Culture

AURORA, Colo. (July 28, 2020) - Researchers at the University of Colorado School of Medicine have discovered a protein in fruit fly embryos, dubbed Marie Kondo, that destroys maternal proteins. Much like namesake, author and clutter consultant Marie Kondo, this gene removes unnecessary molecules, keeping embryos organized.

Fertilized egg cells are loaded with maternal molecules that control the earliest steps of embryonic development. A critical stage of development is when the embryo destroys these inherited molecules and begins to make its own. These molecules include proteins and messenger RNAs (which encode instructions for making proteins). Existing research had identified how messenger RNAs are destroyed, but how maternal proteins are discarded, however, has been unknown.

According to the study, published in the journal eLife, researchers discovered the presence of the Marie Kondo protein by screening ~150 possible enzymes using a trick where destruction of maternal proteins could be seen with fluorescent microscopy. After months of work, they identified the enzyme and gave it the name "Marie Kondo."

"Ordinarily, when we talk about getting rid of maternal gene products, we tend to focus on mRNA, or the coded information for making a protein," says Olivia Rissland, assistant professor of biochemistry and molecular genetics at the University of Colorado School of Medicine and study co-author. "However, we don't often talk about destruction of the proteins themselves. One implication of our study is that, during early stages of development, destruction of maternal proteins might be more tightly controlled than we had thought."

Rissland says this discovery opens the door to more research into embryonic protein destruction. "The reason why we started looking at these proteins is because they control RNA. Now, we want to see what other proteins are destroyed and how protein destruction affects early development, not just in fruit flies, but in other animals too."

RIVERSIDE, Calif. -- A pair of researchers at the University of California, Riverside, has used machine learning to understand what a chemical smells like -- a research breakthrough with potential applications in the food flavor and fragrance industries.

"We now can use artificial intelligence to predict how any chemical is going to smell to humans," said Anandasankar Ray, a professor of molecular, cell and systems biology, and the senior author of the study that appears in iScience. "Chemicals that are toxic or harsh in, say, flavors, cosmetics, or household products can be replaced with natural, softer, and safer chemicals."

Humans sense odors when some of their nearly 400 odorant receptors, or ORs, are activated in the nose. Each OR is activated by a unique set of chemicals; together, the large OR family can detect a vast chemical space. A key question in olfaction is how the receptors contribute to different perceptual qualities or percepts.

"We tried to model human olfactory percepts using chemical informatics and machine learning," Ray said. "The power of machine learning is that it is able to evaluate a large number of chemical features and learn what makes a chemical smell like, say, a lemon or a rose or something else. The machine learning algorithm can eventually predict how a new chemical will smell even though we may initially not know if it smells like a lemon or a rose."

According to Ray, digitizing predictions of how chemicals smell creates a new way of scientifically prioritizing what chemicals can be used in the food, flavor, and fragrance industries.

"It allows us to rapidly find chemicals that have a novel combination of smells," he said. "The technology can help us discover new chemicals that could replace existing ones that are becoming rare, for example, or which are very expensive. It gives us a vast palette of compounds that we can mix and match for any olfactory application. For example, you can now make a mosquito repellent that works on mosquitoes but is pleasant smelling to humans."

The researchers first developed a method for a computer to learn chemical features that activate known human odorant receptors. They then screened roughly half a million compounds for new ligands -- molecules that bind to receptors -- for 34 odorant receptors. Next, they focused on whether the algorithm that could estimate odorant receptor activity could also predict diverse perceptual qualities of odorants.

"Computers might help us better understand human perceptual coding, which appears, in part, to be based on combinations of differently activated ORs," said Joel Kowalewski, a student in the Neuroscience Graduate Program working with Ray and the first author of the research paper. "We used hundreds of chemicals that human volunteers previously evaluated, selected ORs that best predicted percepts on a portion of chemicals, and tested that these ORs were also predictive of new chemicals."

Ray and Kowalewski showed the activity of ORs successfully predicted 146 different percepts of chemicals. To their surprise, few rather than all ORs were needed to predict some of these percepts. Since they could not record activity from sensory neurons in humans, they tested this further in the fruit fly (Drosophila melanogaster) and observed a similar result when predicting the fly's attraction or aversion to different odorants.

"If predictions are successful with less information, the task of decoding odor perception would then become easier for a computer," Kowalewski said.

Ray explained that many items available to consumers use volatile chemicals to make themselves appealing. About 80% of what is considered flavor in food actually stems from the odors that affect smell. Fragrances for perfuming cosmetics, cleaning products, and other household goods play an important role in consumer behavior.

"Our digital approach using machine learning could open up many opportunities in the food, flavor, and fragrance industries," he said. "We now have an unprecedented ability to find ligands and new flavors and fragrances. Using our computational approach, we can intelligently design volatile chemicals that smell desirable for use and also predict ligands for the 34 human ORs."

Rates of elevated psychological distress, including depression and anxiety symptoms, were found among Australian adults during the peak of the COVID-19 outbreak in Australia, according to a new study published July 28, 2020 in the open-access journal PLOS ONE by Jill Newby of the University of New South Wales at the Black Dog Institute, Sydney, Australia, and colleagues.

The acute and long-term mental health impacts of the COVID-19 pandemic are largely unknown. Research into previous pandemics has shown higher rates of illness fears, psychological distress, insomnia and other mental health problems in people with pre-existing mental illness, front-line health care workers, and survivors of the disease. Research into the mental health impacts of COVID-19 is needed to inform policy decisions, prevention efforts, treatment programs, and community support systems.

In the new study, researchers used an online survey, administered March 27 through April 7--now considered to be the peak of the COVID-19 outbreak in Australia--to examine mental health responses to the pandemic among 5070 Australian adults. The online questionnaire asked participants about their fears, behavioral responses to COVID-19, psychological distress, alcohol use, and physical activity. A similar survey had already been carried out among 2,174 Australians in early March, when cases in the country were still low.

The population included in the survey was not representative of the overall population; 70% had pre-existing mental health diagnoses, 86% were female, and 75% were Caucasian. Although few participants had contracted COVID-1019 (0.15%), more than one-quarter (25.9%) were very or extremely worried about contracting the virus and more than half (52.7%) were very or extremely worried about their family and friends. While the questionnaires could not be used to make any diagnoses, most participants reported that their mental health had worsened during the outbreak, with 55% saying it had worsened a little and 23% saying it had worsened a lot. Around half of all participants reported moderate to extreme loneliness and worry about their financial situation. Between 20.3 and 24.1% of people surveyed had been experiencing severe or extremely severe levels of depression, anxiety and stress over the week preceding their survey, and another 18 to 22% had moderate symptoms.

Newby says: "We wanted to provide a snapshot of the mental health of the general community during the COVID-19 outbreak and look into the impact of the enforcement of social distancing laws, in Australia." She adds, "We don't know what the long-term impacts of the pandemic will be, but these figures certainly show a negative impact on mental health in the short-term."

What The Study Did: The association of neighborhood race/ethnicity and poverty with COVID-19 infections and related deaths in urban U.S. counties are examined in this observational study.

Authors: Samrachana Adhikari, Ph.D., of the New York University Grossman School of Medicine in New York, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.16938)

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While data and news reports show that Black and Hispanic communities are disproportionately affected by the 2019 Coronavirus Disease (COVID-19) pandemic, the role that neighborhood income plays in COVID-19 deaths is less clear. New analyses by a team of researchers at NYU Grossman School of Medicine examine the interplay between race/ethnicity and income on COVID-19 cases and related deaths in 10 major U.S. cities. The researchers found that non-white counties had higher cumulative incidences and deaths compared to predominantly white counties--and this was true for both low-income and high-income communities.

The findings - recently published online in JAMA Network Open - suggest that racial disparities in COVID-19 cases and deaths exist beyond what can be explained by differences in poverty rates. The researchers found that even among communities with higher median income, predominantly non-white communities still bore a greater burden of the virus - almost three times the incidence and deaths - compared to neighborhoods that identified as majority white. Yet income also plays an important contributing role. Indeed, the starkest racial/ethnic contrast between majority non-white and predominantly white counties was found when restricted to low-income counties only, where residents from predominantly non-white communities died from COVID-19 at nine times the rate as those living in predominantly white counties.

"While we expected to see greater numbers of COVID-19 cases and deaths in predominantly non-white, low-income communities, we were surprised that this relationship still held even after we accounted for poverty rates," said Samrachana Adhikari, PhD, assistant professor, Department of Population Health, NYU Grossman School of Medicine, and lead author of the study. "Given our findings, we believe that structural racism may explain these racial disparities in number of cases and deaths noted in Black counties."

How the Study was Conducted

Using publicly available data from the 2018 U.S. Census Small Areas Income and Poverty Estimates program, the Centers for Disease Control, and state health departments, the researchers examined cumulative COVID-19 cases and deaths per 100,000 across 158 urban counties (accounting for 64 percent of confirmed COVID-19 cases) spanning 10 large U.S. cities: New York City, Boston, New Orleans, Detroit, Los Angeles, Atlanta, Miami, Chicago, Philadelphia, and Seattle. Using the census data, the team linked median income and proportion of non-white residents in each county and used statistical analysis to identify differences in cumulative incidents and death, and their association with neighborhood race/ethnicity and poverty levels. All data analyzed included COVID-19 cases and deaths observed through May 10, 2020.

"We have known for decades that racism kills. Racism is a public health issue which has been implicated in the racial gap in mortality and in health outcomes," says Gbenga Ogedegbe, MD, MPH, professor of Population Health and Medicine at NYU Langone and one of the study's co-authors.

"Because the differences in COVID-19 cases and mortality cannot be explained by poverty alone, our findings give credence to our hypothesis that structural racism underlies the disproportionately higher rates of COVID-19 infections and alarmingly high rates of deaths in predominantly Black communities. The fact that non-white residents died from the virus at higher rates than white residents in both wealthier and poorer communities should be a major alarm bell to policymakers at the national and local government levels, academic medical centers, and the country at large," says Ogedegbe.

One of the study's limitations, according to Adhikari, is that it covers only large metropolitan areas and that the data analyzed are aggregated at the county level. More granular data at the individual level, as well as a breakdown of residents by race and ethnicity, would provide greater insight into the drivers of this troubling association, as well as expose most affected neighborhoods in need of more robust public health interventions, says Adhikari.

Following a decade-long effort, scientists have mapped out the genome of an aphid-like pest capable of decimating vineyards. In so doing, they have discovered how it spreads -- and potentially how to stop it.

The research team's work on the genome was published this past week in a BMC Biology paper. In it, they identified nearly 3,000 genes enabling the insect, phylloxera, to colonize and feed on grape vines by creating what are essentially nutritionally enhanced tumors. The insects live in and feed off of the structures they create.

"In effect, phylloxera creates its own refrigerator on the plant that it can feed from whenever it wants," said Paul Nabity, an assistant professor of plant-insect ecology at UC Riverside. In addition to feeding the insects, these structures also protect them from attack by other parasites.

A heavy phylloxera infestation, as occurred in the Pacific Northwest last year, could cause grapevines to lose their leaves. If the infestation reaches the roots, the plants could die.

The tumor-like structures, known as galls, disrupt the vine's ability to move nutrients and feed itself. They also create wounds in roots that make grapevines more susceptible to fungi and other pathogens, ultimately killing the vines.

Claude Rispe from the French National Institute for Agriculture, Food, and Environment led the research team, while Nabity helped identify how phylloxera secrete molecules that can change the immune system of grapevines.

"These molecules alter the plant's defense systems and make it so that the plant doesn't know it's being attacked," Nabity said.

When phylloxera was accidentally introduced to Europe in the 1860s, it nearly brought French viticulture to an end, causing vines to weaken and die. French and American scientists collaborated on a solution that is still used today.

Native North American grapevines co-evolved with phylloxera and are now resistant to it. However, most of the grapes we eat and drink are European varieties. As a result, growers have to graft North American roots onto their European grapevines to give them tolerance to this insect.

Though phylloxera are considered negative, not all of their effects on plants are necessarily bad. When they feed on plants and start creating gall structures, they change the cells in the leaf surface. Protective cells on the leaves become tiny pores called stomata, which allow movement of gases in and out of the cells.

"We think this is a means to reduce the negative impact on its host," Nabity said. "Stomata can create carbon gains for plants that can offset how much the insects are taking from it."

Now that the genes involved in the attack on non-native grapes have been identified, it may be possible to engineer phylloxera-resistant grapevines.

"Growers currently have to graft roots to make their plants viable," Nabity said. "A lot of money and effort could be saved with pest-resistant rootstocks."

In most organisms, small bits of RNA play a key role in gene regulation by silencing gene expression. They do this by targeting and docking onto complementary sequences of gene transcripts (also RNA molecules), which stops the cell machinery from using them to make proteins. This mechanism is called RNA interference (RNAi), and it is critically important in biology.

Remarkably, the RNAi phenomenon is not necessarily confined to single cells; it can also manifest in other tissues and organs far away from the cell of origin. Researchers have been able to observe it mostly in plants, but also in "lower" animals such as the nematode worm C. elegans.

Proteins and DNA ruled out

Still, one key question had so far gone unanswered: which messenger substance traverses cells and tissues? "We were able to rule out proteins 20 years ago, once it was discovered that RNAi can travel in plants," says Olivier Voinnet, Professor of RNA Biology at ETH Zurich. RNAi requires that the messenger docks to a complementary sequence of the gene transcript to be silenced. "Proteins alone don't have this capability. DNA leaving the cell nucleus is also unlikely," Voinnet continues. "The most likely candidate has always been an RNA molecule." What has been unclear until now is which precise type and form of RNA - long, short, single-? or double-?stranded, bound to proteins or not.

Double-?stranded fragments travel far and wide

But now, the ETH researchers are shedding light on this process in a new study. They are the first to demonstrate unequivocally that these distant messengers in plants are short double?stranded RNA molecules. These consist of pairs (or double-?strands) of just 21 to 24 nucleotides (the building blocks of RNA) called small interfering RNAs, or siRNAs for short.  The team's paper was recently published in the journal Nature Plants.

siRNAs usually emerge as large and complex populations from the genomes of viruses that have infected a cell. But a cell's own genes can also serve as blueprints for these molecules. As a result, cells can use RNAi to silence not only invading viruses but also their own genes.

Because RNAi moves, plants have the amazing capacity to modulate gene expression at a distance. This might be particularly important for them to constantly adapt their new growth, enabling what is called "phenotypic plasticity".

To move or not to move

In their new study, the researchers ruled out the possibility that other types of nucleic acids or complexes composed of RNA and proteins move across plant cells. "We can definitively show that double?stranded siRNAs are necessary and sufficient to induce RNAi in distant cells and tissues of plants," Voinnet says.

Not only did the ETH researchers identify the elusive long-?distance messengers, they also show, in their study, how siRNAs move and carry out their function. They found that, as long as an siRNA molecule exists as a free double-?strand, it is mobile because it cannot bind to a matching RNA transcript. To bind, it first has to be "uploaded" to a specific Argonaute (AGO) effector protein. Only once bound to the correct AGO protein can the siRNA silence the target transcript; the process eventually destroys the fragment itself. The model plant used for the study has ten different AGO proteins, several of which recognise matching siRNA fragments with specific signatures; these signatures are not homogeneous among the large cohorts of mobile siRNAs produced from viruses or the plant's own genes.

AGO proteins determine siRNA movement patterns

Different AGO proteins occur in distinct cells and tissues. The ETH researchers found that as part of the uploading process, matching AGO proteins "consume" a fraction of siRNAs in the cell of origin, but the non-?loaded fraction can exit the cell.

Depending on the presence or absence of certain AGO proteins within the cells traversed by the mobile siRNAs, the molecules, again, will be consumed or not. For example, if there are a plethora of AGO proteins on hand, they will trap plenty of siRNAs with various signatures, essentially stopping movement. If a cell contains hardly any AGO, on the other hand, then most siRNAs will leave and travel greater distances. And finally, if a cell contains large quantities of only one specific AGO, then only those siRNAs with the matching signature will be consumed, while the others will move. In other words, siRNAs are selectively filtered and consumed as they make their way through the plant tissue.

Until now, the plant RNAi community had thought that RNAi moves along linear gradients. However, this does not take into account that AGO proteins selectively use up some siRNAs - but not others - as they move. The new study points out that this consumption process is, in fact, anything but linear.

Countless movement patterns

"The amount and diversity of AGO proteins in traversed cells coupled to the siRNA-?intrinsic signatures function together as a kind of molecular sieve, the form of which may differ from cell type to cell type along the siRNA path. Depending on the spatial configuration of this sieve, a wide variety of siRNA movement patterns can be produced," Voinnet explains. He adds: "Even more interestingly, some AGOs can be induced by stress or developmental signals such that the spatial shape of the sieve can change and evolve at any given time".

The countless movement patterns thus lend the mobile RNAi system almost boundless flexibility and versatility in shaping gene expression across distances. Now that they have understood the process, the team of researchers is trying to engineer artificial sieves in plants as a way to control, with high precision, when and where specific siRNAs can move, a method which could have applications in agriculture. 

The huge task of phasing out coal requires a detailed roadmap to sequence coal plant retirement with a range of policy instruments and support for key stakeholders which will expand current notions of a just transition, leading energy experts have said.

Governments should be prepared to pay billions of pounds to operators of coal-fired power plants in agreements to shut down their plants early, a new paper published in Nature Climate Change today recommends.

The paper recommends extensive compensation should also be considered for regional economies hardest hit by the loss of coal producers and energy-intensive industries that will have to absorb higher energy prices in order to ensure a just transition to greener energy production.

To prevent regions such as the coal belt in the United States or dependent communities in Germany and Poland being abandoned after coal, the study recommends governments should foot the bill for extensive improvements to localised transport and communication infrastructure, higher education provision, new business opportunities and the relocation of government services.

And to shield the poor from electricity price rises resulting from replacing coal plants with more costly alternative power generation, governments and regulators should consider Just Transition measures including adjusting electricity tariffs, investing in community benefit funds or subsidizing energy efficiency through weatherization and retrofits programmes targeted at the most in need or vulnerable.

Benjamin K Sovacool, Professor of Energy Policy in the Science Policy Research Unit (SPRU) at the University of Sussex Business School, said: "Paying billions to some of the world's biggest polluters to avert a climate catastrophe they helped to create may sound unpalatable to some environmentalists

"But compensating the biggest losers from coal phase-out, alongside improving equity and accountability processes, will go a long way towards achieving all the other aspects of a just energy transition including legitimacy, desirability, speed of transition and financing.

"Simply put: a just transition requires more than just safeguarding jobs, and involves protecting the resilience of entire communities across both high-carbon as well as low-carbon energy pathways."

In the new paper published today, 13 energy experts led by Michael Jakob and Jan Christoph Steckel from the Mercator Research Institute on Global Commons and Climate Change (MCC) in Berlin outline that while the power sector must stop using coal without carbon capture-and-storage within 30 years, coal combustion currently accounts for 40% of global CO2 emissions from energy and coal use with growing demand in China, India and other Asian countries.

To quicken the rate of coal phase-out to meet the Paris Agreement timelines, the study authors recommend governments remove all coal subsidies immediately to create a level playing field for clean energy sources.

Dr Steckel said: "In my view, the novel twist we give to the debate is that we need to think of "who's losing" beyond a "particular group", "get them paid", and we also propose how this could be financed via a tax on carbon."

And policymakers and legislators should also consider imposing additional carbon costs on coal plants to accelerate phase-out and raise funds in support of affected workers, communities and consumers, the academics recommend.

Dr Jakob, lead author of the study, said: "Coal phase-out can only succeed if it takes into account social objectives and priorities. It is crucial that the modalities of coal phase-out are seen as fair and that the process corresponds to political realities. Policymakers need to understand in more detail who will be affected by a transition away from coal, how these societal groups can be effectively compensated and how powerful vested interests can be counterbalanced."

Coal phase-out is also likely to affect the competitiveness of other industries such as steel, aluminium, chemicals, and other important components of industrial strategy, the study warns.

To counter the risk of carbon leakage through the migration of energy-intensive industries to regions with laxer climate measures, policymakers should consider a range of measures including carbon contracts for difference or mechanisms of technology transfer .

Co-author Professor Frank Jotzo, from the Australian National University's Crawford School of Public Policy and Director of the Centre for Climate Economics and Policy at ANU, said: "What is needed in the transition away from coal is a clear way forward for regional economies and communities, creating prospects for new jobs and business opportunities, while limiting adverse impacts on consumers and energy-intensive industries."

Coronavirus tracing applications for the detection of infection chains are currently being developed and made available across the world. Such contact-tracing apps are a central component of national strategies for relaxing restrictions. However, for these apps to be successful, they must be widely accepted and ac-tively used by a large proportion of the population. An international research team led by the University of Göttingen has investigated how decision-makers can use app designs to achieve mass acceptance. The results of the study have been published in the European Journal of Information Systems.

The study focuses on three particular aspects that also play a prominent role in public debate. How should privacy be respected? What inconveniences are acceptable? And who benefits from using the app? In order to find answers to these questions, the research team designed various coronavirus tracing apps. The ac-ceptance of the various app designs was then examined in an experimental study. The results show that these aspects are weighted differently within the population. For example, while privacy is important for people who are critics of such an application as well as for those who are undecided about it, convenience, which is optimized for example through low battery consumption or by being user-friendly, seems to be particularly important for those who are undecided.

"The key challenge in developing an application for contact-tracing, compared to the other apps we use every day, resides less in the implementation of the core technical functionalities," explains Dr Simon Trang, Assistant Professor for Information Security and Compliance at the University of Göttingen and first author of the study, "the main concern must rather be to present an app that is accepted by the broad, heteroge-neous mass of the population. If this proves unsuccessful, the entire project will fail. Mass acceptance thus becomes the main design requirement for decision-makers in this new class of mobile apps". Co-author Dr Manuel Trenz, Professor for Interorganizational Information Systems at the University of Göttingen, adds: "The decision makers therefore have to ask themselves which specific part of the population still needs to be convinced in order to achieve mass acceptance and make the app a success. And then one should fo-cus on those aspects that we have identified as particularly important for these groups."

It seems crucial to communicate the beneficial outcomes of the app in a certain way. Arguments that focus on the benefits to society convince the critics and undecided (for example: "Protect the population"), while highlighting benefits to the individual (for example: "Protect yourself") can be ineffective or even counter-productive. "Surprisingly, we also find this negative effect when both benefits are communicated together," reports co-author Dr Welf Weiger, Assistant Professor of Digital Marketing at the University of Göttingen and Alfaisal University. The researchers therefore recommend a clearly focused communication strategy that emphasizes the benefits of contact-tracing apps to society - as opposed to what many countries are cur-rently doing.

Professor Monideepa Tarafdar from Lancaster University Management School and one of the authors of the new study said: "More than half of the population must install and actively use the app in order for it to be effective and for lockdown to be lifted safely. In light of the urgency of the situation, and the fact the gov-ernment will roll it out voluntarily, getting a true understanding of how to get the masses to accept - and crucially, use - one single app, is the most important consideration for developers. Our study reveals that one app simply cannot fit all - so the government needs to understand what the majority of us think about the system in order for it to be successful."

"Our results provide an explanation for the failure of existing contact-tracing apps such as those in France and Norway. At the same time, the results provide decision-makers in countries where these apps are still being developed with important insights into key considerations for designing these applications to contrib-ute effectively to the containment of the Covid-19 pandemic and the return to normal life," concludes Trang.

In addition to the medical and economic crisis, the COVID-19 pandemic has also affected many people's subjective well-being. This is the result of a long-term study by psychologists from Leipzig University and Saint Louis University with 979 people from all over Germany. The study examined changes in subjective well-being between December 2019 and May 2020. This study, led by organizational psychologists Hannes Zacher and Cort W. Rudolph, found that between March and May 2020 - in the early stage of the pandemic - average life satisfaction and the experience of positive feelings decreased significantly, on average around 0.2 points each on a seven-point scale. Surprisingly, there was also a slight decrease in the experience of negative feelings such as anger and fear during this phase. The researchers have just published the results of their study in the renowned scientific journal American Psychologist.

In the investigation, subjective well-being was defined and measured as high levels of life satisfaction and the frequent experience of positive feelings such as joy, as well as the rare experience of negative feelings such as anger or fear. The personal assessment of the pandemic, for example as a threat or a challenge, as well as various functional and dysfunctional coping strategies such as problem solving or alcohol consumption were examined as factors influencing subjective well-being during the early stage of the COVID-19 pandemic.

While the scientists found no evidence for changes in subjective well-being when surveying people in the period before the COVID-19 pandemic, between December 2019 and March 2020, this changed significantly in the weeks afterwards due to the crisis. People who rated the pandemic as a challenge and the consequences of the pandemic as controllable generally showed a higher level of subjective well-being. In addition, people reported higher subjective well-being when they actively solved problems, focused on the positive aspects of the crisis and received social support. On the other hand, those who perceived the crisis as a threat, denied it, or blamed themselves for the consequences of the crisis felt less well. The same was true for people who tried to cope with the crisis with alcohol or drugs.

"Psychologists can take advantage of the results by helping to improve their clients' general skills in making constructive assessments in times of crisis and using successful coping strategies," says Zacher. The Volkswagen Foundation is funding the continuation of the long-term study over the next 18 months with €50,000. The study will examine how the COVID-19 pandemic affects changes in the world of work, such as acceptance of the home office, virtual teamwork, and job insecurity, as well as the development of physical and mental health.

For eradication of HIV-1 infection, it is important to elucidate the detailed features and heterogeneity of HIV-1-infected cells in vivo. In this study, a hematopoietic stem cell-transplanted humanized mouse model infected with a gene-modified HIV-1 was used to reveal multiple characteristics of HIV-1-producing cells in vivo.

A research group at The Institute of Medical Science, The University of Tokyo (IMSUT) using HIV-1-infected cells performed "multiomics" analyses, which are technologies recently developed to comprehensively investigate the features of biological samples.

"Our findings describe multiple characteristics of HIV-1-producing cells in vivo, which could provide clues for the development of an HIV-1 cure.", said the lead scientist, Kei Sato, Associate Professor (Principal Investigator) in the Division of Systems Virology, Department of Infectious Disease Control, IMSUT.

The results of this research were published in Cell Reports on July 14, 2020.

Study for "HIV-1 cure"

For eradication of HIV-1 infection, it is important to gain an in-depth understanding of the wide-ranging characteristics of HIV-1-infected cells in vivo.

Recently developed 'omics' analyses (*1) can be a powerful tool to identify the characteristics of HIV-1-infected cells. However, it should be noted that a large majority of the CD4+ T cells(*2) in infected individuals are uninfected, and therefore, the transcriptional profiles of "bulk" CD4+ T cells in vivo do not reflect those of "pure" HIV-1-producing cells.

Multiomics analysis to comprehensively reveal the features of HIV-1-infected cells in vivo

In this study, the research group used a human hematopoietic stem cell-transplanted humanized mouse model that maintains human leukopoiesis under relatively stable immunological conditions in vivo and a replication-competent reporter HIV-1, and used four recently developed techniques to investigate viral genomics and transcriptomics.

According to the research group, this study consisted of the four following analyses:

First, droplet digital PCR revealed the presence of potential reservoirs in infected humanized mice. Second, ligation mediated PCR showed the preference of HIV-1 to integrate into open chromatin regions, as suggested by the association of the epigenetic modifications of integration sites with viral production. Third, digital RNA-sequencing quantified the absolute copy number of viral transcripts in the HIV-1-producing cells in vivo and further identified the differentially expressed genes between virus-infected and uninfected cells. Finally, single-cell RNA-sequencing revealed and characterized the heterogeneity of the HIV-1-producing cells in vivo.

Associate Professor Sato emphasized "To our knowledge, this study is the first investigation to describe multiple aspects of HIV-1-producing cells and also the first comprehensive investigation of the characteristics of HIV-1-infected cells in vivo" .

A protein produced by the human immune system can strongly inhibit corona viruses, including Sars-Cov-2, the pathogen causing Covid-19. An international team from Germany, Switzerland and the USA successfully showed that the LY6E-Protein prevents coronaviruses from causing an infection. "This finding might lead to the development of new therapeutic approaches against coronaviruses," says Professor Stephanie Pfänder from the Department for Molecular and Medical Virology at Ruhr-Universität Bochum (RUB), lead author of the study published by the team in the journal Nature Microbiology on 23 July 2020.

Strengthening influenza viruses, impairing corona viruses

The LY6E protein plays a role in various diseases: US researchers Professor John Schoggins and Professor Charles Rice discovered that the protein enhances the infectivity of influenza viruses. In contrast, coronaviruses are inhibited by LY6E.

Funded by a Marie Curie Individual Fellowship of the European Union, Stephanie Pfänder, who was then working at the Institute of Virology and Immunology in Switzerland, visited Charles Rice's lab at Rockefeller University in New York in 2017, in order to identify genes that prevent coronavirus infections. "This led to the discovery that LY6E has the opposite effect on coronaviruses compared to influenza viruses," explains the researcher. Further investigations showed that the protein exerted this inhibitory effect on all analysed coronaviruses, including the pathogens causing Sars and Mers as well as Sars-Cov-2 which causes Covid-19.

Viruses unable to fuse

Tests with different cell cultures showed that LY6E affects the ability of the virus to fuse with the host cells. "If the virus is unable to fuse with these cells, it can't cause infection," explains corresponding author Professor Volker Thiel from the University of Bern.

The validation in an animal model succeeded thanks to a collaboration with the laboratory of John Schoggins at the Southwestern Medical Center of the University of Texas. The experiments conducted there led to the discovery that the mouse variant of the protein called Ly6e is crucial for the protection of immune cells against infections. In the absence of Ly6e, immune cells such as dendritic cells and B-cells become more susceptible to infection and their numbers decrease dramatically. Mice lacking Ly6e in immune cells are highly susceptible to a normally non-lethal mouse coronavirus and succumb to infection.

Understanding basic concepts

The researchers point out that the mouse coronavirus used in the experiment differs significantly from the pathogen causing the current Covid-19 outbreak - for example, it causes hepatisis rather than respiratory disease. Nevertheless, it is widely accepted as a model for understanding the basic concepts of coronavirus replication and immune responses in a living animal.

"Our study provides new insights into how important these antiviral genes are for the control of viral infection and for an adequate immune response against the virus," say the authors. "Since LY6E is a naturally occurring human protein, we hope that this knowledge will aid the development of therapies that may one day be used to treat coronavirus infections." A therapeutic approach that mimics the mechanism of action of LY6E may provide a first line of defence against novel coronavirus infections.

UNIVERSITY PARK, Pa. -- By reconstructing the evolutionary history of SARS-CoV-2, the virus that is responsible for the COVID-19 pandemic, an international research team of Chinese, European and U.S. scientists has discovered that the lineage that gave rise to the virus has been circulating in bats for decades and likely includes other viruses with the ability to infect humans. The findings have implications for the prevention of future pandemics stemming from this lineage.

"Coronaviruses have genetic material that is highly recombinant, meaning different regions of the virus's genome can be derived from multiple sources," said Maciej Boni, associate professor of biology, Penn State. "This has made it difficult to reconstruct SARS-CoV-2's origins. You have to identify all the regions that have been recombining and trace their histories. To do that, we put together a diverse team with expertise in recombination, phylogenetic dating, virus sampling, and molecular and viral evolution."

The team used three different bioinformatic approaches to identify and remove the recombinant regions within the SARS-CoV-2 genome. Next, they reconstructed phylogenetic histories for the non-recombinant regions and compared them to each other to see which specific viruses have been involved in recombination events in the past. They were able to reconstruct the evolutionary relationships between SARS-CoV-2 and its closest known bat and pangolin viruses. Their findings appear today (July 28) in Nature Microbiology.

The researchers found that the lineage of viruses to which SARS-CoV-2 belongs diverged from other bat viruses about 40-70 years ago. Importantly, although SARS-CoV-2 is genetically similar (about 96%) to the RaTG13 coronavirus, which was sampled from a Rhinolophus affinis horseshoe bat in 2013 in Yunnan province, China, the team found that it diverged from RaTG13 a relatively long time ago, in 1969.

"The ability to estimate divergence times after disentangling recombination histories, which is something we developed in this collaboration, may lead to insights into the origins of many different viral pathogens," said Philippe Lemey, principal investigator in the Department of Evolutionary and Computational Virology, KE Leuven.

The team found that one of the older traits that SARS-CoV-2 shares with its relatives is the receptor-binding domain (RBD) located on the Spike protein, which enables the virus to recognize and bind to receptors on the surfaces of human cells.

"This means that other viruses that are capable of infecting humans are circulating in horseshoe bats in China," said David L. Robertson, professor of computational virology, MRC-University of Glasgow Centre for Virus Research.

Will these viruses be capable of jumping directly from bats into humans or will an intermediate species be required to make the leap? According to Robertson, for SARS-CoV-2, other research groups incorrectly proposed that key evolutionary changes occurred in pangolins.

"SARS-CoV-2's RBD sequence has so far only been found in a few pangolin viruses," said Robertson. "Furthermore, the other key feature thought to be instrumental to SARS-CoV-2's ability to infect humans -- a polybasic cleavage site insertion in the Spike protein -- has not yet been seen in another close bat relative of the SARS-CoV-2 virus. Yet, while it is possible that pangolins may have acted as an intermediate host facilitating transmission of SARS-CoV-2 to humans, no evidence exists to suggest that pangolin infection is a requirement for bat viruses to cross into humans. Instead, our research suggests that SARS-CoV-2 likely evolved the ability to replicate in the upper respiratory tract of both humans and pangolins."

The team concluded that preventing future pandemics will require better sampling within wild bats and the implementation of human disease surveillance systems that are able to identify novel pathogens in humans and respond in real time.

"The key to successful surveillance," said Robertson, "is knowing which viruses to look for and prioritizing those that can readily infect humans. We should have been better prepared for a second SARS virus."

Boni added, "We were too late in responding to the initial SARS-CoV-2 outbreak, but this will not be our last coronavirus pandemic. A much more comprehensive and real-time surveillance system needs to be put in place to catch viruses like this when case numbers are still in the double digits."

While there is little doubt that COVID-19 will have lasting impacts on health and the economy, a group of researchers is bringing attention to the effects the pandemic could have on the careers of scientific researchers. Carnegie Mellon University and Max Planck Institute physicist Ulrike Endesfelder, University of Stuttgart's Dirk Pflüger and Technische Universität Braunschweig's Timo de Wolff launched a Twitter campaign #StopPandemicBias, which aims to bring broader understanding to how COVID-19 will impact scientists. Using the hashtag, they hope to crowdsource ideas that will mitigate the impact of the pandemic on research careers.

They also published their concerns in a letter in the July 30 issue of Nature.

"Being unaffected by COVID-19 is a new privilege. The disadvantaged are among both the applicants for positions, grants and publications and their selecting peers, and their voices currently are not heard in our community. Pandemic bias will hinder or even stop the careers of many in our community and prevent access to many trying to enter scientific research," said Endesfelder. Endesfelder has personally felt these challenges. She was set to move her laboratory to Carnegie Mellon in the spring of 2020 but remains in Germany due to travel restrictions.

Citing the highly collaborative and participatory nature of science, the group believes that researchers who are most greatly impacted by COVID-1¬9 -- those who are overwhelmed with care-giving responsibilities, those who are unable to do research outside of the laboratory setting, those who are unable to travel and those who are sick themselves -- will be held back from advancing in their careers. For example, a single parent who must home school their children might not have time to submit grants or review articles, or a recent graduate might not be able to travel to interview for a job. These limitations imposed by the pandemic could create barriers that do not exist for those who are not largely affected by the pandemic.

"For the disadvantaged, the obstacles are immense: you cannot compromise on safety when belonging to a risk group; find your next position amidst hiring freezes and budget cuts; pursue international careers when restrictions prevent travel; say no to dependents who need your care; or stay productive when suffering from COVID-19," said Endesfelder.

"We are concerned that scientists who cannot devote time to grant applications or aren't able to access their labs to produce the data they need for career-advancing publications or can't get a visa to report to their new job will face severe setbacks in the advancement of their careers. And if these barriers are too much to surmount, we may lose a significant number of future scientists to other industries. We also are concerned that there will be fewer diverse voices in science. With less people reviewing grants and papers, we will lose diverse opinions that are necessary for moving science forward," Pflüger said.

The researchers suggest a number of actions the scientific community can take to help prevent this bias. This includes supporting scholars who are unable to travel for opportunities, reviewing more articles and grants and taking over teaching responsibilities for affected colleagues. They also urge institutions and funders to reconsider upcoming deadlines and criteria to create more leniency to those impacted by COVID-19.

"All of us need to contribute, and all of us have something at stake. Now is the time to act. There is no silver bullet, but we all have numerous points of direct influence. We feel that there are opportunities for significant change and we need to start the conversation now," de Wolff said.

They urge members of the scientific community to join the conversation on Twitter using #StopPandemicBias, where people can submit and discuss ways to help.

An extensive international study led by Prof. Illana Gozes of Tel Aviv University's Department of Human Molecular Genetics and Biochemistry found deposits of the tau protein typically found in Alzheimer's patients in tissues taken from the postmortem brain of a 7-year-old autistic child.

The child suffered from the ADNP syndrome, a mutation that causes a deficiency/malfunctioning of the ADNP protein essential for brain development. In light of these findings, the researchers tested an experimental drug called NAP, originally developed for Alzheimer's disease, on nerve cells in a model of ADNP syndrome with the mutation that induced Alzheimer's-like symptoms. The experiment was a success, with the damaged nerve-like cells returning to normal function.

The study was conducted in close collaboration with researchers from TAU's Blavatnik School of Computer Science, Sheba Medical Center, and a variety of research institutions across Europe, including the biotechnology institute BIOCEV in the Czech Republic, the Aristotle University of Thessaloniki in Greece, the University of Antwerp in Belgium, and the University Hospital Centre in Zagreb, Croatia. The study was published on July 13 in the journal Translational Psychiatry.

Prof. Gozes explains that the current study is based on tissues taken from the brain of a 7-year-old boy with ADNP syndrome who died in Croatia. "When we compared the postmortem ADNP syndrome brain tissues to tissue from the brain of a young person without ADNP syndrome, we found deposits of the tau protein in the ADNP child, a pathology that characterizes Alzheimer's disease," Prof. Gozes says.

The researchers then "treated" damaged nerve-like cells carrying an ADNP mutation similar to the deceased child's mutation with a drug candidate called NAP. NAP was developed in Prof. Gozes's laboratory and was originally intended to be used to help treat Alzheimer's disease. "NAP is actually a short active fragment of the normal ADNP protein," says Prof. Gozes. "When we added NAP to the nerve cells carrying an ADNP mutation, the tau protein bound to the nerve cell skeleton properly, and the cells returned to normal function.

"The fact that NAP treatment has been successful in restoring the normal function of neuronal-like cell models with impaired ADNP raises hopes that it may be used as a remedy for ADNP syndrome and its severe implications, including autism," Prof. Gozes continues. "Moreover, because other genetic disorders related to autism are characterized by tau pathologies in the brain, we hope that those suffering from these syndromes will also be able to benefit from NAP treatment in the future."

NAP (also called CP201) has been classified as an "orphan drug" by the US Food and Drug Administration and is currently in the preparatory stages of a clinical trial in children with ADNP syndrome through the company Coronis Neurosciences.

In another phase of the study, the researchers sought to broaden their understanding of the effects of the mutation that causes ADNP syndrome. To do this, they extracted the genetic material mRNA (messenger RNA) from the tissues of the deceased child and performed an expression analysis of about 40 proteins in the same child, encoded by the mRNA. Full genetic sequencing was also performed to determine protein expression in white blood cells taken from three other children with ADNP syndrome.

An in-depth study was carried out on all of the data obtained in the genetic sequencing using advanced bioinformatics computational tools. The data were compared to online databases of protein expression data from healthy individuals, revealing a variety of characteristics that were common to the children with the syndrome but very different from the normal appearance of these proteins.

Prof. Gozes concludes that "the significance of these findings is that the mutation that causes ADNP syndrome damages a wide range of essential proteins, some of which bind to the tau protein, among other things, and impair its function as well. This creates various pathological effects in the brains and other tissues of children with ADNP syndrome, one of which is the formation of tau deposits, known to be a characteristic of Alzheimer's disease.

"The vast and in-depth knowledge we have accumulated through the present study opens the door to further extensive and diverse research. We hope and believe that we will ultimately reach the goal of developing a drug or drugs that will help children with autism resulting from genetic mutations."

American Friends of Tel Aviv University supports Israel's most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. TAU is ranked ninth in the world, and first in Israel, for producing start-up founders of billion-dollar companies, an achievement that surpassed several Ivy League universities. To date, 2,500 US patents have been filed by Tel Aviv University researchers -- ranking TAU #1 in Israel, #10 outside of the US and #66 in the world.

Journal

Translational Psychiatry

DOI

10.1038/s41398-020-00904-4