Culture

It's no secret that studies show that sexually diverse youth - in particular, lesbian, gay and bisexual (LGB) youth - use more cannabis and experience more mental health challenges than their heterosexual peers.

But what about the changes that occur in the rates of cannabis use: do they precede those related to mental health or is it the other way around? A new study from Université de Montréal offers some answers.

In the Journal of Abnormal Psychology, Kira London-Nadeau, a doctoral student and CIHR Vanier Scholar in the Department of Psychology at UdeM and the CHU Sainte-Justine Research Centre, provides an update.

In her study, conducted under the direction of Professor Natalie Castellanos-Ryan and with the support of Professors Jean Séguin and Sophie Parent, London-Nadeau analyzed data collected from 1,548 adolescent boys and girls - including 128 LGB adolescents - as part of the Longitudinal Study of Child Development in Quebec supported by CIHR and the Institut de la Statistique du Québec.

Participants were followed from the age of five months and the study was based on their responses to questionnaires collected at ages 13, 15 and 17. Although there was an association between depressive symptoms at age 15 and increased cannabis use at age 17 in the general sample, the association was five times stronger among LGB youth.

According to London-Nadeau, this relationship may signal a practice of LGB youth self-medicating with cannabis to cope with depressive symptoms. The use of cannabis for these purposes could also indicate that other sources of support for depressive symptoms are lacking or inadequate for the realities of LGB youth.

Unexpectedly, the study also found that anxiety symptoms among LGBs at age 15 predicted reduced cannabis use at age 17. This finding thus seems to run counter to the finding of an association between depression and cannabis use in the LGB group.

"The difference between the depression-cannabis relationship and the anxiety-cannabis relationship could indicate different realities that LGB youth would experience, particularly with respect to their public display of their minority sexual orientation," said London-Nadeau.

Thus, the researcher believes that social factors related to the experience of a minority sexual orientation would play an important role in both cannabis use and mental health challenges and the relationship between the two among adolescents.

In this regard, London-Nadeau emphasizes the need for youth services, particularly mental health services, to be better equipped to understand the issues specific to sexual diversity communities.

"As a teenager, you're constantly trying to figure out your identity as a person, which in itself is pretty difficult," said the young researcher, who identifies herself as gay. "When you add the discovery of a minority sexual orientation to that identity development, things get even more complicated."

"Now it's a matter of digging deeper into the why of these associations and making sure to include other communities that may be having similar experiences, including trans and non-binary teens, as well as sexually and gender diverse young adults," she continued.

"These results will be crucial for these communities, as they will allow us to better target their needs to ultimately achieve a more equitable level of parity in their health."

GAINESVILLE, Fla. --- Plants are DNA hoarders. Adhering to the maxim of never throwing anything out that might be useful later, they often duplicate their entire genome and hang on to the added genetic baggage. All those extra genes are then free to mutate and produce new physical traits, hastening the tempo of evolution.

A new study shows that such duplication events have been vitally important throughout the evolutionary history of gymnosperms, a diverse group of seed plants that includes pines, cypresses, sequoias, ginkgos and cycads. Published today in Nature Plants, the research indicates that a genome duplication in the ancestor of modern gymnosperms might have directly contributed to the origin of the group over 350 million years ago. Subsequent duplications provided raw material for the evolution of innovative traits that enabled these plants to persist in dramatically changing ecosystems, laying the foundation for a recent resurgence over the last 20 million years.

"This event at the start of their evolution created an opportunity for genes to evolve and create totally new functions that potentially helped gymnosperms transition to new habitats and aided in their ecological ascendance," said Gregory Stull, a recent doctoral graduate of the Florida Museum of Natural History and lead author of the study.

Taking a closer look at gymnosperms

While having more than two sets of chromosomes - a phenomenon called polyploidy - is rare in animals, in plants it is commonplace. Most of the fruits and vegetables we eat, for example, are polyploids, often involving hybridization between two closely related species. Many plants, including wheat, peanuts, coffee, oats and strawberries, benefit from having multiple divergent copies of DNA, which can lead to faster growth rates and an increase in size and weight.

Until now, however, it's been unclear how polyploidy may have influenced the evolution of gymnosperms. Although they have some of the largest genomes in the plant kingdom, they have low chromosome numbers, which for decades prompted scientists to assume that polyploidy wasn't as prevalent or important in these plants.

Gymnosperm genetics are also complex. Their large genomes make them challenging to study, and much of their DNA consists of repeating sequences that don't code for anything.

"What makes gymnosperm genomes complex is they seem to have a proclivity for accumulating lots of repetitive elements," said study co-author Douglas Soltis, Florida Museum curator and University of Florida distinguished professor. "Things like ginkgos, cycads, pines and other conifers are loaded with all this repetitive stuff that has nothing to do with genome duplication."

However, a recent collaborative effort among plant biologists, including Soltis, to obtain massive numbers of genetic sequences from more than 1,000 plants has opened new doors for scientists attempting to piece together the long history of land plant evolution. Stull, now a postdoctoral researcher at the Chinese Academy of Sciences' Kunming Institute of Botany, and his colleagues used a combination of these data and newly generated sequences to give gymnosperms another look.

Genome duplication gave rise to gymnosperms

By comparing the DNA of living gymnosperms, the researchers were able to peer back in time, uncovering evidence for multiple ancient genome duplication events that coincided with the origin of major groups.

Gymnosperms have undergone significant extinctions throughout their long history, making it difficult to decipher the exact nature of their relationships. But the genomes of all living gymnosperms share the signature of an ancient duplication in the distant past, more than 350 million years ago. More than 100 million years later, another duplication gave rise to the pine family, while a third led to the origin of podocarps, a group containing mostly trees and shrubs that today are primarily restricted to the Southern Hemisphere.

In each case, analyses revealed a strong link between duplicated DNA and the evolution of unique traits. While future studies are needed to determine exactly which traits arose due to polyploidy, possible candidates include the strange egglike roots of cycads that harbor nitrogen-fixing bacteria and the diverse cone structures found across modern conifers. Podocarp cones, for example, are highly modified and look deceptively like fruit, said Stull: "Their cones are very fleshy, have various colors and are dispersed by different animals."

Competition and climate change led to extinction and diversification

Stull and his colleagues also wanted to know whether genome duplications influenced the rate at which new gymnosperm species evolved through time. But instead of a clear-cut pattern, they found a complex interplay of extinction and diversification amidst a backdrop of a significantly changing global climates.

Today, there are about 1,000 gymnosperm species, which may not seem like many when compared with the 300,000 or so species of flowering plants. But in their heyday, gymnosperms were much more diverse.

Gymnosperms were still thriving prior to the asteroid extinction event 66 million years ago, best known for the demise of dinosaurs. But the dramatic ecological changes brought about by the impact tipped the scales: After the dinosaurs disappeared, flowering plants quickly began outcompeting gymnosperm lineages, which suffered major bouts of extinction as a result. Some groups were snuffed out entirely, while others barely managed to survive to the present. The once flourishing ginkgo family, for example, is today represented by a single living species.

But the results from this study indicate that at least some gymnosperm groups made a comeback starting around 20 million years ago, coinciding with Earth's transition to a cooler, drier climate.

"We see points in history where gymnosperms didn't just continue to decline, but they actually diversified in species numbers as well, which makes for a more dynamic picture of their evolutionary history," said co-author Pamela Soltis, Florida Museum curator and UF distinguished professor.

While some gymnosperms failed to cope with the dual specter of climate change and competition, others had an advantage in certain habitats due to the very traits that caused them to lose out in their ancient rivalry with flowering plants. Groups such as pines, spruces, firs and junipers got fresh starts.

"In some respects, gymnosperms maybe aren't that flexible," Pamela Soltis said. "They kind of have to 'wait around' until climate is more favorable in order for them to diversify."

In some environments, gymnosperms adapted to live at the extremes. In pine forests of southeastern North America, longleaf pines are adapted to frequent fires that incinerate their competition, and conifers dominate the boreal forests of the far north. But take away the fire or the cold, and flowering plants quickly start to encroach.

While gymnosperms are still in the process of diversifying, they've been interrupted by human-made changes to the environment. Currently, more than 40% of gymnosperms are threatened by extinction due to the cumulative pressures of climate change and habitat loss. Future studies clarifying how their underlying genetics enabled them to persist to the present may give scientists a better framework for ensuring they survive well into the future.

"Even though some conifer and cycad groups have diversified considerably over the past 20 million years, many species have highly restricted distributions and are at risk of extinction," Stull said. "Efforts to reduce habitat loss are likely essential for conserving the many species currently threatened by extinction."

Errors in the metabolic processes of mitochondria are responsible for a variety of diseases such as Parkinson's and Alzheimer's. Scientists needed to find out just how the necessary building blocks are imported into the complex biochemical apparatus of these cell areas. The TOM complex (translocase of the outer mitochondrial membrane) is considered the gateway to the mitochondrion, the proverbial powerhouse of the cell. The working group headed by Professor Chris Meisinger at the Institute of Biochemistry and Molecular Biology at the University of Freiburg has now demonstrated - in human cells - how signaling molecules control this gate. A signaling protein called DYRK1A modifies the molecular machinery of TOM and makes it more permeable for enzymes that are important for the cell metabolism. The group has thus discovered the first signaling protein that directly influences this import process in humans. Their work has been published in the journal Nature Communications.

Developmental disorders in a new light

In neurodevelopmental disorders such as autism, microcephaly and Down's syndrome, DYRK1A is defective. "The connection with mitochondria is new. These results allow us to better understand these disorders and develop treatment strategies," says Dr. Adinarayana Marada, a member of Meisinger's team.

"For a long time, researchers thought that the TOM complex was a rigid structure in the mitochondrial membrane whose doors were always open," Meisinger explains. His team recently demonstrated signaling mechanisms in baker's yeast that alter the subunits of the TOM complex depending on the metabolic state of the cell, or in response to sudden stress. In this way, the cell can specifically control the influx of precursor proteins for building elements of the metabolism, and it can adapt the function of the mitochondria to an altered cellular state. Whether such mechanisms also exist in humans was previously unknown.

DYRK1A acts upon the TOM complex

The first authors of the study, Dr. Corvin Walter and Dr. Adinarayana Marada of Meisinger's research group, developed a systematic approach to track down signaling mechanisms such as those triggered by protein kinases, in humans. Over several years, they tested candidates using cell biological and bioinformatic methods and found what they were looking for - DYRK1A, one such protein kinase, acts on the TOM complex. "With this, we actually found the needle in the haystack," says Walter.

Three decades ago, child development researchers found that low-income children heard tens of millions fewer words in their homes than their more affluent peers by the time they reached kindergarten. This "word gap" was and continues to be linked to a socioeconomic disparity in academic achievement.

While parenting deficiencies have long been blamed for the word gap, new research from the University of California, Berkeley, implicates the economic context in which parenting takes place -- in other words, the wealth gap.

The findings, published this month in the journal Developmental Science, provide the first evidence that parents may talk less to their kids when experiencing financial scarcity.

"We were interested in what happens when parents think about or experience financial scarcity and found evidence that such strain could suppress their speech to their children," said study senior author Mahesh Srinivasan, a professor of psychology at UC Berkeley.

"Our results suggest that parenting training may not be sufficient to close the academic achievement gap without addressing the broader issue of income inequality," Srinivasan added.

The study's preliminary results lend credence to the developmental and educational benefits of such poverty-cutting government programs as the federal American Rescue Plan's Child Tax Credit and other supplemental cash payouts for needy families.

"Existing interventions toward eliminating the word gap have often focused on improving parenting skills," Srinivasan said. "But our findings suggest that relieving parents of their financial burdens, such as through direct cash transfers, could also substantially change the ways they engage with their kids."

In the first experiment, researchers sought to observe how parents would interact with their children (in this case, 3-year-olds) after the parents were asked to describe times in which they had recently experienced scarcity. A control group of parents were instead asked to describe other recent activities.

Of the 84 parents in the study, those in the experimental group who described their experiences of financial scarcity spoke less to their 3-year-olds during laboratory observations than parents who reflected on other forms of scarcity (like not having enough fruit), or parents who had not been asked to recollect experiences of resource insecurity.

The second experiment used existing data collected via LENA technology, tiny "talk pedometer" devices worn by children that record their conversations and count the words they hear and say.

As the researchers predicted, analyses revealed that parents engaged in fewer conversational turns with their children at the month's end, a time that typically coincides with money being tight as parents await paychecks or other sources of income.

"Because we had recordings from the same parents at different times of the month, we could essentially use parents as their own controls," said study lead author Monica Ellwood-Lowe, a Ph.D. student in psychology at UC Berkeley.

"This allowed us to really pinpoint differences in their speech patterns when they were more or less likely to be experiencing financial strain, independent of any of their own personal characteristics."

The term "word gap" was coined in the early 1990s when University of Kansas researchers Betty Hart and Todd Risley tracked verbal interactions in the homes of 42 families to study early language development in the children's first three years.

Each day, the researchers recorded an hour of conversation in each household, then counted all the words the children heard during those recording times.

The results were detailed in their 1995 book, Meaningful Differences in the Everyday Experience of Young American Children, and in a 2003 follow-up article, "The Early Catastrophe: The 30 Million Word Gap by Age 3."

While some have questioned Hart and Risley's methodology, their basic finding has been replicated many times, prompting calls for approaches to narrow the disparity. Enter Srinivasan and his research team:

"It struck us that what was missing from the conversation about the word gap was the possibility that poverty, and the many difficult experiences associated with it, could itself affect parents' speech," Srinivasan said.

Preliminary findings support the researchers' hypothesis but also call for a deeper dive into the relationship between money worries and parents' verbal engagement with their children, he said.

"This research doesn't mean that children whose parents are struggling financially are doomed to have smaller vocabularies," Ellwood-Lowe said. "The takeaway here is really just the importance of making sure parents have the resources they need to parent."

"If you are worried about putting food on the table tonight, or scraping together money for that medical bill, or figuring out where to enroll your child in school now that you have been evicted from your neighborhood, you may be less likely to narrate the color of the sky to your child as you ride together on the bus," the study concludes.

The link between on-road traffic and air pollution is well-known, as are the negative health impacts of pollution exposure. However, the many factors that may influence commuters' exposure to pollutants - such as frequency, time, and duration of commute - and the overall impact of commuting remains a matter of on-going scientific discovery.

Dr. Jenna Krall, assistant professor at the George Mason University College of Health and Human Services, is using statistical methods to better understand exposure to air pollution. Krall studies how commuting patterns impact exposure to fine particulate matter (PM2.5) from various traffic-related sources such as tailpipe emissions, road salts, and brake wear.

New research from Krall and colleagues published in Environmental Research examines commuter characteristics to better understand how factors such as departure time, commute length, and number of trips are associated with exposure to PM2.5. Building on a study of 46 women's exposure to PM2.5 using personal air pollution monitors, the new research clustered commuters to determine whether these clusters were associated with traffic pollution exposures. The new study reveals that commuters that travel to work during rush hour have higher overall exposure to traffic-related air pollution compared to sporadic commuters, though the difference was not statistically significant.

As COVID-19 infection rates decline in most areas of the country and employers weigh whether to continue work-from-home policies, studies such as this provide important insight into the role that daily commutes can play in personal air pollution exposure and the public's health.

"This is one of the first studies to utilize in-vehicle monitoring, specifically on-board diagnostics data loggers, to understand real-world commuting behaviors for environmental health," said Krall, "Linking these data with personal air pollution monitoring allowed us to better understand how commuter characteristics are associated with sources of air pollution exposures."

"The current research cannot tell us whether modifying commutes, for example by avoiding highways or commuting outside of rush hour, will lower traffic pollution exposures for commuters. More research is needed to determine what changes would be effective to lower exposures," says Krall.

Krall's on-going research seeks to distinguish between similar sources of traffic pollution, such as pollution generated by brake wear or from tailpipe emissions, and to develop statistical methods to better estimate exposure to pollution sources.

Study participants included 46 women commuters in northern Virginia who were exposed to pollution generated by mobile vehicles, road salts, and other sources throughout a 48-hour period.

Although people in early 2020 hoarded toilet paper, washed their hands incessantly, and wouldn't leave home, 11 months later the public pushed the envelope on COVID-19 safety precautions and ignored warnings as time went on, a new University of California, Davis, study suggests.

Researchers in the Department of Communication examined people's reactions and expressions of anxiety about news articles on Twitter. Additionally, they investigated reactions to fear-inducing health news over time, despite the steadily rising COVID-19 death toll, said Hannah Stevens, a doctoral student in communication and lead author of the paper.

The paper, "Desensitization to Fear-Inducting COVID-19 Health News on Twitter: Observational Study," was published in the Journal of Medical Internet Research Infodemiology on July 16. The researchers examined how COVID-19 news articles shared to Twitter were first met with anxiety-ridden tweets early in the pandemic, during a coinciding spike in instances of panic-buying, extreme social distancing and quarantine measures. Despite the increased death toll, those behaviors then gave way over time to less concerned responses to COVID-19 news, along with increases in societal risk-taking during that time period.

"COVID-19 has made an indelible mark on history, and now it's time to consider what went wrong so we can do better in communicating more effectively during future health crises, and even now, as the delta variant becomes more widespread," said Stevens. "First and foremost, we need to understand how and why scary health news lost impact over time, despite the rapidly increasing death toll."

The authors set out to test the hypothesis that early fear-based health messages in news reports significantly motivated individuals to take actions to control the threat, yet over-exposure to the same messages desensitized people -- or made them less likely to feel anxious over time.

During a period of 11 months, the team used a computerized methodology to analyze linguistic anxiety levels in hundreds of COVID-19 news articles on Twitter, along with the anxiety levels in corresponding user tweets. They then correlated the findings with the COVID-19 death toll in the United States.

"Our study shows a need to delve deeper into how to re-sensitize the public and motivate them to take action in the face of an ongoing emergency. Testing the effectiveness of various health-risk communication strategies could quite possibly mean the difference between life and death in the future," Stevens said.

"If another health crisis occurred today, or COVID-19 takes another turn for the worse, it is essential for public health officials to consider that they are communicating to a desensitized public. I hope that this paper can be an impetus to get that discussion started."

Tokyo, Japan - Designing materials that have the necessary properties to fulfill specific functions is a challenge faced by researchers working in areas from catalysis to solar cells. To speed up development processes, modeling approaches can be used to predict information to guide refinements. Researchers from The University of Tokyo Institute of Industrial Science have developed a machine learning model to determine characteristics of bonded and adsorbed materials based on parameters of the individual components. Their findings are published in Applied Physics Express.

Factors such as the length and strength of bonds in materials play crucial roles in determining the structures and properties we experience on the macroscopic scale. The ability to easily predict these characteristics is therefore valuable when designing new materials.

The density of states (DOS) is a parameter that can be calculated for individual atoms, molecules, and materials. Put simply, it describes the options available to the electrons that arrange themselves in a material. A modeling approach that can take this information for selected components and produce useful data for the desired product--with no need to make and analyze the material--is an attractive tool.

The researchers used a machine learning approach--where the model refines its response without human intervention--to predict four different properties of products from the DOS information of the individual components. Although the DOS has been used as a descriptor to establish single parameters before, this is the first time multiple different properties have been predicted.

"We were able to quantitatively predict the binding energy, bond length, number of covalent electrons, and the Fermi energy after bonding for three different general types of system," explains study first author Eiki Suzuki. "And our predictions were very accurate across all of the properties."

Because the calculation of DOS of an isolated state is less complex than for bonded systems, the analysis is relatively efficient. In addition, the neural network model used performed well even when only 20% of the dataset was used for training.

"A significant advantage of our model is that it is general and can be applied to a wide variety of systems," study corresponding author Teruyasu Mizoguchi explains. "We believe that our findings could make a significant contribution to numerous development processes, for example in catalysis, and could be particularly useful in newer research areas such as nano clusters and nanowires."

Testing of an entire Italian town shows antibody levels remain high nine months after SARS-CoV-2 infection, whether symptomatic or asymptomatic.

Researchers from the University of Padua and Imperial College London tested more than 85 percent of the 3,000 residents of Vo', Italy, in February/March 2020 for infection with SARS-CoV-2, the virus that causes COVID-19, and tested them again in May and November 2020 for antibodies against the virus.

The team found that 98.8 percent of people infected in February/March showed detectable levels of antibodies in November, and there was no difference between people who had suffered symptoms of COVID-19 and those that had been symptom-free. The results are published today in Nature Communications.

Antibody levels were tracked using three 'assays' - tests that detect different types of antibodies that respond to different parts of the virus. The results showed that while all antibody types showed some decline between May and November, the rate of decay was different depending on the assay.

The team also found cases of antibody levels increasing in some people, suggesting potential re-infections with the virus, providing a boost to the immune system.

Lead author Dr Ilaria Dorigatti, from the MRC Centre for Global Infectious Disease Analysis and the Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA) at Imperial, said: "We found no evidence that antibody levels between symptomatic and asymptomatic infections differ significantly, suggesting that the strength of the immune response does not depend on the symptoms and the severity of the infection.

"However, our study does shows that antibody levels vary, sometimes markedly, depending on the test used. This means that caution is needed when comparing estimates of infection levels in a population obtained in different parts of the world with different tests and at different times."

Professor Enrico Lavezzo, from the University of Padua, said: "The May testing demonstrated that 3.5 percent of the Vo' population had been exposed to the virus, even though not all of these subjects were aware of their exposure given the large fraction of asymptomatic infections.

"However, at the follow-up, which was performed roughly nine months after the outbreak, we found that antibodies were less abundant, so we need to continue to monitor antibody persistence for longer time spans."

The team also investigated the infection status of household members, to estimate how likely an infected member is to pass on the infection within the household. Their modelling suggests that there was a probability of about 1 in 4 that a person infected with SARS-CoV-2 passes the infection to a family member and that most transmission (79 percent) is caused by 20 percent of infections.

This finding confirms that there are large differences in the number of secondary cases generated by infected people, with the majority of infections generating no further infections and a minority of the infections generating a large number of infections.

The large differences in how one infected person may infect others in the population suggests that behavioural factors are key for epidemic control, and physical distancing, as well as limiting the number of contacts and mask wearing, continue to be important to reduce the risk of transmitting the disease, even in highly vaccinated populations.

The team's dataset, which includes the results of the two mass PCR testing campaigns conducted in February and March and the antibody survey conducted in May and then again in November, also allowed them to tease apart the impact of various control measures.

They showed that, in the absence of case isolation and short lockdowns, manual contact tracing alone would not have been enough to suppress the epidemic.

Project lead Professor Andrea Crisanti, from the Department of Life Sciences at Imperial and the Department of Molecular Medicine at the University of Padua, said: "Our study also shows that manual contact tracing - the search for positive individuals on the basis of known and declared contacts - would have had a limited impact on the containment of the epidemic, had it not been accompanied by a mass screening."

Dr Dorigatti added: "It is clear that the epidemic is not over, neither in Italy nor abroad. Moving forward, I think that it is of fundamental importance to continue administering first and second vaccine doses as well as to strengthen surveillance including contact tracing. Encouraging caution and limiting the risk of acquiring SARS-CoV-2 will continue to be essential."

In February 2020, a trio of bio-imaging experts were sitting amiably around a dinner table at a scientific conference in Washington, D.C., when the conversation shifted to what was then a worrying viral epidemic in China. Without foreseeing the global disaster to come, they wondered aloud how they might contribute.

Nearly a year and a half later, those three scientists and their many collaborators across three national laboratories have published a comprehensive study in Biophysical Journal that - alongside other recent, complementary studies of coronavirus proteins and genetics - represents the first step toward developing treatments for that viral infection, now seared into the global consciousness as COVID-19.

Their foundational work focused on the protein-based machine that enables the SARS-CoV-2 virus to hijack our own cells' molecular machinery in order to replicate inside our bodies.

From structure to function to solutions

"It has been remarked that all organisms are just a means for DNA to make copies of itself, and nowhere is this truer than in the case of a virus," said Greg Hura, a staff scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) and one of the study's lead authors. "A virus's singular task is to make copies of its genetic material - unfortunately, at our expense."

Viruses and mammals, including humans, have been stuck in this battle for millions of years, he added, and over that time the viruses have evolved many tricks to get their genes copied inside us, while our bodies have evolved counter defenses. And although viruses often perform a long list of other activities, their ability to harm us with an infection really does come down to whether or not they can replicate their genetic material (either RNA or DNA, depending on the species) to make more viral particles, and use our cells to translate their genetic code into proteins.

The protein-based machine responsible for RNA replication and translation in coronaviruses - and many other viruses - is called the RNA transcription complex (RTC), and it is a truly formidable piece of biological weaponry.

To successfully duplicate viral RNA for new virus particles and produce the new particles' many proteins, the RTC must: distinguish between viral and host RNA, recognize and pair RNA bases instead of highly similar DNA bases that are also abundant in human cells, convert their RNA into mRNA (to dupe human ribosomes into translating viral proteins), interface with copy error-checking molecules, and transcribe specific sections of viral RNA to amplify certain proteins over others depending on need - while at all times trying to evade the host immune system that will recognize it as a foreign protein.

As astounding as this sounds, any newly evolved virus that is successful "must have machines that are incredibly sophisticated to overcome mechanisms we have evolved," explained Hura, who heads the Structural Biology department in Berkeley Lab's Molecular Biophysics and Integrated Bioimaging Division.

He and the other study leads - Andrzej Joachimiak of Argonne National Laboratory and Hugh M. O'Neill at Oak Ridge National Laboratory - specialize in revealing the atomic structure of proteins in order to understand how they work at the molecular level. So, the trio knew from the moment they first discussed COVID-19 at the dinner table that studying the RTC would be particularly challenging because multitasking protein machines like the RTC aren't static or rigid, as molecular diagrams or ball-and-stick models might suggest. They're flexible and have associated molecules, called nonstructural and accessory proteins (Nsps), that exist in a multitude of rapidly rearranging forms depending on the task at hand - akin to how a gear shifter on a bike quickly adapts the vehicle to changing terrain.

Each of these Nsp arrangements give insights into the protein's different activities, and they also expose different parts of the overall RTC surface, which can be examined to find places where potential drug molecules could bind and inhibit the entire machine.

So, following their serendipitous convergence in Washington, the trio hatched a plan to pool their knowledge and national lab resources in order to document the structure of as many RTC arrangements as possible, and identify how these forms interact with other viral and human molecules.

Science during shutdowns

The investigation hinged on combining data collected from many advanced imaging techniques, as no approach by itself can generate complete, atomic-level blueprints of infectious proteins in their natural states. They combined small-angle X-ray scattering (SAXS), X-ray crystallography, and small-angle neutron scattering (SANS) performed at Berkeley Lab's Advanced Light Source, Argonne's Advanced Photon Source, and Oak Ridge's High Flux Isotope Reactor and Spallation Neutron Source, respectively, on samples of biosynthetically produced RTC.

Despite the extraordinary hurdles of conducting science during shelter-in-place conditions, the collaboration was able to work continuously for more than 15 months, thanks to funding for research and facility operations support from the Department of Energy's Office of Science National Virtual Biotechnology Laboratory (NVBL). During that time, the scientists collected detailed data on the RTC's key accessory proteins and their interactions with RNA. All of their findings were uploaded into the open-access Protein Data Bank prior to the journal article's publication.

Of the many structural findings that will help with drug design, one notable discovery is that assembly of the RTC subunits is incredibly precise. Drawing on a mechanical metaphor once more, the scientists compare the assembly process to putting together a spring-based machine. You can't put a spring in place when the rest of the machine is already in position, you must compress and place the spring at a specific step of assembly or the whole device is dysfunctional. Similarly, the RTC Nsps can't move into place in any random or chaotic order; they must follow a specific order of operations.

They also identified how one of the Nsps specifically recognizes the RNA molecules it acts upon, and how it cuts long strands of copied RNA into their correct lengths.

"Having the vaccines is certainly huge. However, why are we satisfied with just this one avenue of defense?" said Hura. Added Joachimiak: "This was a survey study, and it has identified many directions we and others should pursue very deeply; to tackle this virus we will need multiple ways of blocking its proliferation."

"Combining information from different structural techniques and computation will be key to achieving this goal," said O'Neill.

Due to the similarity of RTC proteins across viral strains, the team believe that any drugs developed to block RTC activity could work for multiple viral infections in addition to all COVID-19 variants.

Reflecting back to the beginning of their research journey, the scientists marvel at the lucky timing of it all. When we started to talk, said Hura, "we had no idea that this epidemic would soon become a pandemic that would change a generation."

African swine fever (ASF), first detected in Germany in domestic pigs on 15 July 2021, does not pose a health hazard to humans. "The ASF pathogen cannot be transferred to humans", explains Professor Dr. Dr. Andreas Hensel, President of the German Federal Institute for Risk Assessment (BfR). "No risk to health is posed by direct contact with diseased animals or from eating food made from infected domestic pigs or wild boar".

The ASF pathogen is a virus which infects domestic pigs and wild boar and which leads to a severe, often lethal, disease in these animals. It is transferred via direct contact or with excretions from infected animals, or through ticks. The ASF virus is endemic to infected wild animals in Africa, but there have also repeatedly been outbreaks in southern Europe. The pathogen has been spreading north-westwards since 2007 from Georgia through Armenia, Azerbaijan and Russia. Cases of ASF have been registered in wild boar along with outbreaks in domestic pigs in the Baltic states since 2014. The virus has also been detected in Romania, Hungary, Poland and the Czech Republic. In September 2018, the pathogen was also found in wild boars in Belgium and thus for the first time in Western Europe. On 10 September 2020, the ASF virus has been detected for the first time in Germany in a wild boar in Brandenburg. The first cases of ASF in domestic pigs in Germany were detected in two pig farms in Brandenburg on 15 July 2021.

The pathogen is very stable and can remain infectious in food over several months. If unheated food or food scraps from infected animals are fed to non-infected animals, the virus can therefore spread to previously ASF-free regions, thus infecting domestic pig herds too.

Although the ASF virus does not pose a hazard or a risk to humans, the meat of domestic pigs and wild boar should always be prepared under hygienic conditions, just like all other raw meats, as it can also contain other pathogens, advises the BfR. It should be kept refrigerated and prepared separately from other foods before cooking. When heating, a temperature of 70 degrees Celsius or higher should be reached at all parts of the food for at least two minutes, the BfR recommends.

The BfR has compiled some frequently asked questions about ASF for further information. They can be downloaded on the BfR website.

https://www.bfr.bund.de/en/frequently_asked_questions_about_african_swine_fever__asf_-205379.html

A coronavirus related to the virus that causes Covid-19 in humans has been found in UK horseshoe bats - according to new collaborative research from the University of East Anglia, ZSL (Zoological Society of London), and Public Health England (PHE).

However, there is no evidence that this novel virus has been transmitted to humans, or that it could in future, unless it mutates.

UEA researchers collected faecal samples from more than 50 lesser horseshoe bats in Somerset, Gloucestershire and Wales and sent them for viral analysis at Public Health England.

Genome sequencing found a novel coronavirus in one of the bat samples, which the team have named 'RhGB01'.

It is the first time that a sarbecovirus (SARS-related coronavirus) has been found in a lesser horseshoe bat and the first to be discovered in the UK.

The research team say that these bats will almost certainly have harboured the virus for a very long time. And it has been found now, because this is the first time that they have been tested.

Importantly, this novel virus is unlikely to pose a direct risk to humans, unless it mutates.

A mutation could happen if a human infected with Covid-19 passes it to an infected bat, so
anyone coming into contact with bats or their droppings, for example those engaged in caving or bat protection, should wear appropriate PPE.

Prof Diana Bell, an expert in emerging zoonotic diseases from UEA's School of Biological Sciences, said: "Horseshoe bats are found across Europe, Africa, Asia and Australia and the bats we tested lie at the western extreme of their range.

"Similar viruses have been found in other horseshoe bat species in China, South East Asia and Eastern Europe.

"Our research extends both the geographic and species ranges of these types of viruses and suggests their more widespread presence across more than 90 species of horseshoe bats.

"These bats will almost certainly have harboured this virus for a very long time - probably many thousands of years. We didn't know about it before because this is the first time that such tests have been carried out in UK bats.

"We already know that there are different coronaviruses in many other mammal species too," she said. "This is a case of 'seek and you will find'.

"Research into the origins of SARS-CoV-2, the virus that causes Covid-19 in humans, has focussed on horseshoe bats - but there are some 1,400 other bat species and they comprise 20 per cent of known mammals.

"Our findings highlight the need for robust genotype testing for these types of viruses in bat populations around the world. And it raises an important question about what other animals carry these types of viruses."

Prof Andrew Cunningham, from the Zoological Society of London, said: "Our findings highlight that the natural distribution of sarbecoviruses and opportunities for recombination through intermediate host co-infection have been underestimated.

"This UK virus is not a threat to humans because the receptor binding domain (RBD) - the part of the virus that attaches to host cells to infect them - is not compatible with being able to infect human cells.

"But the problem is that any bat harbouring a SARS-like coronavirus can act as a melting pot for virus mutation. So if a bat with the RhGB01 infection we found were to become infected with SARS-CoV-2, there is a risk that these viruses would hybridise and a new virus emerge with the RBD of SARS-CoV-2, and so be able to infect people.

"Preventing transmission of SARS-CoV-2 from humans to bats, and hence reducing opportunities for virus mutation, is critical with the current global mass vaccination campaign against this virus."

Prof Bell added: "The main risks would be for example a bat rehabilitator looking after a rescued animal and infecting it with SARS-CoV2 - which would provide an opportunity for genetic recombination if it is already carrying another sarbecovirus.

"Anyone coming into contact with bats or their droppings, such as bat rescuers or cavers, should wear appropriate PPE - in order to reduce the risk of a mutation occurring.

"We need to apply stringent regulations globally for anyone handling bats and other wild animals," she added.

The new virus falls within the subgroup of coronaviruses called sarbecoviruses which contains both SARS-CoV-2 (responsible for the current pandemic) and SARS-CoV (responsible for the initial 2003 SARS outbreak in humans).

Further analysis compared the virus with those found in other horseshoe bat species in China, South East Asia and Europe and showed that its closest relative was discovered in a Blasius's bat from Bulgaria in 2008.

The UK discovery was made by undergraduate ecology student Ivana Murphy, from UEA's School of Biological Sciences, who collected bat droppings as part of her final year research dissertation. Jack Crook conducted the genetic analyses in partnership with other researchers at PHE.

A total of 53 bats were captured, and their faeces collected in sterile bags. The research was conducted under strict Health and Safety protocols. Full PPE was worn and Ivana was regularly tested for Covid-19 to avoid any chance of cross contamination. The bats were released immediately after their droppings had been collected.

Ivana said: "More than anything, I'm worried that people may suddenly start fearing and persecuting bats, which is the last thing I would want and would be unnecessary. As like all wildlife, if left alone they do not pose any threat."

UK policymakers preparing trade deals post-Brexit can learn important lessons from New Zealand's 'unique drug agency' the Pharmaceutical Management Agency (PHARMAC), if prices for therapies and access to key drugs are to be protected, say researchers behind a new study.

Over two decades, New Zealand has managed to reduce spending on drugs significantly and consistently despite maintaining access for its population to key treatments. As such, it is an outlier among the world's richest nations: no other OECD country has managed to achieve this.

The investigation from researchers at the universities of Bath and Durham suggest New Zealand's success can largely be ascribed to its drug agency PHARMAC. PHARMAC is unique because it not only assesses drugs scientifically, but also negotiates their prices with pharma companies.

Its equivalent in England is NICE, however whereas NICE focuses on the scientific assessment of drugs, price negotiations with drug companies rest with NHS England. There is speculation that given the attractiveness of the UK as a market for multinational drug companies, new trade deals being agreed by the UK could undermine NICE's ability to assess new drugs and determine whether they represent value for money.

For example, the researchers argue that if trade deals grant pharmaceutical companies new powers to challenge NICE's decisions through new forms of appeals mechanisms this could be a 'game changer', providing companies with additional tactics to drive up prices.

Their study, which involved analysis of policy documents produced alongside New Zealand's trade talks with other countries, freedom of information requests and interviews with key experts and policymakers, points to what could go wrong with drug prices and drug access in the UK post-Brexit.

Researcher, Dr Piotr Ozieranski from the University of Bath's Centre for the Analysis of Social Policy explained: "The implications of this study are particularly important post-Brexit and especially in the context of trade policy because of the potential impact these new deals will have on drug prices. The key issue is whether NICE is sufficiently protected for the independent, expert analysis it gives to ensure value for money for the NHS.

"Another key lesson from the study is that not only is PHARMAC protected from commercial influence, it is also trusted with maximum flexibility in negotiating drug prices with manufacturers. Depending on the situation, it can negotiate prices before a drug even reaches the market or, conversely, stall negotiations until it is about to lose patent protection and become cheaper. It also encourages price competition among companies by setting up competitive tenders and play-offs, as well as negotiating with multiple applicants at the same time."

Ben Main from the University of Durham, commented: "New Zealand's success in ensuring continued access to drugs whilst consistently driving down prices is not by accident; even more so because, unlike the UK, New Zealand cannot use the argument of a large population to secure lower prices. PHARMAC is a brilliant negotiator and uses flexibility to achieve good deals. Healthcare policymakers in the UK can learn from this model.

"However, our work raises an important question for UK policymakers: Is it worth granting NICE extra powers that would allow it to emulate some of the tactics used by PHARMAC? While price negotiations are typically shrouded in secrecy, New Zealand's evident success suggests that experts can be trusted not only with evaluating drugs scientifically but also striking favourable deals with the industry."

The paper also highlights the importance of protecting NICE from political interference.

Ben Main added: "Crucially, PHARMAC wields much policy authority, which is bolstered by social and political support even though some of its decisions may at times deny access to promising drugs to some patients. This contrasts with NICE's position, which on occasions has been challenged by politicians and NHS officials wanting to secure funding for specific therapies which did not pass - or were unlikely to pass - NICE's evaluation criteria. By and large, PHARMAC is not part of party politics."

Main also draws attention to how the industry has sought legal changes to the way PHARMAC operates: "One key lesson surrounds the issue of transparency. In other institutional contexts a lack of transparency surrounding decision making is a criticism levelled at policymakers. What we see is that over the last decade in New Zealand there is 'transparency' on industry's terms - a weapon to offset PHARMAC's authority - and a lack of transparency on PHARMAC's terms which has enabled their spending model and offset industry's dominant market position."

New Zealand's policymakers have sought to insulate PHARMAC's power by legally exempting its decisions from being potentially challenged as 'anti-competitive' by drug companies (Section 53 of the New Zealand Public Health and Disability Act 2000). On top of this, after lengthy negotiations, New Zealand refused to sign a Trans-Pacific Partnership treaty with the US, whose 'transparency and disclosure requirements' included provisions which could be used to challenge PHARMAC's decisions.

Instead, it signed a Progressive Trans-Pacific Trade Treaty (CPPTP) with eight other countries. CPPTP is unlikely to affect PHARMAC, however to further safeguard this, New Zealand subsequently suspended the application of its procedural rules in relation to PHARMAC.

Proteins constitute an essential dietary component that help in the growth and repair of the body. Composed of long chains of amino acids, proteins promote the growth of skeletal muscles, the group of muscles that help us move. Humans have been aware of the benefits of proteins for long. However, recent studies have shown that having the right amount of protein at the right time of the day is essential for proper growth. This is called 'Chrononutrition,' in which when you eat is as important as what and how you eat.

The reason behind this is the body's internal biological clock, called the 'circadian rhythm.' This rhythm is followed by all cells and controls life functions like metabolism and growth. Interestingly, protein digestion and absorption have been found to fluctuate across day and night according to this clock. Moreover, earlier studies have reported that intake of protein at breakfast and lunch promotes skeletal muscle growth in adults. However, details on the effect of the time of protein intake on muscle growth and function have remained elusive till date.

Fortunately, researchers from Waseda University, led by Professor Shigenobu Shibata, recently endeavored to understand the effect of the distribution of protein intake through the day on muscles. They fed laboratory mice two meals per day containing either high (11.5% by proportion) or low (8.5% by proportion) protein concentrations. The researchers noted that protein intake at breakfast induced an increase in muscle growth, determined by assessing induced hypertrophy of the plantaris muscle in the leg, when compared with the effects of protein intake at dinner. Specifically, the ratio of muscle hypertrophy determined against the growth of the control muscle was 17% higher in mice fed 8.5% protein at breakfast, than that in mice fed 11.5% protein at dinner, despite the former group consuming a low proportion of protein overall. They also found that intake of a type of protein called the BCCA, short for branched-chain amino acids, early in the day increased the size of skeletal muscles specifically.

To confirm the association of these effects with the workings of the circadian rhythm, the researchers next engineered whole-body mutant ClockΔ19 or muscle-specific Bmal1 knockout mice lacking the genes that control the biological clock. They repeated diet distribution experiments on these mice but did not observe similar muscle change, which confirmed the involvement of the circadian rhythm in muscle growth in the context of protein intake.

Excited about the findings of their study published in a recent issue of the Cell Reports, Prof. Shibata emphasizes, "Protein-rich diet at an early phase of the daily active period, that is at breakfast, is important to maintain skeletal muscle health and enhance muscle volume and grip strength."

To check if their findings were applicable to humans, the team recruited women in their study and tested if their muscle function, determined by measuring skeletal muscle index (SMI) and grip strength, varied with the timing of the protein-rich diet consumed. Sixty women aged 65 years and above who took protein at breakfast rather than at dinner showed better muscle functions, suggesting the possibility of the findings to be true across species. Additionally, the researchers also found a strong association between SMI and the proportion of protein intake at breakfast relative to total protein intake through the day.

Prof. Shibata is hopeful that the findings of their study will lead to a widespread modification in the current diet regime of most people across the Western and Asian countries, who traditionally consume low amounts of protein at breakfast. He therefore stresses, "For humans, in general, the protein intake at breakfast averages about 15 grams, which is less than what we consume at dinner, which is roughly 28 grams. Our findings strongly support changing this norm and consuming more protein at breakfast or morning snacking time."

It seems, a simple change in our dietary regime can be our key to ensuring healthy muscles!

Chemical synapses transmit information within the nervous system. When a presynaptic cell is electrically excited, synaptic vesicles fuse with the presynaptic membrane causing messenger substances within the vesicles to be released into the synaptic cleft. These then bind to receptors in the postsynaptic cell where they trigger an electrical signal once again. The temporal and spatial sequence of the incoming signals determines how information is processed and transmitted in the brain. In order to sustain their function in the long term, chemical synapses need to recycle synaptic vesicles to make them available for renewed signal transmission. Professor Carsten Duch and Professor Martin Heine and their respective research groups at Johannes Gutenberg University Mainz (JGU) are investigating how the release and recycling of synaptic vesicles are coordinated. "Exocytosis and endocytosis rates at chemical synapses need to be coordinated to achieve reliable signal transmission in the brain," the biologists explained. Together with Dr. Ulrich Thomas, group leader at the Leibniz Institute for Neurobiology in Magdeburg, Duch and Heine have revealed in a PNAS paper how spatiotemporally separated presynaptic calcium signals independently regulate exocytosis and endocytosis of synaptic vesicles, i.e., their release and recycling.

Co-existence of different types of voltage-gated calcium channels at the presynapse

At chemical synapses, incoming electrical impulses are converted into chemical signals and relayed on to the next cell. The process entails calcium ions first flowing through voltage-dependent membrane channels into the presynapse, i.e., the upstream nerve cell that transmits the signal to the postsynaptic cell. This calcium influx is tightly constrained in both time and space and results in exocytosis of synaptic vesicles from a specialized vesicle reservoir. Presynaptic calcium signals also regulate synaptic vesicle recycling, but here the temporal and spatial requirements are different. One unresolved question is how presynaptic electrical activity can lead to calcium signals with different temporal and spatial profiles in the presynaptic terminal.

By combining genetic modifications with electrophysiological and optophysiological measurements at the neuromuscular synapse of the Drosophila melanogaster genetic model organism, the research team was able to demonstrate that the presynapse harbors two different types of voltage-gated calcium channels, Cav2 and Cav1. These, however, were found to be spatially segregated. Both types of channels open when electrical signals arrive, but only Cav2 channels, which reside in active zones of the presynapse, are required for exocytosis of synaptic vesicles. Cav1 channels are situated outside active zones and augment endocytosis of synaptic vesicles via activity-dependent calcium influx. Thus, knockdown of Cav2 by means of genetic manipulation prevents synaptic transmission, whereas knockdown of Cav1 decreases the rate of synaptic vesicle endocytosis, thereby enhancing synaptic depression during sustained activity. This is how calcium signals mediated by two different populations of largely independent voltage-gated calcium channels regulate two essential functions of the presynapse in response to neuronal activity, namely the release and recycling of synaptic vesicles.

Functional separation of Cav1 and Cav2 by means of a calcium pump

A key question was how calcium signals through different channels could be functionally separated at the nanometer scale of the presynaptic terminal, because calcium after all is a highly diffusible intracellular messenger. According to the researchers, different vital functions of calcium signals through Cav1 and Cav2 channels are separated by a membrane-anchored calcium buffer. Cav2 channels are found within presynaptic active zones at distances of 70 to 140 nanometers from readily releasable synaptic vesicles. This distinct localization of Cav2 results in the emergence of temporally and spatially tightly regulated calcium signals within so-called nano-domains during presynaptic electrical activity, and these are essential for temporally precise synaptic transmission. Cav1 localizes around active zones, in theory allowing calcium influx simultaneously through both types of channels to result in mixed signals with no measurable delay. However, mixed signals of this type are prevented by the plasma membrane calcium pump (PMCA). PMCA is located outside active zones and isolates them from the dynamic regulation of endocytosis achieved by Cav1-mediated calcium influx. Because Cav1, Cav2, and PMCA have been identified also at central synapses in the brains of mammals, these proteins may represent a conserved functional triad for separate activity-dependent regulation of exocytosis and endocytosis of synaptic vesicles.

Calcium channels and the regulation of essential synaptic functions

In the future, Duch's and Heine's research groups will continue to explore the interactions of calcium channels and their associated molecules at the presynapse. Calcium signals in the presynaptic terminal regulate other essential synaptic functions beyond exocytosis and endocytosis. These include the regulation of synaptic vesicle movements between distinct specialized reservoirs as well as the control of fixed synaptic transmission strengths, which are restored by compensatory mechanisms after perturbation. This homeostatic synaptic plasticity is essential for reliably processing information in the brain. As part of a project within Collaborative Research Center 1080 on Molecular and Cellular Mechanisms in Neural Homeostasis, Duch's and Heine's groups are investigating how spatiotemporally separated presynaptic calcium signals independently control exocytosis and endocytosis, the transport of vesicles between different reservoirs, and synaptic homeostasis. "Calcium signals are extremely well suited to precisely adapt a variety of vital synaptic functions to differing neuronal activities, but we are only just starting to work out the mechanisms that independently regulate these functions," Duch and Heine commented on their neurobiology research.

The economic and environmental pros and cons of melting Arctic ice creating shorter shipping routes through the polar region are weighed up in ground-breaking research from UCL experts in energy and transport.

They conclude that policy makers must properly assess the environmental trade-offs and costs in addition to the commercial benefits and opportunities in Arctic shipping. The authors also want to see more incentives to drive technological developments that will accelerate the uptake of green fuels and technologies.

The Arctic is the fastest-warming region on the planet.

Shorter Arctic shipping routes, which mean less fuel used are already used by a handful of ships, when areas of the Arctic ice melt during the summer. But the period when these routes are navigable is predicted to extend with increases in global warming and, if warming fails to remain within the 1.5?C/2?C limit set out in the Paris agreement, permanent Arctic ice may be a thing of the past.

The research, published in Transportation Research Part A: Policy and Practice, looked at the financial competitiveness of Arctic shipping, considering the impact of emissions from these vessels on the environment.

They looked at two policy scenarios, one being business-as-usual, where there is no policy on emissions, and the other operating under an Arctic specific zero-emissions policy, where ships which could run using energy from renewable sources were considered.

When environmental costs are ignored, fossil fuel based residual fuel oil is cheaper than alternative fuels. However, when the environmental impacts of accelerating climate change and the adverse effects of ship emissions on human health are considered, residual fuel ships are no longer feasible because of their contribution to greenhouse gas and air pollutant emissions.

The experts conclude that, in the second scenario, green ammonia fuel cell ships are the most commercially viable and that policies which facilitate the introduction of such zero carbon fuels and zero emission technologies should be encouraged. Green ammonia is an example of a fuel that can be emissions free in both its production and use, given a green electric infrastructure.

Lead author Joseph Lambert (UCL Energy Institute) said: "Significant change is under way in the Arctic region due to global warming and from a shipping perspective we should prepare for what this means through assessing all the opportunities, risks and trade-offs that aren't exclusively financial. These routes may become more financially competitive as global warming increases and Arctic ice retreats, but more factors must be considered. It is critical that the Arctic ice maintains its permanency - in order to stay within global warming targets and to protect the region's ecology."

Co-author Dr Tristan Smith (UCL Energy Institute), who supervised the research, said: "This is a novel work that shows the economic costs alongside the environmental costs for the Arctic route, as well as showing how certain technology choices, that could be incentivised through policy, could significantly reduce the environmental costs that would otherwise arise from Arctic shipping. The paper shows a clear justification for governments to intervene now to prevent a melting Arctic's enabling of a reduction in shipping costs because of further acceleration of the degradation of this crucial ecosystem."

The researchers say impacts that need to be explored include the effects of ecological damage, and how policy can be structured to address the environmental concerns.