticles in their roots and shoots.

Nanoparticles are a burgeoning trend in several fields, including medicine, consumer products and agriculture. Depending on the type of nanoparticle, some have favorable surface properties, charge and magnetism, among other features. These qualities make them ideal for a number of applications. For example, in agriculture, nanoparticles may be used as antimicrobials to protect plants from pathogens. Alternatively, they can be used to bind to fertilizers or insecticides and then programmed for slow release to increase plant absorption.

These agricultural practices and others, like irrigation, can cause nanoparticles to accumulate in the soil. However, with the different types of nanoparticles that could exist in the ground and a staggeringly large number of terrestrial plant species, including food crops, it is not clearly known if certain properties of nanoparticles make them more likely to be absorbed by some plant species than others.

"As you can imagine, if we have to test the presence of each nanoparticle for every plant species, it is a huge number of experiments, which is very time-consuming and expensive," said Xingmao "Samuel" Ma, associate professor in the Zachry Department of Civil and Environmental Engineering. "To give you an idea, silver nanoparticles alone can have hundreds of different sizes, shapes and surface coatings, and so, experimentally testing each one, even for a single plant species, is impractical."

Instead, for their study, the researchers chose two different machine learning algorithms, an artificial neural network and gene-expression programming. They first trained these algorithms on a database created from past research on different metallic nanoparticles and the specific plants in which they accumulated. In particular, their database contained the size, shape and other characteristics of different nanoparticles, along with information on how much of these particles were absorbed from soil or nutrient-enriched water into the plant body.

Once trained, their machine learning algorithms could correctly predict the likelihood of a given metallic nanoparticle to accumulate in a plant species. Also, their algorithms revealed that when plants are in a nutrient-enriched or hydroponic solution, the chemical makeup of the metallic nanoparticle determines the propensity of accumulation in the roots and shoots. But if plants are grown in soil, the contents of organic matter and the clay in soil are key to nanoparticle uptake.

Ma said that while the machine learning algorithms could make predictions for most food crops and terrestrial plants, they might not yet be ready for aquatic plants. He also noted that the next step in his research would be to investigate if the machine learning algorithms could predict nanoparticle uptake from leaves rather than through the roots.

"It is quite understandable that people are concerned about the presence of nanoparticles in their fruits, vegetables and grains," said Ma. "But instead of not using nanotechnology altogether, we would like farmers to reap the many benefits provided by this technology but avoid the potential food safety concerns."

Although each organism has a unique genome, a single gene sequence, each individual has many epigenomes. An epigenome consists of chemical compounds and proteins that can bind to DNA and regulate gene action, either by activating or deactivating them or producing organ- or tissue-specific proteins. As it is a highly dynamic material, it can provide a large amount of information to shed light on the evolution of the various tissues and organs that make up the body.

Now, a team from the Institute of Evolutionary Biology (IBE), a joint centre of the Spanish National Research Council (CSIC) and Pompeu Fabra University, has carried out the largest study to date on the regulatory elements in the genome of primates. The exhaustive analysis conducted by the research team led by Tomas Marquès-Bonet, principal investigator of the Comparative Genomics research group at the IBE, has analysed a wide spectrum of signals regulating genes in the great apes and in humans, including weak activity signals that have been overlooked in previous studies. The study, co-led by the researcher David Juan of the IBE, has revealed that in humans, the weakest regulatory signals, that are not usually studied, play an important role in the regulation of genes linked to brain. The research opens the door to deciphering the impact that these signals may have on the evolution of humans and other primates.

The research lab has carried out the largest study to date on the regulatory elements in the genome of primates.

The research team used high resolution to analyse epigenomic signals in cell lines of great apes and humans. In particular, the research provides new epigenomic data for four species of great apes and other primates: chimpanzees, gorillas, orangutans and macaques.

"In the study we used lymphoblastoid cell lines from humans and other primates because they provide a solid foundation as a model. Then we compared epigenomic signals between the different species, including the weakest activity signals in our analysis", comments Raquel García, a PhD with the Comparative Genomics group of the IBE and first author of the article.

"When we focused on detecting those specific characteristics of humans in the weakest epigenomic signals, we saw that they are related to brain functions", explains Paula Esteller, a PhD student with Marquès-Bonet's group and study co-author. "This opens the door to studying the role of weak epigenomic signals in depth, as they may play an important role in various organs of humans and of other primates".

The study includes weak epigenomic signals, usually ignored, and it has been seen that in humans they are related to brain functions.

The study, carried out using lymphoblastoid cells, which are easily accessible and easy to culture, suggests that this model could provide information on other more inaccessible tissues, such as the brain. The research could help understand how primates' cells are regulated and which of these mechanisms have been conserved over the course of evolution. The study also provides a comprehensive resource of genomic and epigenomic data on primates that are made available to the entire scientific community.

Philadelphia, June 16, 2021 - The SARS-CoV-2 virus that causes COVID-19 may have the ability to reactivate dormant tuberculosis (TB). In a novel study scientists report in The American Journal of Pathology that infection with a specific coronavirus strain reactivated dormant Mycobacterium tuberculosis (MTB) in mice. This knowledge may help to develop new vaccines for COVID-19 and avoid a potential global tuberculosis epidemic.

The COVID-19 pandemic caused by the SARS-CoV-2 virus demonstrates the ability of an emerging virus to affect masses and strain and disrupt the workings of modern healthcare systems around the world. A significant number of infected COVID-19 individuals have recovered. However, a possible host defense or antiviral mechanism against the virus is yet to be identified. There are concerns that in the long-term, the virus might activate dormant bacterial infections such as TB in select infected individuals, as alarmingly, TB is already present in one quarter of the world population. Viral infections such as the influenza virus or SARS-CoV-1 are known to cause transient immune suppression that leads to reactivation of dormant bacterial infection. The highest death rate during the Spanish flu pandemic of 1918 was in patients with TB, and patients with TB or multidrug-resistant TB had a worse prognosis than others during the influenza A (H1N1) pandemic in 2009.

"There is an urgent need to study the association of COVID-19 with dormant TB reactivation to avoid a potential global TB pandemic," explained lead investigator Bikul Das, MD, PhD, Department of Stem Cell and Infectious Diseases, KaviKrishna Laboratory, Guwahati Biotech Park, Indian Institute of Technology, Guwahati, India; and Department of Stem Cell and Infection, Thoreau Lab for Global Health, University of Massachusetts, Lowell, MA, USA. "It is important to understand the host defense mechanism against this disease to develop a better vaccine and/or treatment. We therefore postulated that, similar to bacteria, adult stem cells may also exhibit an altruistic defense mechanism to protect their niche against external threat."

Investigators studied the coronavirus strain murine hepatitis virus-1 (MHV-1) infection in the lung in a mouse model (dMtb) of mesenchymal stem cell (MSC)-mediated MTB dormancy. This showed 20-fold lower viral loads than the dMtb-free control mice by the third week of viral infection and a six-fold increase of altruistic stem cells (ASCs), thereby enhancing the defense. Tuberculosis was reactivated in the dMtb mice, suggesting that dormant TB bacteria hijack these ASCs to replicate in the lung to cause pulmonary TB. Results suggest that these ASCs are transient (they expand for two weeks and then undergo apoptosis or cellular suicide) and exhibit antiviral activities against MHV-1 by secreting soluble factors.

"These findings are important because they reveal a novel ASC defense mechanism against mouse coronavirus infection, which could be used to develop novel therapeutic approaches against COVID-19," noted Bikul Das. "The finding of TB reactivation in a stem cell-mediated Mtb dormancy mouse model during MHV-1 coronavirus infection indicates that in the long-term, post-pandemic, the SARS-CoV-2 virus might activate dormant bacterial infections. This is a significant finding considering the current coronavirus pandemic, where many individuals in India and other developing countries with dormant TB infection may see an increase in active TB cases post COVID-19. The ASC-mediated defense mechanism may be targeted to develop vaccines against viral infections and avoid a potential global TB pandemic."

The presence of pro-inflammatory cytokines in the blood can boost the effects of daily cannabis use and heighten the risk of developing psychosis in adulthood. Similar results have been observed, also in the presence of cytokines, when cannabis is used during adolescence. Psychotic disorders have symptoms such as delirium, loss of a sense of reality, hallucinations, hearing voices, and cognitive and social impairments.

A study by researchers at the University of São Paulo's Ribeirão Preto Medical School (FMRP-USP) in Brazil, reported in an article in the journal Psychological Medicine, finds for the first time that individuals exposed to a combination of these two factors - the presence of pro-inflammatory cytokines in the blood and cannabis use (either daily or during adolescence) - are more likely to suffer from psychosis than those who are exposed to neither or to only one. According to the authors, the study provides "the first clinical evidence that immune dysregulation modifies the cannabis-psychosis association".

The study was part of a project conducted by the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI), a consortium of research centers in 13 countries, including Brazil. An article published in The Lancet Psychiatry by the consortium in 2019 showed that daily cannabis use increased the likelihood of suffering from a psychotic disorder threefold.

In the more recent study, the researchers analyzed data for 409 people aged 16-64, including patients experiencing their first psychotic episode and community-based controls. The sample was drawn from the populations of Ribeirão Preto and 25 other cities in the region. The variables analyzed included cannabis use frequency (daily, not daily or never), duration (five years or less), and onset age (in adolescence or later).

In addition to the questionnaire on cannabis use, the researchers measured various cytokines in plasma donated by the volunteers and calculated scores representing their systemic inflammatory profiles. They also collected clinical and socio-demographic data, especially variables known as confounders, such as age, gender, schooling, ethnicity, body mass index, smoking, and use of psychoactive substances. The results obtained were independent of confounding factors.

"Not everyone who uses cannabis develops psychosis. This suggests that the association may be modified by other factors, which may be biological, genetic or environmental," said Fabiana Corsi-Zuelli, first author of the article. "In a previous study conducted as part of my master's research, we identified a correlation between plasma cytokines and the first psychotic episode. Following up on this discovery, and the consortium's recent publication showing a higher incidence of psychosis among subjects who used cannabis on a daily basis, our next step was to see if the biological factor [inflammatory profile] affected the link between cannabis use and psychosis."

The main conclusion was that such a link did indeed exist. "We found a statistically significant correlation between inflammatory profile and cannabis use on a daily basis or during adolescence. In sum, the results showed that immune system dysfunction can modify the association between cannabis use and psychosis and that a combination of these two factors increases the odds of suffering from a psychotic disorder," she said.

Corsi-Zuelli is currently a PhD candidate in FMRP-USP's graduate program in neurology and neurosciences, with support from São Paulo Research Foundation - FAPESP.

The principal investigator for the project is Cristina Marta Del-Ben, a professor at FMRP-USP's Department of Neurosciences and Behavioral Sciences. According to Del-Ben, risk factors for psychosis may be biological, including genetic predisposition and problems during pregnancy, as well as environmental, including traumatic experiences during childhood and adolescence, and exposure to psychoactive substances, especially cannabis.

"The mechanisms of the disorder are poorly understood," she said. "Our findings show that frequent current use of cannabis or use of the drug in adolescence is a risk factor for psychosis. We didn't detect the same correlation with occasional or recreational use. In the multicenter study, which included European cities with varying levels and types of cannabis availability, we also found that the risk of psychosis is greater in users of stronger cannabis strains with a THC content or 10% of higher." THC (delta-9-tetrahydrocannabinol) is the primary psychoactive constituent of cannabis or marijuana.

The medical explanation of psychosis is that it is a neuropsychiatric syndrome associated with anatomical and functional alterations in the brain, possibly linked to changes in the action of dopamine, a key neurotransmitter for communication among neurons. Excessive dopamine or direct damage to certain brain regions can lead to hallucinations, delusions, delirium and disorganized behavior.

Other neurotransmitters, such as glutamate, have also been implicated in the neurobiology of psychosis. Specialists are currently discussing what they call the neuroimmune link, and how immune system dysregulation may trigger neurochemical, morphological and behavioral alterations that heighten the risk of developing psychiatric disorders.

Psychotic symptoms may be present in several psychiatric disorders, which may or may not be affective. Recent research has taken note of cases of psychosis in patients infected by SARS-CoV-2. Treatment of psychosis involves a combination of medication, psychotherapy and family support.

Next steps

According to Corsi-Zuelli, the origin of the inflammatory alterations involved in psychosis is still obscure, but it may arise from a combination of genetic and environmental factors. "The inflammation seen in psychiatric disorders is considered low-level and isn't as severe as in patients with autoimmune diseases or sepsis," she said. "Nevertheless, experimental studies suggest it entails sufficient dysregulation to produce neurochemical and behavioral alterations."

The researchers plan next to study genetic variants associated with the immune system and use neuroimaging data to explore the link with environmental risk factors. "Focusing in this way on the interactions between genetics and the environment will help us understand the neurobiology of psychosis, especially the role played by the immune system," she said.

The association between inflammation and psychiatric disorders is highly relevant to clinical practice and has received growing attention. "It's important to the search for alternative treatments for these disorders, and also to answering often neglected questions relating to the physical health of psychiatric patients," Corsi-Zuelli said.

According to Del-Ben, in the pipeline for next steps is a partnership with Geraldo Busatto Filho, a professor at the Medical School (FM) in USP's main campus, to investigate whether inflammatory markers in blood are linked to brain alterations in some of the patients studied.

The research has twice received international recognition. The Society of Biological Psychiatry selected the study for its Predoctoral Scholars Award, which was to have been formalized at SOBP's 2020 annual meeting in New York, but the pandemic forced a postponement until April 2021, when the meeting was held online. And the study was selected by the Schizophrenia International Research Society (SIRS) for presentation at its 2020 Congress, also held online.

Besides the scholarship awarded to Corsi-Zuelli, FAPESP also supported the research via four other grants: 2012/05178-0, 2013/11167-3, 2017/13353-0, and 2018/07581-2.

NEW YORK, NY (June 16, 2021)--Spectacular images of a molecule that shuttles omega-3 fatty acids into the brain may open a doorway for delivering neurological therapeutics to the brain.

"We've managed to obtain a three-dimensional structure of the transporter protein that provides a gateway for omega-3s to enter the brain. In this structure, we can see how omega-3s bind to the transporter. This information may allow for the design of drugs that mimic omega-3s to hijack this system and get into the brain," says first author Rosemary J. Cater, PhD, a Simons Society Fellow in the Mancia Lab at Columbia University Vagelos College of Physicians and Surgeons.

The study was published online on June 16 in the journal Nature.

A major challenge in treating neurological diseases is getting drugs across the blood-brain barrier--a layer of tightly packed cells that lines the brain's blood vessels and zealously blocks toxins, pathogens, and some nutrients from entering the brain. Unfortunately, the layer also blocks many drugs that are otherwise promising candidates to treat neurological disorders.

Essential nutrients like omega-3s require the assistance of dedicated transporter proteins that specifically recognize them and get them across this barrier. "The transporters are like bouncers at a club, only letting molecules with invites or backstage passes in," Cater says.

The transporter--or bouncer--that lets omega-3s in is called MFSD2A and is the focus of Cater's research. "Understanding what MFSD2A looks like and how it pulls omega-3s across the blood-brain barrier may provide us with the information we need to design drugs that can trick this bouncer and gain entry passes."

To visualize MFSD2A, Cater used a technique called single-particle cryo-electron microscopy.

"The beauty of this technique is that we're able to see the shape of the transporter with details down to a fraction of a billionth of a meter," says study co-leader Filippo Mancia, PhD, associate professor of physiology & cellular biophysics at Columbia University Vagelos College of Physicians and Surgeons and an expert in the structure and function of membrane proteins. "This information is critical for understanding how the transporter works at a molecular level."

For cryo-EM analysis, protein molecules are suspended in a thin layer of ice under an electron microscope. Powerful cameras take millions of pictures of the proteins from countless angles which can then be pieced together to construct a 3D map.

Into this map researchers can build a 3D model of the protein, putting each atom in its place. "It reminds me of solving a jigsaw puzzle," Mancia explains. This technique has become remarkably powerful in visualizing biological molecules in recent years, thanks in part to Joachim Frank, PhD, professor of biochemistry & molecular biophysics at Columbia University Vagelos College of Physicians and Surgeons, who won the Nobel Prize in 2017 for his role in developing cryo-electron microscopy data analysis algorithms.

"Our structure shows that MFSD2A has a bowl-like shape and that omega-3s bind to a specific side of this bowl," Cater explains. "The bowl is upside down and faces the inside of the cell, but this is just a single 3D snapshot of the protein, which in real life has to move to transport the omega-3s. To understand exactly how it works, we need either multiple different snapshots or, better yet, a movie of the transporter in motion."

To understand what these movements might look like, a second co-leader of the study, George Khelashvili, PhD, assistant professor of physiology and biophysics at Weill Cornell Medicine, used the 3D model of the protein as a starting point to run computational simulations that revealed how the transporter moves and adapts its shape to release omega-3s into the brain. A third co-leader of the study, David Silver, PhD, professor at the Duke-NUS Medical School in Singapore and pioneer in MFSD2A biology, together with his team tested and confirmed hypotheses derived from the structure and the computational simulations on how MFSD2A works to pinpoint specific parts of the protein that are important.

The team also included researchers from the New York Structural Biology Center, the University of Chicago, and the University of Arizona, all using their specific skills to make this project possible.

The team is now investigating how the transporter first recognizes omega-3s from the bloodstream. "But our study has already given us tremendous insight into how MFSD2A delivers omega-3s to the brain, and we are really excited to see where our results lead to," Cater says.

The long relationships between stars and the planets around them - including the Sun and the Earth - may be even more complex than previously thought. This is one conclusion of a new study involving thousands of stars using NASA's Chandra X-ray Observatory.

By conducting the largest survey ever of star-forming regions in X-rays, a team of researchers has helped outline the link between very powerful flares, or outbursts, from youthful stars, and the impact they could have on planets in orbit.

"Our work tells us how the Sun may have behaved and affected the young Earth billions of years ago," said Kostantin Getman of Pennsylvania State University in University Park, Pennsylvania who led the study. "In some ways, this is our ultimate origin story: how the Earth and Solar System came to be."

The scientists examined Chandra's X-ray data of more than 24,000 stars in 40 different regions where stars are forming. They captured over a thousand stars that gave off flares that are vastly more energetic than the most powerful flare ever observed by modern astronomers on the Sun, the "Solar Carrington Event" in 1859. "Super" flares are at least one hundred thousand times more energetic than the Carrington Event and "mega" flares up to 10 million times more energetic.

These powerful flares observed by Chandra in this work occur in all of the star-forming regions and among young stars of all different masses, including those similar to the Sun. They are also seen at all different stages in the evolution of young stars, ranging from early stages when the star is heavily embedded in dust and gas and surrounded by a large planet-forming disk, to later stages when planets would have formed and the disks are gone. The stars in the study have ages estimated to be less than 5 million years, compared to the Sun's age of 4.5 billion years.

The team found several super-flares occur per week for each young star, averaged over the whole sample, and about two mega-flares every year.

"We want to know what kinds of impact - good and bad - these flares have on the early lives of planets," said co-author Eric Feigelson, also of Penn State. "Flares this powerful can have major implications."

Over the past two decades, scientists have argued that these giant flares can help "give" planets to still-forming stars by driving gas away from disks of material that surround them. This can trigger the formation of pebbles and other small rocky material that is a crucial step for planets to form.

On the other hand, these flares may "take away" from planets that have already formed by blasting any atmospheres with powerful radiation, possibly resulting in their complete evaporation and destruction in less than 5 million years.

The researchers also performed detailed modeling of 55 bright super- and mega-flares and found that most of them resemble long-lasting flares seen on the Sun that produce "coronal mass ejections," powerful ejections of charged particles that can damage planetary atmospheres. The Solar Carrington Event involved such an ejection.

This work is also important for understanding the flares themselves. The team found that the properties of the flares, such as their brightness and frequency, are the same for young stars with and without planet-forming disks. This implies that the flares are likely similar to those seen on the Sun, with loops of magnetic field having both footprints on the surface of the star, rather than one anchored to the disk and one to the star.

"We've found that these giant flares are like ones on the Sun but are just greatly magnified in energy and frequency, and the size of their magnetic loops," said co-author Gordon Garmire from the Huntingdon Institute for X-ray Astronomy in Huntingdon, Pennsylvania". Understanding these stellar outbursts may help us understand the most powerful flares and coronal mass ejections from the Sun."

An international team of physicists led by the University of Minnesota has discovered that a unique superconducting metal is more resilient when used as a very thin layer. The research is the first step toward a larger goal of understanding unconventional superconducting states in materials, which could possibly be used in quantum computing in the future.

The collaboration includes four faculty members in the University of Minnesota's School of Physics and Astronomy--Associate Professor Vlad Pribiag, Professor Rafael Fernandes, and Assistant Professors Fiona Burnell and Ke Wang--along with physicists at Cornell University and several other institutions. The study is published in Nature Physics, a monthly, peer-reviewed scientific journal published by the Nature Research.

Niobium diselenide (NbSe2) is a superconducting metal, meaning that it can conduct electricity, or transport electrons from one atom to another, with no resistance. It is not uncommon for materials to behave differently when they are at a very small size, but NbSe2 has potentially beneficial properties. The researchers found that the material in 2D form (a very thin substrate only a few atomic layers thick) is a more resilient superconductor because it has a two-fold symmetry, which is very different from thicker samples of the same material.

Motivated by Fernandes and Burnell's theoretical prediction of exotic superconductivity in this 2D material, Pribiag and Wang started to investigate atomically-thin 2D superconducting devices.

"We expected it to have a six-fold rotational pattern, like a snowflake." Wang said. "Despite the six-fold structure, it only showed two-fold behavior in the experiment."

"This was one of the first times [this phenomenon] was seen in a real material," Pribiag said.

The researchers attributed the newly-discovered two-fold rotational symmetry of the superconducting state in NbSe2 to the mixing between two closely competing types of superconductivity, namely the conventional s-wave type--typical of bulk NbSe2--and an unconventional d- or p-type mechanism that emerges in few-layer NbSe2. The two types of superconductivity have very similar energies in this system. Because of this, they interact and compete with each other.

Pribiag and Wang said they later became aware that physicists at Cornell University were reviewing the same physics using a different experimental technique, namely quantum tunneling measurements. They decided to combine their results with the Cornell research and publish a comprehensive study.

Burnell, Pribiag, and Wang plan to build on these initial results to further investigate the properties of atomically thin NbSe2 in combination with other exotic 2D materials, which could ultimately lead to the use of unconventional superconducting states, such as topological superconductivity, to build quantum computers.

"What we want is a completely flat interface on the atomic scale," Pribiag said. "We believe this system will be able to give us a better platform to study materials to use them for quantum computing applications."

In addition to Pribiag, Fernandes, Burnell, Wang, the collaboration included University of Minnesota physics graduate students Alex Hamill, Brett Heischmidt, Daniel Shaffer, Kan-Ting Tsai, and Xi Zhang; Cornell University faculty members Jie Shan and Kin Fai Mak and graduate student Egon Sohn; Helmuth Berger and László Forró, researchers at Ecole Polytechnique Fédérale de Lausanne in Switzerland; Alexey Suslov, a researcher at the National High Magnetic Field Laboratory in Tallahassee, Fla.; and Xiaoxiang Xi, a professor at Nanjing University in China.

The University of Minnesota research was supported primarily by the National Science Foundation (NSF) through the University of Minnesota Materials Research Science and Engineering Center (MRSEC). The research at Cornell was supported by the Office of Naval Research (ONR) and NSF. The work in Switzerland was supported by the Swiss National Science Foundation.

Clinical research on COVID-19 has boomed in the 18 months since the disease first appeared. Countless papers have looked at the topic from almost every possible angle, including methods of detection.

For a new paper published in the journal Clinical Microbiology Reviews, a team of researchers led by Concordia engineers sifted through hundreds of papers on COVID-19 detection tools and technologies. They wanted to categorize and understand what exists, what is lacking and what can be improved. The result is a thorough assessment of the field citing almost 600 separate papers that cover an extensive body of literature.

"The upsurge of publications and new technologies in a very short time made it very difficult to follow for anyone interested in the topic," says the study's primary investigator and lead author Hamid Tali, a PhD student in the Department of Chemical and Materials Engineering.

"Our study looks at these technologies' performance characteristics, their challenges and the gaps in our current knowledge and future directions. We describe the lessons learned throughout the pandemic on the diagnostics of this virus, which will be helpful in the case of a future pandemic."

The authors believe that the paper provides a rich "one-stop shop" resource for people interested in the topic, including experts in clinical microbiology and non-experts who want to know more about different methods.

"Having such a comprehensive review on this gigantic subject in a single place is of great value as it will significantly save time from researchers. It will help them grasp the state-of-the-art technologies in this area as fast as possible, get inspired and directed about current challenges and better define their research objectives," Tali adds.

Sana Anbuhi, an assistant professor of chemical and materials engineering, is the paper's senior author. She and Jason LeBlanc of Dalhousie University are the corresponding authors. Zubi Sadiq and Oyejide Oyewunmi of Concordia and Carolina Camargo, Bahareh Nikpour, Narges Armanfard and Selena Sagan of McGill University are co-authors.

ASSURED is the goal

The authors point out that the explosion of detection techniques and tools -- some of questionable quality -- came from the need to expand testing rapidly while supply chains were disrupted by the virus's global spread. Some techniques are more accurate; others are more affordable. Some require sophisticated lab equipment; others do not.

The World Health Organization's internationally recognized ASSURED criteria for point-of-care diagnostic devices helped them assess the various tests being used. The acronym stands for affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and deliverable to end users. This helped the researchers determine the strengths and weaknesses of the existing diagnostic tools.

"Some sensors are sensitive and specific, meaning they detect the presence of COVID-19 but they are not user-friendly or need bulky machinery and highly trained people to operate it," Anbuhi explains. She says the most effective tools in use now are nucleic acid amplification tests, which are highly effective at detecting ribonucleic acid (RNA).

Engineers for health

The researchers hope that identifying current weaknesses in our diagnostic tools will help avoid the need of adopting drastic measures like lockdowns and shuttering the economy when the next pandemic emerges.

"We hope that this will help guide researchers toward an ideal device that can be used by anyone, anywhere at a very low cost," Tali says.

Finally, the authors note that engineers rarely publish a paper in a journal for clinical microbiologists.

"The diagnostics of COVID-19 is an interdisciplinary subject. And so writing a comprehensive review required collaboration across four different research groups, each with its own area of expertise."

RIVERSIDE, Calif. -- Supermassive black holes, or SMBHs, are black holes with masses that are several million to billion times the mass of our sun. The Milky Way hosts an SMBH with mass a few million times the solar mass. Surprisingly, astrophysical observations show that SMBHs already existed when the universe was very young. For example, a billion solar mass black holes are found when the universe was just 6% of its current age, 13.7 billion years. How do these SMBHs in the early universe originate?

A team led by a theoretical physicist at the University of California, Riverside, has come up with an explanation: a massive seed black hole that the collapse of a dark matter halo could produce.

Dark matter halo is the halo of invisible matter surrounding a galaxy or a cluster of galaxies. Although dark matter has never been detected in laboratories, physicists remain confident this mysterious matter that makes up 85% of the universe's matter exists. Were the visible matter of a galaxy not embedded in a dark matter halo, this matter would fly apart.

"Physicists are puzzled why SMBHs in the early universe, which are located in the central regions of dark matter halos, grow so massively in a short time," said Hai-Bo Yu, an associate professor of physics and astronomy at UC Riverside, who led the study that appears in Astrophysical Journal Letters. "It's like a 5-year-old child that weighs, say, 200 pounds. Such a child would astonish us all because we know the typical weight of a newborn baby and how fast this baby can grow. Where it comes to black holes, physicists have general expectations about the mass of a seed black hole and its growth rate. The presence of SMBHs suggests these general expectations have been violated, requiring new knowledge. And that's exciting."

A seed black hole is a black hole at its initial stage -- akin to the baby stage in the life of a human.

"We can think of two reasons," Yu added. "The seed -- or 'baby' -- black hole is either much more massive or it grows much faster than we thought, or both. The question that then arises is what are the physical mechanisms for producing a massive enough seed black hole or achieving a fast enough growth rate?"

"It takes time for black holes to grow massive by accreting surrounding matter," said co-author Yi-Ming Zhong, a postdoctoral researcher at the Kavli Institute for Cosmological Physics at the University of Chicago. "Our paper shows that if dark matter has self-interactions then the gravothermal collapse of a halo can lead to a massive enough seed black hole. Its growth rate would be more consistent with general expectations."

In astrophysics, a popular mechanism used to explain SMBHs is the collapse of pristine gas in protogalaxies in the early universe.

"This mechanism, however, cannot produce a massive enough seed black hole to accommodate newly observed SMBHs -- unless the seed black hole experienced an extremely fast growth rate," Yu said. "Our work provides an alternative explanation: a self-interacting dark matter halo experiences gravothermal instability and its central region collapses into a seed black hole."

The explanation Yu and his colleagues propose works in the following way:

Dark matter particles first cluster together under the influence of gravity and form a dark matter halo. During the evolution of the halo, two competing forces -- gravity and pressure -- operate. While gravity pulls dark matter particles inward, pressure pushes them outward. If dark matter particles have no self-interactions, then, as gravity pulls them toward the central halo, they become hotter, that is, they move faster, the pressure increases effectively, and they bounce back. However, in the case of self-interacting dark matter, dark matter self-interactions can transport the heat from those "hotter" particles to nearby colder ones. This makes it difficult for the dark matter particles to bounce back.

Yu explained that the central halo, which would collapse into a black hole, has angular momentum, meaning, it rotates. The self-interactions can induce viscosity, or "friction," that dissipates the angular momentum. During the collapse process, the central halo, which has a fixed mass, shrinks in radius and slows down in rotation due to viscosity. As the evolution continues, the central halo eventually collapses into a singular state: a seed black hole. This seed can grow more massive by accreting surrounding baryonic -- or visible -- matter such as gas and stars.

"The advantage of our scenario is that the mass of the seed black hole can be high since it is produced by the collapse of a dark matter halo," Yu said. "Thus, it can grow into a supermassive black hole in a relatively short timescale."

The new work is novel in that the researchers identify the importance of baryons--ordinary atomic and molecular particles -- for this idea to work.

"First, we show the presence of baryons, such as gas and stars, can significantly speed up the onset of the gravothermal collapse of a halo and a seed black hole could be created early enough," said Wei-Xiang Feng, Yu's graduate student and a co-author on the paper. "Second, we show the self-interactions can induce viscosity that dissipates the angular momentum remnant of the central halo. Third, we develop a method to examine the condition for triggering general relativistic instability of the collapsed halo, which ensures a seed black hole could form if the condition is satisfied."

Over the past decade, Yu has explored novel predictions of dark matter self-interactions and their observational consequences. His work has shown that self-interacting dark matter can provide a good explanation for the observed motion of stars and gas in galaxies.

"In many galaxies, stars and gas dominate their central regions," he said. "Thus, it's natural to ask how the presence of this baryonic matter affects the collapse process. We show it will speed up the onset of the collapse. This feature is exactly what we need to explain the origin of supermassive black holes in the early universe. The self-interactions also lead to viscosity that can dissipate angular momentum of the central halo and further help the collapse process."

RESEARCH TRIANGLE PARK, N.C. -- A new approach to studying conjugated polymers made it possible for an Army-funded research team to measure, for the first time, the individual molecules' mechanical and kinetic properties during polymerization reaction. The insights gained could lead to more flexible and robust soft electronic materials, such as health monitors and soft robotics.

Conjugated polymers are essentially clusters of molecules strung along a backbone that can conduct electrons and absorb light. This makes them a perfect fit for creating soft optoelectronics, such as wearable electronic devices; however, as flexible as they are, these polymers are difficult to study in bulk because they aggregate and fall out from solution.

"Conjugated polymers are a fascinating class of materials due to their inherent optical and electronic properties which are dictated by their polymer structure," said Dr. Dawanne Poree, program manager, U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory. "These materials are highly relevant to a number of applications of interest to Army and DoD including portable electronics, wearable devices, sensors, and optical communication systems. To date, unfortunately, it has been difficult to develop conjugated polymers for targeted applications due to a lack of viable tools to study and correlate their structure-property relationships."

With Army funding, researchers at Cornell University employed an approach they pioneered on other synthetic polymers, called magnetic tweezers, that allowed them to stretch and twist individual molecules of the conjugated polymer polyacetylene. The research was published in the journal Chem.

"Through the use of novel single-molecule manipulation and imaging approaches, this work provided the first observations of single-chain behaviors in conjugated polymers which lays the foundation for the rational design and processing of these materials to enable widespread application," Poree said.

Previous efforts to address the solubility of conjugated polymers have often relied upon chemical derivatization, in which the structures are modified with functional groups of atoms. However, that approach can affect the polymer's innate properties.

"The conjugated polymer is really a prototype," said Dr. Peng Chen, the Peter J.W. Debye professor of chemistry and chemical biology at Cornell. "You always modify it to tailor it for applications. We are hoping everything we measured - the fundamental properties of synthesis kinetics, the mechanical property - become benchmark numbers for people to think about other polymers of the same category."

In 2017, Chen's group was the first to use the magnetic tweezers measurement technique to study living polymerization, visualizing it at the single-molecule level. The technique had already been used in the biophysics field for studying DNA and proteins, but no one had successfully extended it to the realm of synthetic polymers.

The process works by affixing one end of a polymer strand to a glass coverslip and the other end to a tiny magnetic particle. The researchers then use a magnetic field to manipulate the conjugated polymer, stretching or twisting it, and measuring the response of a single polymer chain that grows.

The amounts are so small, they stay soluble in solution, the way bulk amounts normally would not.

The team measured how long chains of conjugated polymers, which consist of hundreds of thousands of monomer units, grow in real time. They discovered these polymers add a new monomer per second, a much faster growth than their nonconjugated analogs.

"We found that while growing in real time, this polymer forms conformational entanglements," Chen said. "All polymers we have studied form conformational entanglements, but for this conjugated polymer this conformational entanglement is looser, allowing it to grow faster."

By pulling and stretching individual conjugated polymers, so-called force extension measurements, the researchers were able to assess their rigidity and better understand how they can bend in different directions while remaining conjugated and retaining electron conductivity.

They also discovered the polymers displayed diverse mechanical behaviors from one individual chain to the next-behaviors that had been predicted by theory but never observed experimentally.

The findings highlight both the uniqueness of conjugated polymers for a range of applications as well as the strength of using a single-molecule manipulation and imaging technique on synthetic materials.

"Now we have a new way to study how these conjugated polymers are made chemically and what is the fundamental mechanical property of this type of material," Chen said. "We can study how these fundamental properties change when you start tailoring them for application purposes. Maybe you can make it more mechanically flexible and make the polymer longer, or adjust the synthesis condition to either synthesize the polymer in a faster or slower way."

DALLAS (SMU) -- A team of SMU biological scientists has confirmed that P-glycoprotein (P-gp) has the ability to remove a toxin from the brain that is associated with Alzheimer's disease.

The finding could lead to new treatments for the disease that affects nearly 6 million Americans. It was that hope that motivated lead researchers James W. McCormick and Lauren Ammerman to pursue the research as SMU graduate students after they both lost a grandmother to the disease while at SMU.

In the Alzheimer's brain, abnormal levels of amyloid-β proteins clump together to form plaques that collect between neurons and can disrupt cell function. This is believed to be one of the key factors that triggers memory loss, confusion and other common symptoms from Alzheimer's disease.

"We were able to demonstrate both computationally and experimentally that P-gp, a critical toxin pump in the body, is able to transport this amyloid-β protein," said John Wise, associate professor in the SMU Department of Biological Sciences and co-author of the study published in PLOS ONE.

"If you could find a way to induce more P-glycoprotein in the protective blood-brain barrier for people who are susceptible to Alzheimer's disease, perhaps they could take such a treatment and it would help postpone or prevent the onset of the disease," he said. Wise stressed that the theory needs more research.

The SMU (Southern Methodist University) study also provides strong evidence for the first time that P-gp may be able to pump out much larger toxins than previously believed.

P-gp is nature's way of removing toxins from cells. Similar to how a sump pump in your house removes water from the basement, P-gp swallows harmful drugs or toxins within the cell and then spits them back outside the cell.

"You find P-gp wherever the body is looking to protect an organ from toxins, and the brain is no exception," explained co-author Pia Vogel, SMU professor and director of SMU's Center for Drug Discovery, Design and Delivery.

Amyloid-β's large size created questions about whether P-glycoprotein could actually inhale it and pump it back out.

"Amyloid-β is maybe five times bigger than the small, drug-like molecules that P-glycoproteins are well-known to move. It would be like taking New York pizza and trying to stuff that whole slice in your mouth and swallow it," Wise said.

The fact that P-gp appears to be able to do just that "greatly expands the possible range of things that P-gp can transport, which opens the possibility that it may interact with other factors that were previously thought impossible," said McCormick, a former SMU graduate student in biological sciences.

The research was personal

SMU researchers might never have investigated the link between P-gp and amyloid-β proteins if not for McCormick's dogged pursuit of the connection. The Ph.D. student, who graduated in 2017, had seen preliminary work suggesting that P-gp might play a role in pulling amyloid protein out of the brain and asked his faculty advisors, Vogel and Wise, if he could take some time to check it out.

The professors concede they first tried to discourage him because they were more focused on P-gp's role in creating resistance to chemotherapy in cancer patients. However, McCormick was "passionate," about figuring out if P-gp might be able to shield someone from getting Alzheimer's, Vogel said.

He devoted hours of his own time to use a computer-generated model of P-glycoprotein that he and Wise created. The model allows researchers to dock nearly any drug to the P-gp protein and observe how it would behave in P-gp's "pump." Vogel, Wise and other SMU scientists have been studying the protein for years to identify compounds that might reverse chemotherapy failure in aggressive cancers.

McCormick completed the computational work with the help of his fiancé, Ammerman, who got her Ph.D in biology from SMU in May.

Together, they ran multiple simulations of the P-gp protein using SMU's high performance computer, ManeFrame II, and found that each time, P-gp was able to "swallow" amyloid-β proteins and push them out of cells.

"For the scientist in me, it was just absolutely amazing that this pump could consume something that big," Vogel said. "John [Wise] and I did not predict that would be possible."

Two in vitro experiments confirmed the computational work

The researchers conducted two experiments in the lab to confirm the computational results.

In one experiment, Ammerman used lab-purchased amyloid-β proteins that had been dyed fluorescent green, allowing them to be easily spotted easily in a microscope. In multiple trials, Ammerman exposed human cells to these amyloid-β proteins. She used two types of human cells -- one where P-gp was strongly expressed and one where P-gp was not. This allowed Ammerman to test the difference between the two and see if P-gp was pumping amyloid-β out.

The amyloid proteins were clearly shown to be pushed out of the human cells that had overexpressed P-gp in them, supporting the theory that P-gp removes amyloid proteins on contact.

Another in vitro experiment reached the same conclusion from a different direction. Former graduate student Gang (Mike) Chen worked in SMU's Center for Drug Discovery, Design and Delivery to show that an Alzheimer's-linked amyloid-β caused changes in the P-gp's usage of adenosine triphosphate (ATP), indicating that there was a physical interaction between the two.

ATP hydrolysis produces the energy that P-gp uses to transport toxins or drugs out of the cell. When no toxins are present, P-gp's rate of ATP stays pretty low. When challenged with transporting cargo, P-gp's ATP hydrolysis activity usually increases quite dramatically.

"Even though our work can't help our grandparents, I hope that it might help others in the future," Ammerman said. "The more we know, the more power we have - and researchers after us - to address and target these devastating diseases."

A new study looking at the way human cells activate the immune system in response to SARS-CoV-2 infection could open the door to even more effective and powerful vaccines against the coronavirus and its rapidly emerging variants keeping the global pandemic smoldering.

Researchers from Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and the Broad Institute of MIT and Harvard say it’s the first real look at exactly what types of “red flags” the human body uses to enlist the help of T cells—killers sent out by the immune system to destroy infected cells. Until now, COVID vaccines have been focused on activating a different type of immune cell, B cells, which are responsible for creating antibodies. Developing vaccines to activate the other arm of the immune system—the T cells—could dramatically increase immunity against coronavirus, and importantly, its variants.

In their findings, published in Cell, the researchers say current vaccines might lack some important bits of viral material capable of triggering a holistic immune response in the human body. Based on the new information, “companies should reevaluate their vaccine designs,” says Mohsan Saeed, a NEIDL virologist and the co-corresponding author of the paper.

Saeed, a BU School of Medicine assistant professor of biochemistry, performed experiments on human cells infected with coronavirus. He isolated and identified those missing pieces of SARS-CoV-2 proteins inside one of the NEIDL’s Biosafety Level 3 (BSL-3) labs. “This was a big undertaking because many research techniques are difficult to adapt for high containment levels [such as BSL-3],” Saeed says. “The overall coronavirus research pipeline we’ve created at the NEIDL, and the support of our entire NEIDL team, has helped us along the way.”

Saeed got involved after he was contacted by genetic sequencing experts at the Broad Institute, computational geneticists Pardis Sabeti and Shira Weingarten-Gabbay. They hoped to identify fragments of SARS-CoV-2 that activate the immune system’s T cells. 

“The emergence of viral variants, an active area of research in my lab, is a major concern for vaccine development,” says Sabeti, a leader in the Broad Institute’s Infectious Disease and Microbiome Program. She is also a Harvard University professor of systems biology, organismic and evolutionary biology, and immunology and infectious disease, as well as a Howard Hughes Medical Institute investigator.

“We swung into full action right away because my laboratory had [already] generated human cell lines that could be readily infected with SARS-CoV-2,” Saeed says. The group’s efforts were spearheaded by two members of the Saeed lab: Da-Yuan Chen, a postdoctoral associate, and Hasahn Conway, a lab technician.

From the outset of COVID pandemic in early 2020, scientists around the world knew the identity of 29 proteins produced by SARS-CoV-2 virus in infected cells—viral fragments that now make up the spike protein in some coronavirus vaccines, such as the Moderna, Pfizer-BioNTech, and Johnson & Johnson vaccines. Later, scientists discovered another 23 proteins hidden inside the virus’ genetic sequence; however, the function of these additional proteins was a mystery until now. The new findings of Saeed and his collaborators reveal—unexpectedly and critically—that 25 percent of the viral protein fragments that trigger the human immune system to attack a virus come from these hidden viral proteins.

How exactly does the immune system detect these fragments? Human cells contain molecular “scissors”—called proteases—that, when the cells are invaded, hack off bits of viral proteins produced during infection. Those bits, containing internal proteins exposed by the chopping-up process—like the way the core of an apple is exposed when the fruit is segmented—are then transported to the cell membrane and pushed through special doorways. There, they stick outside the cell acting almost like a hitchhiker, waving down the help of passing T cells. Once T cells notice these viral flags poking through infected cells, they launch an attack and try to eliminate those cells from the body. And this T cell response isn’t insignificant—Saeed says there are links between the strength of this response and whether or not people infected with coronavirus go on to develop serious disease.

“It’s quite remarkable that such a strong immune signature of the virus is coming from regions [of the virus’ genetic sequence] that we were blind to,” says Weingarten-Gabby, the paper’s lead author and postdoctoral fellow in the Sabeti lab. “This is a striking reminder that curiosity-driven research stands at the basis of discoveries that can transform the development of vaccines and therapies.”

“Our discovery … can assist in the development of new vaccines that will mimic more accurately the response of our immune system to the virus,” Sabeti says.

T cells not only destroy infected cells but also memorize the virus’ flags so that they can launch an attack, stronger and faster, the next time the same or a different variant of the virus appears. That’s a crucial advantage, because Saeed and his collaborators say the coronavirus appears to delay the cell’s ability to call in immune help.

“This virus wants to go undetected by the immune system for as long as possible,” Saeed says. “Once it’s noticed by the immune system, it’s going to be eliminated, and it doesn’t want that.”

Based on their findings, Saeed says, a new vaccine recipe, incorporating some of the newly discovered internal proteins making up the SARS-CoV-2 virus, would be effective in stimulating an immune response capable of tackling a wide swath of newly emerging coronavirus variants. And given the speed with which these variants continue to appear around the world, a vaccine that can provide protection against all of them would be a game changer. 

In a study of more than 10,600 adult patients hospitalized with COVID-19, women had significantly lower odds than men of in-hospital mortality. They also had fewer admissions to the intensive care unit and less need for mechanical ventilation. Women also had significantly lower odds of major adverse events, including acute cardiac injury, acute kidney injury, and venous thromboembolism, according to an article in the peer-reviewed Journal of Women's Health. Click here to read the article now.

"This comprehensive analysis is the largest study to date that directly assesses the impact of sex on COVID-19 outcomes," stated Rachel-Maria Brown, MD, Zucker School of Medicine at Hofstra/Northwell, and coauthors. "Our study strongly demonstrates female sex to be associated with lower odds of in-hospital outcomes, major adverse effects and all-cause mortality as compared to male sex after controlling for confounding variables." The authors propose some of the protective factors that may contribute to these findings.

In the accompanying editorial entitled "Lessons Learned from COVID-19 Sex Disparities," Annabelle Santos Volgman, MD, Rush University Medical Center, and coauthors, suggest various mechanisms by which female sex may confer a protective advantage against COVID-19 infection. One advantage may be the extra X chromosome, which carries multiple genes responsible for innate and adaptive immunity.

Volgman and coauthors emphasize that "although women have less mortality risk with COVID-19, we need to exercise caution not to send a message to deliver subpar care to women with COVID-19 or decrease measures to prevent their infection. Our evolving knowledge should not reduce attention paid to women admitted for COVID-19."

EAST LANSING, Mich. - The original Star Trek television series took place in a future when space is the final frontier, but humanity hasn't reached that point quite yet.

As researchers like Michigan State University entomologists Sarah Smith and Anthony Cognato are reminding us, there's still plenty to discover right here on Earth.

Working in Central and South America, the duo discovered more than three dozen species of ambrosia beetles -- beetles that eat ambrosia fungus -- previously unknown to science. Smith and Cognato described these new species on June 16 in the journal ZooKeys.

The Spartans also selected an unusual naming theme named in deference to the female beetles who have helped their species survive and thrive by boldly going where they hadn't before.

Many of the new species are named for iconic female science fiction characters, including Nyota Uhura of "Star Trek"; Kara "Starbuck" Thrace from the 2000s "Battlestar Galactica" TV series; and Katniss Everdeen from "The Hunger Games" books and movies.

"One of our colleagues from London was asking if it's good to name a species after popular characters, if the popularity would backfire and make people think this is frivolous," said Cognato, director of the Albert. J. Cook Arthropod Research Collection. He's also an entomology professor with appointments in the College of Agriculture and Natural Resources and the College of Natural Science.

"But overall, our colleagues think it's a good thing," Cognato said. "It gives us a chance to talk about taxonomy -- the science of classifying organisms -- and about diversity."

Understanding the world's biodiversity is one of the major drivers of this and related research. Scientists estimate that there are 10 million nonbacterial species in the world and that humans have classified only about 20% of those.

"And some are lost before they're ever discovered," said Smith, who is the curator of the A. J. Cook Arthropod Research Collection. When people disrupt native ecosystems with farming and mining, for example, undiscovered species can face extinction before researchers know about them.

For this project, the team did some of its field work in Peru, where illegal gold miners can be particularly devastating to forests. "They're turning the forest into a wasteland" Smith said. "It may never recover."

Working in such threatened areas, Smith and Cognato are helping identify beetle species before it's too late, as well as characterizing a rich variety of physical traits and behaviors.

To be clear, they did this field work long before the pandemic struck, starting around 2008. But it takes time to perform the thorough investigations required to ensure that a species is indeed distinct from its closely related cousins.

"With South America, it can be really hard to know whether a species is new or not, just because the fauna is so poorly studied," Smith said.

With the stay-at-home orders in effect, she and Cognato had time to focus on projects that had been simmering on the backburner, such as this one that details ambrosia beetles they had collected belonging to the genus Coptoborus.

These tiny beetles make their homes by boring into trees. Once inside, they sustain their nests by cultivating fungus that serves as food. There, a mother produces many female offspring and one or two dwarfed males. The main job of those males is to mate with their sisters, creating a new generation of females prepared to disperse and produce a new brood. This all leads to another reason for studying these beetles: they can become pests.

These females arrive at trees ready to bore inside, start a fungus farm and reproduce. Though most prefer to nest in dead or dying parts of trees, some can attack fully healthy trees that are ecologically and economically important. For example, there are species within the genus known to attack balsa trees in Ecuador, the world's leading exporter of balsa wood.

And if tree-dwelling beetles find their way into nonnative habitats, they can pose large threats to trees that have no natural defenses against the insects. Michiganders are all too familiar with the emerald ash borer, which has claimed millions of ash trees in the state. Another nonnative species of fungus-farming beetle devastated redbay laurels and avocado trees in the Southern U.S.

By identifying species abroad, in their native habitats, researchers including Smith and Cognato are helping the U.S. better prepare for if and when a new pest shows up here. And, historically speaking, Coptoborus beetles are hardy travelers.

Their ancestors originated about 20 million years ago, likely in Southeast Asia, before emigrating and making homes across much of the tropics.

"That's one of the reasons we chose to name them after female sci-fi characters. Not to anthropomorphize too much, but you have these adventurous females that were blown off their log or had their wood-encased home thrown into the ocean by a mudslide," Cognato said. If these mated females made it to a new land, they could start a new population, allowing the species to proliferate.

"Along the way, there were so many ways to die, but they ended up colonizing an entire continent."

Fast forward to now and there are thousands of ambrosia beetle species, including more than 70 of the Coptoborus genus -- and counting. In christening the new beetles, Smith and Cognato got some inspiration by finding similarities between the beetle and its namesake.

For instance, the C. uhura was given its name because its reddish color, reminiscent of the uniform worn by Nichelle Nichols's Uhura character in the original "Star Trek" TV series.

And Sigourney Weaver's Ellen Ripley character in the "Alien" film franchise had a shaved head in the movie "Alien 3." One of the beetles, now named C. ripley, was also glabrous, or without hair.

Other names were selected because the duo just liked the characters and found them inspiring. For example, the C. scully beetle was named after Dana Scully, Gillian Anderson's character on "The X-Files."

The character is also behind what's known as the "Scully Effect." By showing a successful female scientist on TV, the show helped raise awareness of science, technology, engineering and mathematics -- or STEM -- professions among young women.

In their paper, Smith and Cognato wrote, "We believe in the 'Scully Effect' and hope future female scientists, real and fictional, continue to inspire children and young adults to pursue STEM careers."

Smith and Cognato also took the opportunity to name some beetles in honor of real-life people who have made an impact on their work and their lives.

For example, the C. erwini, is named after a renowned entomologist and friend Terry Erwin, who passed away in 2020. Erwin helped popularize a technique called canopy fogging to collect beetle specimens living in treetops.

"Without his dedication to canopy fogging, this species and most of those described in this publication may never have been discovered," Smith and Cognato wrote in their study, which is part of a special issue in memory of Erwin, who was also editor-in-chief of ZooKeys.

Also, the C. bettysmithae is named after Smith's grandmother, Catherine "Betty" Smith. Sarah remembers Betty's incredible strength in battling cancer and her help fostering her granddaughter's scientific interest.

"My grandmother supported me a lot with entomology," Smith said. "I used to spend many weekends with her, and she'd take me out to catch dragonflies."

Now, she and Cognato are out catching and characterizing insects that are new to science. In doing so, they're helping protect native ecosystems, painting a more complete picture of the planet's bountiful biodiversity and even drawing some attention to the power of naming and classifying things.

"Taxonomy was probably one of the first sciences of humans. You can find evidence of it throughout history and across cultures," Cognato said.

This naming likely started so humans could easily share information about which plants were safe to eat and which animals were dangerous. This is still valuable information today, but naming has evolved to help us appreciate even more dimensions of life on Earth.

Think about being a kid in a park or backyard, Cognato said, and the innate desire to know and name the animals there, say, robins or squirrels. Classification builds connection.

"It helps us communicate and it helps us live better," Cognato said. "It helps us understand the world and biodiversity."