Monthly Archives: September 2021

Higher entropy observed in SARS-CoV-2 genomes from the first COVID-19 wave in Pakistan – DocWire News

Posted: September 1, 2021 at 12:05 am

This article was originally published here

PLoS One. 2021 Aug 31;16(8):e0256451. doi: 10.1371/journal.pone.0256451. eCollection 2021.

ABSTRACT

BACKGROUND: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan.

MATERIALS AND METHODS: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan. Site specific entropy analysis compared mutation rates between strains isolated before and after June 2020.

RESULTS: In March, strains belonging to L, S, V and GH clades were observed but by October, only L and GH strains were present. The highest diversity of clades was present in Sindh and Islamabad Capital Territory and the least in Punjab province. Initial introductions of SARS-CoV-2 GH (B.1.255, B.1) and S (A) clades were associated with overseas travelers. Additionally, GH (B.1.255, B.1, B.1.160, B.1.36), L (B, B.6, B.4), V (B.4) and S (A) clades were transmitted locally. SARS-CoV-2 genomes clustered with global strains except for ten which matched Pakistani isolates. RNA substitution rates were estimated at 5.86 x10-4. The most frequent mutations were 5 UTR 241C > T, Spike glycoprotein D614G, RNA dependent RNA polymerase (RdRp) P4715L and Orf3a Q57H. Strains up until June 2020 exhibited an overall higher mean and site-specific entropy as compared with sequences after June. Relative entropy was higher across GH as compared with GR and L clades. More sites were under selection pressure in GH strains but this was not significant for any particular site.

CONCLUSIONS: The higher entropy and diversity observed in early pandemic as compared with later strains suggests increasing stability of the genomes in subsequent COVID-19 waves. This would likely lead to the selection of site-specific changes that are advantageous to the virus, as has been currently observed through the pandemic.

PMID:34464419 | DOI:10.1371/journal.pone.0256451

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Higher entropy observed in SARS-CoV-2 genomes from the first COVID-19 wave in Pakistan - DocWire News

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A Pediatric Research Institution is Setting the Pace for Monitoring SARS-CoV-2 Mutations and COVID-19 Variants – Yahoo Finance

Posted: at 12:05 am

As the coronavirus evolves, health authorities across the globe rely on the work of scientists at Childrens Hospital Los Angeles, who use genomic sequencing to track mutations.

LOS ANGELES, August 31, 2021--(BUSINESS WIRE)--The COVID-19 pandemic has introduced many new words into our everyday lives. Beyond N-95 and quarantine, new terms like Delta variant are now commonplace. But what is a variant? How are variants identified? And why is it important to track them?

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210831005726/en/

Xiaowu Gai, PhD, Jennifer Dien Bard, PhD, and their colleagues at Children's Hospital Los Angeles are using genomic sequencing to track SARS-CoV-2 mutations and COVID-19 variants. (Photo: Business Wire)

Scientists at Childrens Hospital Los Angeles have been paying close attention to the behavior of SARS-CoV-2, since the beginning of the pandemic. This means reading out the genetic sequence of the virus from every COVID-19-positive sample to identify mutations. But this also means alerting authorities to notable changes in the virus. Recently, in fact, their research has uncovered mutations recognized by the global scientific community, mutations that may explain why certain versions of the viruslike the Delta variantare so much more contagious.

"Genomic surveillance is critical," says Xiaowu Gai, PhD, Director of Bioinformatics in the Center for Personalized Medicine at Childrens Hospital Los Angeles. "This is the only tool we have to identify mutations. We can track these mutations to help guide public health measures." This tracking has been critical throughout the pandemic.

"Sequencing the genome of SARS-CoV-2 allowed for development of the vaccine," adds Dr. Gai. "Now it remains just as important given the evolving virus and all its variants."

What is a variant?

When a virus infects someone, it replicates, making many copies of itself. Inevitably, mistakes called mutations are made in that process. Sometimes, these mutations make it easier for the virus to be spread or infect cells. When this happens, the new version of the virusor variantwill become more common in the population. The more a virus spreads from person to person, the more chances it has to mutate and for new variants to develop.

Story continues

SARS-CoV-2 has infected more than 200 million individuals worldwide, giving it ample chance to mutate. According to experts, SARS-CoV-2, the virus that causes COVID-19, mutates every couple of weeks. At Childrens Hospital Los Angeles, scientists in the Department of Pathology & Laboratory Medicine and the Center for Personalized Medicine have been tracking these mutations since the beginning of the pandemic in order to identify variants and anticipate the emergence of "variants of concern," which can potentially be more contagious or cause more severe disease.

A virus family tree

Over time, a variant will develop new mutations of its own, leading to multiple sub-lineages, much like a family tree. But not all mutations are cause for concern. In fact, many of them are inconsequential, much like how dropping one letter from a word still leaves a sentence that can be read. In some cases, mutations may even cause the virus to become weaker and die off. But in otherssuch as the current Delta variantthese changes can help a virus spread.

The Centers for Disease Control and Prevention (CDC) reports that the Delta variant is twice as contagious as previous strains. This means that people exposed to the Delta variant are more likely to be infected, and that over time the Delta variant out-competes other variants to become dominant. Today more than 90% of new COVID-19 cases are caused by the Delta variant.

Our understanding and awareness of variants depends on scientists tracking the mutations using a technology called sequencing. With specialized high-throughput machines, scientists can read the entire genetic sequence, sometimes called the genome, of SARS-CoV-2. Then, samples can be compared to determine where mutations have arisen. This allows public health officials to be aware of the presence of different variants and the emergence of new more contagious strains of SARS-CoV-2.

Tracking the virus

At Childrens Hospital Los Angeles, geneticist Dr. Gai and his colleagues have sequenced every COVID-19-positive sample they have received since the beginning of the pandemic, over 3,000 samples to date. In addition to sequencing, Dr. Gais bioinformatics team analyzes the results for viral mutations. This allows them to identify existing and emerging variants to support CHLAs contact tracing and genomic epidemiology efforts to track transmission patterns. The team then shares findings with databases used to by investigators studying COVID-19 around the world.

Sharing information across the globe

Working with Jennifer Dien Bard, PhD, and colleagues in the Department of Pathology & Laboratory Medicine, Dr. Gai and his team have helped CHLA publish the result of multiple SARS-CoV-2 studies, including the largest pediatric COVID-19 study of its time last year, which identified a potential link between certain mutations and severity of disease in children. Another publication demonstrated the effectiveness of public safety measures in limiting the spread of specific strains of the virus.

As the pandemic reaches the year and a half mark, Dr. Gais team is not slowing down. In fact, their recent work has been recognized internationally.

Recently, investigators in the Center for Personalized Medicine analyzed more than 1.3 million SARS-CoV-2 genome sequences from global databases to trace the lineage of the Alpha variant, which emerged in the U.K. in September 2020. The Alpha variant rapidly became dominant, accounting for over 90% of cases in Europe and nearly 60% of COVID-19 cases in the United States, until the emergence of the Delta variant.

The teams most recent work reveals mutations in genes that affect the viruss ability to bind to and infect human cells. One study identified a sub-lineage of the Alpha variant that became officially recognized and named "Q.3." in the internationally recognized SARS-CoV-2 classification system Pangolin. The study was also included in the CDCs COVID-19 Genomics and Precision Public Health Weekly Update and cited by the Global Virus Network, an international resource portal for tracking SARS-CoV-2 mutations.

One of the mutations they reported in the paper (called "M:I82T") is now a recognized feature in the well-known Delta variant. "This mutation affects a protein that sits on the surface of the virus," says Lishuang Shen, PhD, Senior Bioinformatics Scientist at Childrens Hospital Los Angeles and the first author of the publication. "This mutation may indeed be the reason the Delta variant is so much more infectious andin some casesmore deadly."

A second study identified the emergence of a mutation that increased in frequency by more than a factor of 10 in the United States in just two months (February through April of 2021). The team is carefully tracking the mutation for any signs that it may contribute to an emerging variant of concern.

"We need to know what is happening with this virus in as much detail as possible," says Dr. Gai. "Sequencing COVID-19 positive samples allows us to do this." Keeping tabs on the behavior of the virus will alert public health officials to things like how well the vaccine works against new variants.

At the beginning of the pandemic, Dr. Gai and his colleagues in the Department of Pathology & Laboratory Medicine and Center for Personalized Medicine began working around the clock to keep up with testing and sequencing. Almost a year and a half into the pandemic, the team continues to remain vigilant. "The pandemic is not going away," says Dr. Gai, "so neither are we."

The team conducting this work in the Department of Pathology & Laboratory Medicine and the Center for Personalized Medicine includes: Lishuang Shen, first author on both new publications; Jennifer Dien Bard, PhD, the Director of the Clinical Microbiology and Virology Laboratories; Maurice OGorman, PhD, Chief of Laboratory Medicine, Jaclyn Biegel, PhD, Chief of Genomic Medicine and Director of the Center for Personalized Medicine, Timothy Triche, MD, PhD, Co-Director of the Center for Personalized Medicine; Alexander Judkins, MD, Pathologist in Chief and Executive Director of the Center for Personalized Medicine.

View source version on businesswire.com: https://www.businesswire.com/news/home/20210831005726/en/

Contacts

Melinda SmithResearch Communications Specialistmsmith@chla.usc.edu

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Faint Neons Take Over The Outsoles On This Womens Nike Air Max Genome – Sneaker News

Posted: at 12:05 am

Among Nike Sportswears newer propositions, the Nike Air Max Genome quickly become a fan-favorite thanks in large part to its equal-parts heritage and modern design. For its latest ensemble, the model has delivered women a predominantly unassuming colorway, complete with pink and green accents scattered throughout.

Akin to some of the silhouettes inaugural styles, the newly-surfaced pair indulges in a mostly white, off-white and grey arrangement. The mesh, perforated leather and synthetic panels that make up the entirety of the sneakers top-halves are complemented by a South Florida-appropriate rose tone that animates both profiles swoosh logos. Underfoot, the Air Max unit is accompanied by a tread pattern partly-clad in the aforementioned faint neon hues; detailing art the heel also indulges in the statement-making color combination, while not detracting too much from the shoes overall clean look.

No official Nike.com release date has been disclosed, but this womens Air Max Genome is likely to quietly arrive in the coming weeks. In any case, enjoy images of the pair ahead.

Elsewhere in the Swoosh empire, the Air Force 1 High has recently emerged in a number of strapless styles.

Where to Buy

Make sure to follow @kicksfinder for live tweets during the release date.

Womens: $170Style Code: DC4057-100

Images: Nike

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What’s next for the FBI’s Crystal Rogers investigation in Bardstown? – WLKY Louisville

Posted: at 12:02 am

Searching has come to a halt at the Bardstown site currently being targeted in the Crystal Rogers investigation.The FBI renewed its efforts last week nearly a year after it took over the investigation into her disappearance. Agents targeted a subdivision, Woodlawn Springs, where Rogers' boyfriend built three homes, then honed in on one. He built that home, but no longer owns it. Over several days of searching, investigators found "multiple items of interest," but they did not disclose what they were. "During the course of our search thus far, multiple items of interest have been uncovered. Initial analysis shows they are potentially relevant to the investigation into the disappearance of Crystal Rogers," the FBI said in a tweet on Monday. Previous stories:Day 1 coverageDay 2 coverageDay 3 coverageDay 4 coverage Day 6 coverageSo what happens next?The FBI suspended its efforts due to weather as Hurricane Ida remnants move in. Just before 5 p.m. Tuesday, FBI agents told us the time of their return was "unknown at this time." The items that have been recovered are being sent to a crime lab in Quantico, Virginia, for further analysis.There's currently a $25,000 reward for information that would help agents solve the case.What to know about the caseRogers went missing in 2015. Her car was found abandoned with a flat tire on Bluegrass Parkway in Bardstown with her phone, purse and keys still inside.She had five children, one with Houck. While he is the only person since she disappeared to be named as a suspect, he has never been charged. His home was searched last year when the FBI started investigating. They also investigated his brother Nick Houck's home.At one point, investigators zeroed in on Houck's grandmother, Anna Whitesides.Crystal Rogers investigation: Where feds searched last year and whyThe state believed her car may have been used to dispose of Rogers' body. Whitesides, who had previously talked to investigators, later invoked her Fifth Amendment right, refusing to testify when called to court.Before the FBI came in last year, the Nelson County Sheriff's Department was handling the disappearance. A new detective took over the case a couple of years ago when Det. Jon Snow left the Sheriff's Department. Chief Deputy Joedy Gilliland then became the lead until the feds stepped in.Last year, when the FBI began its investigation, officials reported that they had found human remains at the Washington-Nelson county line. The FBI later reported that those remains were not of Rogers and their efforts remained largely quiet up until the latest flurry of activity this week.Just a year after Rogers died, on Nov. 19, 2016, her father was shot and killed on family property near Bluegrass Parkway, and his killing also remains unsolved.

Searching has come to a halt at the Bardstown site currently being targeted in the Crystal Rogers investigation.

The FBI renewed its efforts last week nearly a year after it took over the investigation into her disappearance.

Agents targeted a subdivision, Woodlawn Springs, where Rogers' boyfriend built three homes, then honed in on one. He built that home, but no longer owns it.

Over several days of searching, investigators found "multiple items of interest," but they did not disclose what they were.

"During the course of our search thus far, multiple items of interest have been uncovered. Initial analysis shows they are potentially relevant to the investigation into the disappearance of Crystal Rogers," the FBI said in a tweet on Monday.

Previous stories:

The FBI suspended its efforts due to weather as Hurricane Ida remnants move in.

Just before 5 p.m. Tuesday, FBI agents told us the time of their return was "unknown at this time."

The items that have been recovered are being sent to a crime lab in Quantico, Virginia, for further analysis.

There's currently a $25,000 reward for information that would help agents solve the case.

What to know about the case

Rogers went missing in 2015. Her car was found abandoned with a flat tire on Bluegrass Parkway in Bardstown with her phone, purse and keys still inside.

She had five children, one with Houck. While he is the only person since she disappeared to be named as a suspect, he has never been charged. His home was searched last year when the FBI started investigating. They also investigated his brother Nick Houck's home.

At one point, investigators zeroed in on Houck's grandmother, Anna Whitesides.

Crystal Rogers investigation: Where feds searched last year and why

The state believed her car may have been used to dispose of Rogers' body. Whitesides, who had previously talked to investigators, later invoked her Fifth Amendment right, refusing to testify when called to court.

Before the FBI came in last year, the Nelson County Sheriff's Department was handling the disappearance. A new detective took over the case a couple of years ago when Det. Jon Snow left the Sheriff's Department. Chief Deputy Joedy Gilliland then became the lead until the feds stepped in.

Last year, when the FBI began its investigation, officials reported that they had found human remains at the Washington-Nelson county line. The FBI later reported that those remains were not of Rogers and their efforts remained largely quiet up until the latest flurry of activity this week.

Just a year after Rogers died, on Nov. 19, 2016, her father was shot and killed on family property near Bluegrass Parkway, and his killing also remains unsolved.

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What's next for the FBI's Crystal Rogers investigation in Bardstown? - WLKY Louisville

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Four Years After Harvey: Federal Government Liable, Families Still Fighting for Compensation; There Is Still Time to File a Claim With Attorney Armi…

Posted: at 12:02 am

HOUSTON--(BUSINESS WIRE)--On the four-year anniversary of Tropical Storm Harvey, Armi Easterby, a partner of the Houston-based law firm Williams Hart Boundas Easterby LLP, stated today that, Despite the Army Corps admitting that upstream reservoir flooding poses unacceptable risks to health and human safety, private property, and public infrastructure, it still has done nothing to compensate the families and businesses it flooded during Harvey. Mr. Easterbys reference to this unacceptable risk comes directly from the study published by the U.S. Army Corps of Engineers in October of 2020.

Unfortunately, this unacceptable risk became a reality on August 30, 2017, when thousands of private properties were inundated with contaminated stormwater held back by the Addicks and Barker dams, continued Mr. Easterby. The Court of Federal Claims previously ruled that, under the 5th Amendment, the federal governments use of more than 7,000 acres of private upstream land requires payment of just compensation to eligible claimants. In that ruling, the Court of Federal Claims held, The governments actions relating to the Addicks and Barker Dams and the attendant flooding of plaintiffs properties constituted a taking of a flowage easement under the Fifth Amendment. Thus, the court finds defendant liable.

The ongoing litigation is now in the compensation phase, which will set the amount of compensation owed to various residents of the upstream neighborhoods.

In spite of repeated COVID delays, Armi Easterby is ready to go the distance. While the delays have been frustrating, they have not and will not change our commitment to hold the federal government accountable for its decision to impose flooding on private property with no legal right. Williams Hart Boundas Easterby, LLP has been a fixture of the Houston legal community for 38 years and has served over 200,000 clients since the firms founding in 1983.

Armi Easterby, who has been licensed with the Court of Federal Claims for over 20 years, continues to serve as the co-lead lawyer appointed by the court to protect the rights of individual plaintiffs. Were privileged to represent over 1,500 upstream families and businesses in their 5th Amendment claims against the federal government, and will continue fighting until weve collected just compensation, says Armi Easterby. Mr. Easterby represents property owners in all impacted communities behind the dams, including Bear Creek, Canyon Gate, Twin Lakes, Lakes on Eldridge, Concord Bridge, Concord Colony, Cinco Ranch, Charlestown Colony, Cinco at Willow Fork, Cinco Ranch Equestrian Village, Cinco Ranch Greenway Village, Cinco Ranch Meadow Place, Cinco Ranch Southpark, Concord Fairways at Kelliwood, Grand Lakes, Grand Lakes Phase Three, Grand Mission, Green Trails Oaks, Greens at Willow Fork, Jamestown Colony, Kelliwood Greens, Kingsland Estates, Lakes of Buckingham Kelliwood, Mayde Creek Farms, Park Harbor Estates, Parklake Village, Pine Forest, Savannah Estates, Stone Gate at Canyon Gate, and Windsor Park Estates.

Mr. Easterby presented key evidence in the May 2019 trial which found the government liable for the upstream flooding. To date, approximately 65% of all upstream plaintiffs have hired Armi Easterby and Williams Hart Boundas Easterby, LLP to prosecute their 5th Amendment claims. Upstream residents are banding together to hold the government accountable.

Mr. Easterby concluded with It is important to know that there is still time for upstream residents to file their claims and that thousands of property owners qualify for this important case but have not yet filed. Property owners upstream of the Addicks and Barker dams who experienced flooding in late August of 2017 may have a claim, but must submit it before the statute of limitations expires in order to receive any financial compensation. Contact Armi Easterby at http://www.myreservoirclaim.com or (713) 940-6220 for a free case evaluation.

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Four Years After Harvey: Federal Government Liable, Families Still Fighting for Compensation; There Is Still Time to File a Claim With Attorney Armi...

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FBI suspending Crystal Rogers efforts due to incoming weather, ‘multiple items of interest’ found – WLKY Louisville

Posted: at 12:02 am

After days of searching in a Bardstown subdivision, the FBI is suspending its efforts in the Crystal Rogers investigation for the time being due to incoming weather, but investigators said they have recovered "multiple items of interest."According to a tweet from the FBI in Louisville, investigators expect conditions to deteriorate over the next couple of days due to remnants from Hurricane Ida. The approach weather system is forecast to bring torrential rain to the region.But while the search has been called off for now, the team said in a statement that its efforts in the Woodlawn Springs subdivision haven't gone without progress."During the course of our search thus far, multiple items of interest have been uncovered. Initial analysis shows they are potentially relevant to the investigation into the disappearance of Crystal Rogers," the FBI said.The items have been sent to the FBI lab in Quantico, Virginia, for analysis. The FBI has remained quiet about its efforts, including what they have uncovered.Previous stories:Day 1 coverageDay 2 coverageDay 3 coverageDay 4 coverageOne of the first big updates since the FBI resumed its efforts in Bardstown was Friday when they confirmed an "item of interest" had been recovered. That came after days of searching and excavation in the Nelson County community."This item is being further evaluated and we will release additional information as it becomes available," the FBI tweeted.And over the weekend, for the first time, the FBI announced a $25,000 reward for information in Rogers' disappearance. They are hoping someone in the community will come forward and provide tips that will lead to the identification, arrest and conviction of whoever is responsible for the mother's disappearance.'I just pray this is it': Crystal Rogers' mother feeling encouraged as FBI search continuesThe main message the FBI has been sending to the community is cooperation. Since the team took over the case last year, they have called on residents to come forward and launched a dedicated website for tips to be submitted anonymously."Now is the time to come forward," the FBI said in a statement Friday.People can also call the FBI at 800-225-5324.FBI teams have been in Bardstown for days now, initially descending on the community last Tuesday to follow up on leads gathered over the last year. Those tips took them to the Woodlawn Springs subdivision, where they initially focused on three properties.Those properties were built by Brooks Houck, Rogers' boyfriend, at the time of her disappearance. The FBI then zeroed in on one of the properties, which no longer belongs to Houck. Teams have been digging up and excavating the driveway, and truckloads of concrete have been seen around the subdivision.The FBI said they don't have a timeline on how long it will take to find any clues in her disappearance but "we will continue our efforts as long as it takes."Sherry Ballard, Rogers' mother, said the FBI has been keeping her up to date. She said she's been grateful to the neighbors for keeping her up-to-date, and she's hopeful another day of searching pays off.What to know about the Crystal Rogers caseRogers went missing in 2015. Her car was found abandoned with a flat tire on Bluegrass Parkway in Bardstown with her phone, purse and keys still inside.She had five children, one with Houck. While he is the only person since she disappeared to be named as a suspect, he has never been charged. His home was searched last year when the FBI started investigating. They also investigated his brother Nick Houck's home.At one point, investigators zeroed in on Houck's grandmother, Anna Whitesides.Crystal Rogers investigation: Where feds searched last year and whyThe state believed her car may have been used to dispose of Rogers' body. Whitesides, who had previously talked to investigators, later invoked her Fifth Amendment right, refusing to testify when called to court.Before the FBI came in last year, the Nelson County Sheriff's Department was handling the disappearance. A new detective took over the case a couple of years ago when Det. Jon Snow left the Sheriff's Department. Chief Deputy Joedy Gilliland then became the lead until the feds stepped in.Last year, when the FBI began its investigation, officials reported that they had found human remains at the Washington-Nelson county line. The FBI later reported that those remains were not of Rogers and their efforts remained largely quiet up until the latest flurry of activity this week.Just a year after Rogers died, on Nov. 19, 2016, her father was shot and killed on family property near Bluegrass Parkway, and his killing also remains unsolved.

After days of searching in a Bardstown subdivision, the FBI is suspending its efforts in the Crystal Rogers investigation for the time being due to incoming weather, but investigators said they have recovered "multiple items of interest."

According to a tweet from the FBI in Louisville, investigators expect conditions to deteriorate over the next couple of days due to remnants from Hurricane Ida. The approach weather system is forecast to bring torrential rain to the region.

But while the search has been called off for now, the team said in a statement that its efforts in the Woodlawn Springs subdivision haven't gone without progress.

"During the course of our search thus far, multiple items of interest have been uncovered. Initial analysis shows they are potentially relevant to the investigation into the disappearance of Crystal Rogers," the FBI said.

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The items have been sent to the FBI lab in Quantico, Virginia, for analysis. The FBI has remained quiet about its efforts, including what they have uncovered.

Previous stories:

One of the first big updates since the FBI resumed its efforts in Bardstown was Friday when they confirmed an "item of interest" had been recovered. That came after days of searching and excavation in the Nelson County community.

"This item is being further evaluated and we will release additional information as it becomes available," the FBI tweeted.

And over the weekend, for the first time, the FBI announced a $25,000 reward for information in Rogers' disappearance. They are hoping someone in the community will come forward and provide tips that will lead to the identification, arrest and conviction of whoever is responsible for the mother's disappearance.

'I just pray this is it': Crystal Rogers' mother feeling encouraged as FBI search continues

The main message the FBI has been sending to the community is cooperation. Since the team took over the case last year, they have called on residents to come forward and launched a dedicated website for tips to be submitted anonymously.

"Now is the time to come forward," the FBI said in a statement Friday.

People can also call the FBI at 800-225-5324.

FBI teams have been in Bardstown for days now, initially descending on the community last Tuesday to follow up on leads gathered over the last year. Those tips took them to the Woodlawn Springs subdivision, where they initially focused on three properties.

Those properties were built by Brooks Houck, Rogers' boyfriend, at the time of her disappearance. The FBI then zeroed in on one of the properties, which no longer belongs to Houck. Teams have been digging up and excavating the driveway, and truckloads of concrete have been seen around the subdivision.

The FBI said they don't have a timeline on how long it will take to find any clues in her disappearance but "we will continue our efforts as long as it takes."

Sherry Ballard, Rogers' mother, said the FBI has been keeping her up to date. She said she's been grateful to the neighbors for keeping her up-to-date, and she's hopeful another day of searching pays off.

Rogers went missing in 2015. Her car was found abandoned with a flat tire on Bluegrass Parkway in Bardstown with her phone, purse and keys still inside.

She had five children, one with Houck. While he is the only person since she disappeared to be named as a suspect, he has never been charged. His home was searched last year when the FBI started investigating. They also investigated his brother Nick Houck's home.

At one point, investigators zeroed in on Houck's grandmother, Anna Whitesides.

Crystal Rogers investigation: Where feds searched last year and why

The state believed her car may have been used to dispose of Rogers' body. Whitesides, who had previously talked to investigators, later invoked her Fifth Amendment right, refusing to testify when called to court.

Before the FBI came in last year, the Nelson County Sheriff's Department was handling the disappearance. A new detective took over the case a couple of years ago when Det. Jon Snow left the Sheriff's Department. Chief Deputy Joedy Gilliland then became the lead until the feds stepped in.

Last year, when the FBI began its investigation, officials reported that they had found human remains at the Washington-Nelson county line. The FBI later reported that those remains were not of Rogers and their efforts remained largely quiet up until the latest flurry of activity this week.

Just a year after Rogers died, on Nov. 19, 2016, her father was shot and killed on family property near Bluegrass Parkway, and his killing also remains unsolved.

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FBI suspending Crystal Rogers efforts due to incoming weather, 'multiple items of interest' found - WLKY Louisville

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Republican AGs urge Garland to appeal ruling that determined illegal reentry law to be discriminatory – Fox News

Posted: at 12:02 am

EXCLUSIVE: Twenty Republican state attorneys general are urging Attorney General Merrick Garland to appeal a federal judges ruling that struck down an illegal reentry law after finding it has a "disparate impact on Latinx persons."

"We appreciate that you recently filed a notice of appeal, preserving your ability to defend the law on appeal. We now urge you to follow through by defending the law before the Ninth Circuit and (if necessary) the Supreme Court," the letter from the attorneys general said. "We ask that you confirm expeditiously DOJs intent to do so.

FEDERAL JUDGE DISMISSES ILLEGAL REENTRY CASE, SAYS LAW HAS 'DISPARATE IMPACT ON LATINX PERSONS

Section 1326 makes it illegal for someone who has been deported or denied entry to the U.S. to reenter, punishable by fines and possible jail time.

Federal Judge Miranda Du was ruling in a case concerning someone charged with illegal reentry who had been found in the country illegally in 2019 after having been deported multiple times. She accepted the arguments from the defense that the law is racially motivated and discriminatory.

"Because [the defendant] has established that Section 1326 was enacted with a discriminatory purpose and that the law has a disparate impact on Latinx persons, and the government fails to show that Section 1326 would have been enacted absent racial animus x the court will grant the motion," the ruling said.

SCOTUS REMAIN IN MEXICO RULING' MARKS LATEST IMMIGRATION DEFEAT FOR BIDEN ADMINISTRATION

The case cited Border Patrol data that over 97% of people apprehended at the U.S.-Mexico border in 2000 were of Mexican descent, and 87% in 2010. The government did not dispute disparate impact, but instead attributed it to geography and proportionality noting that Mexico borders the U.S. as well as the history of Mexican employment issues and other factors.

The government also argued that it makes sense that Mexican citizens make up a high percentage of illegal entry defendants "given the suggestion that they made up a disproportionately high percentage of the overall illegal alien population."

"The court is not persuaded," Du wrote.

FEDERAL JUDGE BLOCKS BIDEN ADMIN'S ICE RULES THAT NARROWED ILLEGAL IMMIGRANT ARREST PRIORITIES

Instead, Du accepted the argument that the legislative history shows that racism and eugenics were motivating factors in the passage of legislation in 1929, which formed the basis for the 1952 legislation. She also said there has "been no attempt at any point to grapple with the racist history of Section 1326 or remove its influence on the legislation."

As a consequence, the judge ruled that the law violated the equal protection clause of the Fifth Amendment, and therefore threw out the indictment.

The attorneys general cited the ongoing crisis at the border including comments by officials that the situation is "unsustainable" -- and warned that if the DOJ did not act on appeal, then it would only get worse, calling a failure to appeal "an announcement that would, in effect, tell already-deported aliens that they are free to try again."

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"Indeed acquiescing in the district courts opinion would be tantamount to announcing legalization of illegal re-entry," they write.

They note that Garlands DOJ has filed a notice of intent to appeal, but said they have reason to worry considering what they see as a "surrender" by the administration at the border.

"The States should not have to worry about the administration doing its job and defending federal law. But, given this administrations habit of policymaking through the expedient of strategic surrender, the States have reason to fear."

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Republican AGs urge Garland to appeal ruling that determined illegal reentry law to be discriminatory - Fox News

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Coriell Institute Awarded $4.6 Million from National Human Genome Research Institute to Maintain Biobank – Newswise

Posted: at 12:01 am

Newswise The National Human Genome Research Institute has renewed its collaborative agreement with the Coriell Institute for Medical Research. For another five years, Coriell will continue to manage the NHGRI Sample Repository for Human Genetic Research, a collection of cell lines and DNA for use in research around the world.

The NHGRI Sample Repository for Human Genetic Research is a treasure for genetics research and its an honor to be selected to continue our role as the collections host, said Jean-Pierre Issa, MD, President and CEO of Coriell. The samples contained in this collection were used in several of the mostimportant studies in human genetics and its focus on increasing diversity in human genetics research is potentially transformative.

This collection was first established by NHGRI in 2006 as a public resource for scientists investigating human genetic variation carried by populations living around the world. Fifteen years later, it is still considered one of the most important resources in human genetics and genomics.

The NHGRI Sample Repository for Human Genetic Research contains unique collections of samples such as the landmark International HapMap and 1000 Genomes Projects, which are known for diverse DNA and cell lines characterized by large-scale genomic data.

The future of the NHGRI Repository is exciting, said Laura Scheinfeldt, PhD, Coriells Director of Repository Science and Principal Investigator of the collection. This important collection has supported the human genetics community for many years and will be an important resource to promote the inclusion of global genetic and genomic variation in studies of human health and disease for years to come.

In 2019, the NHGRI Repository joined the Human Pangenome Reference Consortium with Coriells contribution being led by Dr. Matthew W. Mitchell, the Co-Principal Investigator of this collection. This nationwide collaboration was formed in 2019 by distinguished researchers in the field of human genomics to improve the human genome reference sequence and continues to be an important collaborative effort for the NHGRI Repository team at Coriell moving forward.

Over the past five years, the NHGRI Repository has distributed tens of thousands of biospecimens to 47 countries around the world.

About the Coriell Institute for Medical Research

Founded in 1953, the Coriell Institute for Medical Research is a nonprofit research institute dedicated to improving human health through biomedical research. Coriell scientists lead research in personalized medicine, cancer biology, epigenetics, and the genomics of opioid use disorder. Coriell also hosts one of the world's leading biobankscomprising collections for the National Institutes of Health, disease foundations and private clientsand distributes biological samples and offers research and biobanking services to scientists around the globe. To facilitate drug discovery and disease study, the Institute also develops and distributes collections of induced pluripotent stem cells. For more information, visit Coriell.org.

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Studies Show Benefits of Long-Read Sequencing in Toughest Rare Disease Cases – GenomeWeb

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NEW YORK Long-read sequencing can successfully provide diagnoses in previously intractable hereditary disease cases, according to recent studies, suggesting that long-read, whole-genome sequencing is on track to become the first-line genetic test of choice.

Last month, researchers led by Danny Miller and Evan Eichler of the University of Washington described the use of adaptive sampling on the Oxford Nanopore Technologies GridIon platform to identify previously undetected, disease-causing genomic variation in individuals who remained undiagnosed after a complete clinical genetics work-up. In some cases, this included exome sequencing or short-read whole-genome sequencing.

The team used a targeted approach to find pathogenic or "likely pathogenic" variants in six out of 10individuals with suspected Mendelian conditions and variants of unknown significance in two more.They also were able to identify previously known single-nucleotide variants, copy number changes, repeat expansions, and even methylation differences seen in prior testing of 40 patients, providing more detail on structural changes in about 20 cases.

"There's a cost in genetics of running multiple tests and bringing the patient back," Miller said. "This tech can simplify that process and make the analysis a lot more straightforward. It's beneficial for patients and families and for the healthcare system."

Their results, published in the American Journal of Human Genetics, are congruous with similar studies at the HudsonAlpha Institute for Biotechnology and Children's Mercy Hospital, each using long-read technology from Pacific Biosciences.

"We do find thatas presented here, too, that there is clinically significant genetic variation that is undetectable by short-read sequencing," said Tomi Pastinen, director of the Genomic Medicine Center at Children's Mercy. His team is working on a study of more than 200 cases and presented data on 100 patients at this year's American College of Medical Genetics and Genomics virtual conference. The data out so far are evidence that current methods of genetic testing for rare diseases, whether by short-read sequencing or microarrays, are incomplete, he said.

Pastinen suggested that the targeted approach used in the UW-led paper could be used as "a follow-up tool" for other tests or strong clinical hypotheses. "It's not aquantumleap," he said. "But they testeda number ofpositive controls,which isa nice feature."

Miller said the targeted method used by his team was more proof of concept and that long-read WGS "will eventually be theonly clinical genetic test we do," he said. "Because it's a single dataset, you can query multiple times."

Yet many challenges remain, including developing bioinformatics tools andreference datasetsand building a case for reimbursement.

As the name implies, long-read sequencing provides the ability to analyze longer stretches of the genome without having to piece them together from smaller parts, including regions where short reads crap out, such as repetitive regions. Those regions often contain so-called structural variants and many studies have shown that they are associated with disease, including cancers.

Long reads have been effective in detecting SVs but they have their drawbacks. Generally speaking, they offer lower throughput than short-read platforms and, until recently, had significantly lower single-read accuracy.

And they're not without blind spots. A recent study from the Human Genome Structural Variation Consortium published in the American Journal for Human Genetics analyzed SVs in samples from the 1000 Genomes Project. The study found that assembly-based methods of sequencing, which often are based on long reads, missed some large copy number variants that are detected with other methods.

Still, many researchers, like Miller, believe long read WGS is the future of clinical genetic testing, and the companies that make the technologies, namely PacBio and Oxford Nanopore, are driving proof-of-concept studies. In addition to its collaborationwith Children's Mercy, PacBio is working with Rady Children's Hospital in San Diego on a similar study. It has also partnered with Invitae to build an instrument for clinical long-read WGS. Oxford Nanopore, over in the UK, is developing its "Q Line" of instruments intended for clinical use.

Miller, a resident physician in the UW division of medical genetics with a doctorate in physiology, said he developed his chops on the Oxford Nanopore platform sequencing fruit fly genomes but "always had an eye on what I could do with humans, eventually."

The low barrier to entry made his study an "easier pitch, from the perspective of me, at my training level," he said. While Oxford Nanopore also offers ultra-long reads of up to 4 Mb, Miller said he was fine working with 50 kb to 60 kb reads. "They're very useful and I think they will be useful clinically."

For the study, Miller and his team used a special feature of the nanopore platform: the ability to preselect genomic targets and have the device spit out any reads that don't match. This "read-until" feature was introduced in 2014 but unlocked last year for targeted sequencing.

Miller said it's a fast and "straightforward" way of targeting sequences without using hybridization or amplification chemistries. "You just go to a genome browser, type in a gene, get the coordinates, and put it in a BED file," he said. "Then you're done." Moreover, it's pretty cheap. When purchasing reagents at scale, nanopore sequencing costs about $650 per sample, he said, compared to about $1,000 for short-read sequencing.

Pastinen said he wished the authors had compared the "real-life benefits of targeting reads versus doing Oxford Nanopore whole-genome sequencing."

One advantage of WGS is that it's unbiased, said Susan Hiatt, first author of the HudsonAlpha study, published in April in Human Genetics and Genomics Advances. "Whole-genome long-read sequencingis the best way to go for sure. You cando this targeted sequencing, too, if you know where to look."

In the study, her team found disease-causing structural variants in two out of six cases. "We had a guess there was some sort of structural variant, but we weren't looking for a particular gene or set of genes," she said.

"It's only six cases, so we don't know if that's the real diagnostic rate," Hiatt noted. Establishing a diagnostic yield will be a critical next step for the technology. Her team will be looking at another 200 probands over the course of the year using PacBio's platform. Already, they're seeing results. "It's showing us that we are going to find a significant number of variants," she said.

Finding variants is one thing, but putting them in context will be its own challenge. In the UW study, Miller said they were allowed to tell patients and their providers the study resultsif they wanted to receive them. "We clinically validated some of these findings, but in all cases, the institutional review board did not allow us to interpret the results," he said. "It's going to get even more challenging when we dowhole-genome sequencingand find novelstructural variants. How do you explaina complexexpansion of a repeat that altersmethylation? There will bea lot of interesting genetic counseling with long-read sequencing."

Improving the amount and availability of reference data will be key to making calls about clinical significance, Pastinen said. "In principle, you need reference data on similarly targeted but nonaffected samples," he said. "The data resources are not there yet for a robust rollout of all variants. Most of our reference data is our own data of a very small number of individuals. It's insufficient for high production level analysis."

But WGS had the benefit of generating reference data across the genome, which can be used for future cases. The All of Us project will be generating some long-read data from a "normal" population, but Pastinen said there needs to be more data sharing.

Bioinformatics tools are yet another resource the field still needs to develop. In addition to providing more data, HudsonAlpha's additional cases are giving the researchers a chance to experiment with different bioinformatics pipelines.

"There's a lot of different options out there. This will get us comfortable enough to say, 'This is the way we're going to go, so now we can scale it up,'" Hiatt said. So far, a lot of their pipeline comes directly from PacBio, including their SV caller.

And, of course, the field needs to do the ultimate head-to-head comparison with short reads, which would be a start to solving the problem of reimbursement.

"There hasnt, to my knowledge, been a systematic study comparing the incremental diagnostic rate of long reads over short reads," Miller said. "Thats probably what we really need to get payors to reimburse for the test."

"I don't know how insurance will respond," he added. "Justshowingwe can solve rare disease cases, I don'tknow if that's enough."

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Another tool in the box: Creation of a molecular dimmer switch advances gene editing – HDBuzz

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By Dr Leora Fox August 30, 2021 Edited by Dr Sarah Hernandez

A team of scientists recently created an innovative genetic system where a drug taken by mouth could be used to control the action of a gene editor, like those used in CRISPR systems. This has useful applications for research studies in cells and animals, and perhaps most importantly, could lead to improvements in the safety and accuracy of future gene therapies in humans. The technology can be applied broadly for studying genes and diseases, and was developed by researchers with HD expertise, incorporating a drug that is relevant to HD. Though actual clinical trials are a long way off, the company that has recently licensed the technology has an existing interest in HD.

Although the methods for delivery of gene therapies have improved vastly in recent years, it hasnt yet been possible to control the actions of those therapies once they reach their targets in the brain or other parts of the body. Ideally, when modifying human genetics, wed want to be able to fine-tune things like the location of the genetic change, the amount of change that occurs at once, and the ability to stop the change in surrounding cells if it proves harmful those last two have proved to be a particular challenge in gene editing, until now.

A recently developed genetic switch system, dubbed Xon, addresses some of these challenges in a novel way. It was created by a team of scientists led by Beverly Davidson at the Childrens Hospital of Philadelphia, joined by researchers at the pharmaceutical company Novartis. The idea behind Xon was to create a gene editing technology that could be precisely delivered and then controlled over time using a drug that acts like an on/off switch.

Imagine a red traffic light that is on all the time, and can only be disabled with a special tool. Theres no way to move forward until the red light turns off. With the Xon system, scientists can put a stoplight in front of any gene, by inserting the gene and the stoplight together into a genetic package and delivering it to cells in a dish or in a living animal. The new gene is present but inactive, meaning it cant produce messages or proteins, until the stoplight is removed. But when a particular drug reaches the cell, it acts as the tool that turns off the genetic stoplight, activating the gene.

The reason that this is an exciting scientific innovation is that the Xon system allows researchers to insert a gene and turn it on and off by simply adding a drug to a dish of growing cells, or by giving the drug to a research animal. This could be a new way to understand what happens when there is too much or too little of a given gene or protein, or to create a disease model to easily explore genetic interventions at different time points during aging.

In a recent publication in the journal Nature, Davidsons team tested the technology using a variety of genes involved in neurodegenerative diseases and cancers to show that their levels could be controlled based on when and how much of the stoplight-disabler drug was given.

Even more interesting is the potential application of the Xon system to technologies like CRISPR and the future of gene editing as a therapeutic. This recent paper demonstrates the ability of the Xon system to be combined with CRISPR-Cas9 technology, for more precise control of CRISPR editing using a drug fed to mice. Davidsons team demonstrated this using an artificial gene that can make a mouses liver cells glow green. But ultimately the hope is that it could be applied to human therapies.

A system that can help us gain better control of CRISPR gene editing is an exciting prospect because it provides more hope of safely adapting this technology for future medicines. This is not currently possible for most diseases, because direct, irreversible changes to human DNA can have drastic consequences. We wrote recently about the first ever successful safety trial of a CRISPR drug for a human disease that commonly affects the liver. Although it would be marvelous in theory to cut out or correct the HD gene in people, the knife-like CRISPR system almost always leads to additional unwanted changes in other genes. This is why weve so often emphasized that gene editing needs to come a long way before we can apply it to the treatment of human brain cells, which cant be regenerated like cells in the liver.

Coupling Xon with a CRISPR-Cas9 system that targets a disease gene (like the HD gene) would mean that an oral drug could turn the gene editor on and off. The dose could also be adjusted to control the amount of gene editing not just acting as a tool to disable the red stoplight, but also acting as a dimmer switch for precise regulation. Most importantly for safety, if anything went awry, the treatment could be stopped to prevent further changes to their DNA. Right now this is all theoretical, because the Xon system and other gene editing dimmer switches are in early developmental stages. Nevertheless, this publication hints at the possibility of applying it to therapies in people, and Novartis has licensed the Xon technology.

First and foremost, we know that HD is caused by a change to a single gene, so it has always been a prime candidate for genetic therapies, and dozens of researchers and companies worldwide are developing innovative solutions to treat HD at its source. HDBuzz (and HD researchers) always have an eye out for new technologies that improve upon existing methods. Furthermore, the leaders of the team that published the recent Nature paper are respected HD researchers who have devoted much of their careers to the development of gene therapies.

However, the main reason this publication has popped up as news for the HD community is that the Xon system actually relies on an existing drug to flip the gene editing switch and that drug is none other than branaplam. Yep, branaplam, the oral drug developed to treat children with SMA, which Novartis will soon be testing in clinical trials for adults with Huntingtons disease.

This does not mean that Xon gene editing has any part in upcoming trials for HD. It simply means that branaplam, a drug with genetic cut-and-paste abilities, forms part of an elegant new system that can be adjusted to control the activity of any gene scientists want to study. Dimmer switch systems for gene editing could potentially be designed to use a completely different drug, but in these early experiments, Xon and its precise control with branaplam has stood up to many tests of flexibility and accuracy.

The Xon system is a really cool early-stage technology, and though its not ready to be applied to human treatments, it is a novel element of the gene editing toolbox. Furthermore, it was created by researchers with HD expertise, and has now been licensed by a major pharmaceutical company which is already invested in HD therapeutics. That bodes well for its continued development in the study and potential treatment of HD and related genetic disorders.

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Another tool in the box: Creation of a molecular dimmer switch advances gene editing - HDBuzz

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