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Lethal brain infections in mice thwarted by decoy molecule – Washington University School of Medicine in St. Louis

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Discovery of receptor, generation of decoy could help contain outbreaks of Venezuelan equine encephalitis virus

Researchers at Washington University School of Medicine in St. Louis have identified a molecule that protects mice from brain infections caused by Venezuelan equine encephalitis virus (VEEV), a mosquito-borne virus notorious for causing fast-spreading, deadly outbreaks in Mexico, Central America and northern South America.

Researchers at Washington University School of Medicine in St. Louis have identified a molecule that protects mice from brain infections caused by Venezuelan equine encephalitis virus (VEEV), a mosquito-borne virus notorious for causing fast-spreading, deadly outbreaks in Mexico, Central America and northern South America. As the climate changes, the virus is likely to expand its range and threaten more countries in the Americas, including the U.S.

Public health officials have struggled to contain such outbreaks in the absence of effective drugs and vaccines. As a potential drug, the molecule described in a paper published Nov. 18 in the journal Nature could serve as a much needed tool to control the deadly virus.

This virus can infect many species of wild mammals, and every few years it jumps from animals to humans via mosquitoes and causes thousands of infections and many deaths, said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and a professor of molecular microbiology, and of pathology and immunology. Theres concern that with global warming and population growth, well get more outbreaks.

Once injected under the skin by mosquitoes, the virus homes in on neurons. People start experiencing symptoms such as headache, muscle pain, fatigue, vomiting, nausea, diarrhea, sore throat and fever within a week. In the most serious cases, the virus gets past the blood-brain barrier, causing encephalitis brain inflammation that can be fatal in up to a quarter of patients.

To find the potential drug, Diamond and colleagues including first authors Hongming Ma, PhD, an instructor in medicine, and Arthur S. Kim, PhD, a postdoctoral researcher began by searching for the protein handle on the surface of animal cells that the virus attaches to and uses to get inside cells. A drug that stops the virus from grabbing that handle, the scientists reasoned, could stymie infection and prevent disease.

But first they had to make a form of the virus they could work easily with. During the Cold War, the U.S. and the Soviet Union attempted to weaponize the virus, and it is still classified as a select agent, meaning only certain high-security labs are allowed to work with it. So instead, the researchers and their colleagues took Sindbis virus, a related virus that causes mild fever and rash, and swapped out some of its genes for some from VEEV. The resulting hybrid virus, called Sindbis-VEEV, infects cells like authentic VEEV but is unable to cause severe disease.

Using a genetic engineering technique known as genome-wide CRISPR screening, the researchers deleted genes in mouse neuronal cells until they found one called Ldlrad3 whose absence kept Sindbis-VEEV from infecting cells. The missing gene codes for a little-studied surface protein.

Further experiments verified the importance of Ldlrad3. Adding the gene back to neuronal cells restored the viruss ability to infect cells. The human LDLRAD3 gene is almost identical to its mouse equivalent, and knocking out the human gene also reduced infection in multiple cell lines. When the researchers added Ldlrad3 to a different cell type that is normally resistant to infection, the virus was able to infect the cell. Co-author William Klimstra, PhD, at the University of Pittsburgh, separately replicated the findings using authentic, highly virulent VEEV.

Ldlrad3 doesnt appear to be the only way the virus gets inside cells, since a small amount of virus is able to infect cells lacking the protein. But it is clearly the primary way in. Since Ldlrad3 is naturally on our cells and cant be removed, the scientists decided to create a decoy handle using a piece of the Ldlrad3 protein. Any virus particles that mistakenly latch onto the decoy handle would fail to infect cells and instead would get destroyed by the immune system.

To test their decoy in a living animal, the researchers injected mice with authentic virulent VEEV in two different ways: under the skin to mimic a mosquito bite, or directly into the brain. They gave the mice the decoy handle or a placebo molecule for comparison, either six hours before or 24 hours after infection. In all experiments, all of the mice that received the placebo died within a week. In most cases, all of the mice that received the decoy molecule survived, although in the most stringent experiment in which the virus was injected into the brain two of the 10 mice died despite receiving the decoy.

In an outbreak situation, you may be able to use a drug like this as a countermeasure to prevent transmission and further spread, Diamond said.

A major advantage to an antiviral drug based on a human rather than a viral protein is that it is unlikely the virus could evolve resistance to it. Any mutation that enables the virus to avoid the decoy probably would make it unable to attach to cells, too, the researchers said.

Ma H, Kim AS, Kafai NM, Earnest JT, Shah A, Case JB, Basore K, Gilliland TC, Sun C, Nelson CA, Thackray LB, Klimstra WB, Fremont DH, Diamond MS. LDLRAD3 is a receptor for Venezuelan equine encephalitis virus. Nature. Nov. 18, 2020. DOI: 10.1038/s41586-020-2915-3

This study was supported by the National Institutes of Health (NIH), grant numbers R01AI143673, U19AI142790, R01AI095436 and T32 AI007172 and contract number HHSN272201700060C; and the Defense Reduction Threat Agency, grant numbers HDTRA1-15-1-0013 and HDTRA1-15-1-0047.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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TwinStrand Biosciences Licenses Duplex Sequencing Technology to Foundation Medicine – Chinook Observer

SEATTLE, Nov. 18, 2020 /PRNewswire/ --TwinStrand Biosciences today announced it has entered into a worldwide non-exclusive agreement to sublicense two foundational patent families to Foundation Medicine and its affiliates relating to TwinStrand Duplex Sequencing error-correction technology. Duplex Sequencing increases the accuracy of next-generation sequencing as much as 10,000 times, allowing the detection of ultra-low frequency mutations that would otherwise be hidden by technical noise inherent to the sequencing process.

"Staying at the forefront of innovative solutions toadvancecancer care iscentral toour commitment topatients," saidCindy Perettie, chief executive officer at Foundation Medicine. "We are excited to partner with TwinStrand to support doctors in making genomically-informed treatment decisions."

"This agreement validates the strength of TwinStrand's technology and intellectual property portfolio," said Dr. Jesse Salk, chief executive officer at TwinStrand Biosciences. "We are pleased that Foundation Medicine has partnered with us to use our patented technology to achieve the highest possible performance for liquid biopsy testing."

About TwinStrand Biosciences TwinStrand Biosciences is leading the way in identifying rare genetic variants that are undetectable by standard sequencing methods. The company's highly-sensitive and specific Duplex Sequencing technology delivers clearer insights to researchers and clinicians in applications ranging from residual cancer detection to genetic toxicology. This data can inform critical decisions in clinical medicine, public health and other fields of science on a faster timescale, where actions are most impactful. TwinStrand's scientist-leaders have authored more than a dozen peer-reviewed articles using Duplex Sequencing and have developed a portfolio of more than 70 patents and patent applications. The company has partnered with pharmaceutical companies, academic centers, clinical research networks and federal regulatory agencies to bring high precision genomics to the forefront of their science. For more information visitwww.twinstrandbio.com.

About Foundation Medicine Foundation Medicine is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient's unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient's cancer and match them with relevant targeted therapies, immunotherapies and clinical trials. Foundation Medicine's molecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer. For more information, please visit http://www.FoundationMedicine.comor follow Foundation Medicine on Twitter (@FoundationATCG). Foundation Medicine is a registered trademark of Foundation Medicine, Inc.

Media Contact: PR@twinstrandbio.com

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Four years after landing in US, graduating ISU senior is on his way to medical school – Iowa State University News Service

Mohamed Elrashed Shogar, graduating in genetics, stands inside a Molecular Biology Building laboratory where he has conducted much of his undergraduate research. Photo by Christopher Gannon. Larger image. All photos and videos were shot following physical distancing guidelines, and with staff wearing face coverings.

AMES, Iowa A headache started Mohamed Shogars journey to a career in medicine.

His mothers relentless headaches forced her to travel more than 900 miles from their home to Sudans capital, Khartoum, for treatment. She never found relief, and it frustrated Shogar, who is graduating from Iowa State University next weekend with a bachelors degree in genetics.

Shes the reason, Shogar said. She motivated me to pursue a career in medicine.

He was also bothered by the physician shortage in his hometown of Al Fashir. Shogar noticed the same physician shortage when he arrived in the United States and again thought, Why not pursue a career in medicine to help them out?

Shogars mother has a Ph.D. and his father is a high school principal. Education was the biggest priority for his family. So, after graduating high school, Shogar came to the U.S. in 2016.

After traveling to Egypt to meet with the U.S. ambassador and receive a green card, Shogar was on his way.

The first time, when I landed in Chicago, I was so overwhelmed, he said. I didnt know what to expect. I didnt know the language or the culture. I had just finished high school, and the future wasnt clear to me.

He headed to Cedar Rapids, where he lived with his cousin for a few months and talked to newfound friends about his educational options in the state. One friend suggested starting out at a community college before heading to a four-year university. So, Shogar enrolled at Kirkwood Community College and took English as a Second Language classes while working full time at the Nordstrom warehouse. He gained medical experience as a phlebotomist at Mercy Medical Center in Cedar Rapids before taking some courses at the University of Iowa.

In 2018, he transferred to Iowa State to finish his genetics degree. At the same time, hes worked as a phlebotomist at Mary Greeley Medical Center.

I wouldnt have done it without the people who helped me out, he said. Im so grateful for them.

During his first semester in Ames, Shogar had to take organic chemistry considered one of the most difficult courses at Iowa State. He struggled during the first exam and felt defeated. But he went to the office of chemistry professor Arthur Winter for help. They talked about college courses generally, and how to study. On Shogars next organic chemistry exam, he received a near-perfect score.

Shogar found community and friendship in his classes as well as student organizations, such as the Sudan United Association and the Minority Association for Pre-Health Students.

He typically travels back to Sudan every winter to visit his family, but with the ongoing COVID-19 pandemic and his post-graduation plans, that visit is on hold. Right now, hes in the midst of the nerve-wracking process of applying to medical schools.

Shogar said going to school and working through the pandemic has been mentally and emotionally draining.

It also had an impact on my education journey, he said. I was not able to shadow and volunteer, which is a very important part in medical school applications.

He also found a mentor in Mark Hargrove, Morrill Professor of biochemistry, biophysics and molecular biology (BBMB), who talked with Shogar about his plans after graduation. To build his research experience, Gordon connected Shogar with Alan DiSpirito, professor of BBMB, whose lab works with methanobactin to study its effects on Wilsons disease, a genetic disorder that causes excessive copper build-up in the body.

This has been an amazing experience, honestly, Shogar said. Its been such a welcoming environment.

The opportunities that I got here, I dont think I would be able to get in Sudan. In terms of the quality of education, I cant even compare it.

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New Risks of Prescription Opioids Discovered – Medscape

Prescription opioid use increases the risk for major depressive disorder (MDD) and anxiety and stress-related disorders (ASRD), new genetic evidence shows. The findings also suggest MDD is a potential causal risk factor for increased prescription opioid use.

Taken together, the results "support recommendations that caution is needed with prescribing opioids in settings of mood disorders in favor of nonopioid alternatives, with screening for MDD prior to initiating opioid treatment," write the investigators, led by Falk Lohoff, MD, chief of the Section on Clinical Genomics and Experimental Therapeutics at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in Bethesda, Maryland.

"There is growing observational data suggesting that prescription opioid use may impact depression and anxiety disorders. However, observational studies are subject to confounding, which makes determining both the causal nature and direction of these relationships difficult," Lohoff told Medscape Medical News.

The study was published online November 11 in JAMA Psychiatry.

The researchers used genetically informed methods to conduct bidirectional analyses investigating the potential causal associations between the genetic liability for prescription opioid and other nonopioid pain medications and both MDD and ASRD.

The investigators conducted two-sample Mendelian randomization using data from three genome-wide association studies (GWAS) that included more than 737,000 people of predominantly European ancestry.

They found genetic liability for increased prescription opioid use was associated with increased risk of MDD (odds ratio [OR] per unit increase in log odds opioid use, 1.14; 95% CI, 1.06 - 1.22; P < .001) and ASRD (OR, 1.24; 95% CI, 1.07 - 1.44; P = .004).

"Even after accounting for chronic pain which may confound the results given that opioids are often taken for pain and pain is highly comorbid with psychiatric disorders the genetic liability for prescription opioid pain medications increased the risk for depression and anxiety disorders," Lohoff added.

Bidirectional analyses showed that genetic liability for MDD but not ASRD was associated with increased prescription opioid use risk (OR, 1.18; 95% CI, 1.08 - 1.30; P < .001).

"Strikingly," the authors write, "nonopioid analgesics had no direct association with the risk for MDD or ASRD."

"While future research is necessary to further investigate these findings, our paper adds to recent observational evidence that prescription opioids should be used with caution as they might influence the risk for depression and anxiety disorders," said Lohoff.

Commenting on the findings for Medscape Medical News, Roy H. Perlis, MD, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, noted that the "complex relationship between depression and pain, and the treatments for pain, has been recognized for quite a while."

"What is new about this study is the application of a method that has become widely used to understand such complex relationships using genomic data," said Perlis, who was not associated with the current research.

"Every medicine has risks, and the risks of chronic opioid treatment are all too apparent. This study simply reinforces [that] we need to be cautious in opioid prescribing whether or not someone has depression," said Perlis.

He cautioned that the study "can't really distinguish the reason for opioid medication use; so it's at least possible that they're simply confirming the relationship between certain kinds of chronic pain, treated with opioids, and depression."

The study was supported by the National Institutes of Health. The study authors have disclosed no relevant financial relationships. Perlis has received consulting fees for service on scientific advisory boards of Belle Artificial Intelligence, Burrage Capital, Genomind, Psy Therapeutics, Outermost Therapeutics, RID Ventures, and Takeda. He holds equity in Psy Therapeutics and Outermost Therapeutics.

JAMA Psychiatry. Published online November 11, 2020. Full text

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University of Miami Health System Gastroenterologist Honored with Lifetime Disruptor Award – Newswise

Newswise Maria T. Abreu, M.D., a renowned gastroenterologist at the University of Miami Miller School of Medicine, was honored with the Lifetime Disruptor award at the American College of Gastroenterologys 2020 virtual meeting. Healio, an in-depth specialty clinical information service, presented the award, which was based on votes from her peers.

I am always challenging the accepted wisdom, said Dr. Abreu, who is professor of medicine and microbiology and immunology, and director of the University of Miami Health System Crohns & Colitis Center. There is always more to learn about a certain condition or treatment to see if we can do something more to help our patients.

A leader in basic science, translational research, clinical care and education, Dr. Abreu focuses her work on finding better treatments for inflammatory bowel disease (IBD) and other debilitating gastrointestinal conditions. She is also a leader in bringing the genetic and environmental factors of IBD development in the Hispanic population into research and clinical care.

In my laboratory work, I look for new approaches to improving patient care, such as reducing an inflammatory response from the immune system or providing a healthy diet to reduce IBD flare-ups, she said.

The Healio Lifetime Disruptor award, presented this year on Oct. 26, goes to a gastroenterologist or hepatologist who has consistently pushed the gastroenterology field forward through innovative treatments, practice management, patient care, or research. This year more than 1,000 readers and followers voted on eight awards for Healio Disruptive Innovators.

In 2019 Dr. Abreu received the Sherman prize awarded by The Bruce and Cynthia Sherman Charitable Foundation to recognize outstanding achievements in the fight to overcome Crohn's disease and ulcerative colitis. Taking care of patients and finding new ways to help them has been my lifes purpose, she said at the time. Thats what inspires my research the possibility of helping both my patients, as well as those that Ill never see.

Earlier this year, Dr. Abreu was honored with the Research Mentor Award by the American Gastroenterological Association(AGA) Institute CouncilsImmunology, Microbiology & Inflammatory Bowel Diseases Section. It is so important to be educating and mentoring young professionals and help them move ahead with their careers, Dr. Abreu said. They are the future of medicine.

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Oligonucleotide Synthesis Market Increasing Demand with Leading Player, Comprehensive Analysis, Forecast 2027 – TechnoWeekly

The oligonucleotide synthesis market has been experiencing humungous growth across the forecast period of 2017-2025 primarily due to an increase in the research and development activities and speedy FDA approvals in terms of oligonucleotide-based therapies. The biotechnology and pharmaceutical sectors are on a consistent mission of searching alternatives for the treatment of various diseases. This aspect is boosting theoligonucleotide synthesis marketto a great extent as they offer cures and treatments at a relatively low-cost as compared to others. High investments in healthcare and life-science related research programs also assist in increasing the growth rate of the oligonucleotide synthesis market.

As per the report by Transparency Market Research, the global oligonucleotide synthesis market will display11.2 percent CAGR across the forecast period from 2017 to 2025 and will expand from a value of US$1.65 bn in 2016 to US $4.189 bn by 2025.

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Speedy Regulatory Approvals and Increasing Investments to Propel Growth Prospects

Consistent research is undertaken by manufacturers in the oligonucleotide synthesis market and various researchers across the globe to enable the discovery of new drug treatment and vaccines frequently. Investment in the oligonucleotide synthesis market through funding will likely gain traction throughout the forecast period. Collaborations between the government and private companies for the development of academic and research infrastructure are also garnering considerable momentum. Novel approaches for curing chronic conditions through genetic medicines are anticipated to accelerate the growth rate of the oligonucleotide synthesis market.

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Key players of the oligonucleotide synthesis market are involved in mergers and acquisitions frequently. The acquisition of Gene Works by Integrated DNA technologies is a classic instance.

COVID-19 Diagnosis Demand Creating Positive Growth Influence across Oligonucleotide Synthesis Market

Expanding the adoption of PCR technologies across the research and diagnostic sector and the use of oligonucleotide synthesis in polymerase chain reaction (PCR) are expected to surge in the forecast period as PCR is a quick COVID-19 detection method. The advent of PCR has brought unprecedented changes to the COVID-19 testing scenario. It has significantly reduced the time required for results. As reverse transcription polymerase chain reaction (RT-PCR) testing has also become the gold standard for COVID-19 testing, the oligonucleotide synthesis market expects to grow at a rapid rate. Integrated DNA Technology (IDT) has already shipped customized oligonucleotide primers and probes which will help to facilitate more accurate detection of SARS-CoV-2. Speeding up COVID-19 tests is also proving to be a growth generator for the oligonucleotide synthesis market. According to the Government of India officials, over 1 million RT-PCR tests are conducted and it plans to increase the rate of testing further.

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North America to Emerge a Leader in Terms of Growth

Geographically spread across North America, Latin America, the Middle East and Africa, Asia Pacific, and Europe, the oligonucleotide synthesis market is expected to create ripples across North America. The prime factors for a surge in growth across the forecast period are growing application of companies applying oligonucleotides in therapeutics and a large number of COVID-19 infections across the U.S.A. The stronghold of North America over genomics, oncology, proteomics, drug discovery, and diagnostic screening is also a vital aspect for recording exponential growth throughout the forecast period.

Asia Pacific also expects substantial growth across the forecast period as the Association of Southeast Asian Nations (ASEAN). China is experiencing a boost in the demand for genetic sequencing mainly due to the rapidly aging population and expanding healthcare system. Encouraging initiatives are also assisting the growth rate of the oligonucleotide synthesis market. For instance, the Chinese Academy of Sciences launched a $9.2 bn project called Precision Medicine Initiative with an aim to sequence over 100 million human genomes by 2030.

Read our Case study at :https://www.transparencymarketresearch.com/casestudies/innovative-medical-device-manufacturing-start-up

This review is based on TMRs report titled Oligonucleotide Synthesis Market (Product Reagents & Consumables, Equipment, and Synthesized Oligonucleotides (DNA Oligonucleotides and RNA Oligonucleotides); Application Research (Polymerase Chain Reaction and Next Generation Sequencing), Therapeutics (Antisense Oligonucleotides, and Nucleic Acid Aptamers), and Diagnostics; End User Biotechnology & Pharmaceutical Companies, Research Institutes, and Diagnostic Laboratories) Global Industry Analysis, Size, Share, Growth, Trends, and Forecast 2017 2025

The global oligonucleotide synthesis market can be segmented by:

By Product

By Application

By End-users

By Region

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