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Particle accelerators generate high-energy beams of electrons, protons and ions for a wide range of applications, including particle colliders that shed light on nature's subatomic components, X-ray lasers that film atoms and molecules during chemical reactions and medical devices for treating cancer.

As a rule of thumb, the longer the accelerator, the more powerful it is. Now, a team led by scientists at the Department of Energy's SLAC National Accelerator Laboratory has invented a new type of accelerator structure that delivers a 10 times larger energy gain over a given distance than conventional ones. This could make accelerators used for a given application 10 times shorter.

The key idea behind the technology, described in a recent article in Applied Physics Letters, is to use terahertz radiation to boost particle energies.

In today's accelerators, particles draw energy from a radio-frequency (RF) field fed into specifically shaped accelerator structures, or cavities. Each cavity can deliver only a limited energy boost over a given distance, so very long strings of cavities are needed to produce high-energy beams.

Terahertz and radio waves are both electromagnetic radiation; they differ in their respective wavelengths. Because terahertz waves are 10 times shorter than radio waves, cavities in a terahertz accelerator can also be much smaller. In fact, the one invented in this study was only 0.2 inches long.

One major challenge to building these tiny cavity structures is to machine them very precisely. Over the past few years, SLAC teams developed a way to do just that. Instead of using the traditional process of stacking many layers of copper on top of each other, they built the minute structure by machining two halves and bonding them together.

The new structure also produces particle pulses a thousand times shorter than those coming out of conventional copper structures, which could be used to produce beams that pulse at a higher rate and unleash more power over a given time period.

Next, the researchers are planning to turn the invention into an electron gun - a device that could produce incredibly bright beams of electrons for discovery science, including next-generation X-ray lasers and electron microscopes that would allow us to see in real time how nature works on the atomic level. These beams could also be used for cancer treatment.

Delivering on this potential also requires further development of sources of terahertz radiation and their integration with advanced accelerators, such as the one described in this study. Because terahertz radiation has such a short wavelength, its sources are particularly challenging to develop, and there is little technology available at present. SLAC researchers are pursuing both electron beam and laser-based terahertz generation to provide the high peak powers needed to turn their accelerator research into future real-world applications.

Metformin is the first-line treatment for most cases of type 2 diabetes and one of the most commonly prescribed medications worldwide, with millions of individuals using it to optimise their blood glucose levels.

A new research study, conducted over six years in the Sydney Memory and Ageing Study in 1037 Australians (aged 70 to 90 years old at baseline), has revealed an additional effect: individuals with type 2 diabetes who used metformin experienced slower cognitive decline with lower dementia rates than those who did not use the medication.

The findings provide new hope for a means of reducing the risk of dementia in individuals with type 2 diabetes, and potentially those without diabetes who number nearly 47 million people worldwide.

The study was led by researchers at the Garvan Institute of Medical Research and the Centre for Healthy Brain Ageing (CHeBA), UNSW Sydney, and published in the Journal Diabetes Care.

"We've revealed the promising new potential for a safe and widely used medication, which could be life-changing for patients at risk of dementia and their families. For those with type 2 diabetes, metformin may add something extra to standard glucose lowering in diabetes care: a benefit for cognitive health," says first author Professor Katherine Samaras, Leader of the Healthy Ageing Research Theme at the Garvan Institute and endocrinologist at St Vincent's Hospital Sydney.

Protecting brain function

Type 2 diabetes occurs when the body can no longer produce enough insulin to meet its needs, leaving affected individuals unable to maintain blood glucose levels within a normal range. This can lead to long-term health complications, including cognitive decline.

"As they age, people living with type 2 diabetes have a staggering 60% risk of developing dementia, a devastating condition that impacts thinking, behaviour, the ability to perform everyday tasks and the ability to maintain independence. This has immense personal, family, economic and societal impacts," says Professor Samaras.

The researchers of this study investigated data from participants of CHeBA's Sydney Memory and Ageing Study. In this cohort, 123 study participants had type 2 diabetes, and 67 received metformin to lower blood sugar levels. The researchers tested cognitive function every two years, using detailed assessments that measured cognition over a number of capabilities, including memory, executive function, attention and speed, and language.

The findings revealed individuals with type 2 diabetes taking metformin had significantly slower cognitive decline and lower dementia risk compared to those not taking metformin. Remarkably, in those with type 2 diabetes taking metformin, there was no difference in the rate of decline in cognitive function over 6 years compared to those without diabetes.

New use for a common medication

Metformin has been used safely to treat type 2 diabetes for 60 years. It works by reducing the amount of glucose released from the liver into the blood stream and allows the body's cells to better respond to blood glucose levels.

Studies over the last decade have revealed evidence of metformin's benefit in cancer, heart disease, polycystic ovary syndrome and weight management. While the current study suggests metformin may have cognitive benefits for people living with type 2 diabetes, the researchers say it may also benefit those at risk of cognitive decline more broadly.

"This study has provided promising initial evidence that metformin may protect against cognitive decline. While type 2 diabetes is thought to increase dementia risk by promoting degenerative pathways in the brain and nerves, these pathways also occur in others at risk of dementia and it is possible insulin resistance may be the mediator," says Professor Samaras.

"To establish a definitive effect, we are now planning a large, randomised controlled trial of metformin in individuals at risk of dementia and assess their cognitive function over three years. This may translate to us being able to repurpose this cheap medication with a robust safety profile to assist in preventing against cognitive decline in older people."

CHeBA's Sydney Memory and Ageing Study is an observational study of older Australians that commenced in 2005 and researches the effects of ageing on cognition over time.

Professor Perminder Sachdev, senior author of the study and Co-Director of CHeBA, says: "While an observational study does not provide conclusive 'proof' that metformin is protective against dementia, it does encourage us to study this and other anti-diabetic treatments for dementia prevention. Metformin has even been suggested to be anti-ageing. The intriguing question is whether metformin is helpful in people in those with normal glucose metabolism. More work is clearly needed."

Computational biologists at the University of Toronto have developed an artificial intelligence algorithm that has the potential to create novel protein molecules as finely tuned therapeutics.

The team led by Philip M. Kim, a professor of molecular genetics and computer science at the Donnelly Centre for Cellular and Biomolecular Research at U of T's Faculty of Medicine, have developed ProteinSolver, a graph neural network that can design a fully new protein to fit a given geometric shape. The researchers took inspiration from the Japanese number puzzle Sudoku, whose constraints are conceptually similar to those of a protein molecule.

Their findings are published in the journal Cell Systems.

"The parallel with Sudoku becomes apparent when you depict a protein molecule as a network," says Kim, adding that the portrayal of proteins in graph form is standard practice in computational biology.

A newly synthesized protein is a string of amino-acids, stitched together according to the instructions in that protein's gene code. The amino-acid polymer then folds in and around itself into a three-dimensional molecular machine that can be harnessed for medicine.

A protein converted into a graph looks like a network of nodes, representing amino-acids, connected by edges, which are the distances between them within the molecule. By applying principles from graph theory, it then becomes possible to model the molecule's geometry for a specific purpose to, for example, neutralize an invading virus or shut down an overactive receptor in cancer.

Proteins make good drugs thanks to three-dimensional features on their surface with which they bind cellular targets with more precision than the synthetic small molecule drugs that tend to be broad spectrum and can lead to harmful off-target side effects.

Just over a third of all medications approved over the last couple of years were proteins, which also make up the vast majority of top ten drugs globally, Kim said. Insulin, antibodies and growth factors are only some examples of injectable cellular proteins, also known as biologics, already in use.

Designing proteins from scratch remains incredibly difficult however, owing to the vast number of possible structures to choose from.

"The main problem in protein design is that you have a very large search space," says Kim, referring to the many ways in which the 20 naturally occurring amino-acids can be combined into protein structures.

"For a standard-length protein of 100 amino-acids, there are 20100 possible molecular structures, that's more than the number of molecules in the universe," he says.

Kim decided to turn the problem on its head, by starting with a three-dimensional structure and working out its amino-acid composition.

"It's the protein design, or the inverse protein folding problem - you have a shape in mind and you want a sequence (of amino-acids) that will fold into that shape. Solving this is in some ways more useful than protein folding, as you can in theory generate new proteins for any purpose," says Kim.

That's when Alexey Strokach, a PhD student in Kim's lab, turned to Sudoku, after learning in a class about its relatedness to molecular geometry.

In Sudoku, the goal is to find missing values in a sparsely filled grid by observing a set of rules and the existing number values.

Individual amino-acids in a protein molecule are similarly constrained by their neighbours. Local electrostatic forces ensure that amino-acids carrying opposite electric charge pack closely together while those with the same charge are pulled apart.

Strokach first built the constraints found in Sudoku into a neural network algorithm. He then trained the algorithms on a vast database of available protein structures and their amino-acid sequences from across the tree of life. The goal was to teach the algorithm, ProteinSolver, the rules, honed by evolution over millions of years, of packing amino-acids together into smaller folds. Applying these rules to the engineering process should increase the chances of having a functional protein at the end.

The researchers then tested ProteinSolver by giving it existing protein folds and asking it to generate amino-acid sequences that can build them. They then took the novel computed sequences, which do not exist in nature, and manufactured the corresponding protein variants in the lab. The variants folded into the expected structures, showing that the approach works.

In its current form, ProteinSolver is able to compute novel amino-acid sequences for any protein fold known to be geometrically stable. But the ultimate goal is to engineer novel protein structures with entirely new biological functions, as new therapeutics, for example.

"The ultimate goal is for someone to be able to draw a completely new protein by hand and compute sequences for that, and that's what we are working on now," says Strokach.

The researchers made ProteinSolver and the code behind it open source and available to the wider research community through a user-friendly website.

Misconceptions about child marriage (marriage under 18) appear widespread among the American public, potentially hampering efforts to address the practice globally. David Lawson and colleagues at the University of California, Santa Barbara, present these findings in the open-access journal PLOS ONE on September 23, 2020.

Child marriage primarily affects girls and is most common in sub-Saharan Africa and South Asia. Initiatives enacted by the U.N. and other organizations seek to eradicate the practice. However, awareness campaigns often highlight extreme instances of child marriage that don't accurately represent most cases, potentially fostering harmful stereotypes and undermining the goals of such initiatives. The terminology 'child marriage' may also give the false impression that such marriages mainly take place at very young ages.

To help clarify popular understanding, Lawson and colleagues surveyed U.S. residents via Amazon Mechanical Turk. Of 609 participants, half incorrectly guessed that the U.N.'s cut-off age for child marriage is younger than the actual age of 18 years. Most guessed that child marriage primarily occurs at or below the age of 15. In fact, it usually occurs just below 18, leading the researchers to suggest that alternative terminology like 'adolescent marriage' is more appropriate in many contexts.

Most participants believed that child marriages are usually or always forced marriages. The researchers note that this is not always the case, such as when girls elope to marry against parental wishes. The authors argue that a failure to recognize female agency in the decision to marry, may limit the effectiveness of initiatives addressing the harms of early marriage.

Misconceptions also applied to America itself, where child marriage it is rare but only illegal in only four states. Most participants incorrectly guessed that it is banned in all 50, indicating they are unaware of the hypocrisy of efforts to change marriage laws in other nations. Most participants also overestimated the worldwide prevalence of the practice, and incorrectly guessed that it occurs primarily in regions with a Muslim majority.

The authors suggest that misconceptions about child marriage reinforce damaging stereotypes about low-income nations; exaggerating the extent to which girls and women at placed from risk from cultural traditions as opposed to other factors such as poverty. They call for a more nuanced approach to crafting narratives within the movement to end child marriage. Such efforts, they argue, could help minimize misinformation and improve cultural sensitivity.

The authors add: Tagged Manta rays (Mobula alfredi) from the never-studied-before population of New Caledonia showed unprecedented deep dive behaviour. More frequent and deeper dives than ever recorded before, Manta rays of New Caledonia set a new depth range to 672 meters.

Antibiotic resistance is one of the world's most urgent public health threats. In the United States alone, tens of thousands of deaths result each year from drug-resistant strains of common bacteria such as Staphylococcus aureus and Enterococcus faecium, which can cause virtually untreatable hospital-acquired infections. Perilously few new classes of antibiotics are being developed to fight infections that have become resistant to traditional treatments, and bringing any new drugs to market could take decades.

Researchers at UC San Francisco are tackling antibiotic resistance using a different approach: redesigning existing antibiotic molecules to evade a bacterium's resistance mechanisms. By devising a set of molecular LEGO pieces that can be altered and joined together to form larger molecules, the researchers have created what they hope is the first of many "rebuilds" of drugs that had been shelved due to antibiotic resistance. The research was published September 23, 2020, in Nature.

"The aim is to revive classes of drugs that haven't been able to achieve their full potential, especially those already shown to be safe in humans," said Ian Seiple, PhD, an assistant professor in the UCSF School of Pharmacy's Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute (CVRI), and lead author on the paper. "If we can do that, it eliminates the need to continually come up with new classes of drugs that can outdo resistant bacteria. Redesigning existing drugs could be a vital tool in this effort."

In work descibed in the new Nature paper, Seiple and his collaborator James Fraser, Ph.D. a professor in the School of Pharmacy's Department of Bioengineering and Therapeutic Sciences in the UCSF School of Pharmacy, have demonstrated this approach with a class of antibiotics called streptogramins. Until recently, streptogramins were very effective against S. aureus infections, until the bacteria evolved a clever resistance mechanism.

Streptogramins disable bacteria by gumming up the works in the bacterial ribosome, making it impossible for the bacteria to make proteins. But bacteria resistant to streptogramins produce proteins called virginiamycin acetyltransferases (Vats), which recognize these antibiotics when they enter the bacterial cell. The Vats grab the drug and chemically deactivate it before it can bind to the ribosome, rendering it useless.

Streptogramins, like most other antibiotics, are derived from naturally occurring antibiotic compounds produced by other organisms (usually bacteria) that are then tweaked to optimize their performance in the human body. Seiple figured that there must also be a way to make further changes to the drug molecule that would allow it to evade capture by the Vat proteins.

Seiple set out to build new streptogramins from the ground up, rather than modifying existing structures. To make the building process easier, Qi Li, PhD, a postdoctoral fellow in the Seiple lab and co-first author on the paper, created seven molecular modules that can be tweaked as needed to build a set of variations on the streptogramin molecule.

"This system allows us to manipulate the building blocks in ways that wouldn't be possible in nature," said Seiple. "It gives us an efficient route to re-engineering these molecules from scratch, and we have a lot more latitude to be creative with how we modify the structures."

Once Seiple and Li had their building blocks, the next step was to get a molecular-level view of the chemistry involved in order to better understand how to modify and piece together those molecular LEGOs.

For that, Seiple teamed up with Fraser, who specializes in creating visual models of biological molecules.

"My lab's contribution was to say, 'Now that you've got the seven pieces, which one of them should we modify and in what way?'" said Fraser, whose work on the project was supported by the inaugural Sanghvi-Agarwal Innovation Award.

To get answers to that question, Jenna Pellegrino, a graduate student in the Fraser Group and co-first author on the paper, used two complementary techniques, cryo-electron microscopy and x-ray crystallography, to create three-dimensional pictures of the drug at near-atomic resolution, as well as its target the bacterial ribosome, and its nemesis, the Vat protein.

Using the models, Li, Pellegrino, Seiple, and Fraser could see which parts of the streptogramin molecule are essential to the antibiotic's function. Then Li was free to fiddle with the drug's non-essential regions to find modifications that prevented Vats from interacting with the drug while still allowing it to bind to its ribosomal targets and disable the bacterium.

The team found that two of the seven building blocks seemed to offer potentially interesting sites for modification. They made variations of the drug that contained tweaks in those regions and found that these variations had activity in dozens of strains of pathogenic bacteria. The researchers also tested their most promising candidate against streptogramin-resistant S. aureus in infected mice, and found it was over 10 times more effective than other streptogramin antibiotics.

Seiple points out that the knowledge gained through these collaborative experiments can be applied to modifying many other antibiotics.

"We learned about mechanisms that other classes of antibiotics use to bind to the same target," he said. "In addition, we established a workflow for using chemistry to overcome resistance to antibiotics that haven't reached their potential."

Seiple will continue to refine these synthetic streptogramins and then hopes to move the work to the private sector where the reengineered antibiotics could be further developed and tested in human trials. He and Fraser plan to continue working together on reviving other antibiotics that have been shelved because of microbial resistance, refining a set of tools that can help researchers stay one step ahead of bacterial evolution.

"It's a never-ending arms race with bacteria," said Fraser. "But by studying the structures involved--before resistance arises--we can get an idea of what the potential resistance mechanisms will be. That insight will be a guide to making antibiotics that bacteria can't resist."

What The Study Did: The potential use of red blood cell distribution width for risk stratification of patients with COVID-19 was looked at in this observational study.

Authors: John M. Higgins, M.D., and Jonathan C. T. Carlson, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School in Boston, are the corresponding authors.

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

(doi:10.1001/jamanetworkopen.2020.22058)

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

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About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

The warmer it gets, the faster Antarctica loses ice - and much of it will then be gone forever. Consequences for the world's coastal cities and cultural heritage sites would be detrimental, from London to Mumbai, and from New York to Shanghai. That's what a team of researchers from the Potsdam Institute for Climate Impact Research, Potsdam University and New York's Columbia University has found out in their new study, published in Nature (cover story), on how much warming the Antarctic Ice Sheet can survive. In around one million hours of computation time, their unprecedentedly detailed simulations delineate where exactly and at which warming levels the ice would become unstable and eventually melt and drain into the ocean. They find a delicate concert of accelerating and moderating effects, but the main conclusion is that unmitigated climate change would have dire long-term consequences: If the global mean temperature level is sustained long enough at 4 degrees above pre-industrial levels, Antarctic melting alone could eventually raise global sea levels by more than six meters.

"Antarctica holds more than half of Earth's fresh water, frozen in a vast ice-sheet which is nearly 5 kilometers thick," explains Ricarda Winkelmann, researcher at the Potsdam Institute for Climate Impact Research (PIK) and University of Potsdam, and corresponding author of the study. "As the surrounding ocean water and atmosphere warm due to human greenhouse-gas emissions, the white cap on the South Pole loses mass and eventually becomes unstable. Because of its sheer magnitude, Antarctica's potential for sea-level contribution is enormous: We find that already at 2 degrees of warming, melting and the accelerated ice flow into the ocean will, eventually, entail 2.5 meters of global sea level rise just from Antarctica alone. At 4 degrees, it will be 6.5 meters and at 6 degrees almost 12 meters if these temperature levels would be sustained long enough."

Long-term change: it's not rapid, but it's forever

The paper's title refers to the complex physical phenomenon of hysteresis. In this case, that translates into irreversibility. Anders Levermann, co-author and researcher at PIK and Columbia University describes: "Antarctica is basically our ultimate heritage from an earlier time in Earth's history. It's been around for roughly 34 million years. Now our simulations show that once it's melted, it does not regrow to its initial state even if temperatures eventually sank again. Indeed, temperatures would have to go back to pre-industrial levels to allow its full recovery - a highly unlikely scenario. In other words: What we lose of Antarctica now, is lost forever."

The reasons behind this irreversibility are self-enforcing mechanisms in the ice sheets' behavior under warming conditions. Co-author Torsten Albrecht lays out: "In West Antarctica for instance, the main driver of ice loss is warm ocean water leading to higher melting underneath the ice shelves, which in turn can destabilize the grounded ice sheet. That makes glaciers the size of Florida slide into the ocean. Once temperatures cross the threshold of six degrees above pre-industrial levels, effects from the ice surface become more dominant: As the gigantic mountains of ice slowly sink to lower heights where the air is warmer, this leads to more melt at the ice surface - just as we observe in Greenland."

The fate of New York, Tokyo, Hamburg is in our hands

Ice loss and melting have accelerated significantly over the last decades in Antarctica. The authors however have explicitly not addressed the question of time scale in their work, but rather assess the critical warming levels at which parts of the Antarctic Ice Sheet become unstable. Winkelmann explains this approach: "In the end, it is our burning of coal and oil that determines ongoing and future greenhouse-gas emissions and therefore, if and when critical temperature thresholds in Antarctica are crossed. And even if the ice loss happens on long time scales, the respective carbon dioxide levels can already be reached in the near future. We decide now whether we manage to halt the warming. So Antarctica's fate really lies in our hands - and with it that of our cities and cultural sites across the globe, from Rio de Janeiro's Copacabana to Sydney's Opera House. Thus, this study really is another exclamation mark behind the importance of the Paris Climate Accord: Keep global warming below two degrees."

Levermann adds: "If we give up the Paris Agreement, we give up Hamburg, Tokyo and New York."

What The Study Did: Researchers investigated whether cannabis use during pregnancy was associated with various childhood outcomes, including cognition, social problems and brain structure.

Authors: Sarah E. Paul, B.A., and Ryan Bogdan, Ph.D., of Washington University in St. Louis, are the corresponding authors.

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

(doi:10.1001/jamapsychiatry.2020.2902)

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

The cells that make up our body are tiny, each of them measuring only micrometers in diameter. The ensemble of chromosomal DNA molecules that encode the genome, on the other hand, measures almost 2 meters. In order to fit into cells, chromosomal DNA is folded many times. But the DNA is not merely squeezed into the nucleus in a random manor but folded in a specific and highly regulated structure. The spatial organization of chromosomal DNA enables regulated topological interactions between distant parts, thereby supporting proper expression, maintenance, and transport of the genome across cell generations.

Breaks in our DNA, which can occur spontaneously or result from irradiation or chemical insults, can lead to severe problems since they foster mutations and can ultimately lead to cancer. But not every DNA break has disastrous consequences, since our cells have ingenious ways of repairing the damage. One of the main DNA repair pathways involves copying the missing information on the damaged DNA from the replicated sister chromatid. For this to occur, the two DNA molecules of sister chromatids need to come close together at the exact same genomic position. How the two DNA molecules are organized relative to each other to support this important repair pathway, however, has remained unclear.

The team around Daniel Gerlich developed a method that solves this problem. "Current methods to map the folding of DNA have a serious blind spot: They are not able to distinguish identical copies of DNA molecules. Our approach to solve this was to label DNA copies in a way such that we can discriminate them by DNA sequencing" explains Michael Mitter, doctoral student in Dr. Gerlich's lab and first author of the current publication in Nature. Using this approach, the researchers were able to create the first high resolution map of contact points between replicated chromosomes.

"With this new method, we can now study the molecular machinery regulating the conformation of sister chromatids, which will provide insights into the mechanics underlying the repair of DNA breaks and the formation of rod-shaped chromosomes in dividing cells, which is required for proper transport the genome to cell progeny," says Daniel Gerlich about the project, which is financed by the Vienna Science and Technology Fund (WWTF) and was a fruitful collaboration of several research groups at the Vienna BioCenter, including the Ameres and Goloborodko labs at IMBA, and the Peters lab at the neighboring Institute of Molecular Pathology (IMP).

TAMPA, Fla. (Sept. 23, 2020)- More than 200,000 people in the U.S. have died from COVID-19. Some argue that statistic is inaccurate due to inconsistencies in how deaths are being reported. But researchers from the University of South Florida claim that even if those deaths have been correctly measured, the number doesn't fully convey the true mortality effects of COVID-19.

A study published in the Journal of Public Health finds that for each person in the U.S. who died after contracting COVID-19, an average of nearly 10 years of life had been lost. Researchers claim "years of life lost" is a more insightful measure than death count since it accounts for the ages of the deceased. The tool is often used to determine the effects of non-communicable disease, drug misuse and suicide. They believe "years of life lost" is especially appropriate given the range of ages at which individuals have died of COVID-19.

"While death counts are a vital initial measure of the extent of COVID-19 mortality, they do not provide information regarding the age profile of those who died," said lead author Troy Quast, professor of health economics in the USF College of Public Health. "By contrast, years of life lost tell us the extent to which deaths are occurring across age groups and can potentially help healthcare providers and policymakers better target clinical and governmental responses to reduce the number of deaths."

Quast and his research team obtained data from the Centers for Disease Control and Prevention that report COVID-19 death counts by sex, age and state. The study focused on data from Feb. 1 to July 11, during which there had been roughly 130,000 COVID-19 deaths reported. They then compared the ages at death to life expectancies by age and gender from the U.S. Social Security Administration and to population data from the U.S. Census Bureau. When taking those factors into account, they calculated that COVID-19 had caused 1.2 million years of life lost during that timeframe. While the analysis only covered the period through mid-July, if past trends were to have continued, that figure at this point would approach 2 million.

Nearly 80 percent of deaths nationwide occurred among people ages 65 and older. Therefore, geographical areas with a younger population had more years of life lost due to COVID-19. For example, one-sixth of the nation's years of life lost is attributed to New York City, the then-epicenter of the outbreak. Another significant factor is pre-existing medical conditions. Males generally have more pre-existing medical conditions than females and accounted for roughly 55 percent of deaths attributed to COVID-19. Researchers adjusted for the higher rate of pre-existing conditions among COVID-19 decedents by reducing expected life expectancy by 25 percent.

Measuring COVID-19 deaths has been difficult due to evolving diagnostic criteria, testing supply constraints and the uncertainties that occur in over-burdened intensive care units. Quast says it's vital to continue monitoring years of life lost due to COVID-19 to help policy makers and health care providers better understand the extent of the outbreak.

Scientists have developed a tool for studying the biting behaviour of common pathogen-carrying mosquitoes, according to new research published this week in eLife.

The tool, which uses an artificial blood meal and a surface that mimics human skin, will provide detailed understanding of blood feeding without using human subjects as bait. It can also fit conveniently into a backpack, allowing the study of mosquitoes in laboratory and natural environments.

Blood feeding is essential for mosquitoes to reproduce, but it is during blood feeds on human hosts that they pass on pathogens such as malaria.

"Although the initial step in obtaining a blood meal - flying towards a host - is relatively well characterised, the steps that unfold after a mosquito has landed on a host are less well understood," explains first author Felix Hol, a researcher at Institut Pasteur and the Center for Research and Interdisciplinarity, Paris, France. "There is a lack of tools available to measure mosquito biting behaviour, and those that do exist rely on using human hosts which limits the number and type of experiments you can do - you cannot study pathogen-carrying mosquitoes in this way."

This is important because it is thought that factors such as infection can affect a mosquito's feeding behaviour, including the number of feeding attempts they make and the size of the meal they take. In turn, these aspects can alter the transmission dynamics of pathogens. To address this, Hol and colleagues from Stanford University, California, US, Institut Pasteur and CRI (Universite de Paris/INSERM), Paris, France, developed the biteOscope - a tool that allows the high-resolution study of how mosquitoes explore and probe host skin surfaces before taking a meal.

It consists of a bite 'substrate' - a transparent, temperature-controlled surface that mimics body temperature to attract mosquitoes. An artificial meal is applied on top of this and covered with a commonly used membrane that mosquitoes can pierce. The meal resembles blood, allowing mosquitoes to engorge and increase their weight by two to threefold. This bite substrate is then placed in a transparent cage, and an external camera records the mosquitoes' behaviour.

The team tested biteOscope with four medically important species of mosquito and built a computer model to analyse behaviours from images captured of the mosquitoes as they landed on the 'skin'. "We found that the time a mosquito spends exploring skin that does not lead to a successful feed is rarely longer than the duration of a successful feed," says author Louis Lambrechts, Research Director at the Department of Virology, Institut Pasteur. "This suggests that if blood is not found within a certain time, the mosquitoes give up and move on."

They next demonstrated how the tool can track body parts to understand how the mosquitoes 'sense' the surface they are exploring. When they coated the skin mimic with the insect repellent DEET, they found that mosquitoes tended to land and immediately take off, only making contact with their legs, which suggests repulsion is mediated by leg contact.

"We have used the biteOscope to describe the behavioural patterns of four key mosquito species, providing a useful knowledge base for future studies of blood feeding behaviour," concludes author Manu Prakash, Assistant Professor of Bioengineering at Stanford University. "More broadly, we hope that the tools presented here will provide a fresh perspective on mosquito behaviours that are relevant to pathogen transmission and enable researchers to gain a detailed understanding of blood feeding without having to sacrifice their own skin."

Tsukuba, Japan - Normal brain development requires a precise interplay between neuronal and non-neuronal (also called glial) cells. In a new study, researchers from the University of Tsukuba revealed how the loss of protein arginine methyltransferase (PRMT) 1 causes disruptions in glial cells and affects proper brain development.

PRMTs modify specific amino acids of other proteins regulating key cellular functions, such as survival, proliferation and development. Of the many members of the PRMT family that have been identified to date, PRMT1 is one of the most common and controls tissue development and lifespan, as well as stress responses. Because total knockout of PRMT1, i.e., the loss of the protein in all tissues during development, results in failure of embryonic development, recently tissue-specific knockout of PRMT1 has been under increasing scrutiny, in an effort to understand how PRMT1 contributes to tissue development and function.

"We previously discovered that PRMT1 is critical for the function of one type of glial cell, oligodendrocytes, during brain development," says corresponding author of the study Professor Akiyoshi Fukamizu. "The goal of this study was to understand how other glial cells may contribute to the hypomyelination phenotype we observe in PRMT1 conditional knockout mice."

To achieve their goal, the researchers used the same mouse model as in their previous study, in which PRMT1 was knocked out in neural stem cells (NSCs) and cells that are derived from NSCs. These include oligodendrocytes and astrocytes, but not microglia, all of which are important glial cell types in the brain. The researchers performed RNA-sequencing of the outer region of the brain, called the cortex, where these cells reside in neonatal PRMT1 knockout mice. By doing so, they were able to survey changes in gene expression in the brain of mice lacking PRMT1. Interestingly, the researchers found increased expression of genes regulating inflammation, pointing towards the involvement of astrocytes and microglia. Looking closer at markers of inflammation, the researchers found that among a panel of inflammation markers the expression of Interleukin-6 in particular was significantly increased in PRMT1 knockout mice.

The researchers next asked how there is increased inflammation in the brain of neonatal mice lacking PRMT1 and looked closer at astrocytes and microglia. By assaying the brains for markers of astrocytes and microglia, they found signs of severe ongoing inflammation: massive astrogliosis, which is an increase in astrocyte numbers, and an increase in the number of microglia. The latter is particularly intriguing because microglia are not derived from NSCs and hence showed normal expression of PRMT1.

"These are striking results that show how a single protein controls such essential developmental processes in the brain. Our results provide a novel insight into the molecular control of brain development," says first author of the study Assistant Professor Misuzu Hashimoto (Gifu University).

College students are under a lot of stress, even more so lately due to the COVID-19 pandemic. Based on certain personality types, especially neurotic personalities, college health courses could help students develop a more positive stress mindset, according to research from faculty at Binghamton University, State University of New York.

A research team including Binghamton University Health and Wellness Studies Lecturer Jennifer Wegmann sought to evaluate the impact of health education on the change of stress mindset and also to explore the role of personality in the change of stress mindset when there is a specific focus on improving individual health and well-being. Specifically, they sought to assess the relationship between each personality dimension (i.e., neuroticism, extraversion, openness, agreeableness and conscientiousness) and stress mindset change over time.

"The findings surrounding specific personality dimensions were interesting," said Wegmann. "It appears that engaging in health education is beneficial in changing perceptions of stress for some students but not all -- based on personality. For example, significant changes were elicited in students who scored high on the neuroticism scale but no significance was shown for students on the extroversion scale. Neurotic students tend to be worriers with high anxiety. The findings of this research show how focusing on their health, in general, can change these typically high-stressed students' beliefs about the stress they experience."

The researchers conducted an online survey with a group of 423 students taking a college health education course. They asked students to rate the extent to which they agreed with a series of statements. Analyzing the data, the researchers found that students with specific personality types, especially neurotic students, were more likely to improve their stress mindset by engaging in health education.

Wegmann said the most interesting thing about these findings is that change in stress mindset was elicited not through focusing on stress and changing mindsets specifically, but rather by students focusing on their overall health and wellness. Colleges may not have the faculty, space or funding to provide stress-specific courses, but this research shows there is another avenue to help students navigate their stress, Wegmann said.

"This is important for several reasons," said Wegmann. "First, helping students develop a more positive or enhancing stress mindset has been associated with improved mental health, increased performance and productivity. Second, general health education courses are available to large numbers of students. There typically are few, if any, stress-specific courses offered on college campuses,' and if they are offered, many are limited in student capacity."

Wegmann said that the next step is to work on discovering what approach will be helpful for all students.

"According to our research, this approach was not helpful for everyone," said Wegmann. "While these findings are providing novel and interesting information, as a stress researcher who works to help students become more productive and healthy, I want to know what other avenues will reach our students."

September 23, 2020 - More than two-thirds of women orthopaedic surgeons report experiencing sexual harassment during their residency training, according to a survey study in Clinical Orthopaedics and Related Research® (CORR®), a publication of The Association of Bone and Joint Surgeons®. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Sexual harassment of women during orthopaedic training appears pervasive, and its frequency has hardly improved over the past several decades, reports the study by Emily Whicker, MD, of University of Pittsburgh Medical Center and colleagues. "Sexual harassment as reported by women orthopaedic trainees remains pervasive across training programs throughout the United States," the researchers write.

A 'Wake-up Call' for Orthopaedic Surgery: Women Surgeons Say #MeToo

The anonymous online survey targeted members of a professional society for women orthopaedic surgeons. Adapted from a general questionnaire about sexual harassment in the workplace, the survey included questions about the nature of the harassment, who the harasser was, and whether the incident was reported.

Two hundred fifty women orthopaedic surgeons completed the survey, representing a 37 percent response rate. While surveys are susceptible to non-response bias, even if all non-responders had nothing to report in terms of harassment, the proportion of women who experienced harassment would still be one in four. In addition, a large number of women's experiences were represented: of the 250 surgeons responding, 20 percent were current residents and the balance had trained sometime in the past 30 years.

Overall, 68 percent of women said they were sexually harassed during their orthopaedic training. Harassment was reported by 59 percent of current trainees compared to 71 percent for practicing surgeons. The authors had thought that current residents might be less likely to report harassment -at a time of growing awareness including the #MeToo movement. "However, this was not the case, and our results suggest that increased awareness has not yet translated to a decrease in proportion," Dr. Whicker and coauthors write.

Common types of harassment included obscene images, unwanted touching, and unwanted sexual invitations. While about 70 percent of women reporting harassment said they were harassed by other residents who were men, over 40 percent reported harassment by attending surgeons who were men. Rates of reported harassment were similar across US regions.

Only 15 percent of women who were harassed reported the incident. Current residents were more likely to report harassment than past residents: 26 versus 11 percent. The women's reasons for not reporting included negative impact on their careers, feeling that reporting was "pointless" because no action would be taken, or because the harasser was a superior.

The survey adds to previous evidence that women experience high rates of sexual harassment during medical training, and specifically in orthopaedic surgery: a specialty that historically has had low proportions of women surgeons. "In light of these findings, training programs should consider implementing specific training and awareness programs that target not only the trainees, but also attending surgeons," Dr. Whicker and coauthors write. They believe that efforts to recruit more women to orthopaedic surgery and to increase the number of women in leadership and mentorship positions will also be essential.

The new research "has clearly documented and confirmed that sexual harassment exists to a meaningful degree in orthopaedic surgery," according to a CORR Insights® perspective piece by Joseph D. Zuckerman, MD, of NYU Langone Orthopedic Hospital, and professor and chair of the Department of Orthopedic Surgery at NYU Grossman School of Medicine, New York City.. He outlines an approach to correcting the problem - including his experience in recognizing and addressing sexual harassment in his own department.

Dr. Zuckerman believes the survey findings should be a "wake-up call" throughout orthopaedic surgery. "We need to listen to what our female colleagues have described and we need to learn from the experiences they have reported," he concludes. "And most importantly, we need to make it much, much better."

Genome duplications play a major role in the development of forms and structures of plant organisms and their changes across long periods of evolution. Heidelberg University biologists under the direction of Prof. Dr Marcus Koch made this discovery in their research of the Brassicaceae family. To determine the scope of the different variations over 30 million years, they analysed all 4,000 species of this plant family and investigated at the genus level their morphological diversity with respect to all their characteristic traits. The results of this research were published in the journal Nature Communications.

The external form of a plant, also known as its morphology, notably depends on environmental factors and their influences. This is true over short time scales of individual development as well as over the long term on an evolutionary scale. "A plant species always embodies only a portion of the possible breadth of morphological variation in evolution, thus allowing related evolutionary lines to be studied as a group for their morphological disparity," stresses Prof. Koch, who leads the Biodiversity and Plant Systematics research group at the Centre for Organismal Studies (COS) of Heidelberg University. The extent of this disparity can be viewed as evolutionary potential for adaptations to altered environments and an associated differentiation.

To measure the morphological variation, the researchers first recorded the characteristic traits of the 4,000 Brassicaceae species in a checklist describing the identity and correlations of the species. They then constructed a family tree on genus level from next generation sequencing DNA data to visualise and test the underlying evolutionary dynamics. The tree facilitates the study of complex traits and their development over the course of evolution and places them in the context of other processes and events such as genome duplications or major changes in speciation rates. Genome duplications, that is the multiplication of the whole genome in a cell, describe an exceptional process in land plants to make available additional genetic variability.

"One surprising result of our study is that there is no key innovation with respect to the morphological characteristics studied. The character traits constantly change and appear to be arbitrarily assembled over and over. The old evolutionary lines make use of the morphological potential in a different way but do not differ from one another in terms of their disparity. In this way, evolution can proceed quickly and divergently," states Marcus Koch.

These patterns are associated with genome duplications, which reflect the genetic components, as well as a rapid increase in speciation rates as an expression of selection pressure of past and changing environments. Accordingly, present-day Brassicaceae exhibit more than 40 percent polyploid species, which underwent genome duplications and carry a multiple set of chromosomes. "That means that a species like thale cress, Arabidopsis thaliana, has gone through at least three genome duplications over the course of evolution of the flowering plants in the last 160 million years. Yet this species still has only ten chromosomes because the genomes have to be subsequently stabilised and usually scaled back down over the long term," explains Prof. Koch.

The research was conducted mainly in the framework of the DFG priority program "Evolutionary Plant Solutions to Ecological Challenges" (SPP 1529). The data are available in a public access database.