Culture

A new article by Columbia Mailman School researchers Jeffrey Shaman and Marta Galanti explores the potential for the COVID-19 virus to become endemic, a regular feature producing recurring outbreaks in humans. They identify crucial contributing factors, including the risk for reinfection, vaccine availability and efficacy, as well as potential seasonality and interactions with other viral infections that may modulate the transmission of the virus. The article appears in the journal Science.

Shaman is a professor of environmental health sciences and director of the Columbia Mailman School Climate and Health program and a leading authority in modeling infectious disease outbreaks like SARS-CoV-2 and influenza. He was among the first to recognize the importance of asymptomatic spread and the effectiveness of lockdown measures and published highly cited estimations of the hypothetic lives saved had lockdown occurred sooner. He and Galanti, a post-doctoral research scientist in Shaman's research group, also published research finding reinfections with endemic coronaviruses are not uncommon, even within a year of prior infection.

The new paper explores one potential scenario in which immunity to SARS-CoV-2, either through infection or a vaccine, diminishes within a year--a rate similar to that seen for the endemic betacoronavirus that causes mild respiratory illness. The result would be yearly outbreaks of COVID-19. On the other hand, if immunity to SARS-CoV-2 was longer, perhaps through protection provided by immune response to infection with other endemic coronaviruses, we might experience what would initially appear to be an elimination of COVID-19 followed by a resurgence after a few years. Other contributing factors include the availability and effectiveness of a vaccine and the innate seasonality of the virus.

"Should reinfection prove commonplace, and barring a highly effective vaccine delivered to most of the world's population, SARS-CoV-2 will likely settle into a pattern of endemicity," the authors write. "Whether reinfections will be commonplace, how often they will occur, how contagious re-infected individuals will be, and whether the risk of severe clinical outcomes changes with subsequent infection remain to be understood."

Reinfection

Among those who have been infected with COVID-19, serological studies indicate that most infections, regardless of severity, induce development of some SARS-CoV-2-specific antibodies. Yet it remains unclear whether those antibodies are themselves sufficient to provide long-term "sterilizing immunity" to prevent reinfection. For many viruses, insufficient immune response, waning immunity, or mutations that allow it to "escape" immune detection can undermine or circumvent immunity and allow subsequent reinfection, although a prior infection may provide partial immunity and reduce symptom severity.

Co-Infection

Immune response to SARS-CoV-2 may be affected by whether or not someone is currently or was recently infected with another virus. Many studies prior to the pandemic show that infection with one virus can provide short-term protection--about a week--against a second infection. Other studies confirm that simultaneous respiratory virus infections are not associated with increased disease severity. While some SARS-CoV-2 coinfections have been documented, including co-infections with influenza and respiratory syncytial virus, there is insufficient data to draw conclusions. At the population level, a significant seasonal influenza outbreak could strain hospitals already dealing with COVID-19.

Seasonality

Evidence suggests COVID-19 could be more transmissible during winter. Outside the tropics, many common respiratory viruses reemerge seasonally during particular times of the year. The endemic coronaviruses (OC43, HKU1, NL63, 229E) all exhibit seasonality in temperate regions similar to influenza. Similarly, environmental conditions may also modulate SARS-CoV-2 transmissibility--not enough to preclude transmission during the early stages of the pandemic when immunity is generally low but perhaps sufficient to favor recurring seasonal transmission during winter in temperate regions, similar to influenza, once immunity increases.

SAN FRANCISCO, Calif. -- OCTOBER 15, 2020 - In a study published online in Science today, an international team of almost 200 researchers from 14 leading institutions in six countries studied the three lethal coronaviruses SARS-CoV-2, SARS-CoV-1 and MERS-CoV in order to identify commonly hijacked cellular pathways and detect promising targets for broad coronavirus inhibition. In addition, using the molecular insights gained from this multidisciplinary, systematic study of coronaviruses, the group performed an analysis of medical records of approximately 740,000 patients with SARS-CoV-2 that altered clinical outcomes in these patients to uncover approved therapeutics with potential for rapid deployment. These results demonstrate how molecular information can be translated into real-world implications for the treatment of COVID-19, an approach that can ultimately be applied to other diseases in the future.

"This far-reaching international study elucidates for the first time commonalities and, importantly, vulnerabilities, across coronaviruses, including our current challenge with the SARS-CoV-2 pandemic," said Nevan Krogan, Ph.D., director of the Quantitative Biosciences Institute (QBI) at the School of Pharmacy at UC San Francisco, senior investigator at Gladstone Institutes, and lead investigator of the study. "In unique and rapid fashion, we were able to bridge biological and functional insights with clinical outcomes, providing an exemplary model of a differentiated way to conduct research into any disease, rapidly identify promising treatments and advancing knowledge in the fields of both science and medicine. This body of work was only made possible through the collaborative efforts of senior scientific thought leaders and teams of next-generation researchers at premier institutions across the globe."

In this collaboration, academic and private sector scientists from UCSF, QBI's Coronavirus Research Group (QCRG), Gladstone Institutes, EMBL's European Bioinformatics Institute (EMBL-EBI) in Cambridge, England, Georgia State University, Icahn School of Medicine at Mount Sinai in New York, Institut Pasteur in Paris, Cluster of Excellence CIBSS at the University of Freiburg in Germany, University of Sheffield in the UK, and other institutions as well as the companies Aetion, who makes software for analysis of real-world data and genome engineering company Synthego, participated in the research.

Scientific Revelations from a Cross-Coronavirus Study of Protein Function

Building on their previous work published in both Nature and Cell, the researchers studied SARS-CoV-2, SARS-CoV-1 and MERS-CoV comprehensively, using biochemical, proteomic, genetic, structural, bioinformatic, virological and imaging approaches to identify conserved target proteins and cellular processes across coronaviruses. Leveraging the SARS-CoV-2 map of how the SARS-CoV-2 viral proteins interact with their target human host cell proteins, called an "interactome," the team built the protein-protein interaction maps for SARS-CoV-1 and MERS-CoV, highlighting several key cellular processes that are shared across all three coronaviruses. These common pathways and protein targets represent high-priority targets for therapeutic interventions for this and future pandemics.

"Working diligently since the early days of SARS-CoV-2 identification, we came together with the individual strengths of each organization to interrogate the biology and functional activities of these viruses, looking to exploit weaknesses," commented Veronica Rezelj, Ph.D., of Institut Pasteur. "In our latest study, we augmented our knowledge base by driving down into two additional coronaviruses, elucidating mechanisms across viruses that allow potential therapeutic interventions."

Structural Understanding of a Unique Interaction between viral Orf9b and Human Protein Tom70, Which Normally Supports Antiviral Immune Response

Interestingly, the team found that the mitochondrial outer membrane protein Tom70 interacts with both SARS-CoV-1 and SARS-CoV-2 protein Orf9b. Tom70 is normally involved in the activation of mitochondrial antiviral-signaling protein (MAVS) and is essential for an antiviral innate immune response. Orf9b, by binding to the substrate recognition site of Tom70, inhibits Tom70's interaction with heat shock protein 90 (Hsp90), which is key for its function in the interferon pathway and induction of apoptosis upon virus infection.

In a collaboration among more than 60 scientists in the QCRG led by Klim Verba and Oren Rosenberg at QBI, the structure of Orf9b bound to the active site of Tom70 was determined by cryoelectron microscopy (cryoEM) to a remarkable three-angstrom resolution. A noteworthy and rare finding showed that Orf9b, when by itself, forms a dimer and structurally a beta sheet, but exists as an alpha helix when bound to Tom70. Using the structural image of the bound proteins, the scientists were able to discover that a key residue in the interaction with Hsp90 is moved out of position, suggesting that Orf9b may modulate key aspects of the immune response, interferon and apoptosis signaling via Tom70. The functional significance and regulation of the Orf9b-Tom70 interaction require further experimental elucidation. This interaction, however, which is conserved between SARS-CoV-1 and SARS-CoV-2, could have value as a pan-coronavirus therapeutic target.

Pathway Targets for Potential Clinically-Approved Therapeutics

Using the three coronavirus interactomes as a guide, the team performed CRISPR and RNA interference (RNAi) knockouts of the putative host proteins of each virus and studied how loss of these proteins altered the ability of SARS-CoV-2 to infect human cells. They determined that 73 of the proteins studied were important for the replication of the virus and used this list to prioritize evaluation of drug candidates. Among these were the receptor for the inflammatory signaling molecule IL-17, which has been identified in numerous studies as an important indicator of disease severity; prostaglandin E synthase 2 (encoded by PTGES2), which functionally interacts with the Nsp7 protein in all three viruses; and sigma receptor 1, an interactor of Nsp6 from SARS-CoV-1 and SARS-CoV-2, which the group previously showed was a promising drug target in the laboratory setting.

Armed with this knowledge, the group performed a retrospective analysis of medical billing data from approximately 740,000 people who tested positive for SARS-CoV-2 or were presumptively positive.

In the outpatient setting, SARS-CoV-2-positive, new users of indomethacin, a non-steroidal anti-inflammatory drug (NSAID) that targets PGES-2, were less likely than matched new users of celecoxib, an NSAID that does not target PGES-2, to require hospitalization or inpatient services.

In the inpatient setting, again leveraging the medical billing data, the group compared the effectiveness of typical antipsychotics, namely haloperidol, which have activity against sigma receptor 1, versus atypical antipsychotics, which do not. Half as many new users of typical antipsychotics compared to new users of atypical antipsychotics progressed to the point of requiring mechanical ventilation. Typical antipsychotics can have significant adverse effects, but other sigma receptor 1-targeting drugs exist and more still are in development.

"It is critical to note that the number of patients taking each of these compounds represent small, non-interventional studies," commented Dr. Krogan. "They are nonetheless powerful examples of how molecular insight can rapidly generate clinical hypotheses and help prioritize candidates for prospective clinical trials or future drug development. A careful analysis of the relative benefits and risks of these therapeutics should be undertaken before considering prospective studies or interventions."

"These analyses demonstrate how biological and molecular information are translated into real-world implications for the treatment of COVID-19 and other viral diseases," said Pedro Beltrao, Ph.D., group leader at EMBL's European Bioinformatics Institute. "After more than a century of relatively harmless coronaviruses, in the last 20 years we have had three coronaviruses which have been deadly. By looking across the species, we have the capability to predict pan-coronavirus therapeutics that may be effective in treating the current pandemic, which we believe will also offer therapeutic promise for a future coronavirus as well."

ATLANTA--There are common vulnerabilities among three lethal coronaviruses, SARS-CoV-2, SARS-CoV-1 and MERS-CoV, such as frequently hijacked cellular pathways, that could lead to promising targets for broad coronavirus inhibition, according to a study by an international research team that includes scientists from the Institute for Biomedical Sciences at Georgia State University.

In the last 20 years, the world has faced three deadly coronaviruses: SARS-CoV-2, SARS-CoV-1 and MERS-CoV. SARS-CoV-2, the virus that causes COVID-19, has triggered a global pandemic that has already resulted in more than 37 million confirmed cases and more than one million deaths.

The study's findings, published in the journal Science, identify commonalities among coronaviruses and highlight several shared cellular processes and protein targets that should be considered as targets for therapeutic interventions for current and future pandemics.

The results were achieved by a collaboration among nearly 200 researchers from more than 14 leading institutions in six countries. Dr. Christopher Basler, professor and director of the Center for Microbial Pathogenesis in the Institute for Biomedical Sciences, led efforts at Georgia State.

Prior studies have identified more than 300 host cell proteins that can interact with SARS-CoV-2 proteins. In this study, the Basler laboratory screened each of these for their capacity to change how well the virus grows.

"The efforts identified at least 20 host genes whose protein products significantly alter how much virus is produced by infected cells," said Basler, a Georgia Research Alliance Eminent Scholar in Microbial Pathogenesis. "Those proteins represent potential targets for therapeutic intervention. For example, if a cellular protein is required for efficient virus growth, a drug that inhibits the cellular protein should slow the infection."

The multidisciplinary, global study also analyzed the medical records of about 740,000 patients with SARS-CoV-2 to identify approved therapeutics with potential for rapid deployment to treat COVID-19.

NEW YORK, October 15, 2020 -- Aetion co-authored a study published today in Science, which examined lethal coronaviruses SARS-CoV-2, SARS-CoV-1, and MERS-CoV to identify molecular characteristics of potential treatments. The study, which was led by the Quantitative Biosciences Institute at UCSF and involved nearly 200 researchers from leading institutions, applied a novel approach to evaluate molecular hypotheses by analyzing real-world data from COVID-19 patients.

Aetion researchers ran analyses on Real-Time Insights and Evidence, an instance of the Aetion Evidence Platform® with real-time health care data designed to generate evidence on prospective treatments for COVID-19.

Jeremy Rassen, Sc.D., Aetion co-founder, president, and chief science officer and one of the study's authors, made the following statement:

"These results demonstrate the value of using real-world data on COVID-19 to evaluate molecular hypotheses generated in the lab, and represent a new pathway for the use of real-world evidence to support the drug development process. While these findings are based on limited use of these medications in patients with COVID-19, we can further validate the findings with real-world or randomized evidence.

"The reach and severity of COVID-19 has created extreme urgency as researchers work to identify potential therapies and vaccines. Using near real-time healthcare data, we were able to efficiently and rigorously screen prospective interventions for COVID-19, accelerating time to insights from months to a matter of weeks. As COVID-19 treatment candidates emerge, real-world evidence -- properly generated -- has an important role in complementing clinical trials with real-world insights on usage, safety, and effectiveness across the drug lifecycle."

The team of global researchers started with lab-driven hypotheses that suggested certain medications -- those that block the coronavirus's interaction with the enzyme PGES-2 or sigma receptor 1 -- may inhibit viral replication in vivo. To evaluate whether these molecular actions reduced the severity of COVID-19 in clinical settings, Aetion identified nearly 740,000 U.S. COVID-19 patients who shortly after diagnosis began treatment with one of the potential therapies. Aetion researchers assessed whether COVID-19 severity was decreased in these patients as compared to those treated with medications without the hypothesized antiviral properties.

Aetion's analyses showed:

COVID-19-positive new users of indomethacin, a marketed non-steroidal anti-inflammatory drug (NSAID) that inhibits the enzyme PGES-2, appeared substantially less likely to require hospitalization or inpatient services than matched new users of celecoxib, an NSAID that does not target PGES-2; and,

Hospitalized COVID-19-positive new users of typical antipsychotics that have activity against the sigma receptor 1 protein (such as haloperidol, chlorpromazine) were over 50% less likely to require mechanical ventilation as compared to matched new users of atypical antipsychotics (such as quetiapine, olanzapine).

Seeking to inform development of drugs effective against multiple pathogenic human coronaviruses, David E. Gordon and colleagues compared host interactions of MERS-CoV, SARS-CoV-1 and SARS-CoV-2, uncovering host pathways commonly hijacked by all three. Studying patient data showed how COVID-19 patients treated with drugs that acted against selected coronavirus host factors fared, with results that will help guide COVID-19 drug targets, the authors say. SARS-CoV-2, which causes COVID-19, is closely related to the deadly coronaviruses SARS-CoV-1 and MERS-CoV. Significant efforts are focused on developing treatments for COVID-19 but given that other highly virulent human coronavirus strains have emerged and may do so again, therapies that work across coronaviruses would also be valuable. While traditional antivirals target viral enzymes that are often subject to mutation, and thus to the development of drug resistance, targeting the host proteins required for viral replication is a strategy that can avoid resistance and lead to therapeutics with broad-spectrum activity. Focused on this approach, Gordon et al. mapped the interactions between viral and human proteins for SARS-CoV-2, SARS-CoV-1 and MERS-CoV. After expressing viral proteins in human cells, they used mass spectrometry to identify human host proteins that physically associated with each viral protein, looking for conserved interactions across all three viruses. They then used genetic screening to identify host factors that either enhanced or inhibited viral infection. To connect their in vitro molecular data to clinical information for COVID-19 patients, the authors evaluated medical billing data on nearly 740,000 patients in the United States with documented SARS-CoV-2 infection. In this cohort, they studied the use of drugs against selected targets identified in their study, asking whether patients who received them fared better than controls treated with clinically similar drugs that do not act on coronavirus host factors. Patients that received drugs focused against certain selected targets fared better in some cases, the authors report. "Replication in other patient cohorts and further work will be needed to see if there is therapeutic value in these connections," say Gordon et al., "but at the very least we have demonstrated a strategy wherein protein network analyses can be used to make testable predictions from real-world, clinical information."

By exposing larval zebrafish to a well-known optical illusion, researchers at the Max Planck Institute of Neurobiology and National Institute of Genetics in Japan have found a clever way to isolate key clusters of neurons critical to processing the direction of motion in the zebrafish's environment.

Details were published in the journal Neuron in September 2020.

Understanding how animal brains are structured and process information is an active area of research that aims to glean insights into fundamental aspects of biological computation. While human brains are seemingly the most impressive animal brain we know of, they are also extremely complex systems containing about as many neurons as there are stars in the Milky Way galaxy, with trillions of connections among them. This complexity makes studying them extremely difficult. Therefore, it is common to study smaller animal brains with much fewer neurons and interconnections, allowing researchers to probe and experiment with simpler- and easier-to-understand brain dynamics.

While smaller animals, such as the larval zebrafish, have simpler and less complex brains, the number of neurons and interconnections is still very large and thus requires researchers to devise experiments that stimulate only small portions of the brain. One way to do this is to stimulate only certain senses, such as sight or taste. This results in specific brain activity, or neural response, to specific inputs.

The research team relied on visual stimuli to study the key neurons necessary for motion processing in the larval zebrafish. By using a well-known optical illusion, the team was able to induce a motion aftereffect (MAE) response in the fish. MAE is found in most animals and arises through viewing a continuous motion in one particular direction, such as a river flowing from the right to left for an extended period of time. If the river is then shut off and the scene becomes still, the animals now sense motion in the reverse direction, from left to right, for a certain period of time following the removal of the flowing river. This indicates the optical illusion that stationary objects in the scene seem to flow in the reverse direction to the motion seen previously.

The team used MAE in the hopes that the perceived motion from the optical illusion would correspond to a smaller set of neural activity that isolates the truly necessary neurons required for motion processing.

Associate Professor Fumi Kubo, a corresponding author of the study, detailed the effectiveness of using MAE to stimulate brain activity in the zebrafish,

"By examining how these numerous neurons respond to an optical illusion, we found that only a dozen or so neurons are required for motion perception in zebrafish larvae."

Kubo and the team hope to identify how the observed activity fits in with the entire motion processing circuit and study its (inter)connections with the rest of the brain.

"The next step is to find out how these newly discovered neurons are wired within the neural circuit to exert their effect as an important node for motion processing," she said. "Are these neurons connected with visual input? What are their output targets? In a broader perspective, use of other types of optical illusions may identify new circuit elements in the visual processing."

The findings come from a cross-sectional study, published in BMJ Open, of the comments submitted to the US Food and Drug Administration (FDA) 'Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD)--Discussion Paper and Request for Feedback'.

Artificial intelligence (AI) and machine learning (ML) technologies have the potential to transform health care, continually incorporating insights from the vast amount of data generated every day during the delivery of health care. Many such devices must have regulatory approval or clearance before being available for clinical practice, and in the US that regulation falls to the FDA.

The suitability of traditional medical device regulatory pathways for AI/ML have been called into question because the nature of the technology means it is continually evolving and adapting to improve performance. Under the current framework it would mean that as devices evolved they would require further review and approval, which could be time consuming and may affect patient safety and interests. The FDA has therefore proposed a new regulatory framework for modifications to AI/ML and has asked for feedback from the public to refine the regulations.

"The process for developing regulations is, roughly, to get feedback from the public on its initial proposal, make changes and draft regulations or guidance, get more feedback, and eventually finalise," said James Smith, Postdoctoral Scientist at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford and lead author of the report. "Anyone can comment but at present there is no requirement, or even recommendation, to disclose any conflicts of interest. Also, the FDA states that it looks for 'good science' in comments but it is not a requirement to incorporate it. Our goal was to look at the extent and disclosure of financial ties to industry and the use of scientific evidence."

The team analysed all 125 publicly available comments on the FDA proposal between 2 April 2019 to 8 August 2019 and found that 79 (63%) comments came from parties with financial ties to industry in the sector. For a further 29% of comments the presence or absence of financial ties could not be confirmed. The vast majority of submitted comments (86%) did not cite any scientific literature, with only 4% citing a systematic review or meta-analysis.

James said: "What concerns us about these findings is that we don't have a good idea of the impact of these ties and whether they might lead to bias in this specific context. Whether these observations about prevalence of ties hold true in the development of other regulations, we don't yet know, but there is a growing body of evidence showing the influence of industry throughout the medical research enterprise, and this paper adds to that. I hope it will highlight the need for greater transparency."

Gary Collins, Professor of Medical Statistics and a co-author of the study, added: "We were also concerned by the lack of scientific evidence used in comments, and the dominance of industry over academic commenters, despite AI/ML being a very active area of research. But we hope our findings will bring the FDA proposal to the attention of academics and encourage more of them to participate in the next round of feedback on the framework, and other regulatory frameworks, where academic input could be valuable."

Trinity College Dublin researchers have carried out the first multi-centred, international, qualitative study exploring the athlete experience (in their own words) of sporting low back pain (LBP).

LBP is common in rowers and can cause extended time out from the sport and even retirement for some athletes. Rowers from diverse settings (club and university to international standard) in two continents were included in the study.

The findings have been published in the British Journal of Sports Medicine (Thursday, 15th October 2020).

In an Irish context, rowing is currently one of our most successful sports and Rowing Ireland has 4000 registered racing members. About 50% of elite rowers in Ireland will have an episode of rowing related low back pain in a year. Australia is one of the biggest rowing nations in the world. Researchers at Curtin University in Perth, who partnered on this study are globally respected for their back-pain research.

With the evolution of professional sport, the mantra of 'win at all costs' pervades. This attitude is present even in grassroot sports. Focus has shifted from enjoyable participation to prioritising performance outcomes, leading to athletes being regarded as an asset, commodity or an investment.

A culture of toughness and resilience is encouraged but this can create confusion when it comes to reporting pain and injury which is common in sport. Athletes commonly internalise a myth that pain equates to weakness and personal failure. There is a rising interest in the influence of sporting culture on athlete's welfare; athlete abuse through mistreatment following injury is part of this.

For many sports, athletes' health is not prioritised, and this is now recognised as a form of abuse. Some athletes are not provided with a culture and environment where they can report pain and injury without negative consequences. To understand the extent of this issue and to safeguard athletes, their voice and experiences need to be heard in research.

Qualitative research allows athletes to tell their stories in their own words and is a good method of exploring their lived experience. By understanding what an athlete's experience of pain and injury is will lead to a better management of injury and better outcomes. It is likely to contribute to prevention of injury.

The key messages from the study are:

Rowers in this study felt compromised by their LBP and in many cases felt that the prevailing culture and environment did not allow them to be open and honest about their LBP for fear of exclusion.

Many felt that they had to continue competing and training when in pain. This may have increased risk of a poor outcome from their LBP as well as the poor negative emotional/mental experience that they encountered

Rowers experience of LBP can lead to isolation and can have a profound effect on their life beyond sport.

Dr Fiona Wilson, Associate Professor, Physiotherapy, School of Medicine, Trinity College said:

" This study presents a powerful message that athletes fear being judged as weak when they have pain and injury. They feel isolated and excluded when injured. They feel that there is a culture within sport that values them only when they are physically healthy. This leads athletes to hide their pain and injury which is likely to lead to poorer outcomes. Some of this may come from within the athlete and some may be reflective of cultures in some settings in the sport.

Our findings will impact not just rowers but any athlete who has experienced pain and injury, allowing their perspective to be considered. This will lead to the design of more tailored injury management programmes and will also crucially create a sporting environment where an athlete's physical health and welfare is at the core.

The findings from this study can be applied across sports and this has been reflected in the Twitter response to this paper, with athletes and clinicians from diverse sports, recognising these findings from their own experiences."

This release has been removed upon request of the submitting institution. Please contact Emma Gaisford, email: emma.gaisford@port.ac.uk, phone number: 02392842897 for more information.

Presently, the moon does not have an internal magnetic field as it can be observed on Earth. However, there are localized regions on its surface up to several hundred kilometers in size where a very strong magnetic field prevails. This has been shown by measurements on rocks from the Apollo missions. Since then, research has puzzled about the origin of these magnetic spots. One theory is that they are in some way remnants of an ancient core magnetic field. Possibly similar to what can still be observed on Earth today. Here, the core consists of molten and solid iron and its rotation generates the earth's magnetic field. Why the inner field of the Moon has extinguished at some point remains a subject of research.

Another long discussed theory about the local magnetic spots of the moon suggests that they are the result of magnetization processes caused by impacts of massive bodies on the moon surface. A study recently published in the journal Science Advances now shows, that the Moon must have had an internal core dynamo in the past. The researchers came to their conclusion by disproving this second theory with the help of complex computer simulations. It is the result of a large international cooperation between MIT, GFZ-Potsdam, UCLA, the University of Potsdam, the University of Michigan and the Australian Curtin University.

The second thesis was supported among other things by the fact that large and strong magnetic spots were found on the other side of the moon, exactly opposite large lunar craters. Their origin was assumed to be as follows: Because the Moon - unlike the Earth - has no atmosphere to protect it from meteorites and asteroids, such massive bodies can hit it with full force and pulverize and ionize material on its surface. A cloud of charged particles, also called plasma, created in this way flows around the Moon, compresses the magnetic solar wind present in space and thus strengthens its magnetic field. At the same time, the solar wind induces a magnetic field in the moon itself. At the surface opposite the impact, all these fields are amplified and create the observed magnetism in the crustal rock.

Using the examples of some well-known Moon craters as the one we regard as its "right eye", the researchers have now simulated the impact including the plasma formation, the propagation of the plasma around the moon and the course of the field induced in the moon's interior. Using software that was originally developed for space physics and space weather applications, they simulated very different impact scenarios. In this way, the scientists were able to show that the amplification of the magnetic fields due to collisions and ejected material alone was not sufficient to generate the large field strengths as originally estimated and measured on the moon: The resulting magnetic field is a thousand times weaker than necessary to explain the observations. This does not mean, however, that these effects do not exist; they are only comparatively weak. In particular, the simulations showed that the field amplification by the plasma cloud on the rear side of the impact is more likely to occur above the crust, and that the magnetic field inside the moon loses much of its energy via dissipation due to turbulence in the mantle and crust.

"How exactly the magnetic spots were formed still requires more research. But now it is clear that at some point in time an internal magnetic field of the Moon had to be present for this to happen," says Yuri Shprits, Professor at the University of Potsdam and head of the Magnetospheric Physics Section at GFZ-Potsdam. "In addition, this study can help us to better understand the nature of the dynamo-generated magnetic field and the dynamo process on Earth, the outer planets and exoplanets".

A rapid and simple method for testing the efficacy of antibacterial drugs on infectious microbes has been developed and validated by a team of Penn State researchers.

Antimicrobial resistant infection is one of the major threats to human health globally, causing 2.5 million infections and 35,000 deaths annually, with the potential to grow to 10 million deaths annually by 2050 without improved techniques for detection and treatment.

Several rapid testing techniques have been developed, but they do not live up to the reliability of the gold standard technology, which requires 18 to 24 hours for reliable results. In many cases, patients need to be treated with antibiotics in a crisis, leading clinicians to prescribe broad-spectrum antibiotics that may actually lead to greater drug resistance or unacceptable side effects.

"Compared to other methods of detection, our method does not require complex systems and measurement setups," says Aida Ebrahimi, assistant professor of electrical engineering and a senior author on a paper recently posted online in the journal ACS Sensors. "Its simplicity and low cost are among the advantages and coupling our technology to machine learning makes the accuracy of our method comparable to the gold standard method and much better than other rapid methods."

The team tested their method against three strains of bacteria, including a resistant strain, to prove its effectiveness in the lab. Upon further development and validation with a broader range of pathogens and antibiotics, their method can allow physicians to prescribe the minimum dosage of the necessary drug, called the minimum inhibitory concentration (MIC) in a timely fashion.

A phenomenon that other tests fail to account for is that bacteria may initially appear to be dead, but then can revive and multiply after many hours. The team's technology, augmented by machine learning, can predict whether the bacteria will revive or are actually dead, which is critical for accurate determination of the MIC value.

Their technique is called dynamic laser speckle imaging.

"The main advantages of our method are the speed and simplicity," explained Zhiwen Liu, professor of electrical engineering and the second corresponding author. You shine a laser beam on the sample and get all of these light scattering speckles. We can then capture these images and subject them to machine learning analysis. We capture a series of images over time, which is the dynamic part. If the bacteria are alive, you are going to get some motion, such as a small vibration or a little movement. You can get reliable, predictive results quickly, for example within one hour."

In addition to the immediate benefits provided to the patient, the lower concentration of drugs entering the water supply translates to less pollution to the environment, he says.

"One of the exciting aspects of this research has been its multidisciplinary nature. As an electrical engineer, I find it quite fascinating to work on designing and developing an optical diagnostic system as well as performing microbiology assays," said Keren Zhou, the co-lead first author on the paper and a doctoral student in electrical engineering.

His co-lead author, doctoral student Chen Zhou, added, "We plan to further develop our technique to a low-cost and portable platform, which would be especially beneficial for resource-limited settings."

(Vienna, 15 October 2020) Poverty is one of the greatest challenges facing humanity. Globally, one out of every 10 people lives in extreme poverty, defined by the World Bank as living on less than $1.90 per day. Many of them live in rural areas where the poverty rate is 17.2 per cent - more than three times higher than in urban areas. If current trends continue, the number of hungry people will reach 840 million or one ninth of the world's population by 2030 according to the World Food Programme.

Poverty eradication has therefore found a place at the top of the United Nations 2030 Agenda for Sustainable Development. "End poverty in all its forms everywhere" is the first Goal of this Agenda, which is supported by all 193 UN member states. The international community is now stepping up efforts to achieve this goal, especially in response to the severe setback caused by the Covid-19 pandemic. The zoonotic nature of the Covid-19 virus has also illustrated the urgency to reduce human pressure on nature.

One way to relieve this pressure and alleviate poverty is to recognize and further optimize the critical role of forests and trees as allies in the fight against poverty. In the long run, losing forests means losing this fight. This is the central finding of a new global assessment report entitled "Forests, Trees and the Eradication of Poverty: Potential and Limitations".

The report will be launched online on Thursday, 15 October 2020, at 4-5:30 pm CEST, two days ahead of the International Day for the Eradication of Poverty, one day ahead of World Food Day, and on the International Day of Rural Women. All these official days underscore the urgent need for action.

The study consolidates available scientific evidence on the wide range of contributions forests and trees outside forests make to curbing poverty and on the effectiveness of diverse forest management policies, programs, technologies and strategies. It does so based on an understanding of poverty not only in terms of money but also as an obstacle that keeps people from attaining a certain level of well-being and participating fully in society.

"This global assessment comes at a critical time. More extreme weather events associated with climate change, widening inequality, and the spread of infectious diseases, among others, are making an already insecure situation worse for the poor. It is therefore essential to review the role of forests in development in general, and in achieving poverty eradication, in particular." says Hiroto Mitsugi, Assistant Director-General, FAO, and Chair of the Collaborative Partnership on Forests.

A core group of 21 internationally renowned experts from different parts of the world and different scientific backgrounds have worked together for almost two years on the Global Forest Expert Panel (GFEP) on Forests and Poverty. The Panel, chaired by Professor Daniel C. Miller of the University of Illinois at Urbana-Champaign, United States, and led by the International Union of Forest Research Organizations (IUFRO), is an initiative of the Collaborative Partnership on Forests (CPF) chaired by the Food and Agriculture Organization (FAO) of the United Nations.

Professor Miller says, "Forests and trees are critical to the well-being of many of the world's poor people who have been able to harness the goods and services they provide to manage and mitigate risk, especially in the face of crises. To secure and improve this important function, we need to adequately protect, manage and restore forests and to make forests and trees more central in policy decisionmaking."

"Our global assessment examines a variety of policy and management measures implemented by governments, civil society organizations, and the private sector for their potential and limitations to alleviate poverty. While there is no one size fits all solution, we have found that some of the strongest evidence for poverty reduction comes from agroforestry systems, community forest management, ecotourism, and forest producer organisations, among others," Professor Miller explains.

However, benefits and costs from forests and trees to human well-being are unevenly distributed. In many forest and wildlife-rich countries in Africa, for example, timber and tourism are major contributors to national economic accounts, but the benefits may not accrue at the local level - and, worse, local communities may bear the cost of these activities through environmental degradation and restricted access to protected areas.

There are several studies that show that protected areas can reduce poverty, particularly where ecotourism opportunities exist (e.g. in Costa Rica and Thailand) and where local people are involved as stakeholders. However, it is often those who are better off who are more likely to benefit, thus exacerbating local income inequalities.

Much case study evidence also points to clear benefits for the poor derived from community forestry management (CFM), although its potential has not been realised in most countries. Nepal is an exception as its CFM program is considered one of the most successful of its kind in the world. And yet, even there the benefits of CFM are unequally distributed among households, with poor and low caste households benefitting less than more well-off households.

Producer organisations are another relatively successful option to help forest producers overcome challenges such as market access. For example, in Burkina Faso's largely female-dominated shea nut value chain 76% of surveyed women noted improvements in their financial situation as a result of their participation in shea producer groups. A shea union has helped to build many members' social capital and strengthen cohesion even as social divisions along lines of gender, age and ethnicity still affect processes of inclusion and exclusion along this important forest product value chain.

Vanilla production in Madagascar is an example of how agroforestry can provide a pathway out of poverty. Approximately 80% of the world's vanilla is produced in Madagascar, largely in the north-eastern Sava region. There, agroforestry systems focusing on vanilla have become the main source of income for many farmers. However, benefits generally arise from contracts with vanilla exporters or collectors and thus are concentrated among smallholders able to obtain those contracts. Female-headed households, for example, are much less likely to get contracts because of their significant social disadvantages.

Thus, a key finding of the global assessment is that the poor are rarely able to capture the bulk of benefits from forests even as forest and trees are often vital in terms of subsistence. In addition, the Covid-19 pandemic has driven thousands of people back to rural areas and has cut remittances. The full range of its effects on forests and rural livelihoods remains to be seen.

LONDON, ON - Lawson Health Research Institute and the Centre of Excellence on Post-Traumatic Stress Disorder (PTSD) are partnering with a population at high risk of mental illness - Canadian Veterans and spouses of Canadian Veterans - to study how they have been impacted by the COVID-19 pandemic. Through online surveys, the project will hear directly from Veterans and their spouses to assess the pandemic's effects on their wellbeing over time. The team hopes results can be used by health care workers and policymakers to support Veterans and their families during both the current pandemic and future public health emergencies.

"With concerns about COVID-19 infection and drastic changes to everyday life, the pandemic is taking a toll on the health of Canadians," explains Dr. Don Richardson, Lawson Associate Scientist and Director of the MacDonald Franklin Operational Stress Injury (OSI) Research Centre. "And it may be particularly distressing for those vulnerable to mental illness."

Population studies show that Canadian Veterans are at double the risk of mental illness when compared to the rest of the population. They experience higher rates of depression, anxiety and loneliness. Spouses of Canadian Veterans are also at higher risk of distress, sometimes undertaking significant caregiving responsibilities that lead to less independence.

"It's currently unknown how the pandemic will impact Veterans and their spouses, but it could result in particularly serious outcomes," says Dr. Anthony Nazarov, Associate Scientist at Lawson and the MacDonald Franklin OSI Research Centre. "We want to hear from all Canadian Veterans and their spouses, whether they're doing well or not and whether they're seeking care or not."

The study aims to recruit 1,000 Canadian Veterans and 250 spouses of Canadian Veterans. Participants will complete online surveys, available in both English and French, once every three months for a total of 18 months. They will be asked questions about their psychological, social, family-related and physical wellbeing, and any relevant changes to their lifestyle and health care treatment.

"Veterans who regularly access health care services could encounter significant changes, including a move to virtual care appointments. This could lead to increased caregiving responsibilities for spouses," says Dr. Nazarov. "Given the uncertainty surrounding the pandemic, these changes may persist well into the future, mandating a thorough assessment of patient satisfaction and treatment outcomes."

The team hopes results can be used to support the wellness of Veterans and their families during public health emergencies. This includes providing health care professionals and policymakers with information to guide emergency preparedness policies and health care delivery models. They hope results can also be used to recognize early signs of distress in order to target with early interventions.

"We are seeking to understand the impact of COVID-19 on Veterans and their families to identify if this global pandemic is leading to psychological distress or triggering historical traumas," says Dr. Patrick Smith, CEO of the Centre of Excellence on Post-Traumatic Stress Disorder. "The Centre's primary goal is to increase Canadian expertise related to military and Veteran mental health, suicide prevention and substance use disorders. This study can help us understand if the pandemic is having debilitating and life-altering effects, and help us address a potential mental health crisis."

Interested Canadian Veterans and spouses of Canadian Veterans can learn more about the study at http://www.veteransurvey.ca.

Both seasonal migration and the maintenance and use of an effective immune system come with substantial metabolic costs and are responsible for high levels of oxidative stress. How do animals cope in a situation when energy is limited and both costly body functions are needed? A team of scientists led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) investigated whether and how the immune response changes between pre-migration and migration seasons in the Nathusius pipistrelle bat. They confirmed that migratory bats favour the energetically "cheaper" non-cellular (humoral) immunity during an immune challenge and selectively suppress cellular immune responses. Thereby, bats save energy much needed for their annual migration. The results are published in the scientific journal Scientific Reports.

The team of scientists around Christian C. Voigt, head of the Department of Evolutionary Ecology of the Leibniz-IZW, and Gábor Á. Czirják, senior scientist at the Department of Wildlife Diseases of the Leibniz-IZW, assessed the activity of several branches of the immune system of the Nathusius pipistrelle bat before and during migration. The seasonal journey of a 7 g Nathusius pipistrelle is energy-intensive since they fly more than 2.000 km during their annual journeys between the Baltic countries and southern France, and the metabolic turnover during flying is an order of magnitude higher than the basal metabolic rate . "It seems likely that bats will have to trade some body functions such as the immune response against the high cost of flight during migration", Voigt says. In order to verify this conjecture and to elucidate how the immune system is configured during this pivotal time of the year, the team measured the cellular and humoral response of the innate immune system (relative neutrophil numbers and haptoglobin concentration, respectively) and the cellular response of adaptive immunity (relative lymphocyte numbers) before and during migration. They compared baseline levels of these immune parameters and studied them in response to an antigen challenge.

"Our results confirm significant differences between the two periods. We conclude that this species of bat pays attention to the energy requirements of the different branches of immunity when switching from pre-migratory to the migratory season", Voigt explains. Before migration the cellular response of the innate immune response was significantly higher than during migration, whereas the humoral response of the same immune branch was dominant during the migration period. "The Nathusius pipistrelle responds with a strong humoral immune response to a challenge mimicking a bacterial infection. This response is more pronounced during migration, while there is no activation of the cellular response in such a situation", adds Czirják. When the animals embark on their strenuous journeys they reduce the cellular immune response, which is more energy-demanding than the humoral response. With this strategy the Nathusius pipistrelle might save energy during migration.

"The open question is whether or not the focus on humoral immunity during the migration period puts bats at some risk", Voigt says. "It is possible that they are more susceptible to certain pathogens while migrating if bats cannot mount an adequate cellular immune response." These and other related questions are now the topic of further immunological research by the bat research group at the Leibniz-IZW.

REDWOOD CITY, Calif., October 15, 2020 - Synthego, the genome engineering company, has collaborated with The Krogan Lab, a world-renowned scientific research unit at the Quantitative Biosciences Institute (QBI) at the University of California, San Francisco (UCSF), to deliver multiple CRISPR-based engineered cell lines to accelerate the study of potential treatment targets for SARS-CoV-2, the novel coronavirus that causes COVID-19 disease. In a study published in Science, the consortium of researchers used Synthego-engineered cells targeting more than 300 genes that the virus interacts with inside a human cell.

"Utilizing Synthego's industry-leading CRISPR-based genome engineering platform was essential in accelerating our research at QBI's Coronavirus Research Group," said Dr. Krogan, a professor at UCSF, Director of QBI, and a senior investigator at the Gladstone Institutes. "The precision and reproducibility of CRISPR were key to helping us study how SARS-CoV-2 affects cellular pathways and ultimately causes disease, enhancing our validation of promising therapeutic targets that may offer broad protection against infection from coronaviruses."

In this collaboration, Synthego joined academic and private sector scientists from UCSF, QBI's Coronavirus Research Group (QCRG), Gladstone Institutes, EMBL's European Bioinformatics Institute (EMBL-EBI) in Cambridge, England, Georgia Institute of Technology, the Icahn School of Medicine at Mount Sinai in New York, Institut Pasteur in Paris, University of Freiburg in Germany, and University of Sheffield in the UK.

Inspired by UCSF's Nature publication, "A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing," Synthego extended its expertise and platform technologies to validate the targets identified in the study by editing genes individually and as a series. This approach revealed which genes and cellular pathways are essential for the virus to infect and or grow inside human cells through infectivity analysis.

"Contributing to the critical work of an international team of almost 200 researchers from 14 leading institutions in six countries has been a tremendous honor," said Kevin Holden, a co-author of the study and head of Science at Synthego. "Recent publications, combined with our upcoming World CRISPR Day, highlight our growing scientific expertise and leadership in applying the latest genome engineering platform innovations to advancing life sciences research and clinical development."

Dr. Krogan will be speaking in greater detail about the Science study and the collaborative effort at Synthego's upcoming World CRISPR Day symposium, which will also feature a keynote address from Nobel Laureate Jennifer Doudna, Ph.D.