Category Archives: Genome

Two teams of scientists in Italy have collaborated on a project that further analyzed the SARS-CoV-2 genome from locally acquired samples. The analysis of the samples via next-generation sequencing (NGS) reveals a specific level of genetic variability that implies the SARS-CoV-2 genome is stable.The results are useful in the development of a safe and effective vaccine against SARS-CoV-2, as the more stable the virus's genome, the greater likelihood that a vaccine will be effective globally across populations.Technology Networks spoke with Professor Stefano Menzo, virologist, and Dr Valerio Onofri, geneticist, affiliates of the Department of Excellence of Biomedical Science and Public Health, Marche Polytechnic University in Ancona, to learn more about the findings.Molly Campbell (MC): For our readers that may be unfamiliar, please can you explain how next-generation sequencing (NGS) is utilized to explore the genome of the SARS-CoV-2 virus?Valerio Onofri (VO): NGS is a high-throughput method to sequence DNA or RNA. Unlike the classic Sanger sequencing method, NGS provides millions to billions of short nucleotide sequence reads in just a few hours and at lower costs. This method is routinely used to find pathogenetic variants that cause inherited disease or cancer. It is also useful to discover the sequence of an unknown viral, prokaryote or eukaryote genome.When a reference sequence becomes available, NGS labs can sequence a clinical or population sample, align the new sequence to the reference and annotate the differences to determine whether mutations have occurred. We are doing this work now to better understand the SARS-CoV-2 virus. The virus was first sequenced in December 2019 and in February 2020 in Wuhan, China where it originated. When the pandemic spread, many labs like ours began sequencing virus samples from local patients to detect variants and study their significance. NGS provides both fast whole genome sequencing and, thanks to sequencing redundancy, quasispecies analysis (analysis of both major and minor variants).MC: Please can you tell us about The Ion AmpliSeq SARS-COV-2 Research Panel?VO: This panel was designed by Thermo Fisher Scientific to provide an efficient, high-throughput workflow for analyzing the entire SARS-CoV-2 genome on the Ion Torrent platform. Based on the targeted approach by amplicons method, it consists of about 250 PCR cycles to amplify the full SARS-COV-2 genome. Drawing on our expertise from routinely using this method for forensic and medical genetics, we helped Thermo Fisher validate the panel in virus isolates as well as throat/nasal swabs. It is now widely available for NGS-based research to better understand COVID-19.MC: What have your analyses so far revealed about the genetic stability of the SARS-CoV-2 virus?Stefano Menzo (SM): So far, SARS-CoV-2 appears to be a relatively stable virus, meaning it does not display many variants in the quasispecies, compared to other known RNA viruses such as HCV or HIV.MC: What does the SARS-CoV-2 genome reveal about the evolutionary path of the coronavirus?SM: More sequencing of full-length genomes throughout the world will be necessary to better answer this question. For now, we can say the virus has started differentiating in the human population from a common ancestor at a slow/moderate pace.MC: How can this data be utilized in the development of preventatives/ therapeutics against the COVID-19 outbreak?SM: Any vaccine will work best throughout the world if the virus is relatively confined geographically to limit the generation of escape mutants. The same is true for any antiviral treatment.MC: What are your next steps in this research space?SM: We will continue to investigate the viruss evolution by sequencing samples from patients with different clinical outcomes.Professor Stefano Menzo, virologist, and Dr. Valerio Onofri, geneticist, affiliates of the Department of Excellence of Biomedical Science and Public Health, Marche Polytechnic University in Ancona, were speaking to Molly Campbell, Science Writer, Technology Networks.

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Further Analysis of SARS-CoV-2 Genome Suggests It Is Stable - Technology Networks

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Just two weeks after developing a test for COVID-19, Gundersen Medical Foundation researchers have successfully sequenced the complete viral genomes of the virus, an achievement that will help researchers understand its origins and evolution during spread.

The Gundersen Medical Foundation cancer research team, directed by Dr. Paraic Kenny, has been utilizing the Foundations cancer genome sequencing equipment to examine COVID-19 infections in La Crosse County patients and how they correlate with the global pandemic.

To conduct the research, Kenny and his team secured Institutional Review Board approval to use specimens, remaining after the conducting of standard COVID-19 testing, from six of the La Crosse Countys earliest cases of the virus.

At the most basic level, the virus makes occasional spelling mistakes when it copies its genome during infection and these mutations are faithfully carried in all subsequent infections by that particular virus, Kenny says. By sequencing the whole viral genome, we have been able to map the different COVID-19 strains currently in La Crosse County. This allows us to go far beyond positive and negative test results to better understand how the virus spreads within our community and health-care system.

Through its local lab, Kennys research team has been able to document the independent appearance of COVID-19 strains in the Coulee Region, discovering several of the viruses sequenced share molecular fingerprints with viruses that traveled directly from China to Washington state, as well as strains that circulated about a month ago in France and one sub-strain present in community spread.

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Gundersen researchers sequence genomes of COVID-19, results help with tracking and possibly mitigating spread - La Crosse Tribune

President Donald Trump lashed out at The New York Times on Saturday.

So now the Fake News The New York Times is tracing the CoronaVirus origins back to Europe, NOT China. This is a first! I wonder where (sic) the Failing New York Times got for this one? Are there any NAMED sources? Trump wondered.

However, the reporting from The Times was not based on anonymous sources.

New research indicates that the coronavirus began to circulate in the New York area by mid-February, weeks before the first confirmed case, and that travelers brought in the virus mainly from Europe, not Asia, The Times reported on Wednesday.

The story cited now research by geneticists at the Icahn School of Medicine at Mount Sinai and the N.Y.U. Grossman School of Medicine.

Both teams analyzed genomes from coronaviruses taken from New Yorkers starting in mid-March, the newspaper noted. The research revealed a previously hidden spread of the virus that might have been detected if aggressive testing programs had been put in place.

Trump appeared bored on Saturday as he went for his second weekend without playing golf.

Trump spent the early evening praising a West Virginia resident for comments made when they called in to C-SPAN and complaining about Fox News hours before a Fox News interview.

https://twitter.com/realDonaldTrump/status/1249101675509370882

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Trump wonders if COVID-19 genomes gave fake quotes to the NYT in bizarre Saturday outburst - Raw Story

Investigators have identified genomic alterations that appear to be associated with prognosis in men with metastatic castration-sensitive prostate cancer (mCSPC).

Astudy of 424 patients with mCSPC treated at a tertiary care center revealedthat alterations in the androgen receptor (AR), TP53, cell-cycle, MYC oncogenicsignaling pathways occur more commonly in tumors with worse overall survivaland decreased time to castration-resistant disease, whereas alterations in theSPOP and MNT pathways occur more frequently in tumors with a better prognosis,according to findings published in ClinicalCancer Research.

Thegenomics of metastatic castration-sensitive prostate cancer have not been wellcharacterized in the literature, but it is now clear that upfront treatmentintensification with taxanes or next-generation AR-directed therapies offerbenefit in the overall patient population, said the studys co-senior authorWassim Abida, MD, a medical oncologist at Memorial Sloan Kettering CancerCenter in New York. The question remains whether treatment selection ortargeted therapies can be employed based on genomic characteristics.

Theassociation between alterations in cell-cycle genes and TP53 and MYC pathwaygenes and worse outcomes may pave the way for targeted therapy in thesehigher-risk groups, Dr Abida said.

Thestudy compared genomic alterations according to clinical phenotypes: high- vslow-volume disease and de novo vsmetastatic recurrence. Of the 424 patients in the study, 213 men (50%) hadhigh-volume disease (4 or more bone metastases or visceral metastases) and 211(50%) had low-volume disease; 65% had de novometastases and 35% had metastatic recurrence. At the time of sample collection, patients had a medianage of 66 years. The investigators conducted gene sequencing from May 2015 to September2018.

High- vs low-volume disease

Inadjusted analyses, men with higher-volume disease had significant 1.8- and3.7-fold increased risks of castration-resistant disease and death,respectively, compared with men who had low-volume disease. Tumor specimensfrom men with high-volume disease had more copy number alterations.

Amongmen with high-volume disease, the highest-ranking pathways were the NOTCH,cell-cycle, and epigenetic modifiers pathways.

Althoughthe prevalence of CDK12 alterations differed between patients with de novo metastatic and those with metastaticrecurrences, the groups had similar prognoses. I was actually surprised therewere not more dramatic genomic differences between de novo and relapsed disease, said study co-senior author PhilipKantoff, MD, a medical oncologist and Chair of the Department of Medicine atMemorial Sloan Kettering Cancer Center in New York.

Afteradjusting for disease volume and other genomic pathways, the researchers foundthat the rates of castration resistance differed by 1.5-fold and up to 5-fold accordingto alterations in the AR, SPOP (inverse), TP53, cell-cycle, WNT (inverse), andMYC pathways. Overall survival (OS) rates varied from 2- to 4-fold according toalterations in the AR, SPOP (inverse), WNT (inverse), and cell-cycle pathways.PI3K pathway alterations were not associated with prognosis.

Docetaxeland next-generation AR axis-directed therapies have been shown to prolong OS, butit remains uncertain which patients benefit the most from intensifiedtherapies. We did not find any obvious genomic reason to explain thedifferences in docetaxel sensitivity between high- and low-volume disease, DrKantoff said.

Theauthors pointed out that genomic landscape studies of tumor DNA profiling inprostate cancer in general have excluded metastatic castration-sensitive tumors.Instead, most studies have focus on localized disease or metastaticcastration-resistant disease.

DrAbida and his colleagues acknowledged that their study has inherent biases becauseit was hospital based and enrolled patients at an academic referral center.

Moleculardeterminants of castration resistance or survival in patients with mHSPC have beenunclear, but the new study sheds new light on molecular alterations associatedwith poor outcomes in men with mHSPC, particularly alterations in the AR, cellcycle genes, MYC, and TP53 genes, said Joshi Alumkal, MD, the Leader of theProstate/Genitourinary Medical Oncology Section and Associate Division Chieffor Basic Research in the Hematology-Oncology Division at the University ofMichigan School of Medicine.

Severalrandomized phase 3 clinical trials now show a benefit of escalating treatmentin men with mHSPC by adding novel AR-targeting agents or chemotherapy plusmedical castration versus medical castration alone, Dr Alumkal said. Whetherthe addition of any of these specific agents to medical castration isassociated with improved outcomes in patients with poor-risk molecularalterations identified by the new study is a critical next question, he said.

Urologiconcologist James Mohler, MD, Senior Vice President for Translational Researchat Roswell Park Comprehensive Cancer Center in Buffalo, New York, said the new study found relativelysmall differences among the clinical phenotypes, but that is not surprisingbecause the temporal differences in the evolution of tumor biology occur overlong periods of time, much of which precedes clinical presentation. The hazardratios for association between mutational analysis and oncologic outcome insome cases were statistically significant, but are so small as to not beclinically significant. Part of the reason for this may be that prostatecancer, once metastatic, is so complex that no single mutation or single genepathway is driving growth and hence targetable at a high rate beyond the long provenbenefit from androgen deprivation therapy, Dr Mohler said.

Theresults reported by these authors may be disappointing to many clinicians, butare important because they represent a comprehensive analysis of mCSPC. Theauthors appropriately acknowledge that better tumor sampling and morecomprehensive genetic analysis and larger numbers of patients may be requiredto find any benefit to genomic or somatic sequencing, Dr Mohler said. I amafraid that these limitations are not just of their work but a biologicallimitation of aggressive prostate cancer, which makes improving treatment ofadvanced prostate cancer in an individual patient extremely challenging.

Reference

Stopsack KH, Nandakumar S, Wibmer AG, et al. Oncogenic genomic alterations, clinical phenotypes, and outcomes in metastatic castration-sensitive prostate cancer [published online March 27, 2020]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-20-0168

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Genomic Alterations Linked to Outcomes in mCSPC - Renal and Urology News

In this episode of Genetics Unzipped, recorded at the recent Festival of Genomics in London, Kat Arney finds out why its so important to make sure that both academic and commercial research studies are done with rather than on participants.

Research into genetic conditions relies on information from patients and their families, whether thats detailed health records or genomic data. As the tools and techniques for DNA and data analysis become cheaper and more organisations get in on this fast-growing field, its vital to make sure that the most valuable research resource human lives doesnt get overlooked in the rush.

Fiona Copelandis the chair of a support group for UK families affected by primary ciliary dyskinesia or PCD a rare genetic condition that affects the lungs and is the mother of two adult sons with the condition. Shes spent many years acting as a patient representative, engaging with academic and industry scientists looking to involve PCD patients in research into understanding and treating the condition. She explains what her role involves and shares her advice for how researchers can engage and involve patient groups more effectively. Her top tip? Dont make children cry!

Next Arney speaks with Patrick Short. Hes the CEO of Sano Genetics a Cambridge-based startup that aims to connect researchers with patients who want to take part in genomic research. While some companies using patients in research have come under scrutiny for poor handling of data and ethical compliance, Short is keen to help organizations do better and drive change in the fast-growing commercial genomics sector.

Finally, we hear from Shelley Simmonds, a disability rights campaigner and rare disease advocate whose son Fraser was initially given a diagnosis of Duchenne Muscular Dystrophy as a baby. When Fraser didnt seem to be progressing as might be expected for a child with the disease, she and her family got involved in Genomics Englands 100,000 Genomes Project in search of clarity but things turned out not to be quite so simple. Shelley talks what happens when the question Whats wrong with my child? has no answer.

Full transcript, links and references available online atGeneticsUnzipped.com

Genetics Unzippedis the podcast from the UKGenetics Society,presented by award-winning science communicator and biologistKat Arneyand produced byFirst Create the Media.Follow Kat on Twitter@Kat_Arney,Genetics Unzipped@geneticsunzip,and the Genetics Society at@GenSocUK

Listen to Genetics Unzipped onApple Podcasts(iTunes)Google Play,Spotify,orwherever you get your podcasts

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Podcast: Nothing about me without meThe importance of involving patients in genomic research - Genetic Literacy Project

As we enter 14th day of lock-down (April 7, 2020) in India, global death toll has reached more than 74,000, while as total Corona positive confirmed cases stands more than 13 lakh across the world, which is growing only, when you are reading this column. In India the tally stands at 4,281 people infected while as 111 deaths have been reported so far (April 7, 13:40).

The question is, how to deal with the new unseen villain. Is Science of Genomics helping us out? Lets dive a bit into what Genomics is and how it is helping us know this new actor in the epidemic world, SARS-Cov-2 virus, responsible for Covid-19 disease?

What is a Genome?

Genomes or genetic material of any organism are our guides to understanding how life works. Genomics (field which deals with study of Genomes) has revolutionized our understanding of human and pathogen (disease causing microbes) biology and also how the two interact.

Genome is an entire genetic material, containing hereditary information and present inside an organism such as human or bacteria or even virus. Genome consists of Genes. Genes themselves are small parts of larger molecules called DNA molecules (Deoxyribo Nucleic Acid) or RNA molecules (Ribo Nucleic Acid). DNA is a long molecule made up of a repeating string of just four different chemicals. (In scientific terminology these chemicals are also known as bases or nucelotides). Most genes are codes describing how to make different types of proteins. The information in genes is stored in order of these bases or chemicals only.

This digital like storage of information was one of the first big discoveries of modern science. Human genome is made of DNA. Same is the case with animals and plants or even bacteria or while as genome in some viruses is made of RNA only. Humans have an average of about 25,000 genes which control our various characteristic features and if there is some defect in our genes, they might result in diseases such as Haemophilia, Sickle Cell disease, Downss syndrome etc.

Similarly, bacteria have around 4000 genes. In the same way Viruses, which are much smaller than bacteria have genomes which contain information about their body biology and also the information required to make the virus and how they would work as well as interact with other organisms or hosts such as humans.

They also decide how a virus would respond if there is any change in its environment. How a virus would control the host cell (cells which they infect), is all coded in their genomes only. Some mutation or changes in genome of a virus renders him pathogenic or disease causing, which otherwise is non-toxic. Living organisms are mostly made of proteins and fats. Thus, to understand genes is to understand the organism itself.

Now why are viral or bacterial genomes important here?

Genome variations in bacteria and viruses give us a lot of information. For example, how they cause diseases, how they originate, how they interact with the host (organisms they cause diseases) and their pathogenicity or how toxic they are. By sequencing the genome of a bacteria or virus one can, not only determine which genes of bacteria and virus play a role in causing disease but through better understanding can help in creating possible solutions of how to stop them.

Thus, Genomic data is essential not only to build tests for identifying the villain (virus) but also to create drugs and vaccines against them. Whole genome sequencing (WGS) or complete genome sequencing is actually the process of determining the complete DNA sequence of an organisms genome at a single time.

Modern scientific methods such as WGS, enable us better examination of diversity and the analysis of virus populations, their origins as well as mutations they undergo during any epidemic. Genome sequencing has emerged as major and vital diagnostic tool for disease outbreak as well as identification of the disease-causing microbes.

What Novel Corona Virus (SARS-Cov-2) genome analysis has revealed so far?

Bacteria & Viruses differ from each other in two main aspects. One, bacteria are single celled organisms that are found throughout our body and in our environment while as viruses are much smaller than bacteria and live as long as they are inside a host organisms.

Second is antibiotics usually kill most of the bacteria but they arent effective against viruses. A virus has either a DNA or RNA genome. But vast majority of viruses have RNA genome. A virion is an entire virus particle consisting of an outer protein shell called a capsid or capsule and an inner core of nucleic acid (RNA or DNA). Thus, a genome in viruses is often packed within a protein capsule.

Now let us come to Novel Coronavirus, also known as SARS-Cov-2. Despite its similarity to other viruses in the coronavirus family, the virus is relatively unknown. It is thought to spread more easily and has higher mortality rates than some of its better-known counterparts, adding to the existing challenges of any public health crisis of this scale.

Scientific attempts to know the Novel Coronavirus, which causes Covid-19 disease, started with the study of its genetic material by using gene sequencing techniques. One amongst the first attempts of whole genome sequencing of SARS-Cov-2 virus outside China, was made by a group of scientists from Nepal, Colombia, Saudi Arabia, United Kingdom and Japan, from a strain which was taken from a Covid-19 patient in Nepal.

The patient was a Nepalese student of Wuhan University of Technology in Wuhan, China who had returned to Nepal and was showing symptoms such as mild fever, cough and throat congestion. The specimen was collected at the National Influenza Centre, National Public Health Lab-oratory in Kathmandu, Nepal and subsequently its genome was studied at WHO laboratory in University of Hong Kong, Hong Kong. This was done in February 2020 and then subsequently it got published in Microbiology Resource Announcements on 12th March 2020.

Similar attempts of isolation and sequencing of whole genome of the virus were done at many different laboratories of the world. For example genome sequencing was also carried out in African Center of Excellence for Genomics of Infectious Diseases (ACEGID) at Redeemer University, Nigeria. This was a preliminary attempt to reveal the sequence. Around 20th March 2020, the study of SARS-Cov-2 genome was carried out by ICGEB-Trieste, Italy, by a group of scientists, led by Alessandro Marcello.

Likewise, genome analysis was also carried out by a group of scientists from USA, UK and Australia. This particular study was led by Kristian G. Andersen of Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, USA and got published in Nature Medicine on 17th March 2020. These genome detailing procedures have revealed some important features about the virus such as its outer coating also known as Spike protein.

The analysis has shown the high affinity of the outer coating of the virus with humans and that this affinity is a result of natural selection process or evolution of this virus. This study done by Kristian G. Andersen and his colleagues, has revealed that the virus is not a product of any human manipulation, thus debunking many theories about its possible laboratory origins.

The study has also revealed that there have been some mutations in the virus which have changed its outer protein shell and thus facilitated its easy binding with with the human cells (e.g. Lung Cells). The virus has acquired few other mutations which make it so contagious as well as deadly for humans. The study has suggested two possibilities by which it could have evolved and acquired such features and traits which make it so deadly and resistant to all known vaccines & drugs. One is by natural selection in an animal host before it could jump into humans and second is natural selection in humans itself after it got transferred from animals.

More such studies are in progress across many different laboratories just to precisely determine how this animal virus sidestepped the species boundaries to infect humans to such an extent that it soon became a pandemic. The genomic studies would also help us reveal partly the spread and infectiousness in human population.

Genome sequencing of the virus (SARS-Cov-2), causing Covid-19 disease is currently going on in different research laboratories around the world to effectively understand the various strains, their biology and the mutations they undergo, which are causing the epidemic. Genome sequencing is also important in every country which is facing the epidemic to know the course of the disease and thus to explore effective ways which are needed to tackle it.

The war against Covid-19 is not over yet and there are still many unknowns regarding SARS-Cov-2 virus as well as Covid-19 disease, which need to be uncovered. It is just a matter of time before an effective vaccine is developed against the virus, and the villain, which has snatched many souls from their loved ones, is finally defeated by us. I dont know what better way to conclude than with this beautiful line from a play by Shakespeare, Health Shall Live Free and Sickness Freely Die.

Rayies Altaf is a science & technology writer and is currently consultant at Centre for Community Knowledge, Ambedkar University, New Delhi.

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Fighting the invisible: How science of genomics is helping us know novel coronavirus? - Northeast Now

If theres one word to describe hardcore sports fanatics right now, its desperation. With coronavirus-related season suspensions hitting the NBA, NCAA, MLB, NHL, and more, habitual sports-watchers are turning to marble racing, binge-watching Netflix, and asking sportscaster Joe Buck to narrate their sex tapes. (Unsuccessfully. He is, however, providing play-by-plays of peoples backyard chicken coops and dog-exercising.)

If its doom-and-gloom for sports, you can be certain the billion-dollar sports betting industry isnt faring much better. Log in to any of the dozens of sports betting websites with an Andrew Jackson burning a hole in your pocket and youll find your pants singed; theres barely anything live to bet on.

Its been a bloodbath, says Ebbe Groes, CEO of sports betting software company EveryMatrix. The betting volume for regular sports events dropped about 80 percent as there was nothing left to bet on. Thats when we turned to esports.

Over the past four years, online betting sites have been slowly welcoming fans of the volatile but growing industry of livestreamed competitive gaming into their pools and brackets. As two teams of pro gamers go head to head in a League of Legends match live on Twitch, risk-loving viewers tab onto websites like DraftKings, Betway, and Loot.bet hoping to earn a bit of cash from their savvy projections. Now, these sites are describing an exponential surge in betting spurred by the dearth of traditional sports contentdespite some of the risks involved with the Wild West esports industry.

In less than a month, the volume of dollars Groes has seen bet on esports has gone up by a factor of 10. EveryMatrix offers software facilitating esports betting on everything from Fortnite and FIFA to dozens of online betting sites, from Germanys Mybet to Russias 1xBet. Before Covid-19 hit, esports bets constituted just 1 percent of bets he saw. Now, its 35 percent. The typical bet, he says, remains $25 between sports and esports betters.

Especially now with this kind of downtime with sports, esports have stepped up and become the number one offering on DraftKings, says Matt Kalish, cofounder and president of DraftKings North America, which facilitates fantasy sports drafting. Esports fantasy contests are 20 times more popular than they were prior to the pandemic, he says.

For dedicated esports betting site Loot.bet, daily bet volume has grown by 20 percent. In 2019, live bets accounted for 75 percent of volume, but in March 2020 that had grown to 83 percent, says a Loot.bet representative. Were putting this down to the huge number of fans in lockdown, who are watching more live esports streams, and hence placing more live bets.

Seasoned sports betters looking for an easy onboarding into digital gaming are slowly finding their way onto sites that allow betting on sports sims. Fans of Nascar are betting on eNascar, a racing league built on the iRacing simulator. In March, a Pro Invitational Series cropped up; one night drew 1.6 million unique viewers, some of whom were keeping things spicy on betting sites. (DraftKings has a $10,000 winner-take-all Sportsbook Pools contest.) On March 31, 2K Gaming, the NBA, and the NBPA announced the NBA 2K Players Tournament, which will feature competitions between 16 top NBA players, including Kevin Durant and Trae Young. The champion will receive $100,000, to be donated to a charity combating Covid-19. Standard sports betting sites like Bovada are publishing odds.

Although sports sims have the sexiest sell to desperate fans seeking a familiar thrilla nearly one-to-one ratio of play to gameplaybetting sites say theyre seeing low betting volumes so far. However, Loot.bet says that over the past month, the volume of bets it has received on soccer sim FIFA 20 exceeded the combined total of bets placed on Starcraft 2, Call of Duty, and Overwatchgames that arent necessarily huge among esports betters but are popular to watch.

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With Sports on Hold, Restless Gamblers Turn to Videogames - WIRED

It's a similar story at the Majestic Star casinos, owned by Indiana-based Spectacle Entertainment, which continued paying its employees through March 29, despite lacking the financial resources of its Region gaming competitors.

Spectacle also is paying 100% of the cost of employee health benefits through the end of April, according to a company announcement.

"Our team members are our most valuable asset and the champions of our business. Unfortunately, except for some security, surveillance and other critical personnel, we had no choice but to furlough approximately 95% of our workforce on March 30, in accordance with union and non-union guidelines," the company said.

"It is our sincere hope we can get through this critical situation and bring our team back together with as minimal hardship as possible."

Ameristar parent Penn National Gaming Inc. previously announced it had furloughed its employees March 31. Though the company is maintaining employee medical benefits until June 30.

Currently, the only Northwest Indiana casino still paying all of its employees is Michigan City's Blue Chip Casino, owned by Boyd Gaming.

Boyd announced March 27 it would continue employee pay and benefits until April 10. It has not said what will happen after Friday.

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5,000 workers furloughed as coronavirus busts casinos - The Times of Northwest Indiana

Thirty thousand base pairs make up the (relatively tiny) SARS-CoV-2 genome. A singular genome holds limited information. But, by comparing multiple genomes from different patients, animals, places, or time periods, the DNAs information can be unlocked. From where the virus originated to how it spilled over from animals into humans, how quickly it mutates, and how those changes affect infectionsgenome comparisons may provide the answers.

The SARS-CoV-2 genome, initially reported on January 12, has been studied extensively in the last month, with the hope of uncovering useful information about COVID-19. Indeed, the U.K. has established a massive collaboration to sequence as many COVID-19 cases as possible. Some researchers, such as Trevor Bedford, PhD, associate member at the Fred Hutchinson Cancer Research Center in the Vaccine and Infectious Disease Division and an affiliate associate professor in the department of genome sciences and the department of epidemiology at the University of Washington, analyze viral genomes from the pandemic in real time, as the data materialize. These data and analyses are available on the open-source platform Nextstrain, co-developed by Bedford.

In the last month, Bedford has been able to form early hypotheses regarding the virus. One, according to his tweets on March 24, offered information regarding how SARS-CoV-2 mutates and what that might mean for COVID-19 vaccination and immunity. In the thread, Bedford predicts that it will take the virus a few years to mutate enough to significantly hinder a vaccine. He goes on to suggest that we should see occasional mutations to the spike protein of SARS-CoV-2 that allow the virus to partially escape from vaccines or existing herd immunity, but that this process will most likely take years rather than months.

A looming question of the COVID-19 pandemic remains unsolved. That is, how did the virus spillover into humans?

A paper published recently in Nature (originally published in the preprint server bioRxiv on February 18) sought to answer this question. The focus of the paper, Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins, was to analyze the genomes of coronaviruses found in pangolins, and draw conclusions from the data.

Their results: more work needs to be done.

The COVID-19 outbreak has been tentatively associated with a seafood market in Wuhan, China, where, the authors write, the sale of wild animals may be the source of zoonotic infection. Based on genomic data, bats have been suggested as the likely reservoir hosts for SARS-CoV-2. But, it remains unknown if the virus went from bats to humans, or if an intermediate host facilitated the spillover.

The researchers found that, indeed, Malayan pangolinsintercepted from a smuggling operation in southern Chinadid have SARS-CoV-2-related coronaviruses. The authors noted that, Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity to SARS-CoV-2 in the receptor-binding domain.

The authors concluded that this multiple lineage finding of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of novel coronaviruses and should be removed from wet markets to prevent zoonotic transmission.

The role that pangolins play in the emergence of SARS-CoV-2 is still unclear, noted Edward Holmes, PhD, professor at the University of Sydney, Australia and an adjunct professor, Fudan University, Shanghai, China. However, he added, It is striking is that the pangolin viruses contain some genomic regions that are very closely related to the human virus. The most important of these is the receptor-binding domain that dictates how the virus is able to attach and infect human cells.

It is clear that wildlife contains many coronaviruses that could potentially emerge in humans in the future, noted Holmes. A crucial lesson from this pandemic, he continued, to help prevent the next one is that humans must reduce their exposure to wildlife, for example by banning wet markets and the trade in wildlife.

Last week, Nature Medicine published a Correspondence, The proximal origin of SARS-CoV-2, which Holmes co-authored, working with scientists from the department of immunology and microbiology at The Scripps Research Institute, the University of Edinburgh, Columbia University, and Tulane University.

The research, using comparative analysis of genomic data, both proved that SARS-CoV-2 evolved naturally, and disproved the idea that it is a manufactured biological agent.

There is simply no evidence that SARS-CoV-2 came out of a lab, Holmes said.

In doing this work, the group looked closely at the receptor-binding domain (RBD) of the viral spike protein that SARS-CoV-2 uses to bind to cell surface receptors and gain entry into human host cells to help shape their spillover hypotheses. The authors noted that, although the RaTG13 bat virus remains the closest to SARS-CoV-2 across the genome, some pangolin coronaviruses exhibit strong similarity to SARS-CoV-2 in the RBD of the spike protein, including all six key RBD residues. This finding, they concluded, shows that the SARS-CoV-2 spike protein optimized for binding to human-like ACE2 is the result of natural selection.

The genomes of SARS-CoV-2 holds many answers to the questions scientists are searching for at a feverish pace. It is clear that understanding the evolutionary pathway by which this novel coronavirus has transferred to humans will help us not only combat the current pandemic but assist in identifying future threats from other coronaviruses and other species.

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Mining the SARS-CoV-2 Genome for Answers - Genetic Engineering & Biotechnology News

Genomics has come a long way since the central dogma (the notion that DNA is the master controller that calls all the shots) and junk DNA (the expectation that much of the genome is non-functional). If scientists ditch those old dogmas and approach the genome expecting to find reasons for things, they often do.

To-may-to or to-mah-to? The British write flavour; the Americans write flavor, but generally each understands the other without too much difficulty. Genomes, too, have alternate ways of spelling things: GGU and GGC in messenger RNA both spell glycine. No big deal, thought geneticists; these silent mutations cause no change in the resulting protein. At the University of Notre Dame, however, biochemists are finding that the differences in spelling are not just background noise; they alter the proteins folding. Is that good or bad?

Synonymous mutations were long considered to be genomic background noise, but we found they do indeed lead to altered protein folding, and in turn impair cell function, said Patricia Clark, the Rev. John Cardinal OHara professor of biochemistry at the University of Notre Dame, and lead author of the study. Our results show that synonymous variations in our DNA sequences which account for most of our genetic variation can have a significant impact on shaping the fitness level of cellular proteins.

Surely many of these mutations are harmful, as are random mutations in humans that cause genetic disease. But E. coli has been around for a long time. Wouldnt the species have gone extinct by now with the accumulation of defective spellings if they are always deleterious? Other work has suggested a secret code in synonymous variations that fine-tunes expression rates or regulates the supply of a given protein based on environmental conditions. The news release only mentions impairments caused by synonymous variations, but Notre Dame teams paper in PNAS suggests some possible advantages:

Synonymous codon substitutions alter the mRNA coding sequence but preserve the encoded amino acid sequence. For this reason, these substitutions were historically considered to be phenotypically silent and often disregarded in studies of human genetic variation. In recent years, however, it has become clear that synonymous substitutions can significantly alter protein function in vivo through a wide variety of mechanisms that can change protein level, translational accuracy, secretion efficiency, the final folded structure and posttranslational modifications. The full range of synonymous codon effects on protein production is, however, still emerging, and much remains to be learned regarding the precise mechanisms that regulate these effects. [Emphasis added.]

A design perspective would consider every possible function before rendering a judgment that all synonymous variations reduce fitness.

Keeping the genome accurate to a high degree preserves it from collapsing due to error catastrophe. At the time of cell division, proofreading enzymes (what a concept!) perform this vital function. Chelsea R. Bulock et al., writing in PNAS, have found one duplication enzyme that proofreads itself while proofreading its partner! DNA polymerase proofreads errors made by DNA polymerase , the paper is titled.

Pol and Pol are the two major replicative polymerases in eukaryotes, but their precise roles at the replication fork remain a subject of debate. A bulk of data supports a model where Pol and Pol synthesize leading and lagging DNA strands, respectively. However, this model has been difficult to reconcile with the fact that mutations in Pol have much stronger consequences for genome stability than equivalent mutations in Pol. We provide direct evidence for a long-entertained idea that Pol can proofread errors made by Pol in addition to its own errors, thus, making a more prominent contribution to mutation avoidance. This paper provides an essential advance in the understanding of the mechanism of eukaryotic DNA replication.

In other words, Pol is a proofreader of a proofreader. The paper says that Pol is a versatile extrinsic proofreading enzyme. One could think of it as a supervisor checking the work of a subordinate, or better yet, as an auditor or inspector able to fix errors before they cause harm to the product. Why would this be necessary during replication? The authors see a seniority system:

Thus, the high efficiency of Pol at correcting errors made by Pol may result from a combination of two factors: the high proclivity of Pol to yield to another polymerase and the greater flexibility and robustness of Pol when associating with new primer termini.

One proofreader is amazing to consider evolving by a Darwinian mechanism. A proofreader of a proofreader is astonishing. Consider, too, that this proofreading operation occurs in the dark by feel, automatically, without eyes to see.

Now that genetics is long past the heady days of finding that DNA forms a code that is translated, additional discoveries continue to show additional codes and factors that contribute to genomic function. One factor is the high-order structure of DNA. Researchers at South Koreas UNIST center have explored further into the formation of this structure, which involves chromatin wrapping around histone proteins so that long strands of DNA can fit within the compact space of the cell nucleus. As with everything else in genomics, the structure doesnt just happen. It requires a lot of help.

Regulation of histone proteins allows the DNA strands become more tightly or loosely coiled during the processes of DNA replication and gene expression. However, problems may arise when histones clump together or when DNA strands intertwine. Indeed, the misregulation of chromatin structures could result in aberrant gene expression and can ultimately lead to developmental disorders or cancers.

Histone chaperones are those proteins, responsible for adding and removing specific histones [found] at the wrong time and place during the DNA packaging process. Thus, they also play a key role in the assembly and disassembly of chromatin.

Cryo-EM imaging allowed the team to envision the molecular structure of some of these chaperone proteins. Their paper in Nature Communications begins, The fundamental unit of chromatin, the nucleosome, is an intricate structure that requires histone chaperones for assembly. Their cryo-EM images of one particular chaperone named Abo1 reveals a six-fold symmetry with precise locations for docking to histones, its hexameric ring thus creating a unique pocket where histones could bind with energy from ATP. Not only is Abo1 distinct as a histone chaperone, they write, but Abo1 is also unique compared to other canonical AAA+protein structures. Like Lego blocks, Abo1 features tight knob-and-hole packing of individual subunits plus linkers and other binding sites, such as for ATP. And unlike static blocks, these blocks undergo conformational changes as they work.

Such sophistication is far beyond the old picture of DNA as a master molecule directing all the work. It couldnt work without the help of many precision machines like this.

These stories are mere samples from a vast and growing literature indicating higher order in the genome than expected. Here are some more samples readers may wish to investigate:

Researchers at the University of Seville found additional factors involved in the repair of DNA strand breaks. These repairs are essential for the maintenance of genome integrity. The factors they discovered help maintain the right tension in cohesin molecules that hold the chromosomes together until the right time to separate. The news was relayed by EurekAlert!and published in Nature Communications.

Remember Paleys Watch? Researchers at the University of Basel discovered that Inner clockwork sets the time for cell division in bacteria. In PNAS and in Nature Communications, the Basel team elucidates the structure and function of a small signaling molecule that starts the clock, which then informs the cell about the right time to reproduce. They report in the news release:

A team at the Biozentrum of the University of Basel, led by Prof. Urs Jenal has now identified a central switch for reproduction in the model bacteriumCaulobacter crescentus: the signaling molecule c-di-GMP. In their current study,published in the journalNature Communications,they report that this molecule initiates a clock-like mechanism, which determines whether individual bacteria reproduce.

Proteins must fold properly to perform their functions. Small proteins usually fold successfully on their own, but large ones can fall into several misfolding traps that are equally likely as the canonical fold. It appears that the sequence of the sequence in a gene has something to do with this. Interestingly, many of these proteins sequences contain conserved rare codons that may slow down synthesis at this optimal window, explain Amir Bitran et al. in a January 21 paper in PNAS, discovering that Cotranslational folding (i.e., folding that begins as the polypeptide exits the ribosome) allows misfolding-prone proteins to circumvent deep kinetic traps.

Design advocates and evolutionists need to fathom what they are dealing with when discussing origins. Theres nothing like some low-level detail to put the challenge in perspective.

Image credit: Caulobacter crescentus, by University of Basel, Swiss Nanoscience Institute/Biozentrum, via EurekAlert!

Read more from the original source:
More Hints of Order in the Genome - Discovery Institute