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A team from The University of Texas Medical Branch at Galveston has found a Zika virus mutation that may be responsible for the outbreak that occurred in 2015 and 2016.

Mosquitoes primarily transmit the Zika virus. Because it circulates between mosquitoes and animals/humans, they are prone to genetic mutations, making them highly capable of emerging and causing epidemics.

The UTMB team has identified a mutation in the Zika envelope protein that can enhance mother-to-baby transmission in pregnant mice, increase neurological disease and lethality in newborn mice and elevate virus levels in the blood of infected non-human primates.

Our study demonstrates that the Zika envelope mutation V473M, which just occurred before the 2015 epidemic in the Americas, enhances Zika virus particle assembly in infected cells. The enhanced virus assembly leads to increased human disease and maternal transmission, Pei-Yong Shi, I.H. Kempner professor of Human Genetics at UTMB, said. The viral genetic change reported here, combined with the nave herd immunity, may have accounted for the Zika epidemic and severe diseases in 2015 and 2016.

The UTMB team has received grants from the National Institutes of Health and philanthropic support from the Sealy & Smith Foundation; Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation; John S. Dunn Foundation; Amon G. Carter Foundation; Gillson Longenbaugh Foundation; Summerfield G. Roberts Foundation.

RNA viruses are the pathogens most often responsible for outbreaks and epidemics, including Ebola virus and SARS-CoV-2, the virus causing COVID-19, Shi said. Understanding the mechanisms of viral emergence and transmission is essential to detect and respond to future outbreaks. Although the world is currently focusing on COVID-19, I am certain that COVID-19 will not be the last emerging virus we face. Moving forward, building public health capacity and countermeasure technology are the only effective means to overcome these threats.

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University of Texas researchers find mutation that led to 2015-2016 Zika outbreak - Homeland Preparedness News

Blood biomarker: Levels of lipids, such as cholesterol and triglycerides, may be altered in a subgroup of people with autism.

Sebastian Kaulitzki / Science Photo Library / Getty Images

Nearly 7 percent of autistic people in the United States have abnormal blood levels of fatty compounds called lipids, according to a study published today in Nature Medicine1. The studys approach, drawing on multiple datasets, could help researchers parse autism into subtypes, the researchers say.

Past studies have shown a link between this metabolic condition, called dyslipidemia, and autism in people with rare genetic conditions2.But this is the first in-depth, multidimensional analysis to establish a robust association with autism more broadly, says Yuan Luo, study investigator and associate professor of preventive medicine at Northwestern University in Chicago, Illinois.

The study used a comprehensive approach integrating large datasets, including healthcare claims, electronic health records, familial gene sequences and an atlas of developmental gene-expression patterns.

Just as combining geographical data from various maps can help navigation tools create a more comprehensive view of the world, integrating datasets about various facets of autism can help us better understand the condition, says lead investigator Isaac Kohane, professor of biomedical informatics at Harvard University.

Using one modality gives you only one perspective, whereas using multiple modalities gives you a holistic perspective, he says.

Autism is a highly varied condition, with multiple genetic and environmental influences. Analyzing large and diverse datasets can help researchers parse the condition into smaller subgroups with shared phenotypes and devise bespoke treatments, Kohane says.

The new work may also help clinicians identify biological markers for screening autistic children early in development, rather than relying on behavioral traits.

This is important because currently autism diagnosis is only based on symptoms. But when you actually see these symptoms, its already too late, Luo says. [These findings] could be of immediate clinical utility, and we plan to directly test those by future studies, including clinical trials.

First the team mapped out how genes work in concert during prenatal human brain development, a critical time window for autism. They used the BrainSpan online atlas to obtain data on the expression patterns of exons the parts of genes that code for proteins in 26 brain regions. They then narrowed in on clusters of exons that are expressed differently between boys and girls, given sex differences seen in autism.

Next, the researchers identified autism-related mutations found in the exons of autistic people. To do so, they searched a database of genetic sequences for 3,531 people from 50 families with two to five autistic children, looking for mutations shared by all autistic siblings within each family, as well as 1,704 families with autistic and unaffected sibling pairs, focusing on the mutations found only in the children with autism.

They then looked for overlaps between the exon clusters identified via the atlas and those with autism mutations, identifying 33 in common. Some contain the exons of genes involved in lipid protein regulation; mutations in them could lead to low levels of lipoproteins, cholesterol and triglycerides in the blood. The findings point to a possible association between autism and dyslipidemia, the researchers say.

To test this theory, the team analyzed medical records of 2.75 million people at Boston Childrens Hospital in Massachusetts, 25,514 of whom are children with autism. As a group, autistic children show significant alterations in blood lipid profiles compared with age-matched controls. For example, children with autism have higher triglyceride levels, regardless of age, medication, sex or metabolic conditions, such as obesity or diabetes.

The team examined healthcare claims for more than 34 million people across the United States, including 80,714 autistic people. They found that 6.6 percent of people with autism have dyslipidemia.

The study also found that parents with a history of dyslipidemia have up to 16 percent greater odds of having autistic children a result the researchers hope to investigate further in future studies, Luo says.

The findings jibe with previous research showing that dyslipidemia-associated genes are involved with several mechanisms key to neuronal function, such as controlled cell death.

However, its still unclear how lipids may affect the human brain, says Michael Snyder, professor of genetics at Stanford University in Palo Alto, California, who was not involved in the study. More research manipulating lipid levels by either knocking out dyslipidemia-associated genes in mice or using medication may offer a clearer understanding of this association.

In particular, researchers should try using lipid-lowering drugs, such as statins, in autistic people with dyslipidemia to determine whether the treatment improves their lipid levels and eases autism traits, Snyder says.

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Blood lipid levels may be altered in some autistic people - Spectrum

Imagine a coyote, rangy and resilient. Is she ambling through a canyon dotted with sagebrush or loping in an urban alley lined with dumpsters? In recent decades, the latter has become a more common sight. As cities expand, coyotes move right in. Rather than shrinking from the big-city lights, they rummage for opportunities.

But even as individual coyotes thrive, cities' built features are shaping their genomesacross generations, according to a recent study in the Journal of Urban Ecology. A widening genetic gulf separates city coyotes and their country cousins. And as urban space sprawls, coyotes genetic diversity declines. This finding suggests that humans built environment has consequences even for creatures that seem to thrive in our midst.

Scientists already know city coyotes tend to differ from their country counterpartsin behavior: theyre bolder and more exploratory, more likely to eat human-sourced foods and occupy a smaller territory. But the picture of what genetic differences if any might exist between coyotes has been more murky.

About 30 years ago, fewgeneticdifferences existed between coyotes across North America suggesting coyotes moved freely, and so did their genes. Historically, coyotes ranged only across the arid West and Great Plains. Since 1900, they have beenpushing out of their home turf, and today they prowl the continent from coast to coast. Scientists assumed that mobile, adaptable coyotes weren't impeded much by urban sprawl. More recent studies have found coyotes clustering genetically by range or region, but few have honed in on specific urban areas.

Urban coyote

National Park Service

By narrowing their focus to the greater Los Angeles area, scientists from Pepperdine University uncovered a more complex picture lurking in urban coyotes genes. Pulling DNA from 125 samples of muscle, liver, and skin, they examined coyotes living in mountains, farmland, suburbs, and the city. The team mapped coyotes genetic structure alongside the surrounding landscape, accounting for key urban features like freeways and road density.

A clear split between urban and rural coyotes emerged. Rural coyotes living among mountains and natural vegetation formed the largest, most genetically diverse group. Urban coyotes, on the other hand, made up three distinct clusters each with decreased genetic diversity. Researchers could deduce which coyotes roam wide-open spaces and which dodge city traffic.

Rural coyotes shared a similar genetic profile even across long distances, suggesting natural barriers didnt impede their movement or gene flow. Even in coyotes separated by 160 miles, rural coyotes clustered with each other instead of their urban counterparts nearby. The surrounding environment mattered more than the geographic distance.

Why this genetic split between city and country coyotes? It could stem in part from natal-biased habitat dispersal, the researchers suggest. Animals tend to prefer habitats similar to where they grew up. When an urban coyote knows how to avoid the citys hazards and harvest its resources, she is more likely to raise babies with those skills. And when generations of street-smart coyotes stick around the same spot, the genetic gap between them and their country cousins widens.

But this isnt the whole story, the researchers argue. City coyotes werent just genetically distinct from their rural relatives; their DNA also differed from that of other city coyotes. Rather than forming one large group as the rural coyotes did, urban coyotes split into three genetically distinct populations.

The cities built features help explain why. One distinct cluster of city coyotes prowled through downtown Los Angeles, lurked by the Hollywood sign, and roamed near the Long Beach Airport. The coyotes in this clusterhad both DNA and habitat in common hyper-urban areas with high road density.

Scientists found a similar pattern in Orange County. Where major highways and commercial districts sliced through the land, so did a boundary between two distinct coyote populations. Despite roaming a similar urban environment, coyotes on one side of the highway were genetically distinct from their relatives on the other side. Coyotes' genetic structure mirrored the urban terrain.

Coyote

Peter Eades / USFWS

These findings suggest humans built environment shapes coyotes movement, the researchers argue. Major freeways, dense roads, and human development prevent urban coyotes from crossing into other areas. These built barriers keep old residents in, and new migrants out and thus leave a stamp on coyotes DNA across generations.

This is important because when a population becomes isolated, their genetic diversity tends to dwindle. Genetic diversity reflects a populations overall health, as well as an ability to adapt to future changes in the environment. Think of it like a box of tools passed down for a vast, unpredictable, multi-generational home restoration project. If the roof collapses or the plumbing busts, youre going to need more than just a hammer. The more options you have, the better whether theyre hand tools orgenes. Each genetic characteristic represents another option, in a toolbox of past solutions and potential answers.

Even as individual urban coyotes thrive, their collective genetic toolbox shrinks. The citys built features restrict urban coyotes travels more than previously thought, with significant effects on their population genetics. These findings suggest that urbanization even takes a toll on creatures that seem to flourish in human environments.

This result also points to the importance of preserving natural corridors in cities not just for coyotes, but for other urban wildlife, too. Safe passageways allow diverse species to cross between habitats, enabling both physical movement and gene flow. Los Angeles County has made natural corridors a priority by identifying Significant Ecological Areas (SEAs) and planning links between them. In fact, in 2023, Los Angeles is slated to become home to the largest wildlife corridor in the world a highway overpass in the works since 2019.

Coyotes have a reputation as survivors, adaptable and enduring. But urbanization is also here to stay, and scientists are still learning about its genetic implications for our wildlife neighbors. This study highlights the value of better understanding these effects on all creatures in the urban landscape even the most versatile and wily of them all.

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'Hyper urban' coyote genomes are growing apart from their city and rural cousins - Massive Science

An engineer displays an experimental vaccine for the COVID-19 during testing at the Quality Control Laboratory at Sinovac Biotech facilities in Beijing in this April file photo. A total of 27 drugmakers are working on vaccines for the disease.

An engineer displays an experimental vaccine for the COVID-19 during testing at the Quality Control Laboratory at Sinovac Biotech facilities in Beijing in this April file photo. A total of 27 drugmakers are

Photo: Nicolas Asfouri, AFP Via Getty Images

An engineer displays an experimental vaccine for the COVID-19 during testing at the Quality Control Laboratory at Sinovac Biotech facilities in Beijing in this April file photo. A total of 27 drugmakers are working on vaccines for the disease.

An engineer displays an experimental vaccine for the COVID-19 during testing at the Quality Control Laboratory at Sinovac Biotech facilities in Beijing in this April file photo. A total of 27 drugmakers are

Why scientists are worried about a 'Warp Speed' COVID-19 vaccine

As the race for a COVID-19 vaccine heads into the stretch run, scientists are tempering their enthusiasm with caution.

The biotechnology company Moderna and the National Institutes of Health have begun Phase III efficacy trials for their vaccine. The University of Oxford and Pfizer are running combined Phase II and III testing for their respective drugs. All together, drugmakers have 27 vaccines in trials.

The goal of Operation Warp Speed, the U.S. vaccine initiative, is 300 million doses of a safe, effective vaccine by January, and if realized, it would be one of the greatest scientific achievements of all time. On Tuesday, Goldman Sachs predicted the Food and Drug Administration would approve at least one vaccine before the end of the year.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said last month he was hopeful a vaccine would be available by late fall or early winter.

Heres what worries scientists:

FDA regulators will likely face enormous political pressure to approve a vaccine, even one thats not proven safe and effective.

A vaccine thats less effective than billed could cause wider spread of the pandemic, Michael S. Kinch, director of the Centers for Research Innovation in Biotechnology and Drug Discovery at Washington University in St. Louis, writes in Stat News.

A merely short-term effect could encourage vaccinated individuals to resume risky behaviors, which would all but guarantee that the epidemic endures, argues Kinch, who is also a professor of biochemistry and molecular biophysics.

A vaccine would likely erode compliance of social distancing and mask wearing, measures that are proven effective against spread of the virus.

They automatically are going to say, Oh great, Im just going to get my little vaccine, and I can go back and do exactly the things I was doing last year. That is absolutely not true, Maria Elena Bottazzi, associate dean of the National School of Tropical Medicine at Baylor College of Medicine, told Business Insider in an interview.

We dont have enough data.

What we have right now is a collection of animal data, immune response data and safety data based on early trials and from similar vaccines for other diseases, writes Natalie Dean, assistant professor of biostatistics at the University of Florida, in the New York Times.

The evidence that would convince me to get a COVID-19 vaccine, or to recommend that my loved ones get vaccinated, does not yet exist, she says.

If a substandard vaccine is green-lighted without adequate testing or trials, unforeseen harmful side effects could emerge. A weak initial vaccine and/or one with dangerous side effects would likely cause confidence in all vaccines to plummet and strengthen anti-vaccine sentiments. If a safer, more effective vaccine were subsequently developed, the residual mistrust could result in fewer people getting vaccinated.Epidemiologists estimate that to tame the pandemic, at least 70 percent of the population may need to develop immunity, either by vaccine or getting infected. Millions of Americans refusing to get inoculated by a vaccine thats at least 50 percent effective (the minimum level according to the World Health Organization) could thwart that goal.

A vaccine might only provide short-term immunity because of the nature of coronaviruses. Back in April, Dr. David States, professor of human genetics and director of bioinformatics at the University of Michigan, tweeted:

If youre hoping a vaccine is going to be a knight in shining armor saving the day, you may be in for a disappointment. SARS COV2 is a highly contagious virus. A vaccine will need to induce durable high level immunity, but coronaviruses often dont induce that kind of immunity.

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Mike Moffitt is an SFGATE Reporter. Email: moffitt@sfgate.com. Twitter: @Mike_at_SFGate

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Why scientists are worried about a 'Warp Speed' COVID-19 vaccine - New Haven Register

LONDON--(BUSINESS WIRE)--Gyroscope Therapeutics Limited, a clinical-stage retinal gene therapy company, today announced the appointment of leading experts in retinal disease, gene therapy and the complement system to its Clinical and Scientific Advisory Boards. The newly appointed boards will help guide the development of the company's lead investigational gene therapy, GT005, a one-time therapy being developed to potentially slow the progression of dry age-related macular degeneration (AMD), as well as novel gene therapy delivery systems and additional pipeline candidates.

This is an exciting time for Gyroscope and we are honoured to have a group of highly esteemed leaders in retinal surgery, ophthalmology and gene therapy join our Clinical Advisory Board, said Nadia Waheed, M.D., Chief Medical Officer of Gyroscope. We look forward to working with these leaders as we advance the clinical development of GT005 and our proprietary delivery system, with the ultimate goal of helping preserve the sight of millions of people who suffer from vision loss as a result of dry AMD.

We have embarked upon an ambitious journey exploring the potential of gene therapy beyond rare disease and building a pipeline of potential medicines for one of the worlds leading causes of blindness, said Jane Hughes, Ph.D., Chief Scientific Officer of Gyroscope. We are excited to welcome our Scientific Advisory Board members to Gyroscope and to benefit from the insights of some of the worlds leading experts as we advance our understanding of the role of the complement system in retinal diseases.

Members of the Gyroscope Therapeutics Clinical Advisory Board include:

Professor Jacque Duncan, M.D. Professor of Ophthalmology at the University of California, San Francisco School of Medicine.

Jeffrey Heier, M.D. Co-President and Medical Director, Director of the Vitreoretinal Service and Director of Retina Research at Ophthalmic Consultants of Boston.

Professor Allen Ho, M.D. Professor of Ophthalmology at Sidney Kimmel Medical College of Thomas Jefferson University, and Attending Surgeon and Director of Retina Research at Wills Eye Hospital in Philadelphia.

Professor Nancy Holekamp, M.D. Director of Retina Services at Pepose Vision Institute and Professor of Clinical Ophthalmology at the Washington University School of Medicine in St. Louis.

Arshad Khanani, M.D., M.A. Managing Partner, Director of Clinical Research and Director of Fellowship at Sierra Eye Associates, and Clinical Associate Professor at the University of Nevada, Reno School of Medicine.

Professor Robert MacLaren Professor of Ophthalmology at the University of Oxford in the United Kingdom, Consultant Ophthalmologist at the Oxford Eye Hospital, Honorary Professor of Ophthalmology at the UCL Institute of Ophthalmology, Honorary Consultant Vitreoretinal Surgeon at Moorfields Eye Hospital, and an NIHR Senior Investigator. Professor MacLaren is also a member of the Scientific Advisory Board.

Professor Sir Keith Peters, M.D. Senior Consultant to The Francis Crick Institute in London and Regius Professor of Physic Emeritus at the University of Cambridge in the United Kingdom. Professor Peters is also a member of the Scientific Advisory Board.

Professor Hendrik Scholl, M.D. Founder and Director of the Institute of Molecular and Clinical Ophthalmology Basel in Switzerland, and Professor and Chairman of the Department of Ophthalmology at the University of Basel.

Professor David Steel, M.D., MBBS, FRCOphth Consultant Ophthalmologist at Sunderland Eye Infirmary in the United Kingdom and Honorary Professor of Retinal Surgery at Newcastle University in Newcastle upon Tyne, United Kingdom. Professor Steel is also a member of the Scientific Advisory Board.

Professor Bernhard Weber, Ph.D. Head of Institute of Human Genetics, Head of Institute of Clinical Human Genetics, and Director of the Diagnostics Unit for DNA Testing and Vice President of Research of the University of Regensburg, Germany.

Charles Wykoff, M.D., Ph.D. Director of Research at Retina Consultants of Houston, Deputy Chair for Ophthalmology at Blanton Eye Institute, and Clinical Associate Professor of Ophthalmology Weill Cornell Medical College at Houston Methodist Hospital.

Members of the Gyroscope Scientific Advisory Board include:

Professor Alberto Auricchio, M.D. Professor of Medical Genetics at the Department of Advanced Biomedicine, Federico II University in Naples, and Coordinator of the Molecular Therapy Program at Telethon Institute of Genetics and Medicine (TIGEM) in Pozzuoli (NA), in Italy.

Professor Pete Coffey, DPhil Theme Lead of Development, Ageing and Disease at University College Londons Institute of Ophthalmology and the Co-Executive Director of Translation at the University of California Santa Barbaras Center for Stem Cell Biology and Engineering.

Professor Claire Harris Professor of Molecular Immunology at Newcastle University.

Professor David Kavanagh, Ph.D., FRCP Professor of Complement Therapeutics at the National Renal Complement Therapeutics Centre (NRCTC), Newcastle University.

Professor Sir Peter Lachmann, FRS, FMEDSCI Emeritus Sheila Joan Smith Professor of Immunology, University of Cambridge.

Professor Robert MacLaren Professor MacLaren is also a member of the Clinical Advisory Board.

Professor Sir Keith Peters, M.D. Professor Peters is also a member of the Clinical Advisory Board.

Professor Matthew Pickering, Ph.D., M.B., B.S. Professor of Rheumatology, Imperial College LondonHonorary Consultant Rheumatologist, Imperial College Healthcare NHS Trust, and Wellcome Trust Senior Fellow in Clinical Science.

Professor David Steel, M.D., MBBS, FRCOphth Professor Steel is also a member of the Clinical Advisory Board.

Professor Timothy Stout, M.D. Sid W. Richardson Professor and Margarett Root Brown Chair of the Department of Ophthalmology, and Director of the Cullen Eye Institute at Baylor College of Medicine in Houston.

Full biographies for members of the Gyroscope Advisory Boards are available at http://www.gyroscopetx.com.

About Gyroscope Therapeutics: Vision for Life

Gyroscope Therapeutics is a clinical-stage retinal gene therapy company developing and delivering gene therapy beyond rare disease to treat a leading cause of blindness, dry age-related macular degeneration (AMD). Currently, there are no approved treatments for dry AMD.

Our investigational gene therapy, GT005, is designed to restore balance to a part of our immune system called the complement system. An overactive complement system leads to inflammation that damages healthy eye tissues. Our ultimate goal is to slow the progression of dry AMD. Patients in our Phase I/II clinical trial, known as the FOCUS study, receive a single dose of GT005 through an injection under their retina.

Syncona Ltd, our lead investor, helped us create the only retinal gene therapy company to combine discovery, research, drug development, a manufacturing platform, and surgical delivery capabilities. Headquartered in London with locations in Philadelphia and San Francisco, our mission is to preserve sight and fight the devastating impact of blindness. For more information, visit http://www.gyroscopetx.com and follow us on Twitter (@GyroscopeTx) and on LinkedIn.

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Gyroscope Announces Appointment of Leaders in Retinal Disease, Gene Therapy and the Complement System to Its Clinical and Scientific Advisory Boards -...

Noel Rose, an immunologist and microbiologist whose early experiments underpinned the molecular mechanisms of autoimmune disease, died of a stroke July 30. He was 92.

As a young medical student, Rose worked alongside his mentor, Ernest Witebsky of the University at Buffalo, studying organ-specific antigens. The prevailing hypothesis for the last half century had been that the body was incapable of producing antigens against itself, an idea known as horror autotoxicus. Witebskys own academic lineage stretched back to the ideas original progenitor, Paul Ehrlich, who had coined the term in the 18th century.

But Rose showed that rabbits injected with their own thyroid-derived antigens mounted an immune response against the invading molecules that damaged or destroyed the animals thyroid. The body was indeed capable of attacking itself. The results were so outlandish that the first journals refused to publish the findings, and it took years of careful experimentation to finally topple the paradigm of horror autotoxicus.Over the next several decades, Rose would further characterize the genetic and environmental causes of autoimmune diseases, publishing more than 880 articles and book chapters on the subject, according to Johns Hopkins University.

In every aspect, [Rose] is the father of autoimmunity, George Tsokos, a professor of rheumatology at Harvard Medical School, told The Scientist in a profile of Rose this year. The man opened a whole chapter in the book of medicine.

Currently, there are more than 80 recognized autoimmune diseases, including lupus, type 1 diabetes, rheumatoid arthritis, and AIDS, that have sickened more than 20 million Americans. Speaking to The Washington Post in 1995, Rose called autoimmune diseases one of the big three, meaning cancer, heart disease, and autoimmune disease.

Rose was born December 3, 1927, in Stamford, Connecticut. His father, a physician who served during World War II, became a specialist in treating rheumatic fever, now considered to be an autoimmune disease, the Post reports.

Prior to his groundbreaking work, Rose frequently brushed up against the limitations of medical knowledge at the time. When he began his undergraduate degree at Yale University in the mid-1940s, he wanted to study microbiology, but he was only able to attend a handful of classes on the topic. Instead, he majored in zoology and took the electives in microbiology, which were taught by botanistsbacteria were largely thought to be plants at the time, The Scientist reported in June.

Rose decided to complete a PhD ahead of attending medical school. He joined the lab of microbiologist Harry Morton at the University of Pennsylvania in 1948, where he spent the next several years studying the flagella-like motor structures of Treponema pallidum, the bacterium that causes syphilis.

Next, Rose enrolled as a medical student at the University at Buffalo, where he would make many of his most important medical discoveries. It was here, working alongside Witebsky, that he first demonstrated autoimmunity in rabbits.

Rose extracted a protein called thyroglobulin from humans, horses, and pigs, treated it with a solution called Freunds adjuvant to induce an immune response, and injected it into rabbits. Even though the injected thyroglobulin was similar to the protein already in the rabbits body, the animals still produced protective antibodies. This was true even when the protein, primed by the adjuvant that induces an immune response, came from another rabbit, and most surprisingly, when the protein was extracted and re-injected into the same animal. When he looked at the thyroids of these rabbits, he found that they were often damaged, and sometimes destroyed, by the bodys own immune response.

After having their findings rejected during peer review, Witebsky and Rose turned to studying autoimmunity in humans, determined to replicate and refine their work. They focused on Hashimotos disease, a rare thyroid condition with no identifiable cause, showing that serum taken from patients developed the same type of antibodies when exposed to thyroglobulin that they had seen in rabbits. We went ahead and showed that this same destruction applies to humans and that you could induce a disease in an organ by immunizing it with a specific antigen of the same species, Rose had told The Scientist. And that was autoimmunity.

Having overturned the idea of horror autotoxicus, Rose says, the work came out of the walls, and he spent the next several decades furthering the study of autoimmune diseases. He graduated with his MD in 1964 and remained at the University at Buffalo. According to a memorial page by Johns Hopkins University, where his career would eventually take him, his lab at Buffalo was the first to show that the genes for the major histocompatibility complex, closely linked on human chromosome six, contain the primary genes that determine the risk for autoimmune diseases.

Rose moved his lab to Wayne State University in 1973, where he remained for almost a decade before finally accepting a position at Johns Hopkins in 1981 in the Bloomberg School of Public Health. There, Rose focused on environmental conditions that could trigger disease. In many diseases, Rose told The Scientist, genetics was always less than half the risk. We thought something from the environment must be involved.

His later work focused on myocarditis, an inflammation of the heart muscle, and Rose was still working up until his death. He found great promise in the advent of big data and using it to analyze hundreds or thousands and patients to identify the best possible treatments and preventives. What we want to do is avoid the train wreck from the beginning, and I think we can begin to do that, Rose told The Scientist. Thats what Im excited about.

Rose is survived by his wife of 69 years, Deborah, two sons, two daughters, 10 grandchildren, and five great-grandchildren.

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Noel Rose, Who Demonstrated Autoimmunity Exists, Dies at 92 - The Scientist

Study unveils novel mechanism that allows viruses to produce unexpected proteins.

Like a scene out of Invasion of the Body Snatchers,a virus infects a host and converts it into a factory for making more copies of itself. Now researchers have shown that a large group of viruses, including the influenza viruses and other serious pathogens, steal genetic signals from their hosts to expand their own genomes.

This finding is presented in a study published online today and in print June 25 inCell.The cross-disciplinary collaborative study wasled byresearchers at the Global Health and Emerging Pathogens Institute at Icahn School of Medicine at Mount Sinai in New York, and at the MRC-University of Glasgow Centre for Virus Research in the UK.

The cross-disciplinary team of virologists looked at a large group of viruses known as segmented negative-strand RNA viruses (sNSVs), which include widespread and serious pathogens of humans, domesticated animals and plants, including the influenza viruses and Lassa virus (the cause of Lassa fever). They showed that, by stealing genetic signals from their hosts, viruses can produce a wealth of previously undetected proteins. The researchers labeled them as UFO (Upstream Frankenstein Open reading frame) proteins, as they are encoded by stitching together the host and viral sequences. There was no knowledge of the existence of these kinds of proteins prior to this study.

These UFO proteins can alter the course of viral infection and could be exploited for vaccine purposes.

The capacity of a pathogen to overcome host barriers and establish infection is based on the expression of pathogen-derived proteins, said Ivan Marazzi, PhD, Associate Professor of Microbiology at Icahn School of Medicine and corresponding author on the study. To understand how a pathogen antagonizes the host and establishes infection, we need to have a clear understanding of what proteins a pathogen encodes, how they function, and the manner in which they contribute to virulence.

Viruses cannot build their own proteins, so they need to feed suitable instructions to the machinery that builds proteins in their hosts cells. Viruses are known to do this through a process called cap-snatching, in which they cut the end from one of the cells own protein-encoding messages (a messenger RNA, or mRNA) and then extend that sequence with a copy of one of their own genes. This gives a hybrid message to be read.

For decades we thought that by the time the body encounters the signal to start translating that message into protein (a start codon) it is reading a message provided to it solely by the virus. Our work shows that the host sequence is not silent, said Dr. Marazzi.

The researchers show that, because they make hybrids of host mRNAs with their own genes, viruses (sNSVs) can produce messages with extra, host-derived start codons, a process they called start snatching. This makes it possible to translate previously unsuspected proteins from the hybrid host-virus sequences. They further show that these novel genes are expressed by influenza viruses and potentially a vast number of other viruses. The product of these hybrid genes can be visible to the immune system, and they can modulate virulence. Further studies are needed to understand this new class of proteins and what the implications are of their pervasive expression by many of the RNA viruses that cause epidemics and pandemics.

Ed Hutchinson, PhD, corresponding author and a research fellow at MRC-University of Glasgow Centre for Virus Research, said, Viruses take over their host at the molecular level, and this work identifies a new way in which some viruses can wring every last bit of potential out of the molecular machinery they are exploiting. While the work done here focusses on influenza viruses, it implies that a huge number of viral species can make previously unsuspected genes.

Researchers say the next part of their work is to understand the distinct roles the unsuspected genes play. Now we know they exist, we can study them and use the knowledge to help disease eradication, said Dr. Marazzi. A large global effort is required to stop viral epidemics and pandemics, and these new insights may lead to identifying novel ways to stop infection.

Read Viruses Can Steal Our Genetic Code to Create New Hybrid Human-Virus Genes to learn more about this research.

Reference: Hybrid Gene Origination Creates Human-VirusChimeric Proteins during Infection by Jessica Sook Yuin Ho, Matthew Angel, Yixuan Ma, Elizabeth Sloan, Guojun Wang, Carles Martinez-Romero, Marta Alenquer, Vladimir Roudko, Liliane Chung, Simin Zheng, Max Chang, Yesai Fstkchyan, Sara Clohisey, Adam M. Dinan, James Gibbs, Robert Gifford, Rong Shen, Quan Gu, Nerea Irigoyen, Laura Campisi, Cheng Huang, Nan Zhao, Joshua D. Jones, Ingeborg van Knippenberg, Zeyu Zhu, Natasha Moshkina, La Meyer, Justine Noel, Zuleyma Peralta, Veronica Rezelj, Robyn Kaake, Brad Rosenberg, Bo Wang, Jiajie Wei, Slobodan Paessler, Helen M. Wise, Jeffrey Johnson, Alessandro Vannini, Maria Joo Amorim, J. Kenneth Baillie, Emily R. Miraldi, Christopher Benner, Ian Brierley, Paul Digard, Marta uksza, Andrew E. Firth, Nevan Krogan, Benjamin D. Greenbaum, Megan K. MacLeod, Harm van Bakel, Adolfo Garca-Sastre, Jonathan W. Yewdell, Edward Hutchinson and Ivan Marazzi, 18 June 2020, Cell.DOI: 10.1016/j.cell.2020.05.035bioRxiv: 10.1101/597617v1

This study was supported by funders including the National Institute of Allergy and Infectious Diseases and the UK Medical Research Council.

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Invasion of the Body Snatchers: Viruses Can Steal Our Genetic Code to Create New Human-Virus Genes - SciTechDaily

Are you a rightie or a leftie? No, we're not talking politics here, we're talking handedness. And unless you happen to have an abundance of left-handed friends, you might have noticed how rare they are. So why are just1 in 10 of us left-handed?

While no one's been able to definitively explain this, there are plenty of hypothesesthat have beenbuilding for more than a century, and the evidence points to some kind of genetic influence. Why? Because the percentage of lefties is roughly the same,anywhere you look on the globe.

For those of you who kick a ball on a regular basis, you'll be aware that there are natural asymmetries all over the body - you'll likely opt for one foot over the other when you go to kick.

These asymmetries can be found in everything from our feet to our ears, our eyes, and the layout of our brain, Hannah Fry explains over at BBC Future.

If you hold your thumb at arm's length, then look at it using one eye and then the other, the eye that appears to show the thumb closest to you is your strongest. Similarly, you probably tend to answer the phone or listen behind closed doors with one ear rather than the other - that's your strongest ear.

But why aren't left-handed and right-handed people born to a roughly 50:50 ratio?

Some experts suggest thatsocial cooperation, played out over thousands of years, has given righties dominant. In other words, when communities act together - in terms of sharing tools and living spaces - using the same hand as everyone else is beneficial.

Others suggestthatit's to do with the way the brain is arranged in two hemispheres, with the left half controlling the right side of the body, and the right half controlling the left side of the body.

If most people's brains use the left hemisphere to control intensive language and fine motor skills, the thinking goes, that bias results in the right hand being more dominant too.

In fact, one of the more unusual hypotheses to explain the rarity of left-handedness is that a genetic mutation in our distant past caused the language centres of the human brain to shift to the left hemisphere, effectively causing right-handedness to dominate, Alasdair Wilkins explains forio9back in 2011.

And while genetics likely play a large role in determining handedness, it's probably not the whole answer. Left-handed parents are more likely to have left-handed children than right-handed parents - a preference that can even be seen in the womb - but they still tend to have more right-handed children overall.

Researchers have struggled to identify exactly which genes are responsible for increasing the chances of being a leftie.

In 2019, an analysis of 400,000 individual records revealed the first genetic regions associated with handedness - four of them, to be exact.But otherresearchsuggests that there are probably dozens of genes that play a role in determining whether we end up writing with our left hand or our right.

On top of that, other studies have linked factors such asoestrogen levels and birth position to varying levels of left- and right-handedness.

In short, there seem to be a lot of considerations at play, and researchers are having a hard time tying them all together. That meanswe can't yet tell you exactly why you were born left or right-handed, but scientists clearly are working hard at finding an answer.

And when they do, they'll have to explain why some of us appear to be ambidextrous, too.

A version of this article was first published in October 2016.

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Why Are Only 10% of People Left-Handed? Here's What Scientists Know So Far - ScienceAlert

Abstract

BACKGROUND: Provision of pasteurized donor human milk, as a bridge to mothers own milk, is the standard of care for very low-birth-weight infants in hospital. The aim of this research was to confirm that Holder pasteurization (62.5C for 30 min) would be sufficient to inactivate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in donated human milk samples.

METHODS: We spiked frozen milk samples from 10 donors to the Rogers Hixon Ontario Human Milk Bank with SARS-CoV-2 to achieve a final concentration of 1 107 TCID50/mL (50% of the tissue culture infectivity dose per mL). We pasteurized samples using the Holder method or held them at room temperature for 30 minutes and plated serial dilutions on Vero E6 cells for 5 days. We included comparative controls in the study using milk samples from the same donors without addition of virus (pasteurized and unpasteurized) as well as replicates of Vero E6 cells directly inoculated with SARS-CoV-2. We reported cytopathic effects as TCID50/mL.

RESULTS: We detected no cytopathic activity in any of the SARS-CoV-2spiked milk samples that had been pasteurized using the Holder method. In the SARS-CoV-2spiked milk samples that were not pasteurized but were kept at room temperature for 30 minutes, we observed a reduction in infectious viral titre of about 1 log.

INTERPRETATION: Pasteurization of human milk by the Holder method (62.5C for 30 min) inactivates SARS-CoV-2. Thus, in the event that donated human milk contains SARS-CoV-2 by transmission through the mammary gland or by contamination, this method of pasteurization renders milk safe for consumption and handling by care providers.

Mothers milk is the optimal source of nutrition for infants and contains a myriad of bioactive and immunomodulatory factors, including cytokines, lactoferrin, oligosaccharides and secretory immunoglobulins, which help orchestrate immune system development and provide first-line defence against respiratory tract and gastrointestinal tract infection.15 For vulnerable infants, such as very low-birth-weight (born < 1500 g) infants, use of mothers milk is associated with a shorter hospital stay and reduces their risk of sepsis and necrotizing enterocolitis, a severe bowel emergency.69 It is the standard of care in Canada to provide very low-birth-weight infants in hospital with pasteurized donor human milk until their mothers supply is established.10

Past global epidemics, such as HIV/AIDS, have had devastating effects on donor human milk banking because of perceived risks. In the 1980s, with the knowledge that HIV could be transmitted into human milk, 22 of the 23 Canadian donor human milk banks closed.11 Several viruses, in addition to HIV, can be transmitted through human milk, including hepatitis, cytomegalovirus and human T-cell lymphotropic virus type 1.12 Some viruses may be secreted into milk by paracellular passage as tight junctions open in response to maternal illness and inflammation.3 Other routes of transmission include contamination from respiratory droplets, skin, breast pumps and milk containers. Milk banks affiliated with the Human Milk Banking Association of North America (HMBANA) and the European Milk Bank Association (EMBA) pasteurize milk using the Holder method (62.5C for 30 min) before dispensing for use; the Holder method is effective in inactivating the aforementioned viruses.13,14

Very little is known of the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human milk, or its infectivity; however, the virus has been detected in human milk by reverse transcription polymerase chain reaction (RT-PCR) testing.1518 Mothers donating milk are verbally screened for symptoms associated with coronavirus disease 2019 (COVID-19) at HMBANA-affiliated milk banks, but direct assessment for SARS-CoV-2 by nasopharyngeal swabs and RT-PCR testing is not performed. Although there is no direct evidence showing that Holder pasteurization inactivates SARS-CoV-2 in human milk, this virus is known to be heat sensitive.19 The aim of this research was to confirm that Holder pasteurization would be sufficient to inactivate SARS-CoV-2 in donated human milk samples.

The Rogers Hixon Ontario Human Milk Bank in Toronto, Canada, is a provincial milk bank that follows guidelines established by HMBANA, whereby donors are screened by health and lifestyle interview and serology, and counselled about safe procedures for expression, handling and storage of human milk. Once donors have collected a minimum volume of milk at home, the milk is shipped frozen to the milk bank by express priority courier. We chose 1 container of frozen human milk (approximately 150 mL) at random from shipments received from each of 10 donors. The number of samples included align with previous investigations of viral inactivation in human bodily fluids, where it is common to pool samples before spiking with virus.2022 We specifically avoided pooling in this study because of the known variability in human milk composition. After all identifiers had been removed from milk containers, they were transported frozen to the Combined Containment Level 3 Unit at the University of Toronto, where we completed all experiments.

We thawed the milk samples on ice, homogenized them and individually spiked two 840 L aliquots of milk from each woman with 160 L of SARS-CoV-2 SB2 passage 3 (titre = 6.29 107 50% of the tissue culture infectivity dose [TCID50] per mL) to achieve a concentration of 1 107 TCID50 in each 1 mL of milk-containing solution.23 One spiked milk sample from each mother was allowed to sit at room temperature for 30 minutes (unpasteurized milk). We pasteurized the second spiked milk sample from each mother in a water bath by warming the milk to 62.5C, holding for 30 minutes and then cooling in ice to mimic HMBANA and EMBA guidelines.13,14 We processed individual aliquots of milk in hard plastic microfuge tubes of composition similar to containers normally used during Holder pasteurization at the milk bank. Not unexpectedly, given the complex carbohydrate, lipid and immune factor content of human milk, we found undiluted human milk to be cytotoxic to Vero E6 cells, even without SARS-CoV-2. Hence, we diluted all samples 1:100 in serum-free Dulbeccos Modified Eagles Medium (DMEM), the medium used to maintain cultures of Vero E6 cells, before conducting the experimental procedures described below. Although the dilution of the treated samples does result in a 1-log decrease in sensitivity of viable virus detection in the subsequent titration assay, the high input titre of SARS-CoV-2 used to spike the milk samples balances the dilution factor such that a 6-log reduction in viable virus would still be quantifiable.

We used spiked milk samples to determine viral titres in samples from all treatment conditions, as previously described.23,24 Briefly, we prepared 6 serial 10-fold dilutions of each SARS-CoV-2 milk solution (inoculum) and applied 50 L of each to monolayers of Vero E6 cells with DMEM (0.2 106 cells/mL) in flat-bottom 96-well plates. We incubated the plates at 37C and 5% CO2 for 1 hour, with gentle shaking every 15 minutes to promote uniform distribution of the inoculum across the wells. After 1 hour, we removed the inoculum and then reconstituted the plate with 200 L of DMEM with 2% fetal bovine serum, and allowed it to progress for 5 days. Positive controls consisted of undiluted milk-free samples of 160 L of viral stock solution and 840 DMEM (SARS-CoV-2 alone). Negative controls consisted of unpasteurized and pasteurized human milk with no viral inoculum (mock infection).

We observed cytopathic effects at 5 days after infection and reported them as TCID50/mL. We calculated the viral titres using the SpearmanKarber method.25,26 At 5 days after infection, we passaged supernatants onto fresh Vero E6 monolayers in flat-bottom 96-well plates and refreshed the original monolayers with 200 L of DMEM with 2% fetal bovine serum. We monitored these for 14 days for any signs of emergence of breakthrough cytopathic effects not evident in the initial 5 days of culture. The limit of detection for the TCID50 assay was 20 TCID50/mL.

Donors to the Rogers Hixon Ontario Human Milk Bank provide written informed consent that their milk may be used for quality control and research purposes. We obtained human research ethics approval from Sinai Health and the University of Toronto.

Cytopathic effects were identical at 3 and 5 days after infection and are presented in Table 1. We detected no cytopathic activity in any of the SARS-CoV-2spiked milk samples that had been pasteurized using the Holder method (62.5C for 30 min), even after the passaging of inoculum and subsequent observation for 14 days. Of note, in the positive control samples (SARS-CoV-2 alone), this heat treatment did not completely inactivate the virus. In the SARS-CoV-2spiked milk samples that were not pasteurized but were kept at room temperature for 30 minutes, we observed a reduction of approximately 1 log in comparison with virus spiked into DMEM alone, although we observed variability between milk donors (range of reduction 2 log to none). The mean standard deviation TCID50/mL was 1.05 106 1.86 106.

Stability of SARS-CoV-2 in donated human milk with and without Holder pasteurization (TCID50/mL)*

Very few milk samples from women positive for COVID-19 have been tested for SARS-CoV-2. Of the few available cases reported in the literature, there are now at least 3 reports of the presence of SARS-CoV-2 nucleic acid in human milk, although none of these have measured the viability of the virus in these samples. The World Health Organization recommends that human donor milk be fed to low-birth-weight infants when there is an insufficient volume of mothers milk.27 Human milk banking is growing rapidly internationally, with more than 650 milk banks globally that rely on the Holder method to ensure the safety of donor milk.28

Although this technique is assumed to result in inactivation of SARS-CoV-2, it is important to confirm this in a human milk matrix, for the safety of milk bank staff, caregivers and recipients of human donor milk. In this study, pasteurization of human milk spiked with SARS-CoV-2 using the Holder method (62.5C for 30 min) resulted in complete viral inactivation, as measured by TCID50/mL. The high viral titre used to spike samples in these experiments enabled us to confirm a 106 reduction. The impact of pasteurization on coronaviruses in a human milk matrix has not previously been reported in the literature.29

The results are in keeping with evidence of coronavirus inactivation in other matrices, including culture media and plasma using a variety of pasteurization protocols. The virus causing severe acute respiratory syndrome, SARS-CoV, has been shown to be completely inactivated with temperatures as low as 56C for 20 minutes, as well as at higher temperatures, such as 70C for 5 minutes.3033 The virus causing Middle East respiratory syndrome was shown to be inactivated at 56C for 60 minutes.34,35 A recent report by Chin and colleagues showed SARS-CoV-2 in virus transport media to be completely inactivated at 56C for 30 minutes or 70C for 5 minutes.19 In the present investigation, we did not see complete inactivation of SARS-CoV-2 in media that did not contain human milk (positive control) after pasteurization at 62.5C for 30 minutes, which differs from the report of Chin and colleagues. This finding suggested to us that the biological matrix in which the virus resides needs to be considered when assessing effective inactivation conditions.

Interestingly, we observed some reduction in the cytopathic effects of SARS-CoV-2 in milk samples that were not heat treated but held at room temperature for 30 minutes. This is very likely a result of the multitude of immune components found in human milk including secretory 1gA antibodies, lactoferrin, lactadherin, mucins from milk fat globules and oligosaccharides that have significant antiviral activity.1,2 Notably, Hamilton Spence and colleagues reported the same finding for human milk samples inoculated with Ebola virus and held at room temperature for 30 minutes.36

We studied only 10 samples of milk. However, our ability to study more was limited because of the complexity of ensuring safety using the SARS-CoV-2 virus, and this sample size is larger than has been used in similar studies of other viruses.2022

Pasteurization of human milk by the Holder method (62.5C for 30 min) inactivates SARS-CoV-2. In the event that a woman who has COVID-19 donates human milk that contains SARS-CoV-2, whether by transmission through the mammary gland or by contamination through respiratory droplets, skin, breast pumps and milk containers, this method of pasteurization renders milk safe for consumption. Furthermore, previously frozen, thawed human milk appears to contain sufficient antiviral activity to partially reduce the infectivity of SARS-CoV-2 in human milk.

Competing interests: Deborah OConnor serves as the Chair of the Advisory Board (unpaid) and Sharon Unger serves as the Medical Director (paid) of the Rogers Hixon Ontario Human Milk Bank. No other competing interests were declared.

This article has been peer reviewed.

Contributors: All of the authors contributed to the conception and design of the work, and the acquisition, analysis, and interpretation of data. Sharon Unger, Natasha Christie-Holmes and Deborah OConnor drafted the manuscript. All of the authors revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the work. Sharon Unger and Natasha Christie-Holmes are co-first authors.

Funding: This research was funded by the Canadian Institutes of Health Research (FDN no 143233). Indirect support was also received from the University of Toronto and the Temerty Foundation to support enhanced capacity and operations of the Toronto Combined Containment Level 3 Facility during the COVID-19 pandemic. The sources of support had no role in the design or conduct of this review, data interpretation or writing of the manuscript.

Data sharing: Requests for original data should be made to Dr. Sharon Unger, at sharon.unger{at}sinaihealth.ca

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Holder pasteurization of donated human milk is effective in inactivating SARS-CoV-2 - CMAJ

Now, scientists say they have, for the first time, found that dinosaurs suffered from osteosarcoma -- an aggressive malignant cancer that afflicts humans today.

When a lower leg bone or fibula from a horned dinosaur called Centrosaurus apertus that lived 76 to 77 million years ago was unearthed in Dinosaur Provincial Park in Alberta, Canada, in 1989, the malformed end of the fossilized bone was originally thought to be a healing fracture.

But a more detailed analysis, using modern medical techniques that approached the fossil in the same way as a diagnosis in a human patient, revealed that it was osteosarcoma, a bone cancer that in humans today usually occurs in the second or third decade of life.

It's an overgrowth of disorganized bone that spreads rapidly both through the bone and to other organs, including most commonly, the lung.

"Diagnosis of aggressive cancer like this in dinosaurs has been elusive and requires medical expertise and multiple levels of analysis to properly identify," said Dr. Mark Crowther, a professor of pathology and molecular medicine at McMaster University in a press statement.

"Here, we show the unmistakable signature of advanced bone cancer in (a) 76-million-year-old horned dinosaur -- the first of its kind. It's very exciting," said Crowther, author of the paper, which published Monday in the journal Lancet Oncology.

The team analyzing the fossilized bone included professionals from diverse fields including pathology, radiology, orthopedic surgery and paleopathology -- the study of disease and infection in the fossil record.

The bone was examined, cast and CT scanned before a thin slice of the bone was studied under the microscope. Then, powerful three-dimensional reconstruction tools were used to visualize the progression of the cancer through the bone. The investigators ultimately reached a diagnosis of osteosarcoma.

To confirm their diagnosis, the team compared the fossil to a normal fibula from a dinosaur of the same species, as well as to a fibula belonging to a 19-year-old man with a confirmed case of osteosarcoma.

Common biological links

"It is both fascinating and inspiring to see a similar multidisciplinary effort that we use in diagnosing and treating osteosarcoma in our patients leading to the first diagnosis of osteosarcoma in a dinosaur," said Seper Ekhtiari, an orthopedic surgery resident at McMaster University and study co-author.

The fossil specimen is from an adult dinosaur with an advanced stage of cancer that may have invaded other body systems; however, it's not clear if the dinosaur was killed by the cancer.

It was found in a massive bone bed, suggesting it died as part of a large herd of Centrosaurus that was struck down by a flood.

"The shin bone shows aggressive cancer at an advanced stage. The cancer would have had crippling effects on the individual and made it very vulnerable to the formidable tyrannosaur predators of the time," said study-co author David Evans, the James and Louise Temerty endowed chair of vertebrate palaeontology at the Royal Ontario Museum in Toronto in the news release.

"The fact that this plant-eating dinosaur lived in a large, protective herd may have allowed it to survive longer than it normally would have with such a devastating disease."

This study said it aimed to establish a new standard for the diagnosis of diseases in dinosaur fossils and opened the door to more precise diagnoses.

Studying disease in fossils is a complicated task given there are no living references. The diseases of the past, however, will help scientists to gain a better understanding of the evolution and genetics of disease, experts say.

"Evidence suggests that malignancies, including bone cancers, are rooted quite deeply in the evolutionary history of organisms," the paper said.

"This discovery reminds us of the common biological links throughout the animal kingdom and reinforces the theory that osteosarcoma tends to affect bones when and where they are growing most rapidly," said Ekhtiari.

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Dinosaur diagnosed with bone cancer that afflicts humans today - CNN

LEXINGTON, Mass., Aug. 10, 2020 (GLOBE NEWSWIRE) -- LogicBio Therapeutics, Inc. (Nasdaq:LOGC) (LogicBio or the Company), a company dedicated to extending the reach of genetic medicine with pioneering targeted delivery platforms, today reported financial results for the quarter ended June 30, 2020, provided a business update and announced the U.S. Food and Drug Administration (FDA) has cleared the Companys Investigational New Drug (IND) application for LB-001 for the treatment of methylmalonic acidemia in pediatric patients. LogicBio released a separate press release this morning providing further details on the planned Phase 1/2 clinical design for LB-001.

We are thrilled to have received clearance to move forward with this first-in-human clinical trial with our lead product candidate, LB-001, for the treatment of methylmalonic acidemia, a life-threatening congenital genetic disease with no current therapeutic treatment options. This represents a significant milestone in our goal of bringing a treatment to MMA patients as well as for our GeneRide platform. We have maintained continuous dialogue with the centers of excellence that are planned to participate in the Phase 1/2 clinical trial, and we look forward to activating these sites as quickly as possible, said Fred Chereau, CEO of LogicBio. We have instituted systems attempting to mitigate COVID-19 dynamics on our study start-up process and, based on our best estimates, we plan to enroll our first patient in early 2021.

Commenting on the Next Generation Capsid Program, Mr. Chereau said, We are very excited about the recent advances in our novel capsid program, which has generated liver-tropic capsids intended for use in gene editing technologies such as GeneRide and other gene therapy approaches. We are focused on executing across all of our programs and look forward to sharing further details on our novel capsids in early 2021.

Appointment of Daniel Gruskin, M.D. to SVP, Head of Clinical Development

Daniel Gruskin, M.D. was appointed as SVP, head of clinical development in August 2020. Dr. Gruskin has served as interim head of clinical development of LogicBio since June 2020. In April 2020, Dr. Gruskin started consulting with the Company as a special advisor. Previously, Dr. Gruskin served in roles of increasing responsibility at Sanofi Genzyme, most recently as vice president, head of global medical affairs, rare disease, in which capacity he oversaw medical affairs, life cycle management, scientific affairs and other medical and development activities related to metabolic, rare and/or genetic diseases. Prior to his role at Sanofi Genzyme, Dr. Gruskin served as assistant professor, human genetics and pediatrics at Emory University School of Medicine, where he was also the chief of the genetics section at Childrens Healthcare of Atlanta.

Daniel has been instrumental in leading LB-001 clinical development efforts including getting the IND cleared. His deep experience in genetic medicines and metabolic diseases will serve LogicBio well as we look to execute on our goals for both the GeneRide and Next Generation Capsid platforms in search of transformative medicines, said Mr. Chereau.

Anticipated Milestones for 2020 and 2021:

Second Quarter 2020 Financial Results

Three Months Ended June 30, 2020 and 2019

About LogicBio Therapeutics

LogicBio Therapeuticsis dedicated to extending the reach of genetic medicine with pioneering targeted delivery platforms.

LogicBios proprietary genome editing technology platform, GeneRide, enables the site-specific integration of a therapeutic transgene without nucleases or exogenous promoters by harnessing the native process of homologous recombination. LogicBio has received FDA clearance for the first-in-human clinical trial of LB-001, a wholly owned genome editing program leveraging GeneRide for the treatment of methylmalonic acidemia. Patient enrollment is expected to begin in early 2021. In addition, LogicBio has a collaboration with Takeda to research and develop LB-301, an investigational therapy leveraging GeneRide for the treatment of the rare pediatric disease Crigler-Najjar syndrome.

LogicBio is also developing a Next Generation Capsid platform for use in gene editing and gene therapies. Data presented have shown that the capsids deliver highly efficient functional transduction of human hepatocytes with improved manufacturability with low levels of pre-existing neutralizing antibodies in human samples. Top-tier capsid candidates from this effort demonstrated significant improvements over benchmark AAVs currently in clinical development. LogicBio is developing these highly potent vectors for internal development candidates and potentially for business development collaborations.

LogicBio is headquartered inLexington, Mass. For more information, please visitwww.logicbio.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the federal securities laws, including those related to the Companys plans to initiate, advance and complete its planned SUNRISE Phase 1/2 clinical trial of LB-001 in MMA; the timing, progress and results of the Companys research and development activities, including those related to the GeneRide technology platform and Next Generation Capsid Program; its plans for LB-301 in Crigler-Najjar; and the sufficiency of its cash and cash equivalents to fund operating expenses and capital expenditure requirements. These are not statements of historical facts and are based on managements beliefs and assumptions and on information currently available. They are subject to risks and uncertainties that could cause the actual results and the implementation of the Companys plans to vary materially, including the risks associated with the initiation, cost, timing, progress and results of the Companys current and future research and development activities and preclinical studies and potential future clinical trials. In particular, the impact of the COVID-19 pandemic on the Companys ability to progress with its research, development, manufacturing and regulatory efforts, including the Companys plans to initiate, advance and complete its Phase 1/2 clinical trial for LB-001 in MMA, and the value of and market for the Companys common stock, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the United States and in other countries, and the effectiveness of actions taken globally to contain and treat the disease. These risks are discussed in the Companys filings with the U.S. Securities and Exchange Commission (SEC), including, without limitation, the Companys Annual Report on Form 10-K filed on March 16, 2020 with the SEC, the Companys Quarterly Report on Form 10-Q filed on May 11, 2020, and the Companys subsequent Quarterly Reports on Form 10-Q and other filings with the SEC. Except as required by law, the Company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future.

Contacts:

Investors:Brian LuqueAssociate Director, Investor Relationsbluque@logicbio.com951-206-1200

Media:Stephanie SimonTen Bridge CommunicationsStephanie@tenbridgecommunications.com617-581-9333

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LogicBio Therapeutics Reports Second Quarter 2020 Financial Results and Provides Business Updates - GlobeNewswire

The first time I heard nematode worms can teach us something about human longevity, I balked at the idea. How the hell can a worm with an average lifespan of only 15 days have much in common with a human who lives decades?

The answer is in their genesespecially those that encode for basic life functions, such as metabolism. Thanks to the lowly C. elegans worm, weve uncovered genes and molecular pathways, such as insulin-like growth factor 1 (IGF-1) signaling that extends healthy longevity in yeast, flies, and mice (and maybe us). Too nerdy? Those pathways also inspired massive scientific and popular interest in metformin, hormones, intermittent fasting, and even the ketogenic diet. To restate: worms have inspired the search for our own fountain of youth.

Still, thats just one success story. How relevant, exactly, are those genes for humans? Were rather a freak of nature. Our aging process extends for years, during which we experience a slew of age-related disorders. Diabetes. Heart disease. Dementia. Surprisingly, many of these dont ever occur in worms and other animals. Something is obviously amiss.

In this months Nature Metabolism, a global team of scientists argued that its high time we turn from worm to human. The key to human longevity, they say, lies in the genes of centenarians. These individuals not only live over 100 years, they also rarely suffer from common age-related diseases. That is, theyre healthy up to their last minute. If evolution was a scientist, then centenarians, and the rest of us, are two experimental groups in action.

Nature has already given us a genetic blueprint for healthy longevity. We just need to decode it.

Long-lived individuals, through their very existence, have established the physiological feasibility of living beyond the ninth decade in relatively good health and ending life without a period of protracted illness, the authors wrote. From this rare but valuable population, we can gain insight into the physiology of healthy aging and the development of new therapies to extend the human healthspan.

While it may seem obvious now, whether genes played a role in longevity was disputed for over a century. After all, rather than genes, wouldnt access to health care, socioeconomic status, diet, smoking, drinking, exercise, or many other environmental and lifestyle factors play a much larger role? Similar to height or intelligence (however the latter is assessed), the genetics of longevity is an enormously complicated and sensitive issue for unbiased studying.

Yet after only a few genetic studies of longevity, a trend quickly emerged.

The natural lifespan in humans, even under optimal conditions in modern societies, varies considerably, the authors said. One study, for example, found that centenarians lived much longer than people born around the same time in the same environment. The offspring of centenarians also have lower chances of age-related diseases and exhibit a more youthful profile of metabolism and age-related inflammation than others of the same age and gender.

Together, about 25 to 35 percent of the variability in how long people live is determined by their genesregardless of environment. In other words, rather than looking at nematode worm genes, we have a discrete population of humans whove already won the genetic lottery when it comes to aging. We just need to parse what winning means in terms of biology. Genes in hand, we could perhaps tap those biological phonelines and cut the wires leading to aging.

Identification of the genetic factors that underlie extreme human lifespan should provide insights into the mechanisms of human longevity and disease resistance, the authors said.

Once scientists discovered that genes play a large role in aging, the next question was which ones are they?

They turned to genome-wide association studies, or GWAS. This big data approach scans existing genomic databases for variations in DNA coding that could lead to differences in some outcomefor example, long versus short life. The differences dont even have to be in so-called coding genes (that is, genes that make proteins). They can be anywhere in the genome.

Its a powerful approach, but not that specific. Think of GWAS as rudimentary debugging software for biological code: it only looks for differences between different DNA letter variants, but doesnt care which specific DNA letter swap most likely impacts the final biological program (aging, in this case).

Thats a huge problem. For one, GWAS often finds dozens of single DNA letter changes, none powerful enough to change the trajectory of aging by itself. The technique highlights a village of DNA variants, that together may have an effect on aging by controlling the cells course over a lifetime, without indicating which are most important. Its also hard to say that a DNA letter change causally leads to (or protects against) aging. Finally, GWAS studies are generally performed on populations of European ancestry, which leaves out a huge chunk of humansfor example, the Japanese, who tend to produce an outsized percentage of centenarians.

So what needs to change?

Rather than focusing on the general population, the key is to home in on centenarians of different cultures, socioeconomic status, and upbringing. If GWAS are like fishing for a rare species in several large oceans, then the authors point is to focus on pondsdistributed across the worldwhich are small, but packed with those rare species.

Extremely long-lived individuals, such as centenarians, compose only a tiny proportion (~0.01 percent to 0.02 percent) of the United States population, but their genes contain a biological blueprint for healthy aging and longevity, the authors said. Theyre spared from usual age-related diseases, and this extreme and extremely rare phenotype is ideal for the study of genetic variants that regulate healthspan and lifespan.

Its an idea that would usually make geneticists flinch. Its generally thought that the larger the study population, the better the result. Here, the recommendation is to narrow our focus.

And thats the point, the authors argue.

Whatever comes out of these studies will likely have a much larger impact on aging than a GWAS fishing experiment. Smaller (genomic) pond; larger (pro-youth) fish. Whats more, a pro-youth gene identified in one European-based long-living population can be verified in another group of centenarianssay, Japaneseensuring that the gene candidates reflect something fundamental about human aging, regardless of race, culture, upbringing, and wealth.

A genomic screen of centenarians can easily be done these days on the cheap. But thats only the first step.

The next step is to validate promising anti-aging genetic differences, similar to how scientists validated such differences in nematode worms during classic longevity studies. For example, a promising pro-youth gene variant can be genetically edited into mice using CRISPR or some other tool. Scientists can then examine how the mice grow up and grow old, compared to their non-edited peers. Does the gene make these mice more resilient to dementia? What about muscle wasting? Or heart troubles? Or hair greying and obesity?

From these observations, scientists can then use an enormous selection of molecular tools to further dissect the molecular pathways underlying these pro-youth genetic changes.

The final step? Guided by centenarian genes and validated by animal models of aging, we can design powerful drugs that sever the connection between the genes and proteins that drive aging and its associated diseases. Metformin is an experimental pill that came out of aging studies in nematode wormsimagine what studies in human centenarians will yield.

Despite enormous improvements in human health over the past century, we remain far from a situation in which living to 100 years of age in fairly good health is the norm, the authors said.

But as centenarians obviously prove, this is possible. By digging into their genes, scientists may find a path towards healthy longevitynot just for the genetically fortunate, but for all of us.

Image credit:Cristian Newman / Unsplash

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The Secret to Healthy Longevity Is in the Genes of the Oldest Humans Alive - Singularity Hub

A four-day pilot test of Boston Universitys COVID-19 testing program on the Medical Campus last week found no positive cases of the virus among 287 graduate students tested. The success of the trial gives confidence to administrators and test system operators that the complex project can handle the challenges ahead, starting with the arrival of undergraduate students in mid-August, says Gloria Waters, vice president and associate provost for research.

This has been a huge undertaking, says Waters. There will be more than 150 people working on this at five different sites. The goal of the pilot was to try out our testing collection stations and the lab. It was about things like gathering samples and delivering them to the lab, and all of those things have gone very well.

Test results for 283 of the 287 students, all enrolled in the Henry M. Goldman School of Dental Medicine or the School of Medicine, were negative, and test results were inconclusive for 4 students, who have been called back for retesting.

Kilachand CenterHours: 7 am8 pmHourly capacity: 80

808 GalleryHours: 8 am9 pmHourly capacity: 240

Agganis Arena Lobby8 am9 pmHourly capacity: 180

Medical CampusHours: 7 am8 pmHourly capacity: 50

Agganis Arena Rear (Symptomatic)Hours: 8 am9 pmHourly capacity: TBD

Waters says the pilot testing is continuing this week with increasing numbers of tests on the Medical Campus, and also with testing at the Rajen Kilachand Center for Integrated Life Sciences & Engineering, which houses both a testing collection station and the BU Clinical Testing Lab, which will process the tests from BUs five collection stations. As of Wednesday evening, more than 1,000 students on the Medical Campus had been tested, which she called an incredibly robust response by the students.

Last week we never had more than 96 tests in one day, Waters says. On Monday of this week we had 350 on the Medical Campus and another 220 or so graduate students who were invited to be tested at the Kilachand Center. Each week between now and August 15 we will be adding people to be tested.

Once people are tested they will know what to do. They will know how to unwrap the swab and know what to do with it, so future tests should go more quickly. Those are the kinds of things that the pilot is about, and we need to test all of them. We need to be sure that people waiting for tests can stand six feet apart. This is a system with lots of processes, and we are troubleshooting the whole thing.

Kelly Lockard, Advisory Services associate director, says the pilot gave her confidence that BUs system could handle testing on a large scale. We are now focusing on refining a collection process that can accommodate over 6,000 students, faculty, and staff per day, Lockard says, and that feedback from test participants will help guide operational decisions going forward.

Drew Duckett, director of collection site operations for the Back2BU Health and Safety Initiative, says the pilot convinced him that the University has designed and built a safe and efficient collection process. We still have work ahead, says Duckett, who is also Student Health Services associate head athletic trainer. We still must see this operate as smoothly at scale, but I am pleased with the process.

To head up operations at the BU Clinical Testing Lab, Waters brought in experts in healthcare technology and operations. New lab supervisor Lynn Doucette-Stamm, a former vice president of technology at Sitokine, Inc., who has more than 30 years of management and leadership experience in the human genetics and genomics field, describes the Clinical Testing Lab as a state-of-the art facility that will provide the BU community with accurate and timely COVID-19 testing.

Candice Miller, who initially served as a consultant on the COVID-19 testing project, has been appointed managing director of lab operations and is responsible for setting up all of the collection sites. Formerly a vice president at Quest Diagnostics Molecular Biology Laboratory, Miller says the lab will deliver timely results with the highest possible accuracy. We are ready for students and faculty to return to campus with frequent testing in our new high throughput clinical lab, she says

The testing station on the Medical Campus is at 72 East Concord Street. Charles River Campus testing stations are at the Kilachand Center for Integrated Life Sciences & Engineering, the 808 Gallery, the Agganis Arena lobby, and for those who report feeling symptoms of the coronavirus, 925 Commonwealth Avenue Rear, in the back of Agganis Arena. The sites, which are scheduled to begin operations on August 15, will be open for collection from 7 am to 8 pm or 8 am to 9 pm, depending on the site (see the hours of operation sidebar above) and will collect an average of about 500 tests per hour across all sites.

Arriving students, whose numbers are limited to about 750 per day, will go into surveillance collection testing after completing their entrance test. Undergraduates will be tested every three days at one of four collection sites on the Charles River Campus. Graduate students will initially be tested weekly. (The University is covering the cost of all tests for faculty, staff, and students.)

Judy Platt, director of Student Health Services and chair of BUs Medical Advisory Group, says certain groups of students will be prioritized for higher testing frequencies based on a variety of factors, including their living arrangements on campus and their interactions with the campus community. Faculty and staff who test positive will be asked to stay at home and reach out to their primary care physician for further instructions. Student Health Services has quarantine and isolation protocols for all students who have been exposed to the virus or who have COVID-19 symptoms or who have tested positive. In all cases, faculty, staff, and students will receive test results and further instructions, as needed.

Waters says the University will closely monitor test results, as well as a variety of other metrics, and will respond appropriately. She says there is no designated positive test rate that will trigger a specific action.

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BU's COVID-19 Testing Passes Its First Test | BU Today - BU Today

Coronavirus disease 2019 (COVID-19) has spread rapidly and extensively to most countries in the world, resulting in considerable mortality in Europe and the United States, as well as in numerous upper-middle-income countries in South America and Asia. Experts predicted millions of COVID-19 deaths in Africa because many countries in the continent rank poorly on the United Nations Development Programme's Human Development Index. However, more than 4 months after the first cases in Africa were detected, prevalence and mortality are still low. It remains unclear if Africa is really spared from substantial cases and deaths. However, differences between Africa and the most affected countries in reliable reporting and death registration, lockdown stringency, demography, sociocultural aspects, environmental exposures, genetics, and the immune system could help to explain the experience of COVID-19 in Africa.

Africa faces major health and socioeconomic challenges that should have allowed rapid transmission of COVID-19. These include a weak health system (per capita health expenditure of <$50 in most West African countries compared with >$2500 in Europe and the United States), population crowding, poverty, and unhygienic conditions (1). Population densities are very high in most African capital cities such as Dakar (12,617 persons/km2), Abidjan (11,155 persons/km2), or Lagos (13,909 persons/km2), whereas New York City has 7101 persons/km2. However, although community transmission was reported in many major African cities months ago, the predicted number of cases and deaths has not yet been observed (see the figure). Low case numbers are often attributed to insufficient testing. However, many African countries implemented testing early on, and, based on the Our World in Data database (2), more tests per the number of cases were carried out than in other countries at similar phases of the epidemic (see the figure). Regarding the number of deaths, few functional civil registration services and thus statistics exist on the continent, raising questions about the reliability of mortality data. Potential underreporting of COVID-19associated deaths would not be specific to Africa, but the margin of error could be wider. To date, African countries have not indicated acute health emergencies; however, reliable age-stratified data are needed to fully grasp the COVID-19 situation in Africa to allow appropriate measures to be taken.

Measures such as travel restrictions, curfews, and school closures were implemented early in Africa compared with other continents, often before an African country had detected a case (fig. S1). These early responses might have resulted in fewer imported cases and reduced intracountry transmission, allowing sufficient time to prepare the constrained health systems for diagnosis and to prepare strategies for quarantine, contact tracing, and social distancing on a continent that already has experience in such practices to control epidemics such as Lassa fever and Ebola. Although it is likely that the early lockdown in Africa contributed to the slow spread, containment measures are not fully respected in many countries. Most people work in the informal business sector, such as in traditional markets, making strict lockdown measures impossible to implement. Recently, some African governments have been pressured to relax lockdown measures, for example, to carry out congregational prayers in mosques in Senegal. It remains unknown whether relaxation of containment measures will result in increased cases or if other factors are at play.

The majority of COVID-19associated deaths occur in older people. Africa has a comparatively young population, with a median population age of 19.7 years for the continent versus 38.6 years for the United States. Africa's youthful population is reflected in the structure of age-stratified cases (fig. S2). Based on global age-specific case fatality rates for COVID-19 and the age demographics of Africa, COVID-19 deaths would be expected to be only four times (3), rather than the observed 40 times, lower than in Europe or the United States. However, no aggregated data on age-specific case or death rates are available for the continent. There is substantial intergenerational mixing in Africa, and, with more cases of subclinical infections in the young, it could be a matter of time before expansive numbers of cases and deaths are recorded. Alternatively, a more rapid development of herd immunity among the youthful population might lead to fewer severe cases. Data from antibody tests (serosurveys) should clarify if transmission was more widespread with a high rate of asymptomatic and mild cases in African countries than in other countries.

The genetic characteristics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human genetics may be among the reasons for low incidence of severe COVID-19 in Africa. Although the relative contribution from Africa to the SARS-CoV-2 GISAID (Global Initiative on Sharing All Influenza Data) sequence database is small, the isolates found in Africa are representative of the different clades of SARS-CoV-2 found on other continents (fig. S3). Thus, it is unlikely that strains of SARS-CoV-2 in Africa have reduced virulence. Moreover, African-Americans constitute a disproportionate burden of deaths in the United States, so it seems unlikely that the lower mortality from COVID-19 in Africa is due to genetic factors. Nonetheless, the COVID Human Genetic Effort consortium aims to elucidate whether genetics can play a role in the patterns of disease worldwide.

SARS-CoV-2 infection leads to a heterogeneous outcome. About 80% of symptomatic cases are mild to moderate, whereas 20% can develop severe respiratory disease and display high rates of mortality (4). The development of an effective adaptive immune response can limit viral infection, whereas uncontrolled activation of innate immune cells leads to a cytokine storm and hyperinflammation in the lungs, ultimately leading to acute respiratory distress syndrome (ARDS) and multiorgan failure (4, 5). Being able to suppress viral infection early or to temper excessive inflammatory responses are likely complementary mechanisms to prevent severe disease.

Most convalescent symptomatic COVID-19 patients develop virus-specific neutralizing antibodies as well as specific CD4+ and CD8+ T cell responses (5). The efficiency and adequacy of these adaptive responses to clear viral infections depends on multiple factors, including past or concurrent infections with other pathogens. For example, antibodies directed to the four human coronaviruses that cause common colds could cross-react and neutralize SARS-CoV-2 in humans (6), and preexisting cross-reactive T cells can be found in individuals that have not been exposed to SARS-CoV-2 (7), suggesting previous exposure to related human coronaviruses could generate immunological cross-reactivity (7).

There are considerable differences in environmental exposures in Africa, compared with Europe or the United States. Noncommunicable diseases (NCDs)such as cardiovascular diseases, obesity, and type 2 diabetesare risk factors for severe COVID-19. These environmentally and behaviorally driven conditions are increasingly recognized in urban centers in Africa, and most COVID-19 deaths in Africa have been in older people with NCDs. However, infectious diseases such as HIV, tuberculosis, malaria, and other respiratory infections or those caused by helminths (parasitic worms) are prevalent in Africa, but there is currently little information on whether, or how, these infections affect COVID-19 disease progression.

The distribution of coronavirus disease 2019 (COVID-19) cases and deaths per 1 million inhabitants per continent reveals surprisingly low rates in Africa (left). This is despite comparable levels of testing per confirmed cases across continents (right). The dotted lines show the number of tests performed per number of detected cases. Data are from European Centre for Disease Prevention and Control COVID-19 situation updates, United Nations World Population Prospects 2019, and Our World in Data (2).

It is increasingly recognized that the immune system is shaped not only by genetics but also by environmental factors, such as exposure to microorganisms and parasites. This educates the immune system to protect against invading pathogens not only specifically but also nonspecifically through, for example, trained immunity, which involves the reprogramming of innate cells that, on secondary encounter with a pathogen, can show a stronger response (8) or virtual memory (9). Virtual memory T cells (TVM cells) expand in response to cytokines such as helminth-induced interleukin-4 (IL-4), rather than through pathogen-specific antigens, leading to enhanced antiviral effector functions (9). Thus, it can be envisaged that TVM cells are more prevalent in people in Africa owing to the higher exposure to such pathogens. This could contribute to the control of SARS-CoV-2. Additionally, as postulated by the hygiene hypothesis, early and chronic exposure to pathogens leading to relentless immune cell activation in harsh environments induces a strong regulatory immune response to counteract excessive inflammation (10).

The ability to prevent excessive inflammation could be a critical parameter that is associated with COVID-19 outcome. Recent data suggest that inflammatory alveolar macrophages (AMs), which can arise from differentiation of recruited monocytes upon infection, are increased in the lungs of patients with severe COVID-19 (11). It is unclear whether these monocyte-derived AMs are an important source of the cytokine-release syndrome observed during SARS-CoV-2 infection or whether they are involved in the pathogenesis of ARDS. However, monocyte and macrophage inflammatory cytokines, such as IL-6, have been repeatedly observed to be a marker of severe COVID-19, and myeloid cells are thus likely to be associated with the hyperinflammation. Monocytes from African individuals with high exposure to pathogens can be less proinflammatory (12). Thus, their recruitment into the lungs might prevent high cytokine production and therefore lead to better outcomes of COVID-19. Moreover, the airway microbiota, as well as more distal gut microbiota, could play important roles in preventing or potentiating respiratory tract infections and modulating virus-induced inflammation, as has been shown for several respiratory viruses (13). The known variations in microbiota across geographical areas could thus also participate in modulating disease severity and should be studied.

Africa should be part of the roadmap for COVID-19 research. Although there are no available data on the immune responses in African COVID-19 patients, studies show clear differences in the activation, proinflammatory, and memory profiles of the immune cells not only in Africans versus Europeans but also among Africans with high and low exposure to microorganisms and parasites (14) (fig. S4). Does the difference in immunological profiles matter for the outcome of COVID-19 in Africa? This needs further investigation, and the pattern of COVID-19 in urban and rural Africa could be informative.

There are differences in opinion about whether the pattern of SARS-CoV-2 spread is different in Africa compared with that in the United States and Europe. So far, despite a paucity of data, it appears that the virus is spreading differently and potentially with an attenuated outcome in Africa. There has been limited testing of asymptomatic cases or of antibody titers. Therefore, it is unknown whether early interventions were successful in preventing transmission or whether there are differences in susceptibility between populations of different regions. Perhaps the COVID-19 pandemic can emphasize the need for widespread implementation of public health tools, such as high-quality data, accurate diagnostics for track and trace, good communication, and an effective vaccine. Early testing of vaccines in different regions of Africa is essential because the high degree of exposure to pathogens can limit some vaccine responses (15). The first COVID-19 vaccine testing is starting in South Africa (Ox1Cov-19 Vaccine VIDA-Trial), and others are planned. Hopefully, this will stimulate the full participation of Africa in research into the critical factors that hold the key to innovative solutions in the fight against the pandemic.

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COVID-19 in Africa: Dampening the storm? - Science

AUSTIN, Texas & MENLO PARK, Calif.--(BUSINESS WIRE)--Pacific Biosciences of California, Inc. (Nasdaq:PACB), a leading provider of high-quality sequencing of genomes, transcriptomes and epigenomes, and Asuragen, a molecular diagnostics company delivering easy-to-use products for complex testing in genetics and oncology, today announced their clinical research collaboration aimed at developing molecular assays based on PacBios Single Molecule, Real-Time (SMRT) Sequencing technology. The initial focus of the collaboration will be on research in support of assay development for the carrier screening market.

Several of the most common carrier genes for autosomal recessive and X-linked conditions are either technically challenging or inaccessible to amplify and sequence, leading to incomplete coverage and convoluted workflows spread over multiple platforms. Through this collaboration, Asuragen scientists will develop assays that combine the companys AmplideX PCR technology for enriching hard-to-amplify sequences with PacBio SMRT Sequencing, a highly accurate long-read sequencing platform with a unique ability to represent all regions of the genome and to detect any kind of structural or other variation.

Innovative amplification and sequencing technologies have each been instrumental in discovering and characterizing challenging disease-causing structural variants, such as indels, copy number changes, and repeat expansions, said Gary J. Latham, PhD, Senior Vice President of Research and Development at Asuragen. We are excited to work with PacBio to combine the best of both technologies to build assays that can uniformly resolve simple and complex forms of genetic variation for research and clinical applications.

Scientists at Asuragen will develop assays for PacBios Sequel Systems using Asuragens AmplideX PCR technology. AmplideX products are designed to solve testing needs in inherited genetic disorders through easy-to-run assays and optimized workflows that deliver best-in-class performance. Assays will make use of PacBios HiFi long reads, an approach incorporating multiple passes of the same molecule to create a highly accurate consensus sequence.

We are honored to partner with Asuragen, a leader in molecular diagnostics, to apply the unique value of SMRT Sequencing for clinical research, said Jonas Korlach, PhD, Chief Scientific Officer of Pacific Biosciences. Scientists have shown that PacBios long-read sequencing systems offer a high-resolution view of the human genome that is simply not possible with any other sequencing technology. We look forward to working with Asuragen to design assays capable of interrogating challenging genomic regions and identifying the full breadth of natural human genetic variation.

About Asuragen

Asuragen is a molecular diagnostic product company changing the way patients are treated in genetics and oncology. Asuragens diagnostic systems, composed of proprietary chemistry and software, deliver powerful answers using broadly installed instrument platforms. They are simple to adopt and expand the ability to serve patients. Asuragen is a product foundry rapidly and efficiently addressing current and emerging clinical needs, including cancer diagnosis and monitoring, reproductive health and aging, serving laboratories across a patients lifespan with its best in class diagnostic tests. For more information, visit http://www.asuragen.com.

About Pacific Biosciences

Pacific Biosciences of California, Inc. (NASDAQ:PACB), is empowering life scientists with highly accurate long-read sequencing. The companys innovative instruments are based on Single Molecule, Real-Time (SMRT) Sequencing technology, which delivers a comprehensive view of genomes, transcriptomes, and epigenomes, enabling access to the full spectrum of genetic variation in any organism. Cited in thousands of peer-reviewed publications, PacBio sequencing systems are in use by scientists around the world to drive discovery in human biomedical research, plant and animal sciences, and microbiology. For Research Use Only. Not for use in diagnostic procedures. For more information please visit http://www.pacb.com and follow @PacBio.

Forward-Looking Statements

All statements in this press release that are not historical are forward-looking statements, including, among other things, statements relating to market leadership, uses, accuracy, quality or performance of, or benefits of using, our products or technologies, including SMRT technology, the suitability or utility of our methods, products or technologies for particular applications or projects, the expected benefits of the research collaboration with Asuragen, the ability of the Company to be successful in reaching its technological and commercial potential, and other future events. You should not place undue reliance on forward-looking statements because they involve known and unknown risks, uncertainties, changes in circumstances and other factors that are, in some cases, beyond Pacific Biosciences control and could cause actual results to differ materially from the information expressed or implied by forward-looking statements made in this press release. Factors that could materially affect actual results can be found in Pacific Biosciences most recent filings with the Securities and Exchange Commission, including Pacific Biosciences most recent reports on Forms 8-K, 10-K and 10-Q, and include those listed under the caption Risk Factors. Pacific Biosciences undertakes no obligation to revise or update information in this press release to reflect events or circumstances in the future, even if new information becomes available.

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Pacific Biosciences and Asuragen Collaborate to Develop Assays for Carrier Screening and other Applications Based on SMRT Sequencing Technology and...

Around one billion people are infected with parasitic helminths, round worms that live in soil and colonize the human gut through dirty water. Such infections are common in less developed countries where they can leave long-lasting consequences on child development.

Now, researchers at the University of Toronto have discovered that the helminths owe their ability to survive in the low oxygen environment of the human gut to a unique enzyme variantafinding thatraises hopes of new treatments to quell growing resistance of parasites to available medications.

When parasites are outside the body, which they are for a part of their lifecycle, they breathe oxygen just like we do, saysAndrew Fraser,senior author and a professor of molecular genetics at the Donnelly Centre for Cellular and Biomolecular Research at U of Ts Faculty of Medicine. We were trying to understand how these parasites survive inside the human gut where theres almost no available oxygen.

The study,published ine-Life, an online journal for the life-sciences, was co-led by Gustavo Salinas, a professor at Universidad de la Repblica in Uruguay, and Jennifer Shepherd, a professor at Gonzaga University in the U.S.

COQ2 molecular structure with alternately encoded core (in pink) that flips between variants in response to oxygen.

Most animals, including humans, make energy through aerobic or oxygen-dependent metabolism with the help of a molecule called ubiquinone, or UQ. When they are inside their host, parasitic helminths switch to an unusual type of anaerobic metabolism that burns a related molecule called rhodoquinone, or RQ.

In aprevious study, Frasers team uncovered that UQ and RQ are made from different precursor molecules by the same enzyme called COQ2. But how does COQ2 know to use the UQ precursor when theres oxygen around but use the RQ precursor when theres no oxygen?

Somehow there has to be a switch, says Fraser. If we could understand how that switch works and if we could take a small compound and interfere with that switchprevent it from making RQ that might be a way to kill a parasite in humans.

First clues emerged whenMichael Schertzberg, a research technician in the lab, noticed that helminths produce two protein variants of COQ2. The variants are made by alternative splicing, a process through which gene coding segments, or exons, are variably included into templates for protein synthesis, allowing for diverse proteins to be encoded by the same gene. The two COQ2 variants are identical but for a small part encoded by two mutually exclusive exons, dubbed A and E. These are exactly the same size flipping from the A variant to the E variant is like switching a block in a complicated Lego structure.

The researchers next engineeredC. elegansworm strains producing either enzyme variant alone to test their ability to make UQ and RQ. Although not a parasite,C. elegansis a highly related helminth that also uses rhodoquinone. They found that the worms lacking the E variant lost their ability to make RQ and could no longer survive without oxygen.

Genome scanning across diverse animal lineages further strengthened the idea that the E variant is required for life without oxygen. The E variant is not even encoded in the COQ2 gene of most animals, including humans, who need air to live. It is only found in helminths and a few other species known to make RQ, such as oysters and other marine organisms, where it is likely an adaptation to changing oxygen levels in tidal environments.

Importantly, when they looked at the parasitic helminthsAscarisandStrongyloides stercoralis, they found that they also make and switch to the E variant when they are inside the host.

June Tan, a lead co-author and an expert in alternative splicing, has rarely seen in helminths two alternatively spliced variants with such distinct functions, like flipping a switch.

For me the most surprising finding was how restricted the E variant was to just those species that make RQ, says Tan, who is a post-doctoral researcher in the lab.

We think alternative splicing switches the enzyme core around the catalytic site so that it allows them to use a different precursor molecule to make RQ versus UQ.

WhenMargot Lautens, a PhD student in the lab, computationally laid each variant over the reference molecular structure of the enzyme, she found that the A and E exons encode a core segment that is crucial for the catalytic activity. The researchers think that when oxygen levels dip, the enzyme flips its inner core from the prevalent A form to the less common E form which can make RQ and sustain a parasites life.

The finding opens a therapeutic opportunity to specifically target the enzyme in the parasite without touching its counterpart in the host.

If you look at the A form of COQ2, it looks the same in every animal. An inhibitor would act on human too, says Fraser.

But the E variant has key differences and you could target just that form. This gives us a beautiful way to help us find inhibitors that will hit specifically the E form and thats what were doing now.

The research was supported by funding from the Canadian Institutes of Health Research and Agencia Nacional para la Innovacin y la Investigacin ANII in Uruguay.

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U of T researchers identify molecular switch allowing parasites to survive inside hosts without oxygen - News@UofT

The global Gaucher Disease Treatment Market is estimated to reach $2.11 Billion By 2025 and is projected to grow at a CAGR of 2.8% during the forecast period according to a new study published by Polaris Market Research.

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Gaucher Disease Treatment Market Size, Top Companies, Trends, Growth Factors Details by Regions, Types and Applications - Owned

The following information should be read in conjunction with the condensedconsolidated financial statements and the accompanying notes included in Part I,Item 1 of this Quarterly Report on Form 10-Q, and the "Risk Factors" included inPart I, Item 1A of our Quarterly Report on Form 10-Q for the quarter ended March31, 2020, and as updated by Part II, Item 1A of our 2019 10-K, as updated byPart II, Item 1A of this Quarterly Report on Form 10-Q.

SAFE HARBOR CAUTIONARY STATEMENT

risks and uncertainties relating to market demand and acceptance of ourproducts and technology, including ARIES, MultiCode, xMAP, xMAP INTELLIFLEX,VERIGENE, VERIGENE II, Guava, Muse, Amnis, and NxTAG products;

timing of and process for regulatory approvals;

our ability to scale manufacturing operations (particularly with respect to ourproducts that recently received U.S. Food and Drug Administration (FDA)Emergency Use Authorization (EUA) clearance) and manage operating expenses,gross margins and inventory levels;

potential shortages, or increases in costs, of components or other disruptionsto our manufacturing operations;

our ability to obtain and enforce intellectual property protections on ourproducts and technologies;

our ability to successfully develop and launch new products in a timely manner;

competition and competitive technologies utilized by our competitors;

dependence on strategic partners for development, commercialization anddistribution of products;

reliance upon the accuracy and completeness of the information received fromstrategic partners to determine the appropriate financial reporting;

risks and uncertainties associated with implementing our acquisition strategy,and our challenge to identify acquisition targets, including our ability toobtain financing on acceptable terms;

our ability to integrate acquired companies or selected assets into ourconsolidated business operations, and the ability to fully realize the benefitsof our acquisitions;

our ability to comply with applicable laws, regulations, policies andprocedures;

changes in principal members of our management staff;

our increasing dependency on information technology to enable us to improve theeffectiveness of our operations and to monitor financial accuracy andefficiency;

implementation, including any modification, of our strategic operating plans;

uncertainty regarding the outcome or expense of any litigation brought againstor initiated by us;

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Table of Contents

reliance on third party distributors for distribution of specificLuminex-developed and manufactured assay products; and

risks related to the issuance of the Notes and with respect to the ConvertibleNote Hedge Transactions.

OVERVIEW

Flexibility/scalability

Both protein and nucleic acid applications on a single platform

High throughput

Ease of use

Most xMAP-based assays are simple to perform. A test sample is added to asolution containing microspheres that have been coated with reagents. Thesolution is then processed through one of our xMAP Systems, which incorporateproprietary software to automate data acquisition and analysis in real-time.

Cost-effective

Our Amnis/Guava Technologies

Our Non-Automated Technologies

We have multiple assay development activities ongoing and these activities arefocused in the areas of infectious disease, human genetics and pharmacogenomics.

Our ARIES Technology

Our Market Approach

Second Quarter 2020 Highlights

Record revenue, profitability and cash flow generation in the quarterended June 30, 2020.

Consolidated revenue was $109.5 million for the quarter ended June 30, 2020, a32% increase over the prior year period.

Total assay revenue increased to $61.2 million for the quarter ended June 30,2020, a 95% increase over the prior year period.

Sample-to-answer assay revenue increased to $25.8 million for the quarterended June 30, 2020, a 56% increase over the prior year period.

Profitability increased to $12.5 million for the quarter ended June 30, 2020,an increase of more than 350% vs. the prior year period.

Issued $260.0 million principal amount of Notes due in May 2025.

Cash generation of approximately $31.0 million for the quarter ended June 30,2020, before the net proceeds of $217.6 million from the issuance of the Notes.

Received FDA EUA for the ARIES SARS-CoV-2 Assay on April 6, 2020.

Submitted EUA request to the FDA for the xMAP SARS-CoV-2 Multi-Antigen IgGAssay on June 29, 2020, which was subsequently issued on July 16, 2020.

COVID-19 Considerations

BARDA Contracts

Consumables Sales and Royalty Revenue Trends

Growth in Inventory

We expect our areas of focus over the next twelve months to be:

delivering on our revenue growth goals;

accelerating development and commercialization of the assays on oursample-to-answer diagnostic systems;

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Table of Contentscompleting development and commercialization of the next generationsample-to-answer system, VERIGENE II, our next generation xMAP System, xMAPINTELLIFLEX, and our next generation Guava instrument, Guava Next Gen;

improvement of ARIES and VERIGENE gross margins;

placements of our VERIGENE and ARIES Systems, our sample-to-answer platformsand assays;

increasing the growth of our LTG revenue through enrichment of our existingpartner relationships and the addition of new partners;

maintenance and improvement of our existing products and the timelydevelopment, completion and successful commercial launch of our pipelineproducts;

adoption and use of our platforms and consumables by our customers for theirtesting services; and

expansion and enhancement of our installed base of systems and our marketposition within our identified target market segments.

KEY PERFORMANCE INDICATORS

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Table of ContentsRevenues, disaggregated by revenue source, into the following primarycategories:

The Company's ability to meet anticipated product development timelines and todeliver on our planned commercial product launches.

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Table of Contents

RESULTS OF OPERATIONS

THREE MONTHS ENDED JUNE 30, 2020 COMPARED TO THREE MONTHS ENDED JUNE 30, 2019

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This article is brought to you thanks to the collaboration ofThe European Stingwith theWorld Economic Forum.

Author: Habiba Al Alsafar, Associate Professor, Department of Biomedical Engineering, Khalifa University of Science, Technology and Research (KUSTAR) & Elizabeth ODay, Founder and Chief Executive Officer, Olaris Inc

Diagnosing diseases can be complex, because illness is not a fixed state and has to be considered in context. We may be born with factors that predispose us to disease, but our lifestyle dictates if and when undesirable symptoms will manifest themselves.

For example, our middle-eastern forefathers were relatively healthier than us because of a nomadic lifestyle which was considerably more active. Our genes have remained unchanged in our recent history, yet the prevalence of a number of lifestyle diseases such as diabetes and obesity has risen in contemporary middle eastern countries. This is in part due to a shift towards more sedentary lifestyles. The environment and our lifestyles are working in concert with inherent elements (that is, the products of our genome) to contribute to the status of our health.

The intersection of genetics and lifestyle choices is playing an increasingly significant role in managing the health of middle eastern populations. The prevalence of chronic disease, in particular diabetes and its associated complications, is alarmingly high throughout the Gulf States. According to the 2017 report from the International Diabetes Federation, 11% of the population in the Middle East and North Africa (MENA) region has diabetes. Disturbingly, the prevalence is higher in the population of countries like the United Arab Emirates (UAE), where 19.3% of those between the ages of 20 and 79 have type-2 diabetes. A number of major co-morbidities are linked to diabetes and of these, cardiovascular disease is the highest cause of mortality in the UAE, accounting for 40% of mortalities. Non-communicable diseases (NCDs) in total are responsible for 77% of all deaths in the UAE. Both men and women are dying prematurely, resulting in a profound impact on families specifically and the community on the whole. The impact is not only limiting progress and development of the nation, it has a bearing on government spending as treating end-stage disease carries significant costs.

To manage the health of a nation we must shift our attention to examine both genetics and the impact of lifestyle choices.

A recent audit of the worlds genomic data showed that the predominant genomes in public databases belong to Europeans (81%), while only 0.08% of the genome inventory represents ancestries from Arab and Middle Eastern populations. The genomes of people of Asian and African ancestries at 14% and 3% respectively were also relatively low.

A breakdown of non-European genomic data samples

Image: Nature

As alluded to above, the genome is a key part of the puzzle that is required for understanding disease within a population. Efforts are clearly being made to increase our understanding of the genomes of people with middle eastern ancestries and the genomes from efforts in Kuwait, Qatar and the UAE are now available. It comes at a time when sequencing costs have plummeted and are no longer prohibitive. Innovation in genome sequencing technologies does not appear to be slowing, and continued reductions in the cost can be expected.

We have and continue to propose the need to develop collaborative linkages: locally, throughout the region and internationally. Collaboration needs to be encouraged and should involve all sectors of healthcare, including practicing physicians and paramedics, policy-makers and research scientists. It is only through coordinated efforts throughout the region that patients will ultimately be provided with the information that will enable individuals, and their care providers, to make informed decisions about their health and wellbeing. Importantly, strong local leadership is required, because as the Portuguese writer and Nobel laureate Jos Saramago put it: If you dont write your books, nobody else will do it for you. No one else has lived your life.

NCDs account for 77% of all deaths in UAE

Image: WHO

The paradigm shift in healthcare that personalized or precision medicine customizing medical treatment to the individual characteristics, needs and preferences of a patient during all stages of care represents has been made possible through the availability of large datasets compiled by healthcare systems, technological advancements in next-generation genome sequencing and the development of proper analytical tools to identify relationships in vast datasets.

This is a systems biology approach that uses genome, phenome and microbiome data to quantify the wellness of an individual and to provide indicators of their impending disease state. The Pioneer 100 Wellness Project (P100) was a longitudinal study in the US designed to test this approach. It that was conceived on the rationale that as the scale of personal data increases with the convergence of advances in electronic health records sets, big data analysis, individual measurement devices, and consumer-activated social networks, it would be possible to define early warning signs for human diseases. Although the opportunities for observing health transitions in P100 were limited, the results were sufficiently compelling that it has justified refinements for an extended study involving a larger population of more than 100,000 individuals.

Health and healthcareHow is the World Economic Forum bringing data-driven healthcare to life?

The application of precision medicine to save and improve lives relies on good-quality, easily-accessible data on everything from our DNA to lifestyle and environmental factors. The opposite to a one-size-fits-all healthcare system, it has vast, untapped potential to transform the treatment and prediction of rare diseasesand disease in general.

But there is no global governance framework for such data and no common data portal. This is a problem that contributes to the premature deaths of hundreds of millions of rare-disease patients worldwide.

The World Economic Forums Breaking Barriers to Health Data Governance initiative is focused on creating, testing and growing a framework to support effective and responsible access across borders to sensitive health data for the treatment and diagnosis of rare diseases.

The data will be shared via a federated data system: a decentralized approach that allows different institutions to access each others data without that data ever leaving the organization it originated from. This is done via an application programming interface and strikes a balance between simply pooling data (posing security concerns) and limiting access completely.

The project is a collaboration between entities in the UK (Genomics England), Australia (Australian Genomics Health Alliance), Canada (Genomics4RD), and the US (Intermountain Healthcare).

Although currently viewed as a radical shift, preemptive measures have been proposed since the turn of the last century. In 1903, motivated by concerns about the healthcare of his time, Thomas Edison said: The doctor of the future will give no medicine, but will interest his patient in the care of the human frame, in diet and in the cause and prevention of disease. Through the more than 100 years since this statement, preventative strategies have taken hold in some areas of medicine (such as immunization), but there is more to do. In the words of the 11th century Persian physician and polymath Avicenna, There are no incurable diseases only the lack of will. There are no worthless herbs only the lack of knowledge. There is certainly no lack of will, and our knowledge is only expanding.

Therefore, the opportunity to apply personal medicine practices in the UAE to prevent or delay the onset of disease will have substantial social and economic impacts. The American physcian and systems biologist Dr Leroy Hood has predicted that the wellness and prevention market will outgrow the healthcare market, in part due to economic modelling which suggests that the reactive therapeutic route is unsustainable for ageing populations. The time to act is now.

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How studying genetics and lifestyle can shape a healthier MENA region - The European Sting

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Author affiliations: Ghent University, Merelbeke, Belgium (E. Vandoorn, A. Parys, K. Van Reeth); Ghent University and Ghent University Hospital, Ghent, Belgium (I. Leroux-Roels, G. Leroux-Roels); National Animal Disease Center, Ames, Iowa, USA (A. Vincent)

Humans and swine are susceptible to influenza A viruses (IAVs) of hemagglutinin (HA) subtypes H1 and H3, which are widespread in both species. Human IAVs frequently are transmitted to swine, after which the HA surface protein generally undergoes slower antigenic evolution (drift) in swine than in humans (13). Therefore, swine can be considered a reservoir for past human IAVs. Because antigenic drift variants of human IAVs replace each other over time, younger persons only have been exposed to more recent strains and human population immunity against older human IAVs gradually decreases (4). Consequently, human-origin swine IAVs (swIAVs) can be reintroduced into the human population after a certain period and cause a pandemic, as illustrated by the influenza A(H1N1)pdm09 virus (pH1N1) (5). The H1 of this swine-origin virus is related to the H1 of human seasonal H1N1 IAVs that circulated in 19181950. In 2009, only persons born before the 1950s had cross-reactive antibodies against H1N1 viruses, so a pandemic was possible (6,7).

The evolution of swIAVs is different from and more complex than that of human IAVs because of multiple introductions of human IAVs into swine and geographic separation of swine populations (8). H1 swIAV colloquial names indicate their origin and region of circulation. An improved classification system subdivides H1 swIAVs into 3 lineages and 28 clades on the basis of H1 nucleotide sequence homology (9). The lineages are 1A, 1B, and 1C, with the number representing the subtype (H1) and the letter representing the lineage. Clades and subclades are indicated with 13 digits. Classical swine lineage 1A contains IAVs with the human 1918 pandemic H1N1 virus as a common ancestor. Most clades are restricted to America and Asia, but pH1N1 viruses (1A.3.3.2) circulate in swine and humans worldwide. Human seasonal lineage 1B contains swIAVs with an H1 derived from human seasonal IAVs. These human-like H1 swIAVs emerged in Europe in the late 1980s and in North America in the early 2000s. Eurasian avian lineage 1C contains swIAVs that originated from avian IAVs. These avian-like swIAVs emerged in Europe in 1979 and spread to Asia in 1993 (1013). Apart from antigenic evolution in the HA, IAVs also can evolve via exchange of gene segments with other IAVs of different subtypes or clades infecting the same cell, called reassortment (14), which frequently occurs in pigs. A reassortant IAV with an antigenically novel HA and the capacity to infect and spread in humans could cause a pandemic.

Since 2010, 35 zoonotic infections with H1 swIAVs were reported in North America and 10 in Europe (1517; Parys et al., unpub. data). Human population immunity is a major factor determining the pandemic risk for swIAVs. Hemagglutination inhibiting (HI) and virus neutralizing (VN) antibodies in serum are accepted correlates of protection (18). Evaluating humans of different age groups for HI and VN antibody titers against a range of antigenically different swIAVs might help clarify the public health risk.

In a previous seroprevalence study for H3 swIAVs in humans from Luxembourg, we demonstrated a correlation with the nature of the swIAV and its relation to human IAVs on the one hand and the persons birth year on the other (19). A large comparative seroprevalence study for H1 swIAVs is lacking. Previous studies examined limited numbers of H1 swIAVs or samples or did not evaluate the relation between birth year and antibody responses (12,13,2025). In addition, most studies were conducted before or during the 2009 pandemic, but the circulation of pH1N1 viruses in humans likely changed the serologic profile against H1 swIAVs. We assessed prevalence and titers of protective antibodies against all major H1 swIAV clades in various age groups in Belgium in 2017. We also examined the relation between antibodies against human-like swIAVs and their presumed human seasonal ancestor IAV. The results will help assess the public health risk for different H1 swIAVs.

During August 2017January 2018, a total of 549 anonymized serum samples were collected from immunocompetent persons with unknown influenza vaccination or infection history born during 19202017 at Ghent University Hospital (Ghent, Belgium). Samples included 6 per birth year with 1:1 ratio between male and female patients. Exclusion criteria included active oncologic disease or hematologic malignancies, immunosuppressive treatment, organ transplantation, admission to intensive care, and end-stage renal disease on dialysis treatment. This study was approved by the Commission for Medical Ethics of the Ghent University Hospital (approval no. 2017/0834).

Samples were evaluated for antibodies against 11 viruses representing 7 major H1 swIAV clades circulating in Europe, North America, and Asia; 2 human seasonal progenitor IAVs for European and North American human-like swIAVs; and 1 human seasonal IAV that circulated right before the pH1N1 virus (Table 1). We used epidemiologic data (1012) and the H1 classification system (9) to select major H1 swIAV clades. We selected test viruses on the basis of amino acid homology and antigenic relatedness to currently circulating swIAVs of each clade. We selected the human progenitor IAVs based on the literature (26,27).

We downloaded nucleotide sequences of the viruses HA1, the main target of neutralizing antibodies, from Genbank and translated these to amino acids. We used the MUSCLE algorithm for sequence alignment and the Jones-Taylor-Thornton model and nearest-neighbor-interchange heuristic method to construct maximum-likelihood trees in MEGA7 (28). We determined the percent of amino acid homology between test viruses and numbers of identical amino acids in presumed antigenic sites (29) with MEGA7 and R version 3.2.2 (30).

We obtained North American swIAVs and corresponding swine serum from the U.S. Department of Agriculture-Agricultural Research Service. We obtained human seasonal IAVs and corresponding ferret serum from Francis Crick Institute (London, UK), and Asian swIAV from Hong Kong University (Hong Kong). We antigenically characterized test viruses in cross-HI and cross-VN assays with postvaccination swine serum for swIAVs or postinfection ferret serum for human seasonal IAVs. Because serum against A/Brisbane/59/2007 was not available, we used ferret serum against A/Egypt/10/2007 instead; the HA sequence is identical in both. We propagated viruses in MDCK cells; all passages were <6. We calculated antigenic distances from HI and VN titers as described previously (31) and converted these into antigenic dendrograms by using the neighbor-joining method in MEGA7. One antigenic unit represents a 2-fold difference in HI or VN titer.

We tested individual samples in HI assays and pooled samples per birth year in VN assays for antibodies against each test virus. Both assays were performed according to standard procedures (32,33). We expressed antibody titers for HI as the reciprocal of the highest serum dilution showing complete hemagglutination inhibition of 4 hemagglutinating units of virus or, for VN, 50% neutralization of 100 TCID50 (50% tissue culture infective doses) of virus. The starting dilution was 1:20, and we considered a titer of 40 positive.

We calculated geometric mean titers (GMTs) and 95% CIs for HI and VN antibody titers of samples from each birth decade against each test virus by using log2-transformed data. Samples with a titer <20 were assigned a titer of 10. For non-stratified data, we calculated Spearman correlation coefficients (CCs) between HI titers or between VN titers against different viruses. We used Kruskal-Wallis and Mann-Whitney U tests to compare antibody titers between age groups for a certain virus or between viruses for a certain age group. We used Fisher exact test to compare proportions of positive samples. For all statistical tests, we applied Bonferroni adjustment of the p values and we considered corrected p values of <0.05 statistically significant. We performed all analyses by using R version 3.2.2.

Figure 1

Figure 1. Epidemiologic, phylogenetic, and antigenic relationship between influenza A test viruses from classical swine lineage 1A, human seasonal lineage 1B, and Eurasian avian lineage 1C. A) Schematic representation of the H1 IAV...

We tested samples for antibodies against 11 IAVs from the classical swine 1A, human seasonal 1B, or Eurasian avian 1C lineage. HA1 aa sequence homology between viruses of different lineages was <75% with 1935/50 identical amino acids in presumed antigenic sites. Classical swine and avian-like IAVs were phylogenetically most closely related (Figure 1, panel A; Table 2). Within-lineage HA1 aa homology was 82%97%, with 3649 identical amino acids in antigenic sites. Human-like swIAVs and their presumed human seasonal progenitor IAV shared 90%94% aa in the HA1 and 3642 aa in antigenic sites.

Antigenic dendrograms based on cross-HI and cross-VN assays showed similar trends to the phylogenetic tree, except for swOK13 (Tables 35; Figure 1). This North American human-like 1b swIAV (1B.2.2.2) clustered separately from other IAVs of its lineage, including its presumed human ancestor, NC99.

Figure 2

Figure 2. Number of positive human serum samples in the hemagglutination inhibition assay (titer >40) for each test virus compared with the total number of samples tested per birth cohort. Birth cohorts...

Figure 3

Figure 3. Number of positive human serum samples in the virus neutralization assay (titer >40) for each test virus compared with the total number of samples per birth cohort. Birth cohorts are...

We tested human serum samples against human seasonal IAVs related to 1B swIAVs from 1986 (TW86), 1999 (NC99), and 2007 (BR07) to evaluate a persons potential exposure to or vaccination with these IAVs. Overall, 39% were seropositive for TW86, 31% for NC99, and 22% for BR07 in HI and 48% were seropositive for TW86, 51% for NC99, and 29% for BR07 in VN (Figures 2, 3). Seroprevalences and GMTs against TW86 were highest for persons born during 19771986 and lowest for the 2 youngest groups, those born during 19972017 (Tables 6, 7). For NC99 and BR07, HI responses were highest for those born during 19871996, and VN responses were highest for those born during 19371946 (NC99 only) and 19972006. Persons born during 20072017 had minimal responses. Antibody responses against human seasonal IAVs were related to birth year and the year of virus isolation, with peak responses in persons born right before the virus circulated and lowest responses in persons born afterwards.

The major avian-origin swIAV clades are European avian-like 1C.2.1, represented by swG10, and Asian avian-like 1C.2.3, represented by swHK11. For swG10, 10% of all samples tested positive in HI and 7% in VN (Figures 2, 3). Seroprevalence was <20% and GMTs were <20 for all age groups except the oldest, those born during 19201926, with 40% seropositive in HI and GMTs for HI and VN of 24 (Tables 6, 7).

For swHK11, overall seroprevalence was 25% in HI and 34% in VN. Like swG10, responses against swHK11 were highest for those born during 19201926; 52% in HI, 72% in VN, and GMTs 38. Responses were minimal in both HI and VN for persons born during 19471956; 11% in HI, 10% in VN, and GMTs <20.

European human-like swIAV swG12 (1B.1.2.1) represents the human-like H1 swIAV clade circulating in Belgium, and TW86 was selected as its presumed human ancestor virus. At least half of all samples tested positive for swG12, 50% in HI and 59% in VN (Figures 2, 3). We noted statistically significant differences in seroprevalences and GMTs, which were higher (62% in HI and 74% in VN; GMTs 44) in persons born before 1996 than in persons born during 19972017 (5% in HI and in VN; GMTs <20; p<0.001) (Tables 6, 7). GMTs peaked (87) in HI in those born during 19771986 and in VN for those born during 19671976. Results for swG12 were similar to those for its presumed human ancestor virus, TW86.

North American human-like H1 swIAVs (1B.2) result from the introduction of a human IAV in the early 2000s, and we selected NC99 as their presumed human ancestor. For the most prevalent 1 clade (1B.2.2), swAL16 represents subclade 1a (1B.2.2.1), whereas swIL10 and swOK13 represent subclade 1b (1B.2.2.2).

Among samples, 24% tested positive for swAL16 in HI and 39% in VN (Figures 2, 3). Seroprevalences and GMTs were highest in those born during 19871996 in HI (55%; GMT 35) and in those born during 19471956 in VN (70%; GMT 59), but no antibodies against swAL16 were detected in the youngest group, those born during 20072017 (Tables 6, 7). Like for European human-like virus swG12 (1B.1.2.1), antibody responses against North American 1a virus swAL16 (1B.2.2.1) resembled those against its presumed human ancestor virus, NC99.

For the 1b swIAVs (1B.2.2.2), <10% were seropositive (swIL10, 10% in HI and VN; swOK13, 5% in HI and 4% in VN) (Figures 2, 3). We did not see statistically significant differences in seroprevalences between the 2 1b swIAVs or between age groups, with following exceptions. HI-seroprevalence of those born during 19271936 was statistically significantly higher for swIL10 (13%) than for swOK13 (2%; p<0.04). HI seroprevalence for swOK13 of those born during 19771986 was statistically significantly higher (21%) compared with groups born during 19271936 (2%), 19571966 (0), and 20072017 (0; p<0.04). GMTs were <20 in all age groups except those born during 19371956, who had VN GMTs of 2230 against swIL10 (Tables 6, 7). Unlike the other 2 human-like swIAVs tested, responses against 1b swIAVs (1B.2.2.2) did not concur with those against the presumed human ancestor virus NC99. Responses against swIL10 and swOK13 were generally statistically significantly lower than against NC99 (p<0.05).

We used swOH07 as reference virus to evaluate antibody responses against classical swine virus clade (1A.3.3.3) and CA09 as reference virus to evaluate classical swine virus clade pH1N1 (1A.3.3.2), which derived its HA from swIAVs. Overall, 50% of the samples tested positive for swOH07 (50% in HI; 78% in VN) and CA09 (54% in HI; 81% in VN), with high seroprevalences in all age groups (36%100% in HI; 50%100% in VN), except in those born during 19471956 in HI (swOH07, 17%; CA09, 24%) (Figures 2, 3). HI titers peaked in the 2 oldest groups, those born during 19201936; VN titers peaked in the 2 oldest groups and in those born during 19972006 (Tables 6, 7). No statistically significant difference was noted in responses against classical swine (1A.3.3.3) and pH1N1 (1A.3.3.2) IAVs.

Antibody titers against epidemiologically related human and swine IAVs were highly correlated for classical swine viruses swOH07 (1A.3.3.3) and CA09 (1A.3.3.2), European human-like swIAV swG12 (1B.1.2.1) and human ancestor IAV TW86, North American human-like 1a swIAV swAL16 (1B.2.2.1) and human ancestor IAV NC99, and European and Asian avian-like swIAVs swG10 (1C.2.1) and swHK11 (1C.2.3) (CC=0.680.86 in HI; CC=0.630.77 in VN; Table 8). Of note, titers against avian-like and classical swine IAVs also were strongly correlated (CC=0.550.68 in HI; CC=0.490.67 in VN). In contrast, CCs were low between titers against North American human-like 1b viruses swIL10 and swOK13 (1B.2.2.2) and human ancestor virus NC99 (0.420.43 in HI; 0.300.39 in VN [the first value of which is not statistically significant]).

Our results show that serum antibody responses of immunocompetent persons in Belgium against major H1 swIAV clades depend on the swIAV tested and its relation to human seasonal IAVs and the persons birth year. Overall seroprevalences were high (50%) for classical swine (1A.3.3.2, 1A.3.3.3) and for European human-like (1B.1.2.1) swIAVs, intermediate (24%) for North American human-like 1a (1B.2.2.1) and Asian avian-like (1C.2.3) swIAVs, and low (<10%) for North American human-like 1b (1B.2.2.2) and European avian-like (1C.2.1) swIAVs. Our results are consistent with previous studies that aimed to compare antibody responses in nonswine workers with those in persons with frequent swine contact (7,2025), although those studies examined only a limited number of swIAV clades or samples. Overall, most previous studies showed lower seroprevalences for Asian avian-like (2%10%) and European avian-like (05%) swIAVs in the general population or in nonswine workers (13,20,2224). A 2010 study in the United Kingdom also found a lower seroprevalence of 11% for a European human-like (1B.1.2.1) swIAV (24). The major difference between our study and studies conducted before or during the 2009 pandemic is the lower seroprevalence of 3%15% for classical swine IAVs in previous studies (13,20,2224). The circulation of pH1N1 viruses (1A.3.3.2) likely contributes to increased seroprevalence rates against these related classical swine IAVs. In our study, the oldest group, those born during 19201926 who are 9197 years of age, had the highest antibody responses against H1 swIAVs of classical swine (1A.3.3) and avian-like (1C.2) lineages, for which antibody titers were correlated (13,20,21). Responses against human seasonal IAVs and related European and North American 1a human-like H1 swIAVs (1B) generally were highest in those born during 19771996, who are 2140 years of age, and lowest in those born during 19962017, who are 020 years of age. Responses against North American 1b human-like H1 swIAVs (1B.2.2.2) generally were low across all age cohorts.

Antibody responses against past human seasonal IAVs TW86, NC99, and BR07 generally peaked in persons born near the time during which the respective IAV or similar viruses circulated, whereas responses were low in most persons born after. Within an age group, responses generally were highest against an antigenic representative of the virus encountered first. These findings concur with the theory of antigenic seniority: humans are expected to have antibodies against human seasonal IAVs that circulated after their birth, with highest responses against the virus encountered first. Antigenic seniority likely occurs because of periodic boosting of these antibodies by subsequent exposures to related human seasonal IAVs (4,34,35). Antibody titers against European human-like swIAV swG12 (1B.1.2.1) and North American human-like 1a swIAV swAL16 (1B.2.2.1) concur with those against their respective human ancestor viruses TW86 and NC99 because of close antigenic relationship to their ancestor IAV. Overall high seroprevalences against pH1N1 virus CA09 (1A.3.3.2) and antigenically closely related classical swine virus swOH07 (1A.3.3.3) can be explained by recent exposure to currently circulating pH1N1 viruses. Because the oldest persons were born during 19201936, when human IAVs closely related to the 1918 pandemic virus, the ancestor of classical swine IAVs, circulated, they could have had cross-reactive antibodies against classical swine IAVs before 2009. These antibodies might have been boosted by later exposure to pH1N1 viruses, which might account for the high responses in this group (6,7). Consistent with results for serum samples collected after pH1N1 virus infection in a previous study (21), cross-reactivity was higher against the Asian than against the European avian-like H1 swIAV, which differ by only 1 aa in antigenic sites (Table 2). Whether this single amino acid mutation is the reason for the difference in seroprevalence is still unknown (36,37).

European human-like (1B.1.2.1) and North American human-like 1a (1B.2.2.1) H1 swIAVs are antigenically more closely related to their human ancestor than North American human-like 1b (1B.2.2.2) H1 swIAVs (Figure 1; Tables 3, 4). North American human-like H1 swIAVs (1B.2) have been shown to drift 4 times faster than European human-like H1 swIAVs (1B.1). Increased antigenic diversity of the former since 2008 has led to the emergence of swIAVs that are antigenically distinct from the human precursors, mainly within the 1b subclade (3,27). This evolution can explain the recognition of selected European human-like and North American human-like 1a but not North American human-like 1b H1 swIAVs by human serum samples. Because the human ancestor IAVs no longer circulate in humans, swine can be considered a reservoir for old human IAVs. Seroprevalences for European human-like and North American human-like 1a H1 swIAVs are expected to decrease over time because the youngest age groups were never exposed to these human IAVs. On the basis of our results, we estimate that it could take <80 years for the population to become fully susceptible.

Seroprevalences of immunocompetent persons in Belgium for swIAVs representing major H1 swIAV clades suggest that North American human-like 1b (1B.2.2.2) and European avian-like (1C.2.1) H1 swIAVs currently pose the highest risk to public health. North American human-like 1b (1B.2.2.2) swIAVs rapidly drifted away from its human ancestor, whereas European avian-like (1C.2.1) swIAVs never circulated in humans. Seroprevalences of <10% for these viruses are comparable to 2%19% against the pH1N1 virus right before the pandemic (7). Our results suggest that the risk of reintroduction of these H1 swIAVs in the human population might be higher than for H3 swIAVs, given that 20% of persons 0100 years of age from Luxembourg tested seropositive for representative European and North American cluster IV H3 swIAVs in 2010 (19). Seroprevalences against the other currently circulating human-like H1 swIAV clades were higher than against 1B.2.2.2 and 1C.2.1, but these viruses, along with H3 swIAVs, also keep evolving in swine. As they continue to drift away from their human ancestor and population immunity wanes with lack of exposure, these viruses might also pose a risk to public health soon.

We evaluated human population immunity against H1 swIAVs on the basis of serum HI and VN antibodies, which are directed against the highly variable head region of the HA. We did not measure antibodies or T-cell responses against the HA stalk, the neuraminidase, or internal viral proteins, such as the nucleoprotein. Although these immune mechanisms are much less potent than neutralizing anti-HA antibodies, their targets are more conserved between IAVs of humans and swine (3842). Therefore, persons with minimal antibody titers in our study still might have some degree of immunity and protection against zoonotic infection with swIAVs. Furthermore, population immunity is only one aspect determining the pandemic potential of swIAVs (18). Another factor is their ability to spread in humans, which is difficult to investigate (43). Our results stress the need for continuous surveillance and characterization of circulating swIAVs and frequent monitoring of humans for antibodies against these swIAVs.

Ms. Vandoorn was a PhD student at the Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, during the study period. Her primary research interests are swine influenza A virus surveillance in Belgium and the Netherlands and broadly protective vaccination strategies for influenza A viruses.

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Suggested citation for this article: Vandoorn E, Leroux-Roels I, Leroux-Roels G, Parys A, Vincent A, Van Reeth K. Detection of H1 swine influenza A virus antibodies in human serum samples by age group. Emerg Infect Dis. 2020 Sep [date cited]. https://doi.org/10.3201/eid2609.191796

The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.

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Detection of H1 Swine Influenza A Virus Antibodies in Human Serum Samples by Age Group - CDC