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Archive for the ‘Molecular Genetics’ Category

Fighting autoimmunity and cancer: The nutritional key – Science Codex

Friday, May 8th, 2020

Scientists at the Department of Infection and Immunity of the Luxembourg Institute of Health (LIH) revealed a novel mechanism through which the immune system can control autoimmunity and cancer. In the special focus of the researchers were regulatory T cells - a specific type of white blood cells that in general act as a brake on the immune system. The LIH research team led by Prof Dirk Brenner, FNR ATTRACT fellow and Head of Experimental & Molecular Immunology, revealed a mechanism that controls the function of regulatory T cells and determines the balance between autoimmunity and anti-cancer activity. In a preclinical model, the scientists further showed that the elucidation of the metabolic mechanism of a disease can lead to disease reduction by a rationally-designed diet that specifically addresses these metabolic alterations. This sets a new direction for future treatment of metabolic diseases. These findings, which were published today in the leading international journal Cell Metabolism, hold important implications for the development of personalised treatment options for autoimmune disorders and cancer.

"Our immune system is needed for a healthy body function and protects us from all kinds of infections. Particularly important in this respect are T cells, and specifically regulatory T cells. Although these represent only a small fraction of all T cells, they are crucial to keep our immune system in check" explains Prof Brenner. "If regulatory T cells are not functional, the immune system gets out of control and turns against its own body. This can lead to detrimental autoimmune diseases like multiple sclerosis, type I diabetes or arthritis. However, a highly reactive immune system can kill cancer cells very efficiently. This has led to the development of 'checkpoint inhibitors', specific drugs that unleash an immune system attack on cancer cells and which won the Nobel Prize in Medicine in 2018". The Luxembourgish scientists took this angle and revealed a novel mechanism by which this balance between an extreme or subdued immune reaction can be controlled by modifying regulatory T cell metabolism.

Initially, the researchers focused on how regulatory T cells cope with stress. Cellular stress can originate from the cells themselves, for example when they get activated and divide, but also from their environment, especially from nearby tumour cells. Free radicals called reactive oxygen species (ROS) are the molecular mediators of cellular stress. These are harmful for the cells and therefore need to be inactivated. "Free oxygen radicals are 'neutralised' by antioxidants and the major antioxidant in T cells is a molecule known as glutathione. We were surprised when we realised that regulatory T cells had about three times as much glutathione as other T cells. This pointed to an important function", says Henry Kurniawan, first author of the study and PhD student in Prof Brenner's group. Through a sophisticated genetic approach, the scientists removed a gene named 'glutamate cysteine ligase' (Gclc) only in a small population of regulatory T cells in mice. The Gclc gene is instrumental for glutathione production. Prof Brenner's team discovered that free radicals accumulated in these genetically altered regulatory T cells and that these cells lost their ability to act as a brake on the immune system. Strikingly, this led to a massive immune activation and a fatal autoimmune disease.

The team also found that the absence of glutathione in regulatory T cells increased serine metabolism massively. Serine is one of the 22 different amino acids that constitute the building blocks of proteins, which are in turn important for the structure and function of cells. No previous research group had studied the connection between glutathione, free radicals, serine and regulatory T cell function before. Prof Brenner's team characterised the metabolic alteration that led to the observed autoimmune disease in their mutant mice. Based on their findings, they designed a specific nutritional plan with the aim of correcting these disease-causing metabolic shifts. This dietary plan lacked both the amino acids serine and the closely related glycine. Interestingly, this engineered precision diet suppressed the severe autoimmunity and no disease developed. "Importantly, our study shows that the absence of only 2 out of 22 amino acids can cure a complex autoimmune disease. Therefore, elucidating the exact metabolic and molecular basis of a disease offers the possibility to correct these metabolic abnormalities through a special diet that is precisely adapted to the delineated disease mechanism. Our study might be a first step in the direction of the personalised treatment of metabolic diseases and autoimmunity", explains Prof Brenner.

"The relationship between glutathione, free radicals and serine can be used as a 'switch' to modulate immune cell activation. A higher immune cell activity is beneficial for cancer patients. We were intrigued by the idea of using our findings also to boost anti-tumor responses" he adds. Indeed, the team further showed that lower glutathione levels in regulatory T cells and the resulting rise in immune cell activation led to a significant tumour rejection, which might open up new therapeutic avenues for cancer treatment. "These astonishing results show the enormous potential of tweaking metabolism to prevent autoimmunity and target cancer. This could pave the way for the development of a new generation of immunotherapies," explains Prof Markus Ollert, Director of LIH's Department of Infection and Immunity. "The publication of these results in such a competitive and prestigious international journal is a momentous accomplishment not just for our department and institute, but for the entire Luxembourgish biomedical research community", he concludes.

In future projects, the researchers will use their findings to elaborate new approaches for therapeutic intervention. In that respect, the scientists have already proven that their delineated disease-controlling mechanism is also relevant in human regulatory T cells.

Due to its significance, the publication was selected by Cell Metabolism to be featured as the cover story of the May issue of the journal.

Involved research teams

Prof Dirk Brenner is the Deputy Head of Research & Strategy at LIH's Department of Infection and Immunity. He is Professor for Immunology & Genetics at the Luxembourg Center for Systems Biomedicine (LCSB) of the University of Luxembourg and Professor of Allergology at the University of Southern Denmark. He received a prestigious ATTRACT Consolidator grant from the Luxembourg National Research Fund (FNR), in 2015 to set up the Experimental & Molecular Immunology research group at LIH. The FNR-ATTRACT programme supports the national research institutions by expanding their competences in strategic research areas by attracting outstanding young researchers with high potential to Luxembourg.

The present study was performed in close collaboration with a national and international team and involved partners from LIH's Department of Infection and Immunity, LIH's Department of Oncology, the Braunschweig Integrated Center of Systems Biology (BRICS) of the Technische Universitt Braunschweig (Germany), the Helmholtz Centre for Infection Research (Germany), the Campbell Family Institute for Breast Cancer Research at the University of Toronto (Canada), the Institute for Medical Microbiology and Hospital Hygiene at the University of Marburg (Germany), the Department of Environmental Health Sciences at the Yale School of Public Health (USA), the Odense Research Center for Anaphylaxis (ORCA) of the Odense University Hospital (Denmark), the Department of Biomedical Genetics and Wilmot Cancer Institute of the University of Rochester Medical Center (USA), the Departments of Medical Biophysics and Immunology at the University of Toronto (Canada) and the University of Hong Kong (China).

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Fighting autoimmunity and cancer: The nutritional key - Science Codex

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2020 Insights on the Global Infectious Disease Molecular Diagnostics Market – Business and Technological Trends in Major Markets -…

Friday, May 8th, 2020

DUBLIN--(BUSINESS WIRE)--The "2020 Global Infectious Disease Molecular Diagnostics Market for 100 Tests: US, Europe, Japan--Supplier Shares by Test, Volume and Sales Segment Forecasts, Competitive Strategies, Innovative Technologies, Instrumentation Review" report has been added to ResearchAndMarkets.com's offering.

This new seven-country study contains is designed to help current suppliers and potential market entrants identify and evaluate emerging opportunities in the infectious disease molecular diagnostics market during the next five years.

Report Highlights

Rationale

The infectious disease molecular diagnostics market is one of the most rapidly growing segment of the in vitro diagnostics industry. The next five years will witness significant developments in reagent systems and automation, as well as introduction of a wide range of new products that will require innovative marketing approaches. The rate of market penetration into routine clinical laboratories, however, will depend on the introduction of cost-effective and automated systems with amplification methods.

In order to successfully capitalize on the opportunities presented by the infectious disease molecular diagnostics market, many companies are already exploiting new molecular technologies as corporate strategic assets, managed in support of business and marketing strategies. Integrating new technology planning with business and corporate strategies will be one of the most challenging tasks for diagnostic companies during the next five years.

Geographic Coverage

Worldwide Market Overview

Market Segmentation Analysis

Product/Technology Review

Competitive Assessments

Opportunities and Strategic Recommendations

For more information about this report visit https://www.researchandmarkets.com/r/dr0itc

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Human challenge trials are being pushed to develop a vaccine against the coronavirus – World Socialist Web Site

Friday, May 8th, 2020

By Benjamin Mateus 5 May 2020

Without much fanfare, news reports on vaccines against the coronavirus have been focusing on ways to expedite vaccine development through human challenge trials. In a nutshell, such trials would deliberately infect healthy volunteers with the coronavirus after they received the experimental vaccine, to determine its efficacy.

Democratic Representative Bill Foster of Illinois, leading the effort with 34 other members of the House of Representatives, sent a letter to the Food and Drug Administration, stating, A more risk-tolerant development process is likely appropriate in the case of COVID-19 vaccine. The enormous human cost of the COVID-19 epidemic alters the optimization of the risk/benefit analysis.

Josh Morrison, a member of a supposed grass-roots effort, 1 Day Sooner, told Nature magazine, We want to recruit as many people as possible who want to do this, and pre-qualify them as likely to be able to participate in challenge trials would they occur. At the same time, we feel that the public policy decisions around challenge trials will be better informed if they highlight the voice of people interested in participating in such trials. According to the group, thousands from over 50 countries have volunteered.

Vaccine trials are notoriously lengthy, with optimistic estimates of 12 to 18 months to vaccine rollout. Much of the time in vaccine trials is spent in testing the safety and efficacy of a vaccine. These placebo-controlled phase-three trials, in which one group receives the vaccine and another a placebo, typically involve several thousands of participants who are followed long enough to assess differences in disease incidence.

Human challenge trials have been conducted over hundreds of years but are trials of last resort and conducted under special circumstances and much oversight. In the case of COVID-19, they were first raised in late March in a proposal published in the Journal of Infectious Diseases by authors Nir Eyal, Marc Lipstich, and Peter G. Smith. They wrote in their abstract, By replacing conventional phase-three testing of vaccine candidates [with human challenge trials], such trials may subtract months from the licensure process, making efficacious vaccines available more quickly.

The role of vaccines in global health cannot be understated. Smallpox was eradicated in 1977, the last case occurring in Somalia. Polio was eliminated in the United States in 1979. After a global campaign launched in 1994 by the United Nations Food and Agriculture Organization, rinderpest, a viral infection of cattle and domestic buffalo with near 100 percent lethality to livestock, was last confirmed in 2001 and declared eradicated in June 2011.

Measles, a virus for which only humans act as a host, killed 7 million to 8 million children annually until a decade of work led eventually to the development of a vaccine in 1963. Still, and despite an effective vaccine being available, measles infects more than half a million people across the globe, killing more than 140,000 people annually, mostly children under five years of age. Countries with the highest incidence include the Democratic Republic of Congo, Liberia, Madagascar, Somalia, and Ukrainethese five account for almost half of all cases worldwide.

The vaccination program in the United States, according to the CDC, has prevented more than 21 million hospitalizations and 732,000 deaths among children born in the last 20 years. Besides the morbidity and mortality associated with vaccinations, the economic benefits translate to $295 billion in direct costs and $1.38 trillion in total societal costs.

Efforts have been underway to develop a vaccine against the SARS-CoV-2 virus. Many see a vaccine as the only solution to the pandemic. With no pharmaceutical treatments that have shown clear mortality benefits, the present public health measures and supportive medical care remain essentially the only means by which to address the coronavirus and its impact on human populations.

According to the World Health Organization (WHO), there are currently six human trials in the race to develop a vaccine against SARS-CoV-2. Moderna, working in association with the NIAID, and INOVIO Pharmaceuticals are US-based trials, both in phase I. Moderna was the first to begin testing on humans in mid-March, building on its previous work on other coronaviruses. The University of Oxford, in Britain, is in phase I/II trial using a nonreplicating viral vector. The study is being led by Dr. Sarah Gilbert, who previously led work on Disease X, a hypothetical pathogen with pandemic potential adopted by the WHO on their shortlist of blueprint priority diseases. The other three trials are from ChinaCANSINO Biological, SINOVAC, and Beijing Institute of Biological Products. Seventy-seven other trials are in the preclinical evaluation stage.

In October 2016, the World Health Organization issued a statement on regulatory considerations for vaccine trials that pursue human challenge trials to expedite the development of these critical preventative treatments. They write, It is essential that challenge studies be conducted within an ethical framework in which truly informed consent is given. When conducted, human challenge studies should be undertaken with abundant forethought, caution, and oversight. The information to be gained should clearly justify the risks to human subjects.

The WHO notes that if a pathogen has a high case fatality rate and there are no existing therapies to prevent or diminish the impact of the disease and preclude death, then it would not be appropriate to consider such trials. Based on reports, they are planning to publish a response to proposed COVID-19 human challenge trials soon.

Authors Eyal et al., in regard to concerns about a human challenge trial for COVID-19, admit that it could be possible that any protection demonstrated from a vaccine in a human challenge study may not be replicated when the vaccine is used in the population at large.

Additionally, there is no attenuated SARS-CoV-2 virus that can help participants avoid the hazards associated with COVID-19, as was indicated in the WHOs guidance, nor is there a therapeutic that could safely reduce the mortality risk after the participants are infected. More concerning, they write, is that some vaccine constructs against coronavirus may induce more severe disease following infection, as has been reported in animal models of both SARS and MERS vaccine candidates. For this reason, they recommend challenging small groups sequentially to address this issue.

In support of the proposal, they state that these volunteers will have voluntarily consented to take these risks. They write, In the present case, the study would involve multiple tests of comprehension of all risks so that the decision is deeply informed and voluntary. These participants would be isolated in treatment facilities and given the best care possible.

They also justified the conduct of the trial on the grounds that 1) the study will only recruit healthy participants, 2) the vaccine likely will benefit some of those in the trial, 3) in the absence of a vaccine they are likely to be infected anyway, 4) only people with a high baseline risk of getting exposed should be recruited, 5) participants would be afforded the best available care, and 6) potentially some therapeutics may be available to ameliorate morbidity or mortality.

Dr. Beth Kirkpatrick, professor and chair of the Department of Microbiology and Molecular Genetics at the University of Vermont, who runs a human challenge trial unit, explained to STAT that human challenge models for COVID-19 do not exist. She said it would take upwards of two years to design and approve one, given all the ethical and regulatory constraints that they entail.

One of the primary considerations with such a human challenge trial is to establish appropriate endpoints for symptomsflu-like illness or pneumoniaand their implications for the efficacy of the vaccine. As yet, scientists are still puzzled over why some people become ill while others do not, and why symptomatic patients have a constellation of symptoms as compared to others. Additional concerns raised include if the data from such a study will translate to efficacy in all age categories, since the population being tested is young and healthy. Information about vaccine safety would also be compromised in these smaller trials.

The working class must treat with a great deal of skepticism the claimed benefits of such treatments and how such studies are being conducted, especially in the face of a pandemic with a novel coronavirus that at every turn has surprised and baffled scientists and researchers. Given the despair and upheavals caused by this pandemic, volunteers for these trials will likely come from among workers who are at the highest risk for contracting the infection because of the essential nature of their work.

That these human challenge trials are being vigorously supported by the political establishment is deeply concerning. The normal sentiments of mistrust, caution, and vigilance to protect the individuals involved seem absent. Ultimately, the race for vaccine development is rooted in capitalist relations which provide a tremendous profit incentive to the corporations that manufacture them, in addition to the general concern in ruling circles about promoting a back-to-work policy. The human challenge trials become a facilitator for both purposes.

The attempt to cut corners and expedite trials have already led to abject failures, which in the long run only delay the need to determine which therapeutics and vaccines will work and are inherently safe and which present adverse profiles. In the face of the frenzy and despair that is igniting social tensions, it becomes even more necessary to adhere rigorously to scientific principles. Even in desperate times, these principles will save time, life, and resources.

Featured statements on the coronavirus pandemic

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Human challenge trials are being pushed to develop a vaccine against the coronavirus - World Socialist Web Site

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Ongoing Study Reveals Key Factors that Will Drive the Growth of Biological Computers Market During 2019-2027 – Cole of Duty

Friday, May 8th, 2020

The Covid-19 (coronavirus) pandemic is impacting society and the overall economy across the world. The impact of this pandemic is growing day by day as well as affecting the supply chain. The COVID-19 crisis is creating uncertainty in the stock market, massive slowing of supply chain, falling business confidence, and increasing panic among the customer segments. The overall effect of the pandemic is impacting the production process of several industries including Life Science, and many more. Trade barriers are further restraining the demand- supply outlook.

A biological computer is a special type of microcomputer that is specially designed for medical applications. It is an implantable device that is mainly used for various tasks like monitoring the bodys activities or including therapeutic effects, all at the molecular or cellular level. Biological computers are used to produce input and output, and software is composed of DNA, the material of genes, whereas DNA-manipulating enzymes are used as the hardware.

The biological computer market anticipated to grow as rising in the prevalence of cancer and an increase in demand for DNA or gene chips is some of the major factors driving the market growth. However, less awareness of this device is restraining the market growth. Nevertheless, an increase in healthcare expenditure and overall growth in the healthcare industry are influencing the market growth.

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1. Biometrix Technology Inc2. Emulate Inc.3. IBM4. Illumina, Inc.5. IndieBio6. Macrogen Corp7. Merck KGaA8. Microsoft9. Sequenom Inc.10. Thermofisher Scientific

The biological computers market is segmented on the basis of component, application and by end user. Based on component the market is segmented as hardware, software, input and output. On the basis of application the market is categorized as oncology, molecular genetics, nanobiotechnology and others. On the basis of end user the market is categorized as pharmaceutical & biotechnology companies, research centers, healthcare it companies, hospital & clinics and others.

The report provides a detailed overview of the industry including both qualitative and quantitative information. It provides overview and forecast of the in biological computers market based on various segments. It also provides market size and forecast estimates from year 2017 to 2027 with respect to five major regions, namely; North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA) and South & Central America. The biological computers market by each region is later sub-segmented by respective countries and segments. The report covers analysis and forecast of 18 countries globally along with current trend and opportunities prevailing in the region.

The report analyzes factors affecting biological computers market from both demand and supply side and further evaluates market dynamics affecting the market during forecast period i.e., drivers, restraints, opportunities, and future trend. The report also provides exhaustive PEST analysis for all five regions namely; North America, Europe, APAC, MEA and South & Central America after evaluating political, economic, social and technological factors effecting the biological computers market in these regions.

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Ongoing Study Reveals Key Factors that Will Drive the Growth of Biological Computers Market During 2019-2027 - Cole of Duty

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Antibody That Blocks Coronavirus From Infecting Cells Discovered by Scientists – Newsweek

Friday, May 8th, 2020

Scientists have identified an antibody in a lab that they say can prevent the novel coronavirus from infecting cells. The team hopes the antibody could be used to create treatments for COVID-19, the disease caused by the virus.

Since the coronavirus began infecting people in the central Chinese city of Wuhan late last year, more than 3.5 million people have been diagnosed with COVID-19, over a million have recovered and almost 248,000 have died, according to Johns Hopkins University.

The team, whose research was published in the journal Nature Communications, have been exploring whether what are known as monoclonal antibodies could help patients with COVID-19. Currently there is no vaccine or specific treatment for the disease. Monoclonal antibodies are a type of protein created in a lab which can bind to a specific substance in the body. These types of antibodies mimic how the immune system responds to a threat, and are used to treat some forms of cancer.

An antibody named 47D11 was found to bind to the spike protein which the novel coronavirus, known as SARS-CoV-2, uses to enter the body, and block it in a way that neutralizes the pathogen.

To carry out their study, the researchers used mice whose biology was tweaked to create antibodies similar to those found in humans. They injected the animals with spike proteins that the viruses which cause SARS, MERS, and some types of common cold use to invade cells. These viruses are members of the large coronavirus family of pathogens which also includes SARS-CoV-2, the bug which causes COVID-19. The mice produced 51 antibodies capable of neutralizing the spike protein of the injected coronaviruses. This stage of the research was done before SARS-CoV-2 first came to the attention of health officials in late 2019.

The team later watched to see if the antibodies would neutralize SARS-CoV-2 and SARS-CoV in lab samples, and found 47D11 did.

Co-author Berend-Jan Bosch, associate professor of the Utrecht University Infection and Immunity programme, explained in a statement that the research builds on work his team had done previously on antibodies which can target SARS-CoV, the virus which causes SARS.

"Using this collection of SARS-CoV antibodies, we identified an antibody that also neutralizes infection of SARS-CoV-2 [the COVID-19 virus] in cultured cells. Such a neutralizing antibody has potential to alter the course of infection in the infected host, support virus clearance or protect an uninfected individual that is exposed to the virus."

Co-author Frank Grosveld, Academy Professor of Cell Biology at the Erasmus Medical Center, Rotterdam, said: "This discovery provides a strong foundation for additional research to characterize this antibody and begin development as a potential COVID-19 treatment."

Experts not involved in the research welcomed the findings, but also pointed out the study's limitations.

Tony Carr, professor of molecular genetics in the Genome Damage and Stability Centre (GDSC) at the University of Sussex, said in a statement: "The block to infectivity is entirely based on cell culture work, but the previous literature supports the proposal that this reagent should be explored further as a potential treatment."

Penny Ward, visiting professor in Pharmaceutical Medicine at King's College London, said the antibody has the potential to be used to prevent and treat SARS-CoV-2 infection, "however without studying this in an animal model, it is not clear which of these approaches might be most efficient."

The findings would have been more robust if the team were able to show the antibody could prevent and treat COVID19 in animals, she said.

"It is not possible to conclude that the product will be effective in vivo in humans," said Ward.

Polly Roy, professor of virology at the London School of Hygiene and Tropical Medicine, said the data the team created is "very good," and highlighted they are well-known for their work on coronaviruses.

Gary McLean, professor in Molecular Immunology at London Metropolitan University, said: "Because it is not done in people and the antibody is not even found in people as far as we know there are limitations. However it is a nicely done study that could provide a potential biotherapeutic that could be used to treat COVID-19.

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The research complements separate projects looking at whether a century-old technique known as convalescent plasma therapy, where the blood from a person who has recovered from COVID-19 is inserted into a current patient in the hope it will help them beat the disease.

Professor Babak Javid, principal investigator at Tsinghua University School of Medicine, Beijing, and consultant in infectious diseases at Cambridge University Hospitals in the U.K., commented: "This is a very interesting study. One of the most widely touted experimental (though not yet proven) treatments for COVID is the use of convalescent plasma."

He said: "However, use of convalescent plasma is difficult to scale and make widely available as a treatment and has some potential safety concerns since it is a blood product. Therefore there has been intense scientific interest in identifying individual antibodies that can also neutralize SARS-CoV2. This is because we are able to manufacture large quantities of individual antibodies (known as monoclonal antibodies or mAbs) at scale as a pharmaceutical treatment for COVID. Monoclonal antibodies also don't have the safety concerns of administering blood products."

Simon Clarke, associate professor in Cellular Microbiology at the University of Reading, U.K., said in a statement: "Antibodies like this can be made in the lab instead of purified from people's blood and could conceivably be used as a treatment for disease, but this has not yet been demonstrated.

"While it's an interesting development, injecting people with antibodies is not without risk and it would need to undergo proper clinical trials."

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Antibody That Blocks Coronavirus From Infecting Cells Discovered by Scientists - Newsweek

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Coronavirus quickly spread around the world starting late last year, new genetic analysis shows – CNN Philippines

Friday, May 8th, 2020

(CNN) A new genetic analysis of the virus that causes Covid-19 taken from more than 7,600 patients around the world shows it has been circulating in people since late last year, and must have spread extremely quickly after the first infection.

Researchers in Britain looked at mutations in the virus and found evidence of quick spread, but no evidence the virus is becoming more easily transmitted or more likely to cause serious disease.

"The virus is changing, but this in itself does not mean it's getting worse," genetics researcher Francois Balloux of the University College London Genetics Institute told CNN.

Balloux and colleagues pulled viral sequences from a giant global database that scientists around the world are using to share data. They looked at samples taken at different times and from different places, and said they indicate that the virus first started infecting people at the end of last year.

"This rules out any scenario that assumes SARSCoV-2 may have been in circulation long before it was identified, and hence have already infected large proportions of the population," Balloux's team wrote in their report, published in the journal Infection, Genetics and Evolution.

That is one piece of bad news. Some doctors had hoped the virus was circulating for many months and may have quietly infected many more people than has been reported. That would offer the hope that there might be some immunity already built up in some populations.

"Everyone was hoping for that. I was too," Balloux said.

Their findings pour cold water on such an idea. At the most, 10% of the global population has been exposed to the virus, Balloux estimated.

Many different studies have shown that the new coronavirus, often called SARS-CoV-2 by scientists, originated in a bat but had to have infected another animal before it jumped into humans. The first human cases were reported in Wuhan, China, last December.

Viruses make mistakes every time they replicate themselves, and these mutations can be used as what's called a molecular clock to track a virus through time and geography.

"Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host," the team wrote.

"It's very recent," Balloux said. "We are really, really, really confident that the host jump happened late last year."

That's because viral samples taken from all corners of the globe show multiple mutations, and they are similar mutations. "Everything is everywhere," the team wrote.

"It has been introduced and introduced and introduced in almost all countries," Balloux added.

They also found genetic evidence that supports suspicions the virus was infecting people in Europe, the US and elsewhere weeks or even months before the first official cases were reported in January and February. It will be impossible to find the "first" patient in any country, Balloux said.

"All these ideas about trying to find a Patient Zero are pointless because there are so many patient zeros," he said.

Balloux's team's findings were reviewed by other experts, a process called peer review, before they were published in the journal. He said some reports by other teams, published online in what are called pre-print websites, may have drawn incorrect conclusions.

"All viruses naturally mutate. Mutations in themselves are not a bad thing and there is nothing to suggest SARS-CoV-2 is mutating faster or slower than expected. So far we cannot say whether SARS-CoV-2 is becoming more or less lethal and contagious," Balloux said.

Lane Warmbrod, an analyst at the Johns Hopkins Center for Health Security who has been tracking the reports on the genetics of the new coronavirus. She said more studies are needed in animals to demonstrate how changes in the genetics of the virus could make it more or less infectious or pathogenic.

"Just because these studies tell us these mutations are quickly spreading or becoming dominant doesn't mean anything except we know it happened. It doesn't actually tell us anything about what's happening biologically," Warmbrod told CNN.

Reports about mutations can be important for teams working on drugs and vaccines to fight the coronavirus. Vaccines, especially, need to target parts of the virus that are conserved that do not change much over time.

This story was first published on CNN.com, "Coronavirus quickly spread around the world starting late last year, new genetic analysis shows."

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Coronavirus quickly spread around the world starting late last year, new genetic analysis shows - CNN Philippines

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Sallie Permar: Who Are Your Trusted Sources on COVID-19? – Duke Today

Monday, April 27th, 2020

As the COVID-19 pandemic continues, the question of where to turn for solid information has never been more important.

Many Duke experts are being approached now for their expertise and insight. But where do they turn for guidance and the latest information? In this ongoing series, Duke Today asks Duke experts to share their preferred sources.

Dr. Sallie Permar is a physician scientist who focuses on prevention and treatment of neonatal viral infections. A professor of immunology, pathology, pediatrics, molecular genetics and microbiology and associate dean for physician-scientist development, she recently wrote about the effect of the pandemic on medical research.

To stay abreast of how the infectious diseases field is responding to the novel coronavirus, she consults a mix of websites, podcasts and social media.

This Week in Virology, hosted by Vincent Racaniello and fellow virologists, has featured recent guest hosts who are stars of COVID-19 research, such as Drs. Daniel Griffin, Ralph Baric, Mark Denison, Stanley Perlman and Christian Drosten.

Immune, hosted by immunologists Cindy Leifer, Stephanie Langel, Vincent Racaniello, carried a recent two-part series on COVID-19 immunology with Dr. Brianne Barker that was especially compelling.

I also listen to COVID-19: Commonsense Conversations on the Coronavirus Pandemic, with host Dr. Ted OConnell, a family physician and writer.

For the latest on numbers by region, I check Johns Hopkins Universitys COVID-19 map.

COVID-19 guidelines can be found on the Centers for Disease Control website.

For the latest on viral sequence dynamics, I check gisaid.org.

For recent COVID-19 research reports, I consult bioxiv.org and medrxiv.org. The Twitter sources below provide real-time critical reviews of the newly posted manuscripts.

For the latest on epidemiology and case series reports, I consult: - the CDC Morbidity and Mortality Weekly Report and - World Health Organization situation reports.

And for compilations of the latest research I check: - Duke Pharmacist Elizabeth Dodds-Ashleys Daily Digest. - The American Association of Medical Colleges Novel Coronavirus Update by chief scientific officer and former Duke faculty member Dr. Ross McKinney. - Publons compilation of latest research manuscripts, which includes some crowd-sourced reviews.

Finally, great sources to follow on Twitter include:@NIAIDNews; @CEPIvaccines;NIH Vaccine Research Center scientist Kizzmekia Corbett (@KizzyPhD);The laboratory of UNC-Chapel Hills Dr. Ralph Baric (@Baric_Lab);The laboratory of Vanderbilt Universitys Dr. Mark Denison (@Denisonlab);Florian Krammer, an immunologist who is developing antibody assays (@florian_krammer); Virologists Dr. Benhur Lee (@VirusWhisperer) and Angela Rasmussen (@angie_rasmussen);COVID-19 drug developer Timothy Sheahan (@timothysheahan);David Martinez, a former Ph.D. student who is now testing vaccine and therapeutic antibodies in the lab of Ralph Baric (@David_RMartinez).

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Sallie Permar: Who Are Your Trusted Sources on COVID-19? - Duke Today

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Book review: ‘The Future is Faster Than You Think’ – Bowling Green Daily News

Monday, April 27th, 2020

The Future is Faster Than You Think: How Converging Technologies Are Transforming Business, Industries and Our Lives by Peter H. Diamandis and Steven Kotler. New York: Simon & Schuster. 2020, 384 pages, $20 (hardcover).

There is little doubt that the decade to come will be filled with radical breakthroughs and world-changing surprises, Peter H. Diamandis and Steven Kotler observe near the beginning of The Future is Faster Than You Think: How Converging Technologies Are Transforming Business, Industries and Our Lives, their exciting new treatise on what lies just around the corner and the impact it will have on everything.

As the chapters ahead make very clear, every major industry on our planet is about to be completely reimagined, they continue. For entrepreneurs, for innovators, for leaders, for anyone sufficiently nimble and adventurous, the opportunities will be incredible. It will be both a future thats faster than you think and arguably the greatest display of imagination rendered visible the world has yet seen. Welcome to an era of extraordinary.

As someone who has read a fair amount on what various thinkers have written about the wonders and pitfalls the future holds, I tend to be somewhat skeptical of these kinds of hyperbolic proclamations. In the present case, however, after making my way through this exquisite manuscript on where we currently find ourselves as a species, I have come to the conclusion their assessment is justified. We are indeed on the cusp of a revolution that will fundamentally change the world and how we function in it.

As might be expected given the nature of the subject matter, the book is exceptionally well-researched, with 76 pages of source notes at the conclusion of the foreword, 14 chapters and afterword that comprise the main text. Structurally, the content is arranged in three major sections: Part One, The Power of Convergence, consists of the first four chapters; Part Two, The Rebirth of Everything, is made up of the next eight chapters; and Part Three, The Faster Future, finishes out the narrative with chapters 13 and 14.

From my vantage point, Part Two constitutes the real meat and potatoes of their phenomenally insightful and intrinsically thought-provoking prose. The entire section is an interconnected description of what lies just over the horizon, as noted by the cascading chapters: The Future of Shopping, The Future of Advertising, The Future of Entertainment, The Future of Education, The Future of Healthcare, The Future of Longevity, The Future of Insurance, Finance, and Real Estate and The Future of Food. Embedded in these themes is an overarching nod to the future of work, something we all have a vested interest in from a more personal perspective.

As is usually the case with this kind of book, I was naturally drawn to how Diamandis and Kotler envision the tremendous technological innovations occurring at a breakneck pace and transforming education at all levels. Although I was a little apprehensive as I made my way through many of their arguments and the evidence they provided to support them, I was nonetheless encouraged by the optimistic tone that was unmistakable throughout their thesis.

Batch processing children is both an industrial hangover and an educational disaster because of basic biology, they explain in The Future of Education, the eighth chapter and one of my personal favorites for reasons previously indicated. Everyone is wired differently. Some of this is nature, some nurture, but the end result is the same: Were individuals, and theres no standard set of engaging experiences that can maximize learning for all.

But converging technology offers a host of new solutions to the challenges of quality and quantity, the authors continue a little later. Every technology thats currently making an impact on entertainment is doing double duty in education, meaning, as well see in a moment, one-size-fits-all is no match for the app store.

Lets just say I was not disappointed by the portrait they painted of the next phase in educations quickly-evolving manifest destiny.

Diamandis is founder and executive chairman of the XPRIZE, executive founder of Singularity University and the co-founder of Human Longevity Inc., Celularity and Bold Capital Partners. He has degrees in molecular genetics and aerospace engineering from MIT as well as an MD from Harvard Medical School. The founder of more than 20 high-tech companies, Fortune magazine named him one of the Worlds 50 Greatest Leaders in 2014. Kotler is founder and director of the Flow Research Collective as well as a best-selling author and award-winning journalist. His work has appeared in Time, The New York Times Magazine, The Atlantic, Wired and Forbes. His previous books include Stealing Fire, The Rise of Superman, Tomorrowland and Last Tango in Cyberspace.

In the final analysis, Diamandis and Kotler are realistic yet guardedly optimistic about the potential future thats within our grasp. They are not nave to the dangers that lie ahead, but they refuse to be paralyzed by them. In one sense, I interpreted their tome as a call to action an admonition to be more purposeful and rational in how we use the amazing tools we have at our disposal. Keeping the glass half full will take our collective commitment.

To be clear, there will still be terrorism, war and murder, they concede in the afterword. Dictatorship and disease wont go away. But the world will quietly continue to get better. The goal here isnt about creating a life of luxury, but rather a life of possibility. Thanks to the forces of convergence, the technological advances needed for that world of abundance are coming at an ever-increasing pace. Of course, creating that world wont happen automatically. It will still require the largest cooperative effort in history. And this brings us to our final question: What, exactly, are you waiting for?

I see that as a challenge none of us can afford to ignore. This was a very intriguing, sobering, enlightening and ultimately uplifting journey; highly recommended.

Reviewed by Aaron W. Hughey, Department of Counseling and Student Affairs, Western Kentucky University.

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A gene that could unlock the mysteries of COVID-19 – ModernHealthcare.com

Monday, April 27th, 2020

The team's results, posted as a preprint in BioRxiv earlier this month, proposed a handful of ACE2 variants suspected of boosting SARS-CoV-2 binding and, potentially, host susceptibility, along with several variants predicted to dial down ACE2 interactions with the viral spike protein that may be protective.

"What we can conclude is that this new virus has evolved new modality to interact with the ACE2 receptor," Jura noted. "Unfortunately, it seems like there are polymorphisms in the human population that will make some individuals more susceptible to binding this virus because these mutations are enhancing this unique part of the interface."

Seshagiri noted that such insights might make it possible to design potential therapeutic versions of ACE2 that are particularly adept at binding coronavirus spike proteins, thereby preventing the viruses from interacting with an individual's own ACE2 receptors, for example.

In a recent Cell paper, a team from Sweden, Spain, Austria, and Canada proposed its own strategy for engineering soluble, clinical-grade forms of the human ACE2 protein that appeared to dial down early-stage infections by SARS-CoV-2 in otherwise susceptible cell types.

"We are not the first to come up with the idea of saying ACE2 could be a therapeutic," he said, though he suggested that engineering soluble forms of the receptors protein that bind well to SARS-CoV-2 may serve as a strategy for "future proofing" against the emergence of these and other related viruses down the road.

The researchers plan to profile ACE2 polymorphisms in still more human samples for the final version of the study, which will likely be submitted for peer review in the coming weeks, Seshagiri said.

He and MedGenome CEO Rayman Mathoda noted that the diagnostic company, which is active in India and other emerging markets, is also a founding member of a GenomeAsia 100K project.

"We've made a very intentional effort to build on a data-focused set of efforts, where we take our proprietary data as we grow, but build in other data source," Mathoda said.

The investigators are not alone in attempting to establish a baseline understanding of ACE2 variation across and within populations.

At the University of Siena in northern Italy, Alessandra Renieri and her colleagues have been delving into ACE2 genetic variation using available exome sequences for some 7,000 healthy participants in the Network of Italian Genomes project. As they reported in a preprint posted to MedRxiv in early April, the investigators saw significant variation in ACE2 in that retrospective dataset, including both common and rare, missense variants predicted to influence the protein's stability and its interactions with the coronavirus viral spike.

"There is pretty wide genetic variability," Renieri said. "There are both polymorphisms, so variants found in a percentage of the population, and there are also rare variants a lot of rare variants."

It may be possible for the individual centers participating in the Network of Italian Genomes to recontact individuals in the future to try to find out who became infected with SARS-CoV-2 and to assess ACE2 variation alongside clinical outcomes, Renieri noted, though she cautioned that "ACE2 is just one of the many genes that could be involved."

For the reCOVID project, members of the team are seeking funding through the European Commission's Innovative Medicines Initiative IMI2 call for proposals to do functional analyses on ACE2 and other genes, for example, in the hopes of developing candidate therapeutics.

Renieri is also part of a team that been working since mid-March to prospectively collect samples from 2,000 COVID-19 patients at least 21 different hospitals in Italy as part of the GEN-COVID study, part of the COVID-19 Host Genetics Initiative.

For that project, researchers in Italy will use whole-exome sequencing to assess patient samples collected in conjunction with very detailed clinical information, she explained, while collaborators in Finland will genotype the samples for a related genome-wide association study.

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The Indian academic making the world look at flavours and food in a fresh way – The National

Monday, April 27th, 2020

If you are a foodie and love experimenting with flavours, how does a shrimp and egg salad sound for lunch? Or a tender juicy steak, just out of the oven, topped with a dollop of cheddar or Camembert, to be precise. And did you know mushrooms go smashingly well with nearly every common fruit, from apples to apricots and even coconut?

These food pairings may sound unappealing or at least unusual to most people, but Dr Ganesh Bagler of the Indraprastha Institute of Information Technology, New Delhi, says otherwise and he has the data and research to show for it.

Can we encode the intelligence of a chef into a computer, or can a computer fool a chef into thinking a recipe is real?

Akshay Malhotra

The computational gastronomy expert has taken the food and drink industry by storm with his ground-breaking work on flavour molecules and its corresponding database, FlavorDB.

His laboratory has also developed DietRX, an archive of nearly 2,000 foods, their chemical and genetic compositions, and their effect on health, which can enable culinary and drug interventions. (Ayurvedic diets are a historically important example of the belief in healing via appropriate foods.)

The power of data and food together is magic, says Bagler.

Already, chefs such as Garima Arora of Restaurant Gaa in Bangkok, are using Baglers research to fuel their own food experiments. What I find amazing about Baglers research is that his approach actually enables us to know exactly what makes up a cuisine the things that make Indian cuisine Indian, Arora, who is the first Indian woman with a Michelin star to her name, tells The National.

Once we have that knowledge, we can truly get to the main taste of a cuisine, which will help us do away with the flavours and ingredients we dont need.

Baglers work is also critical to Aroras Food Forward India, a non-profit initiative that aims to broaden the narrative around Indian food. It fits into the framework by being a forward-thinking initiative, one that serves the purpose of codifying a cuisine, and identifying, quantitatively, its identity, says project manager Matylda Grzelak.

Bagler, who is now considered the pioneer of computational gastronomy in India, credits curiosity for his success. Having studied various subjects from graduation through to postdoctoral studies quantum mechanics, computer science, computational biology, computational neuroscience and molecular genetics Bagler returned to India in 2010 following a stint at Berlins Max Planck Institute for Molecular Genetics.

He joined the CSIR-Institute of Himalayan Bioresource Technology at Palampur as a researcher, and worked on medicinal plants in the western Himalayas, and on diseases such as cancer and asthma. But it was not enough.

I like to explain things; Im a teacher, he says. This led him to the prestigious Indian Institute of Technology Jodhpur and finally IIIT-Delhi.

Bagler's foray into gastronomy happened when he came across a 2011 paper that took off from British chef Heston Blumenthals food-pairing hypothesis: foods that share flavour molecules will taste better together than those that do not.

For example, chocolate and blue cheese taste great together because they share 73 flavours (Blumenthals interest was piqued when he paired white chocolate and caviar, and hit the right notes). This led to companies such as Foodpairing, which present thousands of combinations of ingredients for chefs to experiment with.

Historically speaking, dishes have evolved over millennia from single-ingredient meals to complex ones, says Bagler. Cooking techniques and creative expression aside, why are some ingredients used together and others not? This was one of the critical questions that led Bagler to expand his research. Food science has been around, but it explored aspects such as the shelf life of foods or how to enhance sensory enjoyment. Now, people are looking at food from a data perspective.

What Bagler did differently was focus on Indian food, which he found is different from other cuisines because of the spices. Breaking down a collection of the late, celebrated Indian chef Tarla Dalals recipes, Bagler realised that spices form the basis of food-pairing in Indian cuisine. Having divided various foods into 26 categories vegetables, dairy, lentils, meats, etc he saw that mixing up items across all other sections did not cause too much of a shift in flavour, but when the spices were shuffled, the taste changed entirely.

Spices are the molecular fulcrum of Indian food

Dr Ganesh Bagler

For example, you could replace spinach with fenugreek leaves in palak paneer and there would not be much change in the dish, but if you replaced turmeric with cinnamon, the very essence of the preparation alters. Spices are the molecular fulcrum of Indian food, says Bagler.

In 2015, Bagler and his team of researchers sent this study to international science journals, which uploaded it to an open server where it was picked up by MIT Tech Review. This changed Baglers life. I only understood the academic value of this work, not its futuristic value, he says. It took me a year to understand that this had led to the creation of a new field of study, and now, over the past five years, Ive been developing the foundations of this area.

From 2,543 of Dalals recipes to nearly 158,000 global recipes, Baglers database has expanded exponentially. Not only is the data free to access on various websites and apps, but the information is also provided in excruciating detail, from the scientific names of elements to a comprehensive flavour network, possible pairings and health benefits. Bagler is also due to launch RecipeDB at a conference postponed amid the Covid-19 crisis where a massive collection of structured recipes will be available for everyone from chefs and cooking enthusiasts, to restaurateurs, multinationals and scientific organisations to use freely.

People know food technology, but they do not know about flavour technology, says Deepika Nadiminti, a flavourist at Mane India, which develops flavours for the dairy, confectionery and drinks industries. Baglers database is an all-in-one resource, where we can identify everything from flavour molecules to physical and chemical properties, and experiment easily, she says.

While Bagler consults for institutions such as the Indian Institute of Hotel Management and Symbiosis School of Culinary Arts, as well as a range of multinationals, chefs also swear by his research, which has significantly reduced time spent on developing new dishes, says Akshay Malhotra, a chef, food consultant and former student of the Culinary Institute of America.

FlavorDB will help us to understand the science behind Indian food, and it is only the beginning of how artificial intelligence will influence the food industry, he says.

This aspect is also key to Baglers future experiments. Can we encode the intelligence of a chef into a computer, or can a computer fool a chef into thinking a recipe is real? says Malhotra.

Can human creativity, which is at the heart of cooking, be reproduced using AI? It remains to be seen. For now, Malhotras observations pertain to FlavorDB complementing chefs instincts about pairing ingredients.

As celebrity chefs Manjit Gill and Akshraj Jodha describe Bagler's work, he is successfully quantifying the knowledge that, until now, was only intuitively available to a cook and everyone from chefs and diners to scientists will benefit from it.

Updated: April 25, 2020 04:57 PM

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Creighton’s Hereditary Cancer Center makes groundbreaking discoveries in cancer research – Omaha World-Herald

Monday, April 27th, 2020

Its difficult for Robin Farias-Eisner, M.D., Ph.D., to condense decades of cancer research into a single conversation. But recent developments call for brevity.

Sitting in his office on the second floor of the Hixson-Lied Science Building, Farias-Eisner, the newest director of Creighton Universitys Hereditary Cancer Center, explains how he and a team of researchers have discovered a new drug with the potential to treat a broad array of illnesses, including ovarian cancer, colon cancer, macular degeneration, heart disease and more.

It would be hard to overstate it, Farias-Eisner says of the potential impact of the find.

The research is one example of how the Hereditary Cancer Center is fulfilling its mission to pursue comprehensive research on all types of cancer. Established in 1984, the center is particularly devoted to cancer prevention through identification of hereditary cancer syndromes.

The center was founded by legendary cancer researcher Henry Lynch, M.D., a Creighton professor and pioneer in the field of cancer genetics. Prior to Lynchs research, prevailing medical thought held that cancer was primarily caused by environmental factors.

Through what doctors today call shoe-leather epidemiology, Lynch tracked down and interviewed cancer patients about their family histories, tracing the inheritance patterns of certain cancers through multiple generations. Researchers now estimate between 5% and 10% of cancers are inherited, according to the National Cancer Institute.

Lynch died at age 94 in June 2019. In July, the University named Farias-Eisner the new head of the Hereditary Cancer Center.

Farias-Eisner came to Creighton from the University of California, Los Angeles. There, as a surgeon-scientist, he earned a Ph.D. in molecular biology and ran his own laboratory specializing in womens cancer research.

My ultimate objective was to take care of women who had cancer, particularly gynecological cancers, because I felt that was an underserved population, Farias-Eisner says.

Through his lab work, Farias-Eisner and co-inventor, UCLAs Srinivasa Reddy, Ph.D., and a team of researchers identified a group of proteins that serve as early identifiers of ovarian cancer. The research led to the development of OVA1, a blood test that is currently being used worldwide to diagnose the disease.

Building on this work, Farias-Eisner, Reddy and a team of researchers developed HM-10/10, an artificial peptide that has been shown to be effective in inhibiting tumor growth in ovarian and colorectal cancers in mice.

In January, a paper detailing the research, Bovine HDL and Dual Doman HDL-Mimetic Peptides Inhibit Tumor Development in Mice was published as the featured article in the Journal of Cancer Research and Therapeutic Oncology. In addition to Farias-Eisner, the paper includes Holly Stessman, Ph.D., assistant professorin the Department of Pharmacology in Creightons School of Medicine.

This is a story of taking discoveries from the research bench and serendipitously arriving at a novel drug for use at the patients bedside, Farias-Eisner says.

The drug, Farias-Eisner says, has the potential to treat other pro-inflammatory diseases, a category which includes macular degeneration, heart disease, Alzheimers disease and endometriosis, among other clinically devastating diseases.

Prior to publishing on its effectiveness as a cancer treatment, Farias-Eisner and the team published another paper in the International Journal of Molecular Sciences showing HM-10/10s potential to treat retinal disease (e.g. macular degeneration).

The reason we wanted to publish in these two areas is to demonstrate the uniqueness of the drug and its clinical applications, Farias-Eisner says. Now that we have these two published papers, we can move toward clinical trials.

Creighton University offers a top-ranked education in the Jesuit, Catholic tradition and a welcoming, supportive environment to a diverse community of educators, professionals and support staff.Read moreabout the university, and connect with Creighton onFacebook,TwitterandInstagram.

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SHS grad involved in COVID-19 testing – SouthCoastToday.com

Monday, April 27th, 2020

SOMERSET When the Westborough based Integrated Genetics asked if any of its employees wanted to relocate to New Jersey for six weeks to do COVID-19 testing, Andrew Lanneville volunteered to go. He said it is a small contribution he can make to help during the coronavirus pandemic, but if he is needed, he is happy he can help.

"I wanted to do it," Lanneville said. "My family and friends and girlfriend have been very supportive of it. My employer has been gracious, always checking in on me, and the people down here are very grateful."

Integrated Genetics is a subsidiary of LabCorp Specialty Training Group. Lanneville, a 2008 graduate of Somerset High School, is a molecular biologist for Integrated Genetics. He is testing DNA samples from the sickest people in hospitals to determine whether they have COVID-19 or not. Lanneville said there are a lot of talented people from different places in the country who are working in the lab.

"People are here because they want to do their part, do what they can," Lanneville said in a telephone interview with The Spectator last Monday. "If they want to run molecular assays and DNA testing, I'm happy to do it and other people are happy to do it, as well."

Lanneville said 10,000 tests per day for COVID-19 were being done in the district in New Jersey where he was working. Last week, he said they were beginning a second method of testing that will take some of the burden off the instrumentation they are using so that they could double the amount of tests they were doing. He said the DNA samples don't just come from New Jersey, but also from New York and other places in the country.

In an article in The New York Times on April 13, the paper reported that the backlog for coronavirus testing in New Jersey was getting worse. At that time, the Times reported that New Jersey had conducted 115,000 tests, about one for every 75 residents. The newspaper article reported that the tests are a critical tool in measuring the disease's spread and a requirement for certain forms of treatment, yet they remain hard to get, and many people are actively discouraged from trying to get the tests. The article said that initially, the backlog was happening because there was not enough test kits, but said now there are not enough swabs and nurses. New Jersey has the second highest caseload of coronavirus cases in the country.

Another article in The New York Times on April 15 reported that, "The American Clinical Laboratory Association, a trade group representing large diagnostic companies like LabCorp and Quest, has recently reported a dip in the daily testing volumes of its members. On Monday, its members processed 43,000 tests, the lowest number since March 20. At one point in early April, members were processing more than 100,000 a day."

Lanneville said the people in the lab do not see the people who the samples come from. He said they don't even know their names. Each sample has a bar code to identify it to protect the identity of the person.

Lanneville said there are two types of testing done to determine if people have COVID-19. One is an antibodies test, which his company does not do. He said that test attempts to detect changes in immnune cells that are preparing to fight the virus. Lanneville said the problem with antibodies testing is that someone may be infected with the virus, but their body may not have changed to fight it yet, so it is possible to get false negatives. The other test, which his company uses, is a DNA test that directly detects the virus. It is called Polymerase Chain Reaction testing, which has been around since 1985. Lanneville said the test is based on a preliminary chain reaction that involves the COVID-19 being copied millions of times, if it is present in the sample from someone's body. He said the test takes a few hours to do.

"It's a little more involved," Lanneville said of the PCR test. "It's a little more technical. It takes a little more time."

Lanneville said sometimes the instrumentation being used to run the tests breaks down because it is being used so much to run samples.

Lanneville said the DNA test is more accurate than the antibodies test. He said reagants, that are like the on ramps and off ramps, are added to the DNA highway. The enzyme polymerase is the car that goes on and off the highway that replicates the viral DNA millions of times to confirm it's present. Lanneville said a process is gone through that can replicate viral DNA many times over if it is in the sample from the person's body. He said if there was COVID-19 in the person's body, there will be millions of copies of it. If the person did not have COVID-19, he said no copies are produced.

"It' very robust," Lanneville said of the PCR test. "It is very obvious who is positive for this virus and who is negative for it."

When Lanneville was interviewed by The Spectator over the phone last Monday, he had been at the lab in New Jersey for three weeks. He said when he first got to the lab, 30 to 32 percent of samples were testing positive for COVID-19, but those numbers rose to 35 to 36 percent. Lanneville said he does not think the increase is alarming because he says physicians are getting a better eye for who has symptoms of COVID-19, the flu or allergies.

Lanneville has worked in clinical laboratories for the last six years. He runs experiments that involve many people. Lanneville has a lot of experience running genetics based tests to see if there is a risk of passing on cystic fibrosis or other types of conditions to family members. He said his clients want more information about how that could affect the health of a child that is going to be born.

Lanneville said the COVID-10 DNA-based testing is a little different than what he usually does in terms of the setting and the patients, but he said the technology, equipment and theories behind the test are the same. He has been working 70 hours a week in the lab in New Jersey.

At Somerset High School, where he took Advanced Placement classes, Lanneville was involved in tennis, soccer, cross country and Model United Nations. After graduating from Somerset High School, Lanneville studied biology and economics at the University of Massachusetts at Amherst. While he is working, he is attending Boston College part-time to study business.

Asked about the risk of being infected with COVID-19 during the testing, Lanneville said, "At this point we are wearing surgical masks and protective face shields, along with gloves and labcoats. In addition, all COVID-19 samples (potentially positive or negative) are manipulated in a fume hood which has a negative pressure to essentially 'pull' the air out of the hood and also has a protective glass shield. There are some times when the samples are briefly exposed to the open air, when loading onto laboratory equipment, and there is no solution other than to minimize that time as much as possible."

"We have heard that another company performing testing in the area now has three technologists with COVID. There is some speculation that it may be due to the fact that the lab in question was manipulating samples in an open air environment. With all of the PPE needed at our disposal, I feel confident that risk of transmission is quite low. Honestly, I may have a higher likelihood of getting it from someone in the public areas of this building, outside of the lab, or the doorways of the hotel I'm staying at."

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Drinking filtered brew coffee is the healthiest, says study – Free Press Journal

Monday, April 27th, 2020

London: We may all be drinking more coffee to help us survive the coronavirus (COVID-19) lockdown, and now researchers have revealed that filtered brew is the safest and healthiest one.

The study, published in the European Journal of Preventive Cardiology, examined links between coffee brewing methods and risks of heart attacks and death and found that coffee drinking was not a dangerous habit. In fact, drinking filtered coffee was safer than no coffee at all. The lowest mortality was among consumers of 1 to 4 cups of filtered coffee per day."Unfiltered coffee contains substances which increase blood cholesterol. Using a filter removes these and makes heart attacks and premature death less likely," said study author Professor Dag S Thelle from the University of Gothenburg in Sweden.

According to the researchers, experiments identified the culprit substances in coffee and found that they could be removed using a filter. A cup of unfiltered coffee contains about 30 times the concentration of the lipid-raising substances compared to filtered coffee.

Between 1985 and 2003, the study enrolled a representative sample of the Norwegian population: 508,747 healthy men and women aged 20 to 79. Participants completed a questionnaire on the amount and type of coffee consumed.

Data was also collected on variables that could influence both coffee consumption and heart diseases, so that these could be accounted for in the analysis. For example, smoking, education, physical activity, height, weight, blood pressure, and cholesterol.

Participants were followed for an average of 20 years. A total of 46,341 participants died. Of those, 12,621 deaths were due to cardiovascular disease. Of the cardiovascular deaths, 6,202 were caused by a heart attack.Compared to no coffee, the filtered brew was linked with a 15 per cent reduced risk of death from any cause during follow up.

For death from cardiovascular disease, the filtered brew was associated with a 12 per cent decreased risk of death in men and a 20 per cent lowered risk of death in women compared to no coffee. "The finding that those drinking the filtered beverage did a little better than those not drinking coffee at all could not be explained by any other variable such as age, gender, or lifestyle habits. So we think this observation is true," Thelle said.

The filtered brew was also less risky than the unfiltered beverage for death from any cause, death due to cardiovascular disease and deaths from heart attacks. "Our analysis shows that this was partly because of the cholesterol-increasing effect of unfiltered coffee," Thelle explained.

The researchers noted that unfiltered coffee did not raise the risk of death compared to abstaining from coffee - except in men aged 60 and above, where unfiltered brew was linked with elevated cardiovascular mortality.

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Mt. Sinai Hospital’s Blood Test to Detect Antibodies to COVID-19 Receives Emergency Use Authorization From FDA – The Jewish Voice

Monday, April 27th, 2020

Edited by: JV Staff

Several days ago, the Mount Sinai Laboratory (MSL), Center for Clinical Laboratories received emergency use authorization from the U.S. Food and Drug Administration (FDA) for an antibody test that was developed, validated, and launched at Mount Sinai by a team of internationally renowned researchers and clinicians of the Icahn School of Medicine at Mount Sinai. This test detects the presence or absence of antibodies to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) and importantly, may also be used to identify positive specimens with an antibody titer (level) up to a dilution of 1:2880 for the identification of individuals with higher antibody titers.

This important regulatory authorization reflects the success of a truly translational medical effort by our basic scientists, pathologists, and clinicians who have risen to the occasion and combined their unparalleled expertise in a way that will help the community at large as we fight this terrible disease, said Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai, and President for Academic Affairs of the Mount Sinai Health System.

A research team led by Florian Krammer, PhD, Professor of Microbiology at the Icahn School of Medicine at Mount Sinai, began working on the serologic test in January 2020, before COVID-19 had been seen in the United States. To make the test, the researchers used animal cells to produce copies of the telltale spike protein that is present on the surface of SARS-CoV-2. That protein is highly immunogenic, meaning that peoples immune cells see it and start making antibodies that can lock onto it. The test involves exposing a sample of blood to bits of the spike protein. If the test lights up, it means that person has the antibodies. Similar to the most commonly used tests for other viruses, such as hepatitis B, this test shows whether a persons immune system has come into contact with SARS-CoV-2.

Our test can pick up the bodys response to infection, in some cases as early as three days post-symptom onset, and is highly specific and sensitive, says Dr. Krammer. We have shared the toolkit needed to set up the test with more than 200 research laboratories worldwide to help mitigate this global crisis.

Once the research test had been developed in Dr. Krammers microbiology lab, Mount Sinais pathology and laboratory medicine experts were able to quickly transfer the technology to The Mount Sinai Hospitals Clinical Laboratories, which are certified by the Clinical Laboratory Improvement Amendments and accredited by the College of American Pathologists, signifying that the laboratory meets or exceeds industry standards for clinical laboratory testing. In this regulated laboratory environment, under the guidance of Carlos Cordon-Cardo, MD, PhD, Irene Heinz Given and John LaPorte Given Professor and Chair of Pathology, Molecular and Cell-Based Medicine, the test was validated.

Our microbiology colleagues generated great science and tools that were brought from the research lab into the clinical space to implement robust and compliant diagnostic tests with great specificity and sensitivity so that we can better care for our patients, says Dr. Cordon-Cardo. We are grateful to the FDA for granting this expanded authorization so that we can deploy this vital test to the community at large.

Under the leadership of David L. Reich, MD, President of The Mount Sinai Hospital, and Judith A. Aberg, MD, Chief of the Division of Infectious Diseases and Immunology in the Department of Medicine, The Mount Sinai Hospital became among the very first in the United States to initiate a convalescent plasma program on Saturday, March 28.

The exchange of ideas between clinicians and scientists and our intense drive to innovate is the catalyst that led to this achievement, says Dr. Reich. Mount Sinai will continue to advance the science and medicine in the fight against COVID-19.

Serologic testing for COVID-19 is a critical tool for helping us to understand the nature of the disease within our communities., says Erik Lium, PhD, Executive Vice President and Chief Commercial Innovation Officer of the Mount Sinai Health System. We continue to broadly partner this technology with industry, recognizing the need to scale serologic testing effectively.

Mount Sinais rich history and leadership in the fields of pathology, microbiology, and immunology helped to make this discovery and clinical application possible. From its beginnings in 1893, the Mount Sinai Department of Pathology, Molecular and Cell-Based Medicine has been a leader in the field. In addition to delivering more personalized pathology services to patients, Mount Sinai was the first major medical center to establish a fully integrated pathology department combining the various arms of testinganatomical, clinical, molecular/genetic, and cytologicalunder a single umbrella and now has the second largest department of its type in the nation.

The Department of Microbiology is led by internationally renowned microbiologist Peter Palese, PhD, who pioneered the field of reverse genetics for negative-strand RNA viruses, a revolutionary technique that is crucial for the study of the structure/function relationships of viral genes, for the investigation of viral pathogenicity, and for the development and manufacture of novel vaccines. It also has significant implications in understanding and preparing for infectious disease pandemics. Dr. Palese has recruited some of the top microbiologists in the world to study viruses and emerging pathogens. And the Division of Infectious Diseases is at the forefront of research, treatment, and prevention of infectious diseases with investigations focused on improving patient outcomes and rapidly translating research findings into patient care.

For inquiries related to commercial licensing of the test, please contact Cynthia Cleto from Mount Sinai Innovation Partners at: [emailprotected]

If you have recently recovered from COVID-19,see if you qualify for convalescent plasma transfusion.

To support COVID-19 research and response efforts, visit https://www.mountsinai.org/covid19research.

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Mt. Sinai Hospital's Blood Test to Detect Antibodies to COVID-19 Receives Emergency Use Authorization From FDA - The Jewish Voice

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Student Spotlight on Mika Matera-Vatnick ’21: Researching Insect Reproduction Genetics – Cornell University The Cornell Daily Sun

Saturday, April 18th, 2020

When Mika Matera-Vatnick 21 received President Martha E. Pollacks email in March announcing the closing of campus, her first thought was, What am I gonna do with my flies?

Matera-Vatnick, like many other undergraduate student researchers on campus, had to abandon her honors thesis research project as classes transitioned online for the remainder of the semester.

Last spring, Matera-Vatnick joined the Wolfner lab, led by Prof. Mariana Wolfner, molecular biology and genetics.

Research is the main thing Im involved with on campus. When Im not in class, Im in the lab, she said.

Currently, her research is on pause, since as of March 28, faculty and students are no longer allowed to work in laboratories, barring Matera-Vatnick access to laboratory equipment that is essential to the continuation of her research.

Matera-Vatnick is exploring the genetic basis of sperm competition in fruit flies the competitive process between sperm of two or more different males to fertilize the same egg during sexual reproduction.

Her passion for genetics started during a summer research experience at the bioethics department at the National Institutes of Health after her freshman year, where she learned about personalized medicine.

We are all unique with our own unique genomes and we need to treat patients based on their individual needs and their own genome. This is what led me to take the genetics and genetics lab courses at Cornell, she said.

Specifically, Matera-Vatnick is researching whether there are certain genes linked to mating plug ejection times.

Mating plugs are gelatinous secretions used in the mating in fruit flies and other species, including various primates such as kangaroos and reptiles. These secretions are deposited by a male into a female genital tract and later harden into a plug that glues the tract together. The plugs prevent females from re-mating, making it possible for females to store sperm.

In my experiments, Im comparing how long different strains of flies take to go through the process of mating plug ejection and seeing if there is a genetic basis and where in the gene this might come from, Matera-Vatnik said.

In fruit flies, the female expels the mating plug within five hours of mating in a process called mating plug ejection. The timing of ejection influences the paternity share of the fruit flys mates, playing an important role in mate competition.

Paris Ghazi / Sun Senior Editor

Matera-Vatnick experimenting in the Wolfner lab.

Matera-Vatnik randomly selected genetically diverse types of fruit flies to assess the time it takes for female fruit flies to undergo mating plug ejection. Mating plug ejection times can be compared to genetic variations across these specific fruit fly lines.

This comparison can reveal key genes associated with mating plug ejection, evolutionary histories of neural circuits and the role of these neuronal pathways in female sexual selection when a female chooses a male to mate with.

Understanding the process of sexual selection in insect reproduction may contribute to developing strategies for controlling pests and disease vectors in agriculture and public health.

Matera-Vatnick spent last summer at Weill Cornell Medicine in New York City learning about computational biology, which is the analysis of biological data through computer simulated models. In contrast to the work she did at WCM, Matera-Vatnick typically conducts her research on fruit flies in a wet lab. A wet lab is a lab where experiments are conducted and chemicals are handled, whereas in a dry lab, data is analyzed with computers and other technology.

Not much is known about the genetic basis that underlies the variations in mating plug ejection timing, but Matera-Vatnik is determined to find out.

I learned so much about how computational tools can be used to answer biological questions that are impossible to answer in a wet lab. I think that combining wet lab and computational power together will bring a unique angle to the questions Im interested in answering, she said.

Though research on campus has been put on hold, Matera-Vatnick is hopeful she can finish this project as her honors thesis.

This is the project that will be my senior thesis project. With all the uncertainty of being here, and hopefully the plan is to stay here over the summer, I want to take this project as far as I can before I graduate, Matera-Vatnick said.

Matera-Vatnick is currently in her hometown Washington, D.C. While she is unable to continue her research at the Wolfner Lab, she still attends weekly lab meetings and will be drafting sections of her honors thesis for the rest of the semester. She plans on taking the MCAT at the end of summer, if permitted.

In the meantime, Matera-Vatnick hopes to make the most of her Cornell research experience, upon her return to campus.

Im trying to take as much as I can from campus, Matera-Vatnick said. Thanks to amazing mentorship from my [Principal Investigator], graduate students and other students in the lab, I can say Im very lucky with who Ive surrounded myself with on campus.

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Student Spotlight on Mika Matera-Vatnick '21: Researching Insect Reproduction Genetics - Cornell University The Cornell Daily Sun

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Worldwide competition to find cure for COVID-19, other deadly viruses – WOGX

Saturday, April 18th, 2020

Great lab race to find cure for COVID-19

Researchers are trying to create and kill some of the most powerful viruses in the world in an ongoing competition.

Orlando, FL(FOX 35 Orlando) - Researchers are trying to create and kill some of the most powerful viruses in the world in an ongoing competition.

Youve heard of the space race, but did you know theres a race to find a cure for COVID-19? Dr. Paul Gulig, Department of Molecular Genetics and Microbiology at the University of Florida's College of Medicine says it's happening in several counties.

"Theres been discussion which tests were better," he says. "There can be an element of competition, almost sportslike and that is were in this altruistically. We generally want to help human health and mankind. At UF and around the world people are working on that."

He adds that when you have a limited resource like grant funding and the demand exceeds the supply, by definition, there is competition.

"We have to have a better grant proposal than the next person or theyre going to get the money and were not."

However, he says its not just about the money.

"Whoever comes up with the best things first is going to be able to come up with bragging rights."

But even with a race in research, he believes something positive has come out of this.

"Research scientists are banning together, I think theyre coming up with ways to collaborate that they havent before."

Dr. Michael Pape, professor of practice at the University of Central Floridas College of Business agrees, saying you can see the difference just by looking at ClinicalTrials.gov.

"There are 45 vaccine related clinical trials going on for COVID-19 and that is within two months. So youve got this type of contrast because of the pace of innovation, the ability to share information."

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Worldwide competition to find cure for COVID-19, other deadly viruses - WOGX

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COVID-19: Hydroxychloroquine Does Not Work Better Than Standard Treatments in Trial – MedicineNet

Saturday, April 18th, 2020

APRIL 17, 2020 -- Hydroxychloroquine (HCQ) does not help clear the SARS-CoV-2 virus or relieve symptoms for COVID-19 patients more than standard care alone and has more side effects, a randomized controlled trial of 150 hospitalized adults in China suggests.

However, two experts caution that because of confounding, the trial is unable to answer convincingly the question of whether HCQ can benefit COVID-19 patients.

Wei Tang, with the Departments of Pulmonology and Critical Care Medicine at Ruijin Hospital, in Shanghai, China, and colleagues enrolled patients with COVID-19 from 16 treatment centers in China in February. They posted their findings on the medRxiv preprint server, but their paper has not been peer reviewed. A coauthor told Medscape Medical News the work has been submitted to a journal.

The overall 28-day negative conversion rate of SARS-CoV-2, which was the primary endpoint, was similar in the two 75-patient treatment groups. The Kaplan-Meier estimate for negative conversion rate was 85.4% in the HCQ plus standard of care (SOC) arm, vs 81.3% in the SOC-only group (P = .341). Negative conversion rates for the two groups were similar at days 4, 7, 10, 14, and 21.

Adverse events were reported in 8.8% of patients in the control group compared with 30% in the HCQ group. Diarrhea was the most common side effect, occurring in 10% of patients in the HCQ group vs none in the control group. Two patients in the HCQ arm had serious adverse events; one experienced disease progression, and the other experienced upper respiratory tract infection.

Patients in the HCQ group received a high loading dose of 1200 mg daily for 3 days followed by a maintenance dose of 800 mg daily for the remaining days. Total duration was 2 weeks for patients with mild or moderate disease and 3 weeks for those with severe disease.

No Difference in Relief of Symptoms

The two arms were similar in alleviation of symptoms by day 28: 59.9% with HCQ plus SOC vs 66.6% with SOC alone.

However, the researchers said that in a post hoc analysis, they found a significant reduction of symptoms after adjusting for the confounding effects of antiviral agents (hazard ratio, 8.83; 95% confidence interval, 1.09 71.3).

In addition, Tang and colleagues report a significantly greater reduction of C-reactive protein (CRP), a biomarker for inflammation, from baseline to day 28 in the HCQ group in comparison with the control group (6.986 vs 2.723 mg/L).

The authors suggest the alleviation of symptoms may come from HCQ's anti-inflammatory effects.

The mean age of the patients was 46 years, and 55% were male. Almost all patients had mild or moderate disease; two had severe disease.

Experts Say Study Arms May Not Have Been Comparable

J. Michelle Kahlenberg, MD, PhD, research professor of rheumatology at the University of Michigan in Ann Arbor, told Medscape Medical News that it's important to note that in the post hoc analysis, 89% of the patients in this trial were receiving other therapy in addition to HCQ.

"When [the researchers] say they saw improvement in symptoms when they removed the confounders, what they actually did was remove the patients from the analysis that got antivirals, and that left 14 patients in each arm," Kahlenberg said.

Moreover, Kahlenberg noted, 20% of patients who received HCQ had mild symptoms, whereas only 9% of those in the SOC group did.

"We don't know how those patients played out in the post hoc analysis whether it was the patients who were really mild that didn't get the antivirals that were left in the hydroxychloroquine group and that's why they had a slightly faster resolution of symptoms," she said.

She said that in this study, the researchers calculated CRP in milligrams per liter, whereas in the United States, it is measured in milligrams per deciliter. The conversion highlights the fact that the reduction in CRP was not terribly noteworthy, she said.

"The patients with COVID who tend to tank and have cytokine storms ? their CRP is much higher," she said. "So the small improvement in CRP wasn't that exciting.

"I don't think this gets us anywhere closer to an answer. It's another muddy study," she said.

Similarly, Christopher V. Plowe, MD, MPH, director of the Global Health Institute at Duke University in Durham, North Carolina, told Medscape Medical News he sees no convincing answers in this study.

Plowe, professor of medicine, molecular genetics, microbiology, and global health at Duke, also noted differences between the two groups at enrollment.

For example, the HCQ group had more than three times the number of patients with shortness of breath (22.1% vs 5.9%); more with sputum production (16.2 vs 5.9%); and more with cough (51.5% vs 38.2%). In addition, the average age was 4 years higher in the HCQ group.

"It makes me wonder whether the randomization was truly random," Plowe said.

Plowe also questioned the authors' statement that they didn't see cardiac arrhythmia events, such as prolonged QT intervals. "I can't see any evidence that they did an EKG on anybody," he said.

"This study leaves the door open to the possibility that hydroxychloroquine may have a clinical benefit. If there is a benefit, it seems to be related to the drug's anti-inflammatory properties. If that's the case, I'm not sure this particular drug, as opposed to others, would be the way to go," Plowe said.

Mixed Results in Other Studies

"Our negative results on the anti-viral efficacy of HCQ obtained in this trial are on the contrary to the encouraging in-vitro results and to the recently reported promising results from a non-randomized trial with 36 COVID-19 patients," the authors write.

However, the 36-patient trial to which they refer has since been called into question, as previously reported by Retraction Watch.

Despite lack of clear evidence of benefit, HCQ is recommended off label for the treatment of COVID-19 by the Chinese National guideline, and the US Food and Drug Administration has issued an emergency-use authorization for the treatment of adult patients with COVID-19.

By contrast, the Infectious Diseases Society of America recently concluded that because of insufficient data, they could not recommend any particular treatment for patients with COVID-19.

References

2020 WebMD, LLC. All Rights Reserved.

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COVID-19: Hydroxychloroquine Does Not Work Better Than Standard Treatments in Trial - MedicineNet

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How does a COVID-19 testing center look like? – The Times of Israel

Saturday, April 18th, 2020

The current time is unprecedented. We havent seen anything like this in the last ~100 years and (hopefully) wont see in the next 100 years. But, as a Ph.D. student in Molecular Genetics, it is moving to answer curious questions that people from non-scientific backgrounds might have regarding how coronavirus works and what can be done to slow it down.

In addition, I was fortunate enough to participate in the COVID-19 testing facility at the Weizmann Institute of Science, Israel. As the number of infections in Israel is going up, the facility at the Israel National Center for Personalized Medicine was commissioned to ramp the testing numbers. The center is one of the most sophisticated, top-of-the-line facilities, which can run ~4000 tests a day at its fullest capacity, while presently only 2500 tests are performed a day in Israel for a population of ~9 million. The idea of this article is to show how a COVID-19 testing facility looks like and take a step-by-step look at the operational pipeline.

A scheme of the operational pipeline for COVID-19 testing

Step 1 at Station A: The nasopharyngeal swab samples are received from hospitals/paramedical service in plastic tubes along with a document containing the patient information. Upon reception, each sample is cleaned and disinfected thoroughly with 70% ethanol and packed in a cooler box for internal transportation.

Team of volunteers at Station A (Image: Weizmann Institute of Science)

Step 2 at Station B: Here, hundreds of tubes are prepared, each containing a special kind of solution, called lysis/shield buffer. The genetic information of the SARS-Cov-2 virus (nCoV-2) is encoded by a molecule called RNA, which is a rather unstable molecule. The solution can stabilize the RNA molecule. It also contains a detergent that can inactivate the viral particles. Each of the tubes carries a unique barcode.

Step 3 at Station C: The swab samples from Station A and the buffer solutions from Station B are brought here. Station C is a biosafe room with biological hoods. These hoods are extremely sterile chambers, free from any biological contamination so that the technicians have minimal chance to come in contact with the virus. Each swab sample is manually inspected and added to the lysis buffer solution inside the hood. The barcode and the sample document are uploaded to an internal tracking software. The viral particles are inactivated from now on and can be handled with less stringency. The test tubes with the samples are then arranged in racks. The remaining swab sample from patients is returned to a fridge in order to be stored for at least 48 hours, in case a repetition of the test becomes necessary.

Step 4 at Station D: The racks (containing the sample in lysis buffer) from Station C are brought to Station D where an automated system can take a small volume containing the patient swab and put into a 96-well plate format. Such 96-well plates are routinely used in molecular biology approaches to detect nucleic acids (DNA/RNA).

Step 5 at Station E: In this station, a robotic liquid handler can assemble all the ingredients required for the subsequent chemical reactions. In the first reaction, the RNA from the virus is converted to its complementary DNA (cDNA) by an enzyme called reverse-transcriptase (co-incidentally, also first discovered in a virus). In the next reaction, the cDNA is acted upon by an enzyme (called DNA-polymerase that can work at high temperature) to produce multiple copies of a part of the cDNA by a process called polymerase chain reaction (PCR). The choice of the part of the cDNA is critical as it gives specificity to the detection of SARS-CoV-2, vis-a-vis other coronaviruses. The output of the test is typically in the form of a number (called, Ct) between 5-40, which is inversely related to the viral load in the patient. Thus, the lower the Ct, the more likely the patient is positive.

To increase the confidence in the test, two such regions of the nCoV-2 cDNA (N1 and N2) are chosen. For a test to be called positive, both N1 and N2 have to return a number below 40. More typically, the number hovers between 30 and 40 for positive cases. For negative cases, the numbers are above 40.

Step 6: In the last step, the data and corresponding patient ID are uploaded to the internal software and the final results are sent to the Ministry of Health.

All the stations are staffed with teams of 3-4 technicians while the entire operation is managed by a control center overlooking all stations and ensuring a smooth relay of materials and information between teams.

The team at the command center ensuring a streamlined operation (Image: Weizmann Institute of Science

Accuracy: RT-PCR based testing for the nCoV-2 virus is an extremely accurate test, with about a 3% chance of being falsely negative. Other than the operational steps, the false-negatives can arise from the presence of an extremely low amount of viral particles in the tested swab, below the detection limit of PCR. According to the US CDC, nasopharyngeal swabs are likely to yield the best results compared to swabs from other parts (nasal, oral, etc,)

What about scaling up?

In the present framework, all actions from Station D onwards (involving inactivated virus) are handled by automation, so it is relatively easy to scale up. However, all activities from receiving the samples to inactivating them are done manually under extreme care by trained professionals so as to minimize contamination of samples or spillage. Thus, it becomes one of the most time- and effort- consuming parts of the operation. Additionally, the collection of swabs is also done by trained front-line workers one-by-one, adding to the effective testing time. Thus, the rate-limiting step of the entire process becomes the collection and pre-processing of the samples, instead of the actual tests. The current end-to-end time (from the reception of the sample to delivery of results) is ~24 hours.

Further reading/watching:

Sandipan Dasgupta is a Ph.D. candidate at Weizmann Institute of Science, Israel and a co-founder of Weizmann Biotech Club. Previously, he was an Israel-Asia Leaders fellow at Israel-Asia Center, Jerusalem. He regularly blogs on India-Israel relations and is passionate about connecting global innovation ecosystems to India.Note: All opinions expressed are personal and are not endorsed by any affiliated institution or organization.

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How does a COVID-19 testing center look like? - The Times of Israel

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Why genetics is key to the evolution of aquaculture – The Fish Site

Saturday, April 18th, 2020

Many species of fish and shellfish have been domesticated relatively recently compared with most livestock species, and so have diverse gene pools with major potential for selective breeding, according to a new review paper in Nature Reviews Genetics.

The development of tools to gain insight into the genetics of these species, and apply such tools for breeding and management, provides opportunities to release that potential, researchers say.

Most aquaculture species can produce many offspring, and large populations with improved genetics can be bred quickly for improved production performance.

The benefits may include improved growth, resistance to disease or robustness in diverse farming environments.

Farmed fish is on course to overtake wild fish as the main source of seafood, and consequently genetic tools and expertise are in high demand to increase the efficiency and sustainability of aquaculture systems, which currently rely mostly on unselected stocks.

Insight into the genomes of species can enable careful selection of a farming population with desirable traits, and monitoring genomic variation will help maintain genetic diversity as farm populations develop.

In the future, technologies such as genome editing could be used to introduce desirable traits, such as disease resistance, into farmed species, and surrogate breeding could be employed to support production of preferred species.

The review paper a collaboration between experts from Universities of Edinburgh, Exeter, Stirling, and Aberdeen is an output of the AquaLeap consortium project.

AquaLeap is funded by the Biotechnology and Biological Sciences Research Council, the Natural Environment Research Council and the Scottish Aquaculture Innovation Centre, in partnership with the Centre for Environment, Fisheries and Aquaculture Science, Hendrix Genetics, Xelect, The National Lobster Hatchery, Tethys oysters, and Otter Ferry SeaFish.

Environmental biologist Dr Eduarda Santos, from the University of Exeter, who is the co-author of the study, said: "The rapid expansion of aquaculture has contributed to increased food security across the globe, however, issues related to domestication of desired species and emergence of diseases, limit its further development.

"Genomics has the potential to offer solutions to many of these limitations by improving our knowledge of the genomes of cultured organisms, genetic selection, and better understanding of the dynamic interactions between genes and the environment, to maximise food production."

Dr Jamie Stevens, also from the University of Exeter and co-author added: "We only have to look at the example of Atlantic salmon to see the immense value of a sequenced genome to the relatively recent optimisation of a wild species for the aquaculture market.

"Similarly, we anticipate the delivery of a genome for other species, including the European lobster, will offer similar opportunities to develop molecular tools with which to rapidly increase the potential of lobster as an aquaculture species and improve the sustainability of its wild populations."

Professor Ross Houston, from the Roslin Institute, agreed, saying: "There is a timely opportunity to harness the potential of farmed aquatic species, to ensure food security for a growing population. Genomic selection and biotechnology can speed up this process, and recent developments in these fields will soon be translated to benefit aquaculture production for many of these species across the world."

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Why genetics is key to the evolution of aquaculture - The Fish Site

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New study suggests COVID-19 hopped from dogs to humans. Here’s why you should be skeptical. – Live Science

Saturday, April 18th, 2020

The novel coronavirus likely originated in bats, but the pathogen may have then hopped into dogs before infecting humans, a new study suggests.

But not everyone agrees with that hypothesis. One expert told Live Science that "there are a lot of weaknesses" in the study and that the data don't support the study's conclusions.

Before the new coronavirus SARS-CoV-2 made the jump to humans, two other coronaviruses, SARS-CoV and MERS-CoV, evolved in bats and passed through other animals on their way to people. SARS-CoV passed through civets and MERS-CoV through camels, and the molecular structure of SARS-CoV-2 suggests that the virus also passed through an intermediate animal, but scientists don't yet know which one.

In February, authors of a preliminary study published to the preprint database bioRxiv suggested that pangolins may bridge the gap between bats and humans, since SARS-CoV-2 and related coronaviruses that infect pangolins sport similar spike proteins a structure on the surface of the virus that allows it to infect cells. But other scientists argued that, despite their spike proteins, pangolin coronaviruses bear many differences to SARS-CoV-2 that make pangolins unlikely to be the source of infection, The New York Times reported.

With the mystery unresolved, biology professor Xuhua Xia of the University of Ottawa in Canada launched his own investigation into how the coronavirus passed from bats to people. His analysis, published April 14 in the journal Molecular Biology and Evolution, offered a new solution: dogs.

Xia reached his conclusion by scanning the genetic code of SARS-CoV-2 and other coronaviruses for a specific feature known as a CpG site, a sequence of genetic code in which the compound cytosine (C) is followed by the compound guanine (G). The human immune system sees CpG sites as a red flag, signaling that an invasive virus is present. A human protein called zinc finger antiviral protein (ZAP) latches onto the CpG sites on the viral genetic code and recruits help to break down the pathogen, according to UniProt, an online protein database. The theory follows that, the fewer CpG sites, the less vulnerable a virus will be to ZAP.

Related: 10 deadly diseases that hopped across species

Xia found that SARS-CoV-2 carries fewer CpG sites than the other known coronaviruses that first evolved in animals, including SARS-CoV and MERS-CoV. In addition, the closest known relative of SARS-CoV-2, the bat coronavirus RaTG13, contains fewer CpG sites than related bat coronaviruses, according to the analysis. "This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression," which would place evolutionary pressure on the virus to shed CpG sites, Xia wrote.

Essentially, in order to survive and reproduce, a pathogen like SARS-CoV-2 needs to be able to evade the hosts immune fighters, and in this case it would mean getting rid of CpG sites that could alert ZAP proteins to the virus.

Unfortunately, little data exists on exactly how much ZAP appears in different animal tissues, Xia told Live Science. So he worked backwards, looking for animal coronaviruses with low CpG levels. He found a coronavirus that primarily infects the canine intestine, and thus inferred that the dog gut might contain adequate ZAP levels to drive viral evolution in this way.

"Only canids seem to have the tissue generating low-CpG CoVs during my study," Xia said. If a precursor to SARS-CoV-2 breached the canine intestine, then this would have "resulted in rapid evolution of the virus" to lose CpG sites and become better equipped to infect humans, he wrote in the paper. Beyond the low CpG levels, the paper did not note other genetic similarities between SARS-CoV-2 and the dog coronavirus, but suggested that the canine gut might provide the right environment for such viruses to evolve.

But why the dog intestine? Some research suggests that ZAP mRNA, which contains instructions to build the protein, appears in both the dog lung and colon but that higher concentrations accumulate in the lungs, Xia said. It may be that a glut of ZAP in the lungs guards the organ from coronaviruses, while the lower concentrations of ZAP in the colon leave the gut open to severe infection, though there are reasons to be cautious in coming to this conclusion, Xia said.

But does this hypothesis make sense?

"I think the data do not support these conclusions," Pleuni Pennings, an assistant professor of ecology and evolution at San Francisco State University, who was not involved in the study, told Live Science in an email. Pennings, whose research group has examined the CpG levels of many viruses, pointed out several weaknesses in the study's logic.

In a 2018 study published in the journal PLOS Genetics, Pennings surveyed CpG levels in the HIV virus and investigated how the pathogen evolves within individual people. She then led a similar study of several other viruses including Dengue fever virus, influenza, and hepatitis B and C to learn how often these bugs lose or gain CpG sites through mutations. Her group found that, in general, mutations that add CpG sites tend to be found in viral samples taken from people less often than mutations that remove CpG sites from the genome.

CpG-creating mutations may be costly to viruses in that they alert the body to infection, so over time, evolutionary forces minimize their appearance, Pennings said. That said, many viruses still carry CpG sites, so the mutations may carry some benefit "even if it comes with a slight cost," she added. So SARS-CoV-2 is not unusual in that way.

"There are many viruses with lower [CpG] values than SARS-CoV-2," Pennings said. "When you look at all viruses, the [CpG] value is not strange at all," she said.

Xia did find that SARS-CoV-2 contains fewer CpG sites than other animal-borne coronaviruses, and assuming that finding is correct, then it raises the question of why that came to be, she added.

But even if there is an evolutionary reason to explain why SARS-CoV-2 lost CpG sites, that evolutionary reason may not give the virus a special advantage for infecting humans, Pennings said.

In his paper, Xia noted that studies have "shown an association between decreased CpG in viral RNA genomes and increased virulence," meaning low-CpG viruses appear associated with more severe infection. However, although evolution favors mutations that delete CpG sites, and there's a general trend tying fewer CpG sites to more severe infection, "it doesnt mean that viruses with low numbers of CpG sites are necessarily more virulent," Pennings said. For example, the BK virus contains very few CpG sites and resides in the kidneys of an estimated 60% to 80% of adults, but typically only triggers symptoms in immunosuppressed people, she noted. (The virus was named the initials of the first person it was isolated from.)

If the CpG levels present in SARS-CoV-2 are somehow related to disease severity, "then this would provide an efficient way for vaccine development," Xia said. In this hypothetical scenario, scientists could eliminate CpG sites from the coronavirus genome in a lab dish, thereby weakening the bug to the point that it could safely be incorporated into a vaccine. But as of yet, no correlation has been drawn between CpG and the relative severity of SARS-CoV-2 infections.

Several pangolin coronaviruses included in Xia's study also contained few CpG sites, on par with SARS-CoV-2 and the bat virus RaTG13. Given other genetic differences between human and pangolin coronaviruses, however, the ancestor shared between this low-CpG pangolin coronavirus and SARS-CoV-2 would likely have existed over 130 years ago, Xia said. "We expect a SARS-CoV-2 progenitor to be much more recent," he said.

But did dogs serve as an intermittent host for the coronavirus? At this point, there's little evidence to suggest so.

Originally published on Live Science.

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New study suggests COVID-19 hopped from dogs to humans. Here's why you should be skeptical. - Live Science

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