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American Society of Clinical Oncology Exclusively Cites myChoice CDx in New Recommendations for Patients with Advanced Ovarian Cancer – BioSpace

Posted: August 21, 2020 at 8:58 pm

SALT LAKE CITY, Aug. 21, 2020 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a global leader in molecular diagnostics and precision medicine, announced today that the American Society of Clinical Oncology (ASCO) has exclusively included Myriads myChoice CDx test in its new recommendations on the use of PARP inhibitors for the treatment and management of certain patients with advanced ovarian cancer. The new recommendations, based on clinical trial results, were published in the Journal of Clinical Oncology.

The guideline, titled PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline, where myChoice CDx was the only named commercial companion diagnostic, states that women with ovarian cancer and germline or somatic mutations in BRCA1 or BRCA2 genes and/or genomic instability as determined by Myriad myChoice CDx are recommended by ASCO for PARP inhibitor therapy. The guideline includes myChoice CDx guided management in both newly diagnosed and recurrent ovarian cancer.

We are thrilled to be a part of the rapidly changing landscape in guiding treatment for patients with ovarian cancer. The new ASCO guidelines highlight the large number of recent studies that have gone into improving ovarian cancer patient outcomes, said Thomas Slavin, M.D., FACMG, DABCC, senior vice president of Medical Affairs for Myriad Oncology.

According to the American Cancer Society, ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. In the United States, it is estimated there will be 21,750 new cases diagnosed and around 13,940 deaths in 2020. A woman's risk of getting ovarian cancer during her lifetime is about one in 78 and the chance of dying from ovarian cancer is about one in 108.

About Myriad myChoice CDx Myriad's myChoice CDx is the most comprehensive homologous recombination deficiency test, enabling physicians to identify patients with tumors that have lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. The myChoice CDx test comprises tumor sequencing of the BRCA1 and BRCA2 genes and a composite of three proprietary technologies (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions). For more information, visit: https://myriad-oncology.com/mychoice-cdx/

About Myriad GeneticsMyriad Genetics Inc., is a leading personalized medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on three strategic imperatives: transitioning and expanding its hereditary cancer testing markets, diversifying its product portfolio through the introduction of new products and increasing the revenue contribution from international markets. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, Vectra, Prequel, Foresight, GeneSight, riskScore and Prolaris are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the new ASCO guideline titled PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline and the Companys myChoice CDx testings place in such guideline; and the Companys strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties associated with COVID-19, including its possible effects on our operations and the demand for our products and services; our ability to efficiently and flexibly manage our business amid uncertainties related to COVID-19; the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decisions in Mayo Collab. Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012), Assn for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), and Alice Corp. v. CLS Bank Intl, 573 U.S. 208 (2014); risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2020, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

Media Contact:Jared Maxwell(801) 505-5027jmaxwell@myriad.com

Investor Contact:Scott Gleason(801) 584-1143sgleason@myriad.com

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American Society of Clinical Oncology Exclusively Cites myChoice CDx in New Recommendations for Patients with Advanced Ovarian Cancer - BioSpace

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Kelly Morgan, MS, CGC, the Future of Telemedicine and Genetic Testing – Cancer Network

Posted: August 21, 2020 at 8:58 pm

While pre- and post-test education on genetic testing helped to educate patients, recent study findings may also highlight the way that telemedicine is revolutionizing the space, according to Kelly Morgan, MS, CGC.

In a recent study, presented at the 2020 ASCO Virtual Scientific Program, the BRCA Founder OutReach (BFOR) offered pre-testing online education with posttest engagement of primary care providers, which appeared to be effective in educating both patients and providers alike.

In an interview with CancerNetwork, Morgan, a genetic counselor at Memorial Sloan Kettering Cancer Center, explained how telemedicine is changing the future of genetic testing.

Transcription:

The current focus is going to be continuing to survey our participants and then analyze and report out our findings. These are sort of our first set of early results. But the goal from there is, there's a lot of different ways in which this information can probably be used in terms of next steps.

One of the things I mentioned was the idea of new ways to engage primary care providers. So that's certainly an area of interest. One thing I didn't mention, but it's also kind of along the lines of where we want to go is we were very happy with the recruitment that we achieved, but at the same time, we think this tool could be used even more broadly, potentially. So finding ways to better distribute this information and engage a broader number of participants. And then lastly, the immediate context for this is thinking about how this model may work for population screening in the Ashkenazi Jewish group. But there are ways that we could pivot this to other situations as well. So, whether that be things like testing family members for an unknown mutation, or maybe there are other groups with predominant risk factors where this model could work as well. So, I think that once we better understand the long term medical outcomes of participants, we will be able to continue to think about different ways that we can improve and change the model and then apply it further in this context and others as well.

I think, now more than ever, is a time where there's almost a digital revolution, if you will, and a lot of technology in the forefront. So, from our perspective, our goal is to find a way to leverage technology in the context of medicine and use it for better. So there's always a lot going on in terms of many different ways to access testing direct to consumer testing. And, you know, if and when this sort of convenience can be combined with medicine, I think there's a lot of opportunities for improved patient care through that partnership.

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Kelly Morgan, MS, CGC, the Future of Telemedicine and Genetic Testing - Cancer Network

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European Commission Approves KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in Combination With Ivacaftor to Treat Cystic Fibrosis in People Ages 12 Years…

Posted: August 21, 2020 at 8:58 pm

Aug. 21, 2020 13:07 UTC

For the first time, up to 10,000 people in Europe ages 12 years and older with one F508del mutation and one minimal function mutation will be eligible for a medicine that treats the underlying cause of cystic fibrosis

People 12 years of age and older who have two F508del mutations will also be eligible for the new triple combination regimen

LONDON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the European Commission (EC) has granted marketing authorization for KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with ivacaftor to treat people with cystic fibrosis (CF) ages 12 years and older with one F508del mutation and one minimal function mutation (F/MF), or two F508del mutations (F/F) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

For the first time, up to 10,000 people in Europe ages 12 years and older with CF who have one F508del mutation and one minimal function mutation will be eligible for a CFTR modulator that treats the underlying cause of the disease. Approval of the triple combination regimen also expands the number of treatment options available to people ages 12 years and older with CF who have two copies of the F508del mutation, the most common CF-causing mutation worldwide.

Today is a significant day for those with CF, their families and Vertex, and one that brings us one step closer towards our ultimate goal of discovering and developing treatments for all patients with CF, said Reshma Kewalramani, M.D., Chief Executive Officer and President, Vertex. I would like to thank our dedicated scientists, as well as study investigators and people with CF who participated in our clinical trials to enable this innovative medicine to be approved in Europe today. Without their commitment, this milestone would not have been possible.

As a result of long-term reimbursement agreements in England, Denmark and the Republic of Ireland, and provisions for access in health care systems such as Germany, eligible patients in these countries will have access to the triple combination regimen in the upcoming weeks. Vertex is committed to working closely with national health authorities and governments in all other countries in Europe to secure access for eligible patients as quickly as possible.

Marketing authorization was based on the results of two global Phase 3 studies, which showed statistically significant and clinically meaningful improvements in lung function (primary endpoint) and all key secondary endpoints, in people with CF ages 12 years and older with one F508del mutation and one minimal function mutation or two F508del mutations in the CFTR gene. The triple combination regimen was generally well tolerated in both studies.

The triple combination regimen has been shown to have a major impact on several outcome measures in people with CF, said Professor Harry Heijerman, Professor and Head of the Department of Pulmonology at University Medical Center Utrecht, Netherlands. The clinical data showed significant improvements in lung function and other important measures, such as sweat chloride levels and quality of life as measured by the CFQ-R respiratory domain score, in patients treated with the triple combination therapy. I now look forward to seeing the impact of the medicine in clinical practice.

About Cystic Fibrosis

Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting approximately 75,000 people worldwide. CF is a progressive, multi-system disease that affects the lungs, liver, GI tract, sinuses, sweat glands, pancreas and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes one from each parent to have CF. While there are many different types of CFTR mutations that can cause the disease, the vast majority of all people with CF have at least one F508del mutation. These mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working and/or too few CFTR proteins at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the early 30s.

About KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a Combination Regimen With ivacaftor

KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with ivacaftor 150 mg was developed for the treatment of cystic fibrosis (CF) in patients ages 12 years and older with one F508del mutation and one minimal function mutation (F/MF) or two F508del mutations (F/F) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. KAFTRIO is designed to increase the quantity and function of the F508del-CFTR protein at the cell surface. The EU submission for KAFTRIO was supported by positive results of two global Phase 3 studies in people ages 12 years and older with CF: a 24-week Phase 3 study in 403 people with one F508del mutation and one minimal function mutation (F/MF) and a four-week Phase 3 study in 107 people with two F508del mutations (F/F).

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London, UK. Additionally, the company has research and development sites and commercial offices in North America,Europe,AustraliaandLatin America. Vertex is consistently recognized as one of the industry's top places to work, including 10 consecutive years on Science magazine's Top Employers list and top five on the 2019 Best Employers for Diversity list by Forbes.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements made by Dr. Reshma Kewalramani and Professor Harry Heijerman in this press release, statements regarding the eligible patient population in Europe, our expectations regarding the timing of access to the triple combination regimen across countries in Europe, and our plans to secure access to our medicine for additional patients in Europe. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy or other reasons, risks related to commercializing medicines in Europe, and other risks listed under Risk Factors in Vertex's annual report and subsequent quarterly reports filed with the Securities and Exchange Commission and available through the company's website at http://www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

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European Commission Approves KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in Combination With Ivacaftor to Treat Cystic Fibrosis in People Ages 12 Years...

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Analysts Mean recommendation for Sarepta Therapeutics Inc. (SRPT) was 1.70: Is this the key time? – The InvestChronicle

Posted: August 21, 2020 at 8:58 pm

Sarepta Therapeutics Inc. (SRPT) is priced at $140.97 after the most recent trading session. At the very opening of the session, the stock price was $144.00 and reached a high price of $144.345, prior to closing the session it reached the value of $148.66. The stock touched a low price of $138.71.

Recently in News on August 11, 2020, Sarepta Therapeutics and University of Florida Announce Collaboration to Accelerate the Discovery and Development of Therapies for Rare Genetic Diseases. Sarepta Therapeutics Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, and the University of Florida today announced a strategic collaboration to enable cutting-edge research for novel genetic medicines. Through the agreement, Sarepta will fund multiple research programs at the University, and will have an exclusive option to further develop any new therapeutic compounds that result from the funded research programs. You can read further details here

Sarepta Therapeutics Inc. had a pretty favorable run when it comes to the market performance. The 1-year high price for the companys stock is recorded $175.00 on 07/20/20, with the lowest value was $78.06 for the same time period, recorded on 03/18/20.

Price records that include history of low and high prices in the period of 52 weeks can tell a lot about the stocks existing status and the future performance. Presently, Sarepta Therapeutics Inc. shares are logging -19.45% during the 52-week period from high price, and 95.66% higher than the lowest price point for the same timeframe. The stocks price range for the 52-week period managed to maintain the performance between $72.05 and $175.00.

The companys shares, operating in the sector of Healthcare managed to top a trading volume set approximately around 1160694 for the day, which was evidently higher, when compared to the average daily volumes of the shares.

When it comes to the year-to-date metrics, the Sarepta Therapeutics Inc. (SRPT) recorded performance in the market was 9.25%, having the revenues showcasing -3.27% on a quarterly basis in comparison with the same period year before. At the time of this writing, the total market value of the company is set at 11.21B, as it employees total of 743 workers.

During the last month, 19 analysts gave the Sarepta Therapeutics Inc. a BUY rating, 2 of the polled analysts branded the stock as an OVERWEIGHT, 1 analysts were recommending to HOLD this stock, 0 of them gave the stock UNDERWEIGHT rating, and 0 of the polled analysts provided SELL rating.

According to the data provided on Barchart.com, the moving average of the company in the 100-day period was set at 144.54, with a change in the price was noted +42.45. In a similar fashion, Sarepta Therapeutics Inc. posted a movement of +43.09% for the period of last 100 days, recording 852,747 in trading volumes.

Total Debt to Equity Ratio (D/E) can also provide valuable insight into the companys financial health and market status. The debt to equity ratio can be calculated by dividing the present total liabilities of a company by shareholders equity. Debt to Equity thus makes a valuable metrics that describes the debt, company is using in order to support assets, correlating with the value of shareholders equity The total Debt to Equity ratio for SRPT is recording 0.67 at the time of this writing. In addition, long term Debt to Equity ratio is set at 0.67.

Raw Stochastic average of Sarepta Therapeutics Inc. in the period of last 50 days is set at 6.23%. The result represents downgrade in oppose to Raw Stochastic average for the period of the last 20 days, recording 10.00%. In the last 20 days, the companys Stochastic %K was 21.79% and its Stochastic %D was recorded 31.90%.

Considering, the past performance of Sarepta Therapeutics Inc., multiple moving trends are noted. Year-to-date Price performance of the companys stock appears to be pessimistic, given the fact the metric is recording 9.25%. Additionally, trading for the stock in the period of the last six months notably improved by 13.70%, alongside a boost of 38.89% for the period of the last 12 months. The shares increased approximately by -11.34% in the 7-day charts and went up by -14.31% in the period of the last 30 days. Common stock shares were lifted by -3.27% during last recorded quarter.

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Analysts Mean recommendation for Sarepta Therapeutics Inc. (SRPT) was 1.70: Is this the key time? - The InvestChronicle

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UCI study finds women with diabetes and high levels of coronary artery calcium at greater risk of death than men – Newswise

Posted: August 21, 2020 at 8:58 pm

Newswise Irvine, CA August 21, 2020 A new study finds women with diabetes and significant levels of calcium in their coronary arteries have higher rates of death from cardiovascular disease and all causes than their male counterparts.

Published in the American Diabetes Association journal, Diabetes Care, researchers from the University of California, Irvine School of Medicine and Cedars-Sinai Medical Center compared the sex-specific impact of coronary artery calcium (CAC) levels in adults with diabetes. CAC was used to predict cardiovascular and all-cause mortality in patients with diabetes. The results of this comparison showed greater CAC predicts cardiovascular and total mortality more strongly in women.

We showed that coronary calcium scores of greater than 100 in a woman with diabetes was associated with higher death rates from cardiovascular diseases and all causes than similar calcium scores in women than in man with diabetes, said Nathan D. Wong, PhD, professor and director for UCIs Heart Disease Prevention Program, and the lead author for the study.

Wong and colleagues studied 4,503 adults with diabetes from a national registry of patients who received coronary calcium heart scans from computed tomography and were followed for causes of death over more than 11 years. Death rates from cardiovascular disease in those who had coronary calcium scores of 101-400 or more, were approximately twice as high in women compared to men. Total death rates in these patients were also higher in women than in men. In analyses adjusted for age and other potential confounders, compared to those with calcium scores of 0, women who had calcium scores of 101-400 and 401 or greater had cardiovascular deaths that were 3.7 and 6.3-fold greater, respectively, compared to men whose risks were 1.6 and 3.5-fold greater, respectively.

Our findings, showing significant levels of coronary calcium to predict mortality from cardiovascular causes more strongly in women than men with diabetes, might also help to explain the poorer prognosis for cardiovascular disease that has been observed for decades in women compared to men with diabetes, said Wong.

Conversely, very low death rates from coronary heart disease and cardiovascular disease seen in those with diabetes who had negative scans (calcium scores of 0), comprising 39 percent of women and 20 percent of men in our study, underscore the point that not all persons with diabetes are risk equivalents for cardiovascular disease, as has been the common belief for decades, noted Cedars-Sinai Medical Centers Daniel Berman, MD, senior author of the study.

Our findings suggest a call-to-action for even more aggressive risk factor management in a woman with diabetes found to have significant levels of coronary calcium to prevent future death from cardiovascular causes said Wong. Previous research conducted by Wong and colleagues, has shown rates of cardiovascular disease to be 60 percent lower in those who are well-controlled for blood sugar, cholesterol, and blood pressure.

The study population was part of the CAC Consortium, directed by Michael Joseph Blaha, MD, MPH, from Johns Hopkins School of Medicine. UCIs Amber Cordola-Hsu, PhD, co-led the study with Wong.

This study was funded in part by the National Institutes of Health and the American Heart Association.

About the UCI School of Medicine

Each year, the UCI School of Medicine educates more than 400 medical students, and nearly 150 doctoral and masters students. More than 700 residents and fellows are trained at UCI Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and masters degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/masters in public health, or an MD/masters degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.

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Reduced physical activity from COVID-19 related restrictions may be linked to higher stress and anxiety levels – 2 Minute Medicine

Posted: August 21, 2020 at 8:58 pm

1. Reduced physical activity as a result of COVID-19 related restrictions may be associated with higher levels of stress and anxiety.

2. Relationships between perceived activity level, stress, and anxiety are confounded by genetic and environmental factors in addition to age and sex.

Evidence Rating Level: 2 (Good)

Due to the Covid-19 pandemic, restrictions have been in place worldwide to limit the spread of the virus. Some of these restrictions also limit the opportunity for physical activity, such as the closure of athletic facilities and shelter-in-place orders. Since past research has associated lack of physical activity to poorer mental health, there is a growing need for empirical research regarding the restrictions effect on physical and mental health outcomes. The aim of this study was to investigate the association between perceived alterations in physical activity (due to the restrictions) and mental health. The study population was 3,971 adults taken from a twin registry in Washington State, including 909 same-sex twin pairs. Twins were used in this study to control for genetic and shared environmental factors, as changes in perceived physical activity were anticipated to be stemming from non-shared environmental factors. Participants completed an online survey which assessed perceived changes in physical activity (increased, decreased, or stayed the same), stress (using the 5-point Likert-type Perceived Stress Scale), and anxiety (using the Brief Symptom Inventory, also on a 5-point scale). The study found that there was no association between physical activity and mental health, in twins who reported an increase or no change in activity (stress: b = 0.089, SE = 0.060, p = 0.139; anxiety: b = 0.117, SE = 0.079, p = 0.141). For twins reporting a decrease or no change in activity, there was a significant association between activity and stress before controlling for the confounding variables (b = 0.036, SE = 0.010, p < 0.001). After controlling for genetics and shared environment though, the association was non-significant (b = 0.017, SE = 0.010, p = 0.090). For twins reporting decreased or no change in activity, the association with anxiety was significant before controlling (b = 0.143, SE = 0.039, p < 0.001), was still significant after controlling for genetics and shared environment (b = 0.134, SE = 0.042, p = 0.002), but was ultimately non-significant after controlling for age and sex, as older twins were more likely to report lower anxiety levels and females more likely to report higher anxiety levels (b = 0.150, SE = 0.106, p = 0.158). Overall, decreased perceived physical activity was linked to higher stress and anxiety, although the association with stress was confounded by genetics and shared environment, and anxiety with age and sex. This study demonstrates that the restrictions in place to protect public health could potentially be detrimental to physical and mental health, which has implications for potential interventions targeted at improving peoples well-being while restrictions are still in place.

Click to read the study in PlosONE

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Research Roundup: Lasting Immunity to COVID-19 and More – BioSpace

Posted: August 21, 2020 at 8:57 pm

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Multiple Studies Suggest Lasting Immunity to COVID-19 After Infection

Although probably not enough time has passed to know definitively, several studies are now suggesting that even mild cases of COVID-19 stimulate lasting immune responses, not only in disease-fighting antibodies, but in B- and T-cells.

Things are really working as theyre supposed to, Deepta Bhattacharya, an immunologist at the University of Arizona, and an author of one of the studies, told The New York Times.

Its difficult, probably impossible, to predict how long those immune responses will last, but many of the researchers believe the results are promising for long-term protection.

This is exactly what you would hope for, Marion Pepper, an immunologist at the University of Washington and an author of a study currently being reviewed by the journal Nature. All the pieces are there to have a totally protective immune response.

Pepper notes that the protective effects cant be completely evaluated until there is proof that people exposed to the virus a second time can fight it off. But the data suggests the immune system is indeed able to fight resistance a second time. Some of this qualification comes from unconfirmed reports of people being reinfected by the virus.

Antibody responses are typically relatively short-lived, disappearing from the blood weeks or months after being produced. Generally, the majority of the B-cells that produce antibodies die off, too. But the body keeps some longer-lived B-cells that are able to manufacture virus-fighting antibodies should the immune system be triggered by re-exposure to the virus. Some stay in the bloodstream while others wait in the bone marrow where they manufacture small numbers of antibodies that can sometimes be observed years, even decades later. Several studies, some by Bhattacharya and Pepper, have identified antibodies at low levels in the blood months after people recovered from COVID-19.

The antibodies decline, but they settle in what looks like a stable nadir, Bhattacharya said. These have been observed about three months after symptoms show up. The response looks perfectly durable.

Additional studies, including one published in the journal Cell, have isolated T-cells from recovered patients that can attack SARS-CoV-2. In laboratory studies, the T-cells produced signals to fight the virus and cloned themselves in large numbers to fight the potential infection.

This is very promising, said Smita Iyer, an immunologist at the University of California, Davis, who was not involved in the new studies, but has researched immune responses to the novel coronavirus in rhesus macaques. This calls for some optimism about herd immunity, and potentially a vaccine.

It's still has not been definitely determined if milder cases of COVID-19 will lead to long-term or even medium-term immunity. There have been some studies that suggest it does not and some newer studies suggesting it does. Iyer notes that the recent paper indicates, You can still get durable immunity without suffering the consequences of infection.

This idea is reinforced by Eun-Hyung Lee, an immunologist at Emory University who was not involved in these studies. He told The New York Times, Yes, you do develop immunity to this virus, and good immunity to this virus. Thats the message we want to get out there.

Why Seasonal Flu Vaccines Only Last a Year

As most everyone knows, flu vaccines only last about a year. Some of this is related to viral mutations. But in fact, the actual immunity itself caused by the vaccine does not appear to last longer than a year, even though the flu vaccine increases the number of antibody-producing cells specific for the flu in the bone marrow. Researchers out of Emory Vaccine Center found that for most newly-generated plasma cell lineages, between 70 and 99% of the cells were gone after one year, but that the levels of antibody-secreting cells in blood correlated with long-term response in the bone marrow.

Gut Bacteria Can Help Immuno-Oncology Therapies

Researchers with the University of Calgary identified gut bacteria that help our immune system fight cancerous tumors. This also helped provide more information about why immunotherapy works in some cases, but not others. By combining immunotherapy with specific microbial therapy, they believe they can help the immune system and immunotherapy be more effective in treating three types of cancer: melanoma, bladder and colorectal cancers. They found that specific bacteria were essential for immunotherapy to work in colorectal cancer tumors in germ-free mice. The bacteria produced a small molecule called inosine that interacts directly with T-cells and together with immunotherapy.

An Online Calculator to Predict Stroke Risk

Scientists at the University of Virginia Health System developed an online tool that measures the severity of a patients metabolic syndrome, a mix of conditions that includes high blood pressure, abnormal cholesterol levels and excess body fat. With it, they can then predict the patients risk for ischemic stroke. The study discovered that stroke risk increased consistently with metabolic syndrome severity even in patients that did not have diabetes. The tool is available for free at https://metscalc.org/.

A Link Between Autism and Cholesterol

Researchers at Harvard Medical School, Massachusetts Institute of Technology (MIT) and Northwestern University identified a subtype of autism that is the result of a cluster of genes that regulate cholesterol metabolism and brain development. They believe this information can help design precision-targeted therapies for this specific type of autism and improve screening efforts for earlier diagnosis of autism. They analyzed the DNA from brain samples that they then confirmed with the medical records of autistic individuals. They found that children with autism and their parents had significant alterations in lipid blood. However, there is much more to be understood, emphasizing the complexity of autism, which is affected by a variety of genetic and environmental factors.

Researchers Grow First Functioning Mini Human Heart Model

Investigators with Michigan State University grew the first miniature human heart model in the laboratory that is complete with all primary heart cell types and a functioning structure of chambers and vascular tissue. They utilized induced pluripotent stem cells which were obtained from consenting adults and created a functional mini heart in a few weeks. The primary value was in giving them an unprecedented view into how a fetal heart develops.

In the lab, we are currently using heart organoids to model congenital heart diseasethe most common birth defect in humans affecting nearly 1% of the newborn population, said Aitor Aguirre, senior author and assistant professor of biomedical engineering at MSUs Institute for Quantitative Health Science and Engineering. With our heart organoids, we can study the origin of congenital heart disease and find ways to stop it.

Another area of focus is that improving on the final organoid will help with future research. Current heart organoids are not identical yet to human hearts and so are flawed in their use as research models.

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Research Roundup: Lasting Immunity to COVID-19 and More - BioSpace

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What in the world is ‘Project Carpaccio’ and which Israeli company is doing business in Abu Dhabi? – CTech

Posted: August 21, 2020 at 8:57 pm

Employee surveillance tools emerge as a serious side effect of Covid-19. Dystopian products that track workers' every move have become hot commodities for managers who had to transition to supervise remote teams. Read more

Israeli-based Pluristem and Abu Dhabi Stem Cells Center sign deal to collaborate in development of cell therapies. Agreement comes just days after Israel and the United Arab Emirates (UAE) announce intention to fully normalize diplomatic relations. Read more

Israel-based Fintica extends R&D collaboration with Nikko Global Wrap after a successful trial. Fintica, a spinoff of Cortica, leverages next-generation AI to understand volatile market and steer investment decisions. Read more

The '5 Key Forces shaping the future of organizations, according to CEO of freelance workforce tool Stoke Talent. Freelancing, Millennials, and Remote Working: everything shaping the future of organizations after Covid-19. Read more

Opinion | Predictive analytics takes center stage in the fight against Covid-19 and the critically ill. Clew Medical's Gal Salomon discusses Covid-19 and how the pandemic has revealed vulnerabilities in healthcare systems around the world. Read more

First-ever AI-based autonomous traffic management platform unveiled in Phoenix, Arizona, thanks to Israeli-founded company. NoTraffic uses its AI to optimize traffic management systems and improve traffic flow in urban areas. Read more

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What in the world is 'Project Carpaccio' and which Israeli company is doing business in Abu Dhabi? - CTech

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Viruses have big impacts on ecology and evolution as well as human health – The Economist

Posted: August 21, 2020 at 8:57 pm

Aug 20th 2020

IThe outsiders inside

HUMANS ARE lucky to live a hundred years. Oak trees may live a thousand; mayflies, in their adult form, a single day. But they are all alive in the same way. They are made up of cells which embody flows of energy and stores of information. Their metabolisms make use of that energy, be it from sunlight or food, to build new molecules and break down old ones, using mechanisms described in the genes they inherited and may, or may not, pass on.

It is this endlessly repeated, never quite perfect reproduction which explains why oak trees, humans, and every other plant, fungus or single-celled organism you have ever seen or felt the presence of are all alive in the same way. It is the most fundamental of all family resemblances. Go far enough up any creatures family tree and you will find an ancestor that sits in your family tree, too. Travel further and you will find what scientists call the last universal common ancestor, LUCA. It was not the first living thing. But it was the one which set the template for the life that exists today.

And then there are viruses. In viruses the link between metabolism and genes that binds together all life to which you are related, from bacteria to blue whales, is broken. Viral genes have no cells, no bodies, no metabolism of their own. The tiny particles, virions, in which those genes come packagedthe dot-studded disks of coronaviruses, the sinister, sinuous windings of Ebola, the bacteriophages with their science-fiction landing-legs that prey on microbesare entirely inanimate. An individual animal, or plant, embodies and maintains the restless metabolism that made it. A virion is just an arrangement of matter.

The virus is not the virion. The virus is a process, not a thing. It is truly alive only in the cells of others, a virtual organism running on borrowed hardware to produce more copies of its genome. Some bide their time, letting the cell they share the life of live on. Others immediately set about producing enough virions to split their hosts from stem to stern.

The virus has no plan or desire. The simplest purposes of the simplest lifeto maintain the difference between what is inside the cell and what is outside, to move towards one chemical or away from anotherare entirely beyond it. It copies itself in whatever way it does simply because it has copied itself that way before, in other cells, in other hosts.

That is why, asked whether viruses are alive, Eckard Wimmer, a chemist and biologist who works at the State University of New York, Stony Brook, offers a yes-and-no. Viruses, he says, alternate between nonliving and living phases. He should know. In 2002 he became the first person in the world to take an array of nonliving chemicals and build a virion from scratcha virion which was then able to get itself reproduced by infecting cells.

The fact that viruses have only a tenuous claim to being alive, though, hardly reduces their impact on things which are indubitably so. No other biological entities are as ubiquitous, and few as consequential. The number of copies of their genes to be found on Earth is beyond astronomical. There are hundreds of billions of stars in the Milky Way galaxy and a couple of trillion galaxies in the observable universe. The virions in the surface waters of any smallish sea handily outnumber all the stars in all the skies that science could ever speak of.

Back on Earth, viruses kill more living things than any other type of predator. They shape the balance of species in ecosystems ranging from those of the open ocean to that of the human bowel. They spur evolution, driving natural selection and allowing the swapping of genes.

They may have been responsible for some of the most important events in the history of life, from the appearance of complex multicellular organisms to the emergence of DNA as a preferred genetic material. The legacy they have left in the human genome helps produce placentas and may shape the development of the brain. For scientists seeking to understand lifes origin, they offer a route into the past separate from the one mapped by humans, oak trees and their kin. For scientists wanting to reprogram cells and mend metabolisms they offer inspirationand powerful tools.

IIA lifestyle for genes

THE IDEA of a last universal common ancestor provides a plausible and helpful, if incomplete, answer to where humans, oak trees and their ilk come from. There is no such answer for viruses. Being a virus is not something which provides you with a place in a vast, coherent family tree. It is more like a lifestylea way of being which different genes have discovered independently at different times. Some viral lineages seem to have begun quite recently. Others have roots that comfortably predate LUCA itself.

Disparate origins are matched by disparate architectures for information storage and retrieval. In eukaryotescreatures, like humans, mushrooms and kelp, with complex cellsas in their simpler relatives, the bacteria and archaea, the genes that describe proteins are written in double-stranded DNA. When a particular protein is to be made, the DNA sequence of the relevant gene acts as a template for the creation of a complementary molecule made from another nucleic acid, RNA. This messenger RNA (mRNA) is what the cellular machinery tasked with translating genetic information into proteins uses in order to do so.

Because they, too, need to have proteins made to their specifications, viruses also need to produce mRNAs. But they are not restricted to using double-stranded DNA as a template. Viruses store their genes in a number of different ways, all of which require a different mechanism to produce mRNAs. In the early 1970s David Baltimore, one of the great figures of molecular biology, used these different approaches to divide the realm of viruses into seven separate classes (see diagram).

In four of these seven classes the viruses store their genes not in DNA but in RNA. Those of Baltimore group three use double strands of RNA. In Baltimore groups four and five the RNA is single-stranded; in group four the genome can be used directly as an mRNA; in group five it is the template from which mRNA must be made. In group sixthe retroviruses, which include HIVthe viral RNA is copied into DNA, which then provides a template for mRNAs.

Because uninfected cells only ever make RNA on the basis of a DNA template, RNA-based viruses need distinctive molecular mechanisms those cells lack. Those mechanisms provide medicine with targets for antiviral attacks. Many drugs against HIV take aim at the system that makes DNA copies of RNA templates. Remdesivir (Veklury), a drug which stymies the mechanism that the simpler RNA viruses use to recreate their RNA genomes, was originally developed to treat hepatitis C (group four) and subsequently tried against the Ebola virus (group five). It is now being used against SARS-CoV-2 (group four), the covid-19 virus.

Studies of the gene for that RNA-copying mechanism, RdRp, reveal just how confusing virus genealogy can be. Some viruses in groups three, four and five seem, on the basis of their RdRp-gene sequence, more closely related to members of one of the other groups than they are to all the other members of their own group. This may mean that quite closely related viruses can differ in the way they store their genomes; it may mean that the viruses concerned have swapped their RdRp genes. When two viruses infect the same cell at the same time such swaps are more or less compulsory. They are, among other things, one of the mechanisms by which viruses native to one species become able to infect another.

How do genes take on the viral lifestyle in the first place? There are two plausible mechanisms. Previously free-living creatures could give up metabolising and become parasitic, using other creatures cells as their reproductive stage. Alternatively genes allowed a certain amount of independence within one creature could have evolved the means to get into other creatures.

Living creatures contain various apparently independent bits of nucleic acid with an interest in reproducing themselves. The smallest, found exclusively in plants, are tiny rings of RNA called viroids, just a few hundred genetic letters long. Viroids replicate by hijacking a host enzyme that normally makes mRNAs. Once attached to a viroid ring, the enzyme whizzes round and round it, unable to stop, turning out a new copy of the viroid with each lap.

Viroids describe no proteins and do no good. Plasmidssomewhat larger loops of nucleic acid found in bacteriado contain genes, and the proteins they describe can be useful to their hosts. Plasmids are sometimes, therefore, regarded as detached parts of a bacterias genome. But that detachment provides a degree of autonomy. Plasmids can migrate between bacterial cells, not always of the same species. When they do so they can take genetic traits such as antibiotic resistance from their old host to their new one.

Recently, some plasmids have been implicated in what looks like a progression to true virus-hood. A genetic analysis by Mart Krupovic of the Pasteur Institute suggests that the Circular Rep-Encoding Single-Strand-DNA (CRESS-DNA) viruses, which infect bacteria, evolved from plasmids. He thinks that a DNA copy of the genes that another virus uses to create its virions, copied into a plasmid by chance, provided it with a way out of the cell. The analysis strongly suggests that CRESS-DNA viruses, previously seen as a pretty closely related group, have arisen from plasmids this way on three different occasions.

Such jailbreaks have probably been going on since very early on in the history of life. As soon as they began to metabolise, the first proto-organisms would have constituted a niche in which other parasitic creatures could have lived. And biology abhors a vacuum. No niche goes unfilled if it is fillable.

It is widely believed that much of the evolutionary period between the origin of life and the advent of LUCA was spent in an RNA worldone in which that versatile substance both stored information, as DNA now does, and catalysed chemical reactions, as proteins now do. Set alongside the fact that some viruses use RNA as a storage medium today, this strongly suggests that the first to adopt the viral lifestyle did so too. Patrick Forterre, an evolutionary biologist at the Pasteur Institute with a particular interest in viruses (and the man who first popularised the term LUCA) thinks that the RNA world was not just rife with viruses. He also thinks they may have brought about its end.

The difference between DNA and RNA is not large: just a small change to one of the letters used to store genetic information and a minor modification to the backbone to which these letters are stuck. And DNA is a more stable molecule in which to store lots of information. But that is in part because DNA is inert. An RNA-world organism which rewrote its genes into DNA would cripple its metabolism, because to do so would be to lose the catalytic properties its RNA provided.

An RNA-world virus, having no metabolism of its own to undermine, would have had no such constraints if shifting to DNA offered an advantage. Dr Forterre suggests that this advantage may have lain in DNAs imperviousness to attack. Host organisms today have all sorts of mechanisms for cutting up viral nucleic acids they dont like the look ofmechanisms which biotechnologists have been borrowing since the 1970s, most recently in the form of tools based on a bacterial defence called CRISPR. There is no reason to imagine that the RNA-world predecessors of todays cells did not have similar shears at their disposal. And a virus that made the leap to DNA would have been impervious to their blades.

Genes and the mechanisms they describe pass between viruses and hosts, as between viruses and viruses, all the time. Once some viruses had evolved ways of writing and copying DNA, their hosts would have been able to purloin them in order to make back-up copies of their RNA molecules. And so what began as a way of protecting viral genomes would have become the way life stores all its genesexcept for those of some recalcitrant, contrary viruses.

IIIThe scythes of the seas

IT IS A general principle in biology that, although in terms of individual numbers herbivores outnumber carnivores, in terms of the number of species carnivores outnumber herbivores. Viruses, however, outnumber everything else in every way possible.

This makes sense. Though viruses can induce host behaviours that help them spreadsuch as coughingan inert virion boasts no behaviour of its own that helps it stalk its prey. It infects only that which it comes into contact with. This is a clear invitation to flood the zone. In 1999 Roger Hendrix, a virologist, suggested that a good rule of thumb might be ten virions for every living individual creature (the overwhelming majority of which are single-celled bacteria and archaea). Estimates of the number of such creatures on the planet come out in the region of 1029-1030. If the whole Earth were broken up into pebbles, and each of those pebbles smashed into tens of thousands of specks of grit, you would still have fewer pieces of grit than the world has virions. Measurements, as opposed to estimates, produce numbers almost as arresting. A litre of seawater may contain more than 100bn virions; a kilogram of dried soil perhaps a trillion.

Metagenomics, a part of biology that looks at all the nucleic acid in a given sample to get a sense of the range of life forms within it, reveals that these tiny throngs are highly diverse. A metagenomic analysis of two surveys of ocean life, the Tara Oceans and Malaspina missions, by Ahmed Zayed of Ohio State University, found evidence of 200,000 different species of virus. These diverse species play an enormous role in the ecology of the oceans.

A litre of seawater may contain 100bn virions; a kilogram of dried soil perhaps a trillion

On land, most of the photosynthesis which provides the biomass and energy needed for life takes place in plants. In the oceans, it is overwhelmingly the business of various sorts of bacteria and algae collectively known as phytoplankton. These creatures reproduce at a terrific rate, and viruses kill them at a terrific rate, too. According to work by Curtis Suttle of the University of British Columbia, bacterial phytoplankton typically last less than a week before being killed by viruses.

This increases the overall productivity of the oceans by helping bacteria recycle organic matter (it is easier for one cell to use the contents of another if a virus helpfully lets them free). It also goes some way towards explaining what the great mid-20th-century ecologist G. Evelyn Hutchinson called the paradox of the plankton. Given the limited nature of the resources that single-celled plankton need, you would expect a few species particularly well adapted to their use to dominate the ecosystem. Instead, the plankton display great variety. This may well be because whenever a particular form of plankton becomes dominant, its viruses expand with it, gnawing away at its comparative success.

It is also possible that this endless dance of death between viruses and microbes sets the stage for one of evolutions great leaps forward. Many forms of single-celled plankton have molecular mechanisms that allow them to kill themselves. They are presumably used when one cells sacrifice allows its sister cellswhich are genetically identicalto survive. One circumstance in which such sacrifice seems to make sense is when a cell is attacked by a virus. If the infected cell can kill itself quickly (a process called apoptosis) it can limit the number of virions the virus is able to make. This lessens the chances that other related cells nearby will die. Some bacteria have been shown to use this strategy; many other microbes are suspected of it.

There is another situation where self-sacrifice is becoming conduct for a cell: when it is part of a multicellular organism. As such organisms grow, cells that were once useful to them become redundant; they have to be got rid of. Eugene Koonin of Americas National Institutes of Health and his colleagues have explored the idea that virus-thwarting self-sacrifice and complexity-permitting self-sacrifice may be related, with the latter descended from the former. Dr Koonins model also suggests that the closer the cells are clustered together, the more likely this act of self-sacrifice is to have beneficial consequences.

For such profound propinquity, move from the free-flowing oceans to the more structured world of soil, where potential self-sacrificers can nestle next to each other. Its structure makes soil harder to sift for genes than water is. But last year Mary Firestone of the University of California, Berkeley, and her colleagues used metagenomics to count 3,884 new viral species in a patch of Californian grassland. That is undoubtedly an underestimate of the total diversity; their technique could see only viruses with RNA genomes, thus missing, among other things, most bacteriophages.

Metagenomics can also be applied to biological samples, such as bat guano in which it picks up viruses from both the bats and their food. But for the most part the finding of animal viruses requires more specific sampling. Over the course of the 2010s PREDICT, an American-government project aimed at finding animal viruses, gathered over 160,000 animal and human tissue samples from 35 countries and discovered 949 novel viruses.

The people who put together PREDICT now have grander plans. They want a Global Virome Project to track down all the viruses native to the worlds 7,400 species of mammals and waterfowlthe reservoirs most likely to harbour viruses capable of making the leap into human beings. In accordance with the more-predator-species-than-prey rule they expect such an effort would find about 1.5m viruses, of which around 700,000 might be able to infect humans. A planning meeting in 2018 suggested that such an undertaking might take ten years and cost $4bn. It looked like a lot of money then. Today those arguing for a system that can provide advance warning of the next pandemic make it sound pretty cheap.

IVLeaving their mark

THE TOLL which viruses have exacted throughout history suggests that they have left their mark on the human genome: things that kill people off in large numbers are powerful agents of natural selection. In 2016 David Enard, then at Stanford University and now at the University of Arizona, made a stab at showing just how much of the genome had been thus affected.

He and his colleagues started by identifying almost 10,000 proteins that seemed to be produced in all the mammals that had had their genomes sequenced up to that point. They then made a painstaking search of the scientific literature looking for proteins that had been shown to interact with viruses in some way or other. About 1,300 of the 10,000 turned up. About one in five of these proteins was connected to the immune system, and thus could be seen as having a professional interest in viral interaction. The others appeared to be proteins which the virus made use of in its attack on the host. The two cell-surface proteins that SARS-CoV-2 uses to make contact with its target cells and inveigle its way into them would fit into this category.

The researchers then compared the human versions of the genes for their 10,000 proteins with those in other mammals, and applied a statistical technique that distinguishes changes that have no real impact from the sort of changes which natural selection finds helpful and thus tries to keep. Genes for virus-associated proteins turned out to be evolutionary hotspots: 30% of all the adaptive change was seen in the genes for the 13% of the proteins which interacted with viruses. As quickly as viruses learn to recognise and subvert such proteins, hosts must learn to modify them.

A couple of years later, working with Dmitri Petrov at Stanford, Dr Enard showed that modern humans have borrowed some of these evolutionary responses to viruses from their nearest relatives. Around 2-3% of the DNA in an average European genome has Neanderthal origins, a result of interbreeding 50,000 to 30,000 years ago. For these genes to have persisted they must be doing something usefulotherwise natural selection would have removed them. Dr Enard and Dr Petrov found that a disproportionate number described virus-interacting proteins; of the bequests humans received from their now vanished relatives, ways to stay ahead of viruses seem to have been among the most important.

Viruses do not just shape the human genome through natural selection, though. They also insert themselves into it. At least a twelfth of the DNA in the human genome is derived from viruses; by some measures the total could be as high as a quarter.

Retroviruses like HIV are called retro because they do things backwards. Where cellular organisms make their RNA from DNA templates, retroviruses do the reverse, making DNA copies of their RNA genomes. The host cell obligingly makes these copies into double-stranded DNA which can be stitched into its own genome. If this happens in a cell destined to give rise to eggs or sperm, the viral genes are passed from parent to offspring, and on down the generations. Such integrated viral sequences, known as endogenous retroviruses (ERVs), account for 8% of the human genome.

This is another example of the way the same viral trick can be discovered a number of times. Many bacteriophages are also able to stitch copies of their genome into their hosts DNA, staying dormant, or temperate, for generations. If the cell is doing well and reproducing regularly, this quiescence is a good way for the viral genes to make more copies of themselves. When a virus senses that its easy ride may be coming to an end, thoughfor example, if the cell it is in shows signs of stressit will abandon ship. What was latent becomes lytic as the viral genes produce a sufficient number of virions to tear the host apart.

Though some of their genes are associated with cancers, in humans ERVs do not burst back into action in later generations. Instead they have proved useful resources of genetic novelty. In the most celebrated example, at least ten different mammalian lineages make use of a retroviral gene for one of their most distinctively mammalian activities: building a placenta.

The placenta is a unique organ because it requires cells from the mother and the fetus to work together in order to pass oxygen and sustenance in one direction and carbon dioxide and waste in the other. One way this intimacy is achieved safely is through the creation of a tissue in which the membranes between cells are broken down to form a continuous sheet of cellular material.

The protein that allows new cells to merge themselves with this layer, syncytin-1, was originally used by retroviruses to join the external membranes of their virions to the external membranes of cells, thus gaining entry for the viral proteins and nucleic acids. Not only have different sorts of mammals co-opted this membrane-merging trickother creatures have made use of it, too. The mabuya, a long-tailed skink which unusually for a lizard nurtures its young within its body, employs a retroviral syncytin protein to produce a mammalian-looking placenta. The most recent shared ancestor of mabuyas and mammals died out 80m years before the first dinosaur saw the light of day, but both have found the same way to make use of the viral gene.

This is not the only way that animals make use of their ERVs. Evidence has begun to accumulate that genetic sequences derived from ERVs are quite frequently used to regulate the activity of genes of more conventional origin. In particular, RNA molecules transcribed from an ERV called HERV-K play a crucial role in providing the stem cells found in embryos with their pluripotencythe ability to create specialised daughter cells of various different types. Unfortunately, when expressed in adults HERV-K can also be responsible for cancers of the testes.

As well as containing lots of semi-decrepit retroviruses that can be stripped for parts, the human genome also holds a great many copies of a retrotransposon called LINE-1. This a piece of DNA with a surprisingly virus-like way of life; it is thought by some biologists to have, like ERVs, a viral origin. In its full form, LINE-1 is a 6,000-letter sequence of DNA which describes a reverse transcriptase of the sort that retroviruses use to make DNA from their RNA genomes. When LINE-1 is transcribed into an mRNA and that mRNA subsequently translated to make proteins, the reverse transcriptase thus created immediately sets to work on the mRNA used to create it, using it as the template for a new piece of DNA which is then inserted back into the genome. That new piece of DNA is in principle identical to the piece that acted as the mRNAs original template. The LINE-1 element has made a copy of itself.

In the 100m years or so that this has been going on in humans and the species from which they are descended the LINE-1 element has managed to pepper the genome with a staggering 500,000 copies of itself. All told, 17% of the human genome is taken up by these copiestwice as much as by the ERVs.

Most of the copies are severely truncated and incapable of copying themselves further. But some still have the knack, and this capability may be being put to good use. Fred Gage and his colleagues at the Salk Institute for Biological Studies, in San Diego, argue that LINE-1 elements have an important role in the development of the brain. In 2005 Dr Gage discovered that in mouse embryosspecifically, in the brains of those embryosabout 3,000 LINE-1 elements are still able to operate as retrotransposons, putting new copies of themselves into the genome of a cell and thus of all its descendants.

Brains develop through proliferation followed by pruning. First, nerve cells multiply pell-mell; then the cell-suicide process that makes complex life possible prunes them back in a way that looks a lot like natural selection. Dr Gage suspects that the movement of LINE-1 transposons provides the variety in the cell population needed for this selection process. Choosing between cells with LINE-1 in different places, he thinks, could be a key part of the process from which the eventual neural architecture emerges. What is true in mice is, as he showed in 2009, true in humans, too. He is currently developing a technique for looking at the process in detail by comparing, post mortem, the genomes of different brain cells from single individuals to see if their LINE-1 patterns vary in the ways that his theory would predict.

VPromised lands

HUMAN EVOLUTION may have used viral genes to make big-brained live-born life possible; but viral evolution has used them to kill off those big brains on a scale that is easily forgotten. Compare the toll to that of war. In the 20th century, the bloodiest in human history, somewhere between 100m and 200m people died as a result of warfare. The number killed by measles was somewhere in the same range; the number who died of influenza probably towards the top of it; and the number killed by smallpox300m-500mwell beyond it. That is why the eradication of smallpox from the wild, achieved in 1979 by a globally co-ordinated set of vaccination campaigns, stands as one of the all-time-great humanitarian triumphs.

Other eradications should eventually follow. Even in their absence, vaccination has led to a steep decline in viral deaths. But viruses against which there is no vaccine, either because they are very new, like SARS-CoV-2, or peculiarly sneaky, like HIV, can still kill millions.

Reducing those tolls is a vital aim both for research and for public-health policy. Understandably, a far lower priority is put on the benefits that viruses can bring. This is mostly because they are as yet much less dramatic. They are also much less well understood.

The viruses most prevalent in the human body are not those which infect human cells. They are those which infect the bacteria that live on the bodys surfaces, internal and external. The average human microbiome harbours perhaps 100trn of these bacteria. And where there are bacteria, there are bacteriophages shaping their population.

The microbiome is vital for good health; when it goes wrong it can mess up a lot else. Gut bacteria seem to have a role in maintaining, and possibly also causing, obesity in the well-fed and, conversely, in tipping the poorly fed into a form of malnutrition called kwashiorkor. Ill-regulated gut bacteria have also been linked, if not always conclusively, with diabetes, heart disease, cancers, depression and autism. In light of all this, the question who guards the bacterial guardians? is starting to be asked.

The viruses that prey on the bacteria are an obvious answer. Because the health of their hosts hostthe possessor of the gut they find themselves inmatters to these phages, they have an interest in keeping the microbiome balanced. Unbalanced microbiomes allow pathogens to get a foothold. This may explain a curious detail of a therapy now being used as a treatment of last resort against Clostridium difficile, a bacterium that causes life-threatening dysentery. The therapy in question uses a transfusion of faecal matter, with its attendant microbes, from a healthy individual to reboot the patients microbiome. Such transplants, it appears, are more likely to succeed if their phage population is particularly diverse.

Medicine is a very long way from being able to use phages to fine-tune the microbiome. But if a way of doing so is found, it will not in itself be a revolution. Attempts to use phages to promote human health go back to their discovery in 1917, by Flix dHrelle, a French microbiologist, though those early attempts at therapy were not looking to restore balance and harmony. On the basis that the enemy of my enemy is my friend, doctors simply treated bacterial infections with phages thought likely to kill the bacteria.

The arrival of antibiotics saw phage therapy abandoned in most places, though it persisted in the Soviet Union and its satellites. Various biotechnology companies think they may now be able to revive the traditionand make it more effective. One option is to remove the bits of the viral genome that let phages settle down to a temperate life in a bacterial genome, leaving them no option but to keep on killing. Another is to write their genes in ways that avoid the defences with which bacteria slice up foreign DNA.

The hope is that phage therapy will become a backup in difficult cases, such as infection with antibiotic-resistant bugs. There have been a couple of well-publicised one-off successes outside phage therapys post-Soviet homelands. In 2016 Tom Patterson, a researcher at the University of California, San Diego, was successfully treated for an antibiotic-resistant bacterial infection with specially selected (but un-engineered) phages. In 2018 Graham Hatfull of the University of Pittsburgh used a mixture of phages, some engineered so as to be incapable of temperance, to treat a 16-year-old British girl who had a bad bacterial infection after a lung transplant. Clinical trials are now getting under way for phage treatments aimed at urinary-tract infections caused by Escherichia coli, Staphylococcus aureus infections that can lead to sepsis and Pseudomonas aeruginosa infections that cause complications in people who have cystic fibrosis.

Viruses which attack bacteria are not the only ones genetic engineers have their eyes on. Engineered viruses are of increasing interest to vaccine-makers, to cancer researchers and to those who want to treat diseases by either adding new genes to the genome or disabling faulty ones. If you want to get a gene into a specific type of cell, a virion that recognises something about such cells may often prove a good tool.

The vaccine used to contain the Ebola outbreak in the Democratic Republic of Congo over the past two years was made by engineering Indiana vesiculovirus, which infects humans but cannot reproduce in them, so that it expresses a protein found on the surface of the Ebola virus; thus primed, the immune system responds to Ebola much more effectively. The World Health Organisations current list of 29 covid-19 vaccines in clinical trials features six versions of other viruses engineered to look a bit like SARS-CoV-2. One is based on a strain of measles that has long been used as a vaccine against that disease.

Viruses engineered to engender immunity against pathogens, to kill cancer cells or to encourage the immune system to attack them, or to deliver needed genes to faulty cells all seem likely to find their way into health care. Other engineered viruses are more worrying. One way to understand how viruses spread and kill is to try and make particularly virulent ones. In 2005, for example, Terrence Tumpey of Americas Centres for Disease Control and Prevention and his colleagues tried to understand the deadliness of the influenza virus responsible for the pandemic of 1918-20 by taking a more benign strain, adding what seemed to be distinctive about the deadlier one and trying out the result on mice. It was every bit as deadly as the original, wholly natural version had been.

The use of engineered pathogens as weapons of war is of dubious utility, completely illegal and repugnant to almost all

Because such gain of function research could, if ill-conceived or poorly implemented, do terrible damage, it requires careful monitoring. And although the use of engineered pathogens as weapons of war is of dubious utilitysuch weapons are hard to aim and hard to stand down, and it is not easy to know how much damage they have doneas well as being completely illegal and repugnant to almost all, such possibilities will and should remain a matter of global concern.

Information which, for billions of years, has only ever come into its own within infected cells can now be inspected on computer screens and rewritten at will. The power that brings is sobering. It marks a change in the history of both viruses and peoplea change which is perhaps as important as any of those made by modern biology. It is constraining a small part of the viral world in a way which, so far, has been to peoples benefit. It is revealing that worlds further reaches in a way which cannot but engender awe.

Editors note: Some of our covid-19 coverage is free for readers of The Economist Today, our daily newsletter. For more stories and our pandemic tracker, see our hub

This article appeared in the Essay section of the print edition under the headline "The outsiders inside"

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Viruses have big impacts on ecology and evolution as well as human health - The Economist

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Encouraging News About Coronavirus Immunity | In the Pipeline – Science Magazine

Posted: August 21, 2020 at 8:57 pm

Weve had some good news on coronavirus immunity recently good because it gives us some more clarity on the whole situation, and because it suggests that both people who have already recovered from the infection and people who will be getting vaccinated can have good protection.

We have this preprint from several of the Boston/Cambridge area institutions, comparing antibody levels in 259 infected patients (out to 75 days post-symptoms) with 1548 pre-pandemic samples. Theyre looking specifically at IgM, IgG, and IgA comparisons. IgM is the first antibody type to appear in response to an infection theyre the ones I mentioned in this post as being five of the Y-shaped units put together. IgG are the ones that most people are talking about when they talk about antibodies in the blood, and IgA are secreted mucosal antibodies, found in the saliva and nasal/lung tissues.That mucosal immunity is surely an important factor in a disease that appears to be spread largely by inhaled airborne droplets.

They estimate that it takes about 11 days to seroconvert after infection, that is, to show evidence that your immune system has raised these new antibodies to the coronavirus. Looking at hospitalized individuals versus milder cases, the former actually seroconverted a couple of days earlier, and their IgM response tended to drop off a bit more quickly. One limitation of this paper is that the coronavirus patient cohort was skewed towards the hospitalized patients, rather than mild infections. But overall they found that IgG antibodies were still detectable in serum 75 days out (the last time point measured) and were a very useful marker for infection, although IgM and IgA had mostly gone back down by then. The paper concludes that although we dont yet know the optimum levels of antibodies for protection (and were still collecting later time points!), the association between RBD-IgG with neutralizing titers and the persistence of these antibodies at late time points is encouraging.

Heres a reporton the same topic from a multicenter team in Canada thats comparing antibody level both in the blood and in saliva. In contrast to the report just mentioned, the authors here found IgA against the coronavirus persisting for at least three months after infection, and correlating well with IgG in the blood. Not every study has shown that sort of persistence, but the authors believe that this might be due to the techniques used for detection. They also found that several of their negative controls samples banked from people pre-pandemic, who had definitely not been exposed to coronavirus also showed IgA titers in saliva, presumably cross-reactive antibodies that were raised from some other infection. It is tempting to speculate, they write,that these preexisting IgA antibodies may provide some stop-gap protection against SARS-CoV-2 in the oral cavity, and if so, it is essential to ascertain their original antigenic specificity.

Then theres this preprint from a team in Arizona, which confirms these results by finding that antibodies against the RBD part of the coronavirus Spike protein persisted for at least three months. In contrast to other reports, they say, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection. They also checked antibodies to the nucleocapsid protein (N) as well as to the spike and found that the N response was more variable. One possibility they raise is that there are cross-reactive antibodies to other coronavirus N proteins (which is a more conserved domain across the various types than the Spike), and that these were raised by previous infections with different viruses.

Moving past antibodies, we have this paper on T-cell responses. The authors, a multinational team led out of the Karolinska Institute in Sweden, have put in a lot of work looking at the T-cell situation in unexposed individuals, people with acute coronavirus infections and those who have recovered, and family members of those patients as well. The acute phase subjects had just the sort of cellular profile youd expect: highly activated and cytotoxic, out there killing virus-infected cells as T-cells were born to do. In the convalescent patients this had calmed down, as its supposed to, and they detected stem-memory-type cells, which is just what youd want to see. Importantly, these were also found in people who had recovered from much milder infections and in the asymptomatic family members tested as well. (The paper provides a great deal of detail on the exact sorts of responses in the various T-cell types that Im not going into, but its valuable information).

They also detected potentially cross-reactive T cells in 28% of people who had donated blood before the pandemic even hit, which is consistent with several other reports. 41% of the overall patients who were seronegative in antibody tests were still positive for T-cells (CD4+ and CD8+ alike) against coronavirus proteins (Spike, nucleocapsid, and membrane). They conclude that the T-cell response is indeed non-redundant and apparently an important part of immunity to this virus, and that using seroprevalence (antibody levels) as a marker for exposure in a population will almost certainly underestimate the real situation. Thats good news, since it would mean that more people have already been exposed (and are to some good degree immune) than we would think. But that doesnt mean that we can blow the all-clear whistle, either, as the various surges in infection around the world have shown: the situation may be better than feared, but we dont seem to be anywhere near herd immunity levels yet. And we would be killing off an awful lot more people to get there without a vaccine.

And finally, we have this report from the University of Washington, which is about as direct a measure of immune protection as were likely to get before the vaccine efficacy trials read out. The authors studied the crew of a fishing vessel, before and after its voyage. Three crew members showed a positive antibody response beforehand, indicating that they had been infected earlier in the epidemic they were not positive in RT-PCR testing, though, indicating that they did not have active infections. In fact, none of the other 120 crew members tested (out of 122 total) had such a positive reading on departure.

But an outbreak occurred on the ship anyway someone was early enough in the infection that they hadnt shown positive yet. This crewmember became sick and the vessel returned to port on Day 18 of the voyage. (Sequencing of viral samples from a number of crew members confirmed that the outbreak seemed to originate from a single source). Testing then and over the next few days showed that 104 of the 120 crew members were now positive for the coronavirus but not the three who had antibodies beforehand. This high attack rate (!) and apparent protection makes a strong case for protective immunity, because God knows everyone on board had plenty of chances to catch the disease.

How long this protection lasts, what part of it is due to antibody response and what part to T cells, and what the exact cutoffs are for those these are the important things we dont quite know yet. But the picture is becoming clearer. And what were seeing is that this virus, which it has definitely has some unusual features, is also something that our immune systems are dealing with in the just the way that you would hope to see. That gives us hope that the vaccines are in turn going to raise protective, lasting responses. We just have to see the details!

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