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Daily Archives: April 21, 2017
Apparently the Trump Administration Is Interested in Monetizing the Moon – Men’s Journal
Posted: April 21, 2017 at 2:03 am
Its been bad news for the funding of many federal agencies since Donald Trump took office, but one of the bright spots in the gray new Washington cloud settled overhead is that NASAs budget escaped comparably intact, suffering only cuts to climate change research. As David Axe reported for Motherboard, Where Trump wants to reduce the EPAs funding by a third, effectively gutting the agency, he's proposing a mere $200 million reduction to the National Aeronautics and Space Administration's current $19.3 billion budget.
A new report points that the Trump administration is leaving NASA intact because it believes it has significant potential to make money.
Thanks to internal communications between NASA and Trumps space transition team... we have some clues as to why Trump seems determined to keep the space agency mostly intact, writes Axe. The administration seems to be very interested in NASA's moneymaking potential.
As far as the Trump Administration is concerned, the money-making value of NASA seems to be tied up in two prominent segments of research and activity: tech development and the moon.
It appears NASA saved their funding by effectively convincing the Trump administration that it was on their side by suggesting that the efforts eventually make it to market, for other sectors to benefit from their work. In a transition memo(scroll down), NASA explains that their funding is split between in-house research efforts and contracting, which private innovation proponents are likely to be happy to hear. NASA further says that once technology reaches maturity, it is often shared with the public. From the memo:
NASA pursues technology development to support both the national innovation system (industry, academia, other government agencies, and the general public) and specific NASA mission requirements As STMD research and technology (R&T) efforts mature, appropriate technologies are transferred to industry and commercialized through multiple programs and approaches to benefit a wide range of users ensuring the nation realizes the full economic value and societal benefit of these innovations.
NASA further clarified that they spread this research "to the broader aerospace community, while protecting our industry partners proprietary interests." In other words, they seek to release everything they can to the public that wont harm a private sector partners proprietary interests.
And while NASA cautions the administration that their primary purpose is academic, they do hint that in the pursuit of the academics, theres something financial to be gained.
Significant portions of the document were dedicated to outlining how and where research was progressing on finding resources on the that would be collectable and, potentially, sustain human life either for the purpose of a mining outpost or maybe colonization one day.
But whether any of that collection could one day make money is an international law question. To extract valuable resources from the Moon for commercial purposes would seem to at least bump up against the 1967 Outer Space Treaty signed by the United States, Russia (then USSR), and 90 other countries, Motherboard explains. The document states: "The exploration and use of outer space, including the Moon and other celestial bodies, shall be carried out for the benefit and in the interests of all countries, irrespective of their degree of economic or scientific development, and shall be the province of all mankind."
So perhaps those moon mining dreams are dead in the water, as the president would never want to violate international law for profit.
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Extension to host seminar on GMOs – messenger-inquirer
Posted: at 2:02 am
Fourth-graders might be on to something.
Once, during a school presentation, Paul Vincelli asked a group of students what they would do with genetic engineering.
One said he'd make broccoli taste like chocolate. Another said she'd make some foods more nutritious for poor people.
"They've got the right idea," he said with a laugh. "I tell audiences (genetic engineering) is like copying and pasting a sentence in a document on your computer."
But Vincelli, Extension professor of plant pathology at the University of Kentucky College of Agriculture, doesn't try to convince anyone to be in for or against genetic engineering he just presents the facts.
He'll do so at the Food Myths and Misconceptions seminar and Q&A at 6 p.m. Tuesday and at noon Wednesday in the Advanced Technology Center's Chandler Conference Room at Owensboro Community and Technical College, 4800 New Hartford Road. It is presented by the Daviess County Cooperative Extension Service.
Vincelli's presentation will cover the scientific aspects of genetic engineering in foods genetically modified organisms, or GMOs that is, the process of introducing new DNA to a plant or animal to alter its genome. Newer technology allows genome editing, a more precise method that can add, remove or substitute specific traits and target specific locations within the genome.
"GMO science is a very broad topic of study," Vincelli said during a phone interview from Fresno, California. He was there to present to the U.S. Department of Agriculture and California State University. He is also published in research journals.
"There are multiple and complex factors, but I like to focus on what we do and don't know about GMOs, and the risks and benefits."
A recent good example of GMO science, he said, lies in East Africa, where the woody root cassava is a foundational part of the diet. When a virus called brown streak disease threatened the food supply, modifying cassava to be disease-resistant was the answer.
Last May, the National Academies of Sciences, Engineering and Medicine released a report stating while genetic alteration can have unintended consequences, their review of about 900 studies and years of disease data shows no increase in health risks due to the consumption of GMOs.
Many non-GMO advocates, though, suggest GMOs pose environmental, human health and economic problems. Theres an ongoing debate among science experts on whether or not glyphosate is linked to cancer, the report states. The herbicide is often used with GMOs and was made popular when patented in the 1970s and sold as Roundup by the agricultural biotechnology corporation Monsanto.
Its widespread use might have weakened its ability to control weeds, which led Monsanto to create Roundup Ready soybean seeds in 1996, followed by corn. Roundup Ready crops are resistant to herbicides, thus farmers can spray for weeds without damaging their crops.
I always say it's not a sustainable weed control approach, but theres a lot of interest in the food system among urban and suburban audiences, and theres much more to it than Roundup Ready, Vincelli said.
"People would like to know what science says about all of these things, so well take a critical look the research and I think we'll have a rich discussion," he said. "I aim to be fair to all sides and just tell it like I see it.
Angela Oliver, 270-691-7360, aoliver@messenger-inquirer.com
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Extension to host seminar on GMOs - messenger-inquirer
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Disease-associated genes routinely missed in some genetic studies … – Penn State News
Posted: at 2:02 am
UNIVERSITY PARK, Pa. Whole-exome DNA sequencing a technology that saves time and money by sequencing only protein-coding regions and not the entire genome may routinely miss detecting some genetic variations associated with disease, according to Penn State researchers who have developed new ways to identify such omissions.
Whole-exome sequencing has been used in many studies to identify genes associated with disease, and by clinical labs to diagnose patients with genetic disorders. However, the new research shows that these studies may routinely miss mutations in a subset of disease-causing genes associated with leukemia, psoriasis, heart failure and others that occur in regions of the genome that are read less often by the cost-saving technology. A paper describing the research appeared online April 13 in the journal Scientific Reports.
Although it was known that coverage the average number of times a given piece of DNA is read during sequencing could be uneven in whole-exome sequencing, our new methods are the first to really quantify this, said Santhosh Girirajan, assistant professor of biochemistry and molecular biology and of anthropology at Penn State and an author of the paper. Adequate coverage often as many as 70 or more reads for each piece of DNA increases our confidence that the sequence is accurate, and without it, it is nearly impossible to make confident predictions about the relationship between a mutation in a gene and a disease. In our study, we found 832 genes that have systematically low coverage across three different sequencing platforms, meaning that these genes would be missed in disease studies.
The researchers developed two different methods to identify low-coverage regions in whole-exome sequence data. The first method identifies regions with inconsistent coverage compared to other regions in the genome from multiple samples. The second method calculates the number of low-coverage regions among different samples in the same study. They have packaged both methods into an open-source software for other researchers to use.
Even when the average coverage in a whole-exome sequencing study was high, some regions appeared to have systematically low-coverage, said Qingyu Wang, a graduate student at Penn State at the time of the research and the first author of the paper.
Low-coverage regions may result from limited precision in whole-exome sequencing technologies due to certain genomic features. Highly-repetitive stretches of DNA regions of the genome where the same simple sequence of As, Ts, Cs and Gs can be repeated many times can prevent the sequencer from reading the DNA properly. Indeed, the study showed that at least 60 percent of low-coverage genes occur near DNA repeats. As an example, the gene MAST4 contains a repeated sequence element that leads to a three-fold reduction in coverage compared to non-repeating sequences. Even when other genes have sufficient coverage, this region of the MAST4 gene falls well below the recommended coverage to detect genetic variations in these studies.
One solution to this problem is for researchers to use whole-genome sequencing, which examines all base pairs of DNA instead of just the regions that contain genes, said Girirajan. Our study found that whole-genome data had significantly fewer low-coverage genes than whole-exome data, and its coverage is more uniformly distributed across all parts of the genome. However, the costs of whole-exome sequencing are still significantly lower than whole-genome sequencing. Until the costs of whole-genome sequencing is no longer a barrier, human genetics researchers should be aware of these limitations in whole-exome sequencing technologies.
In addition to Girirajan and Wang, the research team at Penn State includes Matthew Jensen, graduate student; Naomi S. Altman, professor of statistics; and Cooduvalli Shashikant, professor of molecular and developmental biology, all of whom are also members of the Penn State Huck Institutes of the Life Sciences Bioinformatics and Genomics Program. The work was funded by the March of Dimes Foundation, the U.S. National Institutes of Health, the Brain and Behavior Research Foundation, the Huck Institutes of the Life Sciences, and the Penn State Experiment Station.
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Genetic testing could hold the key to reduce adverse events in heart stent implantation – ETHealthworld.com
Posted: at 2:02 am
by Amrita Surendranath, Masters in Human Genetics, Xcode Life Sciences
In 2010, the US Food and Drug Administration (FDA) issued a warning on the box of the anti-clotting drug Clopidogrel that patients who do not metabolize the drug will not receive the full benefits of the drug. This, in essence, is a landmark that highlights the importance of personalized care in the emerging field of precision medicine. In retrospect, Clopidrogels failure among certain patients hardly seems surprising: patients are genetically diverse, and such variation affects patients response to particular therapies. Roughly 75% of the U.S. population does not metabolize medications normally and 2.2 million severe Adverse Drug Events (ADEs) occur in the U.S. every year. Genetics can account for 20-95% of the variability in an individuals response to drugs. Medicare fined three-quarters of eligible hospitals for re-admissions in 2014. Current FDA guidance recommends that Drug-gene interactions should be considered similar in scope to drug-drug interactions. Precision medicine takes advantage of the genetic diversity that exists to tailor treatments to those patients who are most likely to respond.
Clopidogrel is a widely used anti-clotting drug and according to Dr. P. Manokar, MD, DM, Professor of Cardiology, Sri Ramachandra University Clopidogrel is like a panacea of all cardiac and vascular diseases from Stroke prevention to Peripheral artery disease to coronary Interventions. It is the essence of pharmacotherapy for all Vascular Disease Scenarios. When the outcomes of treatment are poor, it could prompt some patients from taking the treatment while the condition being treated could turn worse, wasting precious time, effort and money.
Dr. Abraham Ooman, a leading Cardiologist, has also shown interest in genetic testing, stating that here is a need for genetic testing to determine the response to Clopidogrel, especially during high risk cardiac interventions like left main stenting, however, he adds a quick note of caution, but clinical studies are unclear about how effective the current methods are. When the approach to care is evidence based instead of resorting to a trial and error method of prescribing medications, it could help avoid side effects associated with drug use and could, possibly, lower health care costs. In recognition of the promise shown by precision medicine, Ex-President of the United States, Barack Obama, in 2015, announced a nationwide research called the Precision Medicine Initiative for conditions associated with cardiovascular disease, neurodegenerative disease, cancer and autoimmune disorders. In Obamas words, most medical treatments have been designed for the average patient, treatments can be very successful for some patients but not for others.
Though there have been considerable strides in the treatment of cardiovascular disease, cardiovascular disease related death is still one of the most common cause of death. This creates a need to utilize precision medicine to identify patients who would benefit from the treatment provided. As Dr. Manokar says It is very difficult to predict who responds to clopidogrel unless you have an event as a consequence of clopidogrel resistance. You begin a search with your backs to the wall situation. Testing would allay the anxiety of the Doctor and the patient equally
The importance of testing for responders, however, lies in the options that are available, as Dr. Manokar says, The other treatment options are tricky. They come with a whole bag of indications and contraindications which make the options difficult to choose. Both Ticagelor and Prasugrel are niche molecules but need huge brainstorming before choosing as an alternative to Clopidogrel. The enthusiasm shared by doctors and the regulators are shared by drug companies too with 28 percent of drugs that were approved by the FDA in 2015, considered to be precision medicine based therapies.
The concept of genetic testing is not new and is an essential medical tool that has been used by the medical community for decades to look deeper into the human body for myriad determinations. Chromosomes are investigated for carrier testing, newborn screening, prenatal diagnosis, diagnostic testing, paternity, genealogy and forensics testing. So, testing for responders is a natural progression and Testing is always cost effective. It offers intangible benefits in terms of allaying anxiety, long term outcomes, more than the tangible benefits in terms of choice of drugs and duration of therapy, said Dr. Manokar. Though, he further stated that the additional cost is an important determinant of the number of patients that we would test routinely. It is important also with respect to Ticagelor switch since it is the most expensive drug in this group.
Clinically, the use of pharmacogenetics could potentially include vast areas like new drug development, drug discovery research, the genetic testing of patients and clinical patient management. The ultimate aim of pharmacogenetics is to predict genetic response of patients to a specific drug to deliver the best possible medical treatment. By predicting the drug response of an individual, it will be possible to increase the success of therapies and reduce the incidence of adverse side effects. Personalized medicine is the logical way forward, however, it should pass the necessary scientific scrutiny of clinical trials, said Dr. Abraham stressing the need to accept this aspect of medical science as the way ahead.
A single method of treatment for everyone is unrealistic in the current understanding of medical science because of the complex interplay between genes, cell metabolism, proteins and environmental influences. As Dr. Manokar puts it, future of pharmacology is going to be pharmacogenomics. Patient centric medicine and genome tailored pharmacotherapy will be the norm rather than the exception.
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Two UChicago Medical Studies Among 2016’s Best Research Papers – The Chicago Maroon
Posted: at 2:02 am
Two University of Chicago Medicineled studies were selected by the Clinical Research (CR) Forum as among the top three best clinical research papers of 2016.
CR Forum is a national organization of senior researchers and leaders in clinical thought from leading academic health centers, pharmaceutical firms, information technology, and nonprofits.
The Herbert Pardes Clinical Research Excellence Award is the CR Forums highest honor, and comes with a $5,000 cash prize. This year, it was awarded to geneticist Carole Ober, Ph.D., University chairman and professor of human genetics, and immunologist Anne Sperling, Ph.D., University associate professor of medicine, for their study, Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children, published August 4, 2016, in the New England Journal of Medicine.
The study examines environmental risk factors for susceptibility to asthma and allergies, comparing two U.S. farming populations: the Amish of Indiana and the Hutterites of South Dakota.
The Distinguished Clinical Research Achievement Awards honor two studies that demonstrate creativity or innovation, and whose works have an immediate impact on the well-being of patients. One of these was granted to University professors Bhakti Patel, M.D., and John P. Kress, M.D., for their study titled Effect of Noninvasive Ventilation Delivered by Helmet vs. Face Mask on the Rate of Endotracheal Intubation in Patients with Acute Respiratory Distress Syndrome.
The study found that helmet ventilation, as opposed to a traditional face mask, dramatically reduced the chances of patients needing a tube ventilator, and made patients 20 percent more likely to survive Acute Respiratory Distress Syndrome.
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Two UChicago Medical Studies Among 2016's Best Research Papers - The Chicago Maroon
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Arkansas Fights to Execute Two Men Without Testing DNA Evidence That Could Exonerate Them – The Intercept
Posted: at 2:02 am
Damien Echols neverplanned to come back to Arkansas. These days, I try to look forward, he wrote in his 2012 memoir, Life After Death.Im tired of looking back. After spending half his life on Arkansass death row he was finally released in 2011 Echols was sick to death of his claim to fame as one of the West Memphis Three. Its a title Id prefer never to hear again, he wrote. It does nothing but remind me of hell.
Echols was wrongfullyaccusedof murdering three 8-year-old boys whose bodies were discovered in the woods in rural Arkansas in 1993. It was the tail end of a bizarre era in American criminal justice, a wave of public hysteria known as thesatanic ritualabuse panic, in which numerous people were wrongly sent to prison for lurid and in some casesnonexistent crimes against children. Echols, who grew up as a misfit in his small Arkansas town, was accusedof being amember of a satanic cult, based on such proof as the fact that helistened to heavy metal, along with the coerced confession of one of his teenage co-defendents, who was mentally disabled.The case inspired multiple documentaries, which transformed Echolss plight into a cause clbre. Hewas grateful for the support, but even on death row the attention eventually took a toll. My entire life had been exposed for anyone and everyone to examine, he wrote. Every day I received letters from people who did nothing but ask the most intimate aspects of my life. There was one letter, though, that disarmed Echols, from a woman who apologized for invading my privacy by seeking me out. That woman, Lorri Davis, later became his wife.
Today Echols lives in New York City, a place that giveshimthe gift of anonymity. But on Friday, April 14, Echols stood on the steps of the Arkansas State Capitol, with Lorriby his side. It was the first time that Echols had returned to the statewhere he was supposed to be executed, a place that filled him with fear. But he felt he had no choice: After nearly 12 years without an execution in the state, in late February Gov. Asa Hutchinson had signed death warrants for eight men, who were to die in pairs on four separate nights before the states supply of a key drug it planned to use as part of its lethal injection cocktail passed its expiration date. These were men Echols had lived with for almost 20 years. When the Arkansas Coalition to Abolish the Death Penalty invited him to speak at a rally at the Capitol, planned for Good Friday, he struggled. My first thought was I cant. I cant do this, he told reporters. But he knew that if he did nothing, I would haveto live the rest of my life knowing that I didnt raise a hand to help these people.
Former Arkansas death row inmate Damien Echols, center, back to camera, speaks at a rally opposing the states upcoming executions, on the front steps of Arkansass Capitol, April 14, 2017, in Little Rock.
Photo: Stephen B. Thornton/The Arkansas Democrat-Gazette/AP
Pale and tattooed up to his neck, Echols wore a black sleeveless shirt, a black Yankees cap, and sunglasses, which he wears around the clock. Echols spent much of his last decade of incarceration insolitary confinement, which he says destroyed his eyesight, making him acutely sensitive to light. Standing to the side as the rally kicked off, a huddle of press and onlookers crowded around Echols, shoving microphones and cameras in his face and snapping photos of the actor Johnny Depp, a longtime friend and supporter who showed up with him. In the two days before he arrived in Little Rock, Echols told reporters, hed slept no more than an hour. He was constantly on the verge of a panic attack, unable to breath, just realizing that Im about to come back here, where they tried to kill me.
The afternoon was hot and muggy. Volunteers in blue T-shirts handed out water bottles. Some held signs over their heads to block the sun. In the crowd, a woman held a posterboard quoting former Arkansas Gov.Winthrop Rockefeller, who once commuted the sentences of every man on death row, saying, What earthly mortal has the omnipotence to say who among us shall live and who shall die? Another sign read Governor Hutchinson: Dont Do This.
At the podium, Rizelle Aaron, president of the Arkansas State Conference of the NAACP, decriedthe hypocrisy of Bible-thumping officials who call themselves pro-life.We allow politicians to come into our churches for an opportunity to profess their faith and commitment to God in the hopes of gaining our votes, he said. They quote scripture from our pulpits andmany of them honor God with their mouths. But their hearts are far from God.Waiting for Echols to speak, a 19-year-old woman named Drew, from Fort Smith, Arkansas, held a sign with his name and a heart underneath. Today she is just one year older than Echols was when he was arrested. I was young at the time, but I definitely remember [the case], she said, recounting the details. Echols and his co-defendants were targeted because they were outcasts, she said, calling Echols a living testament to why the death penalty is so wrong.
Taking the mic, Echols described his fear upon returning to Arkansas and his disgust at the bureaucratic labyrinthof corruptionthat passes for a justice system here. Even after DNA evidence was found to exclude him and his co-defendants, Echolssaid, they still kept trying to kill me, keeping him on death row for two more years.
After the rally, a group of activists and reporters entered the Capitolto deliver boxes of petitions to Hutchinsons office 157,593 signatures,to be exact. Furonda Brasfield, head of the Arkansas Coalition to Abolish the Death Penalty, gave the governors spokesperson, J.R. Davis, a copy of Echolss book. And Paris Powell, an exoneree from Oklahoma a state notorious forsloppyattempts to push through questionable executions told Davishe spent many years on death row as an innocent man. I came to this state just for this reason, he said.
But the governor remained unmoved. Lawyers for the state spent Easter weekend scrambling to respond to subsequentlegal rulings blocking his execution plans. On Easter Sunday, Davistook to Twitterto bickerwith famed anti-death penalty nun Sister Helen Prejean, who has been relentlessly critical of his boss.Nonetheless, by the night of Monday, April 17, a stay of execution was in place for Bruce Ward, who had been set to die that evening. Don Davis was not as lucky. He had already been moved to a cell adjacent to the death chamber at the Cummins Unit, some 80 miles southeast of Little Rock.
Echols was back in New York on Mondayknight, posting on Twitter and Facebook. In interviews, Echols repeatedly described how Don Davis, who was tormented by the crime he committed, brought him food and watched his back. Without the following people I wouldnt be here today, Echols writes in the acknowledgment pages of his book, listing a handful of fellow death row prisoners. Davis is included, along with Marcel Williams, who faces execution on April 24.
J.R. Davis, spokesperson for Arkansas Gov. Asa Hutchinson, speaks after the news that the U.S. Supreme Court stayed the scheduled April 17, 2017, execution of Don Davis.
Photo: John L. Mone/AP
The plan to killDavis became embroiled in chaos and confusion.After the Arkansas Supreme Court ordereda temporary restraining order earlier that day, hislawyer released a statement celebrating the fact that there would be no executions tonight. But state Attorney General Lesley Rutledge immediately askedthe U.S. Supreme Court to vacate the stay, ushering in a new round of dread and anticipation.The death warrant for Davis expired at 11:59 Central time. Outside the prison, activists waited for news. As Davis waited to learn whether he would live or die, reporters tweeted about his last meal fried chicken, strawberry cake while noting that the state appeared to be operating on the assumption it would kill him. Just after 11 p.m., J.R. Davistold reporters they were moving witnesses into place, despite the fact that the U.S. Supreme Court had not yet ruled.
On Twitter, Echols called Arkansas politicians bloodthirsty. He retweeted longtime Arkansas journalist John Brummett, who wrote, Ive never seen such a powerful official hankering to kill and kill now as is being seen in Arkansas political leadership tonight. But officialsfailed in the end. Just beforemidnight, the U.S. Supreme Court ruled against the state of Arkansas, keeping the temporary stay in place. No one would die in the execution chamber that night.
ACLU of Arkansas Executive Director Rita Sklar and others prepare to carry boxes containing petitions to Gov. Asa Hutchinsons office, asking him to stay upcoming executions, April 14, 2017, in Little Rock, Ark.
Photo: Stephen B. Thornton/The Arkansas Democrat-Gazette/AP
The state of Arkansashas not given up its execution plans. But every day they seem to unravel a little more. Tonight, onApril 20, officials planned to killStacey Johnson and Ledell Lee,both of whom insist they are innocent. But late Wednesday afternoon, a circuit court judge imposed a temporary restraining order on the states planned use of vecuronium bromide, the second in Arkansass highly contested three-drug protocol. The provider of the drug, a pharmaceutical company called the McKesson Corporation, accused officialsof misleading the company when it sought out the supply, concealing their intention to use it for executions.
The ruling put allexecutions on hold. Shortly afterward, a second ruling, by theArkansas Supreme Court, granted a stay to Johnson, withlawyers for the Innocence Project successfully arguing thatJohnson has the right to an evidentiary hearing in order to make thecase for DNA testing. Lee, too, has the Innocence Project on his side, as well as lawyers with the ACLU. He, too, has fought forDNA testing, to no avail.
The cases of Johnson and Lee add yet another dimension to a system of capital punishment that has been exposed, again, to be profoundly and frighteninglyflawed. Beyond the immediate chaos and legal wrangling sparked by Hutchinsonsplanned killing spree, the cases of the eight men he originally set to die haveexposed themanyuglysides of thedeath penalty in Arkansas, from themental illnessthat pervades death row, to the failures of the clemency process, to a history of botched executions and experimental killing protocols disguised as science. It was only a matter of time, since the risk of executing an innocent person was sure to come up. When youre carrying out mass executions, its inevitable that innocent people are going to get caught in that net, Echolstweeted on Wednesday.
Innocentor not,Lee and Johnson also represent a legacy of reserving the harshest punishments forblack men accused of crimes against white women. Both wereconvicted of raping and murderingyoung white women in their 20s. Both crimes date back to the early 1990s, and both men were tried twice,in an era when Arkansas defense attorneys were woefully ill-equipped to represent defendants facing the death penalty. In 1990, the Arkansas Gazette surveyed 22 local trial lawyers, finding that half had no capital-murder experience before they were appointed to cases that eventually put their clients on death row.
In Lees case, the records show shocking failures of his defense attorneys, both at trial and post-conviction, which were compounded byegregious conflicts of interest. His trial judge was having an affair with the prosecutor;the two would later get married. The same judge later expressed his regret at appointing a lawyer to Lees state habeas proceeding who showed up to court obviously intoxicated. A state prosecutor raised concerns that the attorneywas slurring his words, stumbling in the courtroom, and speakingincoherently, whileintroducing the same items of evidence over and over again. Later, the judge told the lawyerthat he was unaware he had only recently been inrehab.If I had known that, I would not have put you on this case, he said.
Lee was convicted of murdering and sexually assaulting 26-year-old Debra Reese in 1993. Strangled and beaten to death in her homein Jacksonville, Arkansas, Reese was struck36 times with atire thumper, which her husband, a truck driver, had given to her for protection when he was on the road, according to court records. Lee was arrested the same day. The states theory, as summarized by the Arkansas Supreme Court, was that Leehad set out to commit a robbery andsearched the victims neighborhood until he found the perfect target for his crime.
Yet despite ample blood and fingerprints at the scene,virtually no physical evidence was found to match Lee. The case against him relied on eyewitness testimony now known to be notoriously unreliable along with two main piecesof forensic evidence. One was an apparent blood spot found on a pair of Converse sneakers Leewas wearing at the time of his arrest. According to the Arkansas Supreme Court, astate serologist confirmed the presence of blood, but consumed the entire sample, thus removing the opportunity for independent analysis by the defense. The second piece of evidence wasa hair sample thought to come from a black man and found to be consistent with Lees based on microscopic examination a forensic method that has since been discredited, according to the Innocence Project.
Lawyers this week sought a stay of execution from the Arkansas Supreme Court,arguing that the Converse sneakersandhair fibers should be subject to DNA testing, which has advanced by leaps and bounds since the 1990s. But their argument was rejected. With Leesexecution appearing imminent on Wednesday, attorneys moved to introduce evidence to the Arkansas Board of Parole that Lee suffers frombrain damage and significant intellectual disability, which was never properly presented by previous attorneys. Instead, thetemporary restraining order overthe lethal injection drug is keeping Arkansasfrom taking his life.
Protesters rally against Arkansass planned execution spree.
Photo: Kristin L. P. Pearson
Johnson was convicted twice, in 1994 and 1997, of raping and murdering 25-year-old Carol Jean Heath, in DeQueen, Arkansas. Her body was discovered at her home by a friend, Rose Cassady, in the early morning hours of April 2, 1993. Heath was in a pool of blood, naked exceptfor a T-shirt. Her throat had been deeply cut. After calling the police, Cassady realized Heaths two young children were at the house. According to Cassady, Heaths 6-year-old daughter, Ashley, said, A black man broke in last night.
A police officer interviewed Ashley later that day. She told him that she had been sitting on the couch with her mother when someone knocked on the door. It was a black male, Ashley allegedly said, describing later how the two fought, while she and her 2-year-old brother, Jonathan, hid in the closet.
Johnson did not live in Arkansas at the time, but had returnedto DeQueen to attendhis fathers funeral. Although he was accused of sexual assault, no semen or other such evidence was found at the scene. As with Lee,the primary forensicevidence against Johnson wasa negroid hair. It was tested for DNA, with results that could not excludeJohnson. Attorneys unsuccessfully argued that he had a consensual relationship with Heath. Whilewitnesses conceded that Johnson had been at Heaths home more than once before the crime, at his 1997 retrial, three witnesses strenuously stated that Ms. Heath had not had a relationship with a black man, according to a recent appeal.
At his clemency hearing in late March, Johnson argued that his conviction was rooted in racism, which ledthe state to overlook other leads. There was a lot of evidence that could have shown that it wasnt me, but they ignored it, he told members of the parole board. They just looked at me, they found the big black guy and the little white person that was a victim and that was enough that they needed.
As in Lees case, the Innocence Project points to several untested pieces of evidence that could have significant probative value as well as major scientificadvances that could yield more accurate forensic results than possible in the 1990s. While hairs thought to belong to a white person were found at the scene,those were never tested. The evidence isimportant in addressing an alternate theory of the crime.Johnsons attorneys unsuccessfully pointed to Heaths boyfriend at the time, a white man named Branson Ramsey, who had a history of abuse. At Johnsons 1997 retrial, Ramseys ex-wife testified that her husbandwould punch me or slap me or kick me or bite me. Particularly notable was her claim thathe bit her on my breast. Heath, too, had apparent bite marks on her breasts. Ramsey died in 1998. In response to Johnsons motion for DNA testing last week, the statedismissed the strategy as a classic case of blame-the-dead-guy.
But putting aside the DNA evidence, perhaps the biggest red flag in the case was the states reliance on Heaths traumatized young daughter, Ashley. Though she wasfound incompetent to testify at Johnsons first trial, in 1994, Ashleywas deemed ready to take the stand for the retrial in 1997. The 10-year-old delivered testimony thatseemed heavily influenced by relatives and prosecutors a fact that alarmed members of the Arkansas Supreme Court who reviewed the case years later. In a 4-3 ruling leaving the conviction intact, the dissenting judges noted that Johnsons defense attorneys had been denied access totherapist records that showed Ashleys stories were profoundly inconsistent and that she had been under considerable pressure from her family and the prosecutor to convict Stacey Johnson. Among passagesthey quoted: The DA says shes the only one who can keep him behind bars; Her grandmother told Ashley that she has to keep him behind bars, because if he gets out hell try to kill Ashley next.
Ashley Heath is now in her 40s.In 2015, the last time Johnson was up for execution, she told the parole board thatshe no longerbelieves the death penalty brings justice.I am tired of re-living [the crime], she said. I am ready to put it behind me and move on with my life.
The sun sets over an Arkansas State Police command post outside the Varner Unit of the Arkansas Department of Correction near Varner, Ark., on Monday evening, April 17, 2017.
Photo: Stephen B. Thornton/The Arkansas Democrat-Gazette/AP
On Tuesday, April 18, two days before Lee and Johnson were set to be executed, a black man in Louisiana was officially exonerated.Rodricus Crawford was sent to death row in 2013 by Caddo Parish District Attorney Dale Cox, who later made headlines forsaying thatdeclining death sentences around the country were a bad sign. I think we need to kill more people, he said. Like Hutchison, who is fond of tweeting Bible verses on Sunday, Cox likes to invoke theBible. InCrawfords case, he insistedJesus himself would have supported the death penalty.
Crawford is now the 158th death row exoneree in the country. He isfortunate that the state dropped the charges in his case.Damien Echols was not so lucky. He was only freed after he agreed to take an Alford plea, in which one can plead guilty while maintaining ones innocence. It makes no sense whatsoever, Echols told Amy Goodman of Democracy Now on Monday. The entire reason that it exists is so that the state cant be held responsible for what theyve done to you. As far as Arkansas is concerned, it has never sent an innocent person to death row. The state still maintains that they are infallible, Echols said. Theyve never made a mistake, theyve never killed an innocent person.
Yet one case should still haunt the state. In August 1995, amid loud public outcry, Arkansas executed Barry Lee Fairchild, a black man accused in 1983 of raping and killing 22-year-old Marjorie Greta Mason, who worked as a nurse at Little Rock Air Force Base. It was, at the time, the most publicized and contentious death penalty case in modern Arkansas history, in the words of local columnist John Brummett, who described how, for once, theparole board was deeply divided over whether to recommend clemency for Fairchild. Members ultimately voted 4-2 not to do so, with a seventh member of the board recusing herself because of earlier dealings with the case. Still, she wrote a letter to Gov.Jim Guy Tucker saying there were too many uncertainties about Fairchilds conviction.
The Fairchild case became famous outside Arkansas for embodying the enduring problemswith capital punishment. A black man with IQ scores as low as 60, Fairchildhad been accused of killing a white woman on highly questionable evidence. In an in-depth articlerevisiting the case before his 1995 execution, the Washington Post described how in the absence of forensic evidence, the prosecution case hinged almost completely on Fairchilds videotaped confession. That statement, in which he admitted to being an accomplice to the crime, had been obtainedby a notorious police sheriff named Tommy Robinson, who had a reputation for abuse, as well as for beingopenly, flamboyantly racist. When a state prison refused to help relieve the county jails overcrowding, Robinson, to generate publicity, took a group of his prisoners to the state prison and chained them to a fence, the Post reported.Robinson once was quoted as joking that he treated his black prisoners well, fed them watermelon and chicken, according to the National Journal. With Robinson in charge, a manhunt ensued for the black man who allegedly killedMason.In March 1983, several dozen police officers surrounded the house whereFairchildwas staying. When heemerged, he was attacked by a German Shepherd belonging toRobinson.
Many of the questionsabout Fairchilds guilt emergedafter the conviction, with evidence pointing to his brother as the real perpetrator. Over the phone, the original prosecutor, Chris Raff, who is now retired, recalled thatat the time of the conviction, it was not controversial. Raff did not believe the allegations of Fairchildsmental disability, saying that the facts and players in the case made itgreat fodder for media. But Jeff Rosenzweig, who expresses great respect forRaff, recalls thatlaw enforcement concealed evidence from Raff himself.
Fairchild faced sevenexecution dates before he died. Then-Gov. Bill Clinton setno fewerthan five. At one point, he came within hours of execution, only for a judge to vacate his sentence, based on the conclusion that he never should have been sentenced to die in the first place. Yet Fairchildwould die in the end. His numeroushabeas petitions forestalling his executionlater inspired political efforts to limit the appellate processforpeople on death row. By the timeFairchild was finally executed in 1995, Clinton had been elected president. In 1996, he signed the Antiterrorism and Effective Death Penalty Act, dramaticallycurtailingthe habeas rights of people in prison.
The law has been particularly devastating for those claiming innocence while facing execution, including in Arkansas. Speaking to the board of parole at the clemency hearing for Stacey Johnsonlast month, Rosenzweig tried to explain how AEDPAprevented his client fromgetting his evidence heard. Theextremely tough standard it imposedmeansonly a minuscule percentage of people are able to succeed in federal habeas corpus, he explained. That is why we lost.
With its executionplans increasinglyin doubt, the state of Arkansas remains undeterred and a bitdesperate. In a statement Wednesday evening, Hutchinson said he was surprised and disappointed by the stay imposed by the Arkansas Supreme Court, adding that he would be reviewing his options with Attorney General Leslie Rutledge. In a less measured response, a few hours later a pro-death penalty state senator posted the cellphone number of the chief justice on Twitter.
Throughout it all, Ledell Lee and Stacey Johnson remained in holding cells next to the execution chamber, awaiting the next decision about whether they will live or die. They are still there. In the meantime,Damien Echols continues to speak out,reminding people to stay vigilant. On Thursday, he tweeted: The only reason a judge or politician would not allow DNA testing to be done in a case is because they want to kill no matter what.
Update: April20, 2017: Shortlyafter this story was published, the Arkansas Supreme Court lifted the order blocking the state from usingvecuronium bromide, clearing the way forLedell Lee to be executed tonight.
Top photo: Damien Echols, who was released from death row in 2011, at the Capital Hotel in Little Rock, Ark., April 14, 2017.
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Arkansas Fights to Execute Two Men Without Testing DNA Evidence That Could Exonerate Them - The Intercept
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A Map of Human History, Hidden in DNA – Quanta Magazine
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Ask John Novembre to recall a fun time, and he might tell you about a recent weeklong hackathon. He and his students and postdocs set aside their daily obligations to stay up late eating takeout and crunching data.
This isnt to say that Novembre, a computational biologist, is purely a computer geek (although hell admit thats part of his identity). Yes, his whiteboard-lined walls at the University of Chicago are adorned with symbols and graphs and equations embryos of the clever algorithms and computational tricks that allow him to wrest meaning from some of the largest genomic data sets in the world. But thats just a glimpse of what he does.
Born into a military family, Novembre grew up moving from place to place, spending three years in Uruguay, where his mother is from. His early exposure to human differences I loved geography, I loved languages, I loved history morphed into a deep curiosity about evolution and genetic diversity. His work reflects a broad ambition: to understand how populations vary in time and space. He studies how humanitys genetic code shifts and mixes as groups expand, shrink, migrate, mingle, evolve and die out.
His mathematical chops have served him well in this endeavor. His innovative analyses and new ways of visualizing complex data reveal the genetic signatures of ancestry and the surprising connections between genes and geography. In 2015, at the age of 37, Novembre won a MacArthur fellowship the so-called genius grant which recognizes talented individuals who have shown extraordinary originality and promise for important future advances based on a track record of significant accomplishment.
Yet for all his accolades, Novembre comes across as genuinely humble, quoting colleagues papers the way English majors quote Dickinson and Yeats. Hanging above his desk, within eyeshot of his dry-erase brainstorms, is an old map he thinks is from the 1600s a constant reminder that any human attempt to model the world will always be a very imperfect representation.
Quanta Magazinespoke with Novembre about the motivations behind his work, the challenges of using DNA to interpret the past, and the racial legacy of genetics research. An edited and condensed version of the conversation follows.
QUANTA MAGAZINE: What got you thinking about genetic diversity as a computational problem?
JOHN NOVEMBRE: For me, the path starts pretty far back. In high school, I was a bit of a computer programming nerd. But in my classes, I was learning about the genetic code, which was completely mesmerizing. Then in college, I got a chance to do a summer research internship at Stanford, where I heard a talk by a student who had interned in Luigi Luca Cavalli-Sforzas lab. What they do what theyve become famous for is to look at variations in human genes, how theyre distributed across the globe, and what they can tell us about human history. That was fascinating to me.
I went back to my home campus, and I found a lab working on the population genetics of Quercus gambelii, the Gambel oak. I learned just how difficult a lot of the analysis tools were to use, and how much math and computation is involved in analyzing genetic data. All of a sudden I realized, Wait a minute. Heres this thing I really love programming so why dont I combine these two passions? My day-to-day activity became tinkering with computers, but my larger end is something that intellectually fascinates me, which is understanding genetic variation and how it changes through time.
Early in your career, you made waves by uncovering deficiencies in a common statistical tool known as principal component analysis (PCA). How did this discovery further your work in genetics?
What PCA does is, it takes an individuals genetic data and boils it down to just a few numbers. In learning about how this method works its strengths and its weaknesses I understood that the patterns it produces could reflect spatial structure in population data.
I was hoping to get access to genetic data from a region of the world where theres dense sampling, so that I could see what variation looks like at a continuous scale, where populations kind of blend into one another. And it turned out I was very lucky in that I got invited to join a collaboration with Carlos Bustamante, [then] at Cornell, to analyze one of the largest collections of [genomic data] being applied to human populations. The full data set was 3,192 European individuals. A large fraction of the sample had answered an ancestry questionnaire to say where their grandparents came from, and based on that, we saw we had samples from roughly 37 different origins across Europe.
So what did you learn?
When we applied PCA, right away we saw this major pattern: There was a striking resemblance between where individuals are located in genetic space and their geography where their grandparents came from. Thats really remarkable given how closely related human individuals are. Most geneticists wouldnt have thought you could tease apart very fine-scale structure within continental scales.
How fine-scale are we talking about?
Lets say I took an individual and hid their geographic location and then tried to put them back on a map. How well could I do? When we did this, we could often get within a few hundred kilometers. Even when we looked at German-speaking Swiss versus French-speaking Swiss versus Italian-speaking Swiss, we could see shifts in the genetic distribution.
Im surprised that my grandparents geographic coordinates could have such a notable effect on my genetics, given how often humans migrate. How do you explain this influence?
This is something I want to stress: The effect on your genetics is actually incredibly small. Its just that were looking at so many locations in the genome that we can pick up very small effects. This is the magic of big data: Very subtle patterns become detectable. So its not that where your grandparents live has a huge impact on your genetics. Its actually a very, very minor effect. But when you have hundreds of thousands of measurements, you can start to pick out that an individual seems to come from one location versus another.
What are your thoughts on the ethics of commercial ancestry tests?
I advise for Ancestry.com their DNA branch so Im very sensitive to the challenges of communicating results. On the one hand, projects like our genetic map of Europe show the tremendous potential and power of these tools for learning about ancestry. But then theres also the immense complexity of it: What does it really mean to talk about where an individual is from? We can talk about where our parents and our grandparents are from, or we can go very far back into the past when we all came from Africa. And we can have different ideas about origin, in terms of geographic location versus some kind of cultural or ethnic population.
Id say were still in the early days of really nailing this problem of using genetic data from today to interpret the past. Were still facing the complexity of real biological systems and populations, which resist some of our attempts to use very simple models of history.
In what ways has your work influenced how you think about race?
Its very clear that genetics research has a difficult and dark history. But its been exciting to be part of a new generation doing this kind of work in a time when diversity is much more appreciated and understood and valued and when we have the data to make it even more clear just how poorly conceived racial worldviews have been.
Are you thinking of a particular example?
A very powerful one for me was being part of some of the first teams to look at genome-wide data taken from multiple human populations. You can sort the genome by what regions vary the most across human populations and then ask, OK, what genes are near those locations, and what do we know about them?
If you do this exercise, you will see, at the very extreme top of the list, variants that are involved in skin pigmentation, in eye color, in hair color. So its an empirical fact that the things we use to see differences in each other are outliers in the human genome. Your average set of genes in the human genome is much more similar globally.
You analyzed the first whole-genome sequences of three gray wolf species and compared them to the genomes of three dog species. What did you discover?
That was a big surprise. We were thinking we might find that all three of the dog lineages are most closely related to one of the three wolf lineages. They might all be related to the Israeli wolf, for instance, because maybe dogs were domesticated in the Middle East. Or maybe there were two domestications of dogs, and the dingo would be related to the Chinese wolf while the basenji was related to the Croatian wolf.
But what we saw was that the three dogs were most closely related to each other but not embedded within the genealogy of the three wolves. Our hypothesis is that there was a wolf lineage that dogs were domesticated from that has since gone extinct. The storys gotten incredibly complicated, and I think the final chapters not written yet.
Saverio Truglia for Quanta Magazine
Video:John Novembre explains how he uses genomic data to map human history.
Are you a dog person?
Not particularly, no. I would say my motivation was primarily to try to solve this larger challenge for the whole field, which is: How do we use DNA sequences today as a record of the past? You can swap out the species names for me, and its still interesting. Its still a fun problem.
How has your approach to analyzing genetic data evolved over time?
Theres been increasing movement in my work toward data visualization. Your eye can actually process a large amount of information and interpret complex patterns. With the right visualization tools, you gain a more direct and intuitive understanding of the major features of the data and how they reflect biological processes.
Can you give an example?
One of the tools weve developed is a method that tells us where in a landscape there is more or less gene flow in other words, how individuals are moving between populations. Our analysis infers areas where theres more genetic difference than youd expect per unit of geographic distance, and other areas where theres less. So were able to produce a geographic map that is colored in brown and blue to represent areas of low and high migration.
For example, we looked at genetic data from more than 1,000 elephants sampled across Africa. With our approach, you feed in the data with no prior knowledge, and you get this map of migration rates. You see this brown barrier down Central Africa marking where theres low migration and a blue corridor in the east where theres high migration. Of course, if you know the ecology, you understand: Oh! Thats the forest elephants on one side and the savannah elephants on the other.
Have you applied this method to other populations?
Yes. When we run it on the human data from Europe, for instance, we see it infers a brown area of reduced migration between the U.K. and France, representing essentially the English Channel. We see a lot of blue high migration in the North Sea because of historical connections there, such as Viking contacts between Scandinavia and the U.K. Then we see brown diffusely around Switzerland and Austria, which we think represents the Alps.
Did you get any puzzling results, such as areas of low or high migration that dont seem to jibe with the landscape?
Im more surprised by how often the genetics do align with the geological features. You take a bunch of living individuals and extract a molecule from their bodies and start comparing them to one another, and you can see that the Alps are a feature of our planet. Its kind of wild.
How have the questions youre researching changed from when you started out?
The data types have changed, and the scale of the data has changed. For my Ph.D., I worked on trying to learn what I could from a single genetic variant that was observed in 71 populations. Now its completely routine to have data sets with millions of variants. I couldnt have imagined that wed be where we are today back then. So thats an incredible game-changer, but the core question is still the same: How do we use mathematics and statistical models to interpret population genetic data?
What are the big remaining problems you hope to solve?
I think one holy grail is a method that would allow you to infer how migration rates and population sizes change through time and space. It would be a very complete description of a population and its demographic history.
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DNA’s secret weapon against knots and tangles – Nature.com
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M. Imakaev/G. Fudenberg/N. Naumova/J. Dekker/L. Mirny
DNA loops help to keep local regions of the genome together.
Leonid Mirny swivels in his office chair and grabs the power cord for his laptop. He practically bounces in his seat as he threads the cable through his fingers, creating a doughnut-sized loop. It's a dynamic process of motors constantly extruding loops! says Mirny, a biophysicist here at the Massachusetts Institute of Technology in Cambridge.
Mirny's excitement isn't about keeping computer accessories orderly. Rather, he's talking about a central organizing principle of the genome how roughly 2 metres of DNA can be squeezed into nearly every cell of the human body without getting tangled up like last year's Christmas lights.
He argues that DNA is constantly being slipped through ring-like motor proteins to make loops. This process, called loop extrusion, helps to keep local regions of DNA together, disentangling them from other parts of the genome and even giving shape and structure to the chromosomes.
Scientists have bandied about similar hypotheses for decades, but Mirny's model, and a similar one championed by Erez Lieberman Aiden, a geneticist at Baylor College of Medicine in Houston, Texas, add a new level of molecular detail at a time of explosive growth for research into the 3D structure of the genome. The models neatly explain the data flowing from high-profile projects on how different parts of the genome interact physically which is why they've garnered so much attention.
But these simple explanations are not without controversy. Although it has become increasingly clear that genome looping regulates gene expression, possibly contributing to cell development and diseases such as cancer, the predictions of the models go beyond what anyone has ever seen experimentally.
For one thing, the identity of the molecular machine that forms the loops remains a mystery. If the leading protein candidate acted like a motor, as Mirny proposes, it would guzzle energy faster than it has ever been seen to do. As a physicist friend of mine tells me, 'This is kind of the Higgs boson of your field', says Mirny; it explains one of the deepest mysteries of genome biology, but could take years to prove.
And although Mirny's model is extremely similar to Lieberman Aiden's and the differences esoteric sorting out which is right is more than a matter of tying up loose ends. If Mirny is correct, it's a complete revolution in DNA enzymology, says Kim Nasmyth, a leading chromosome researcher at the University of Oxford, UK. What's actually powering the loop formation, he adds, has got to be the biggest problem in genome biology right now.
Geneticists have known for more than three decades that the genome forms loops, bringing regulatory elements into close proximity with genes that they control. But it was unclear how these loops formed.
Several researchers have independently put forward versions of loop extrusion over the years. The first was Arthur Riggs, a geneticist at the Beckman Research Institute of City of Hope in Duarte, California, who first proposed what he called DNA reeling in an overlooked 1990 report1. Yet it's Nasmyth who is most commonly credited with originating the concept.
As he tells it, the idea came to him in 2000, after a day spent mountain climbing in the Italian Alps. He and his colleagues had recently discovered the ring-like shape of cohesin2, a protein complex best known for helping to separate copies of chromosomes during cell division. As Nasmyth fiddled with his climbing gear, it dawned on him that chromosomes might be actively threaded through cohesin, or the related complex condensin, in much the same way as the ropes looped through his carabiners. It appeared to explain everything, he says.
Nasmyth described the idea in a few paragraphs in a massive, 73-page review article3. Nobody took notice whatsoever, he says not even John Marko, a biophysicist at Northwestern University in Evanston, Illinois, who more than a decade later developed a mathematical model that complemented Nasmyth's verbal argument4.
Mirny joined this loop-modelling club around five years ago. He wanted to explain data sets compiled by biologist Job Dekker, a frequent collaborator at the University of Massachusetts Medical School in Worcester. Dekker had been looking at physical interactions between different spots on chromosomes using a technique called Hi-C, in which scientists sequence bits of DNA that are close to one another and produce a map of each chromosome, usually depicted as a fractal-like chessboard. The darkest squares along the main diagonal represent spots of closest interaction.
The Hi-C snapshots that Dekker and his collaborators had taken revealed distinct compartmentalized loops, with interactions happening in discrete blocks of DNA between 200,000 and 1 million letters long5.
These 'topologically associating domains', or TADs, are a bit like the carriages on a crowded train. People can move about and bump into each other in the same carriage, but they can't interact with passengers in adjacent carriages unless they slip between the end doors. The human genome may be 3 billion nucleotides long, but most interactions happen locally, within TADs.
Mirny and his team had been labouring for more than a year to explain TAD formation using computer simulations. Then, as luck would have it, Mirny happened to attend a conference at which Marko spoke about his then-unpublished model of loop extrusion. (Marko coined the term, which remains in use today.) It was the missing piece of Mirny's puzzle. The researchers gave loop extrusion a try, and it worked. The physical act of forming the loops kept the local domains well organized. The model reproduced many of the finer-scale features of the Hi-C maps.
When Mirny and his colleagues posted their finished manuscript on the bioRxiv preprint server in August 2015, they were careful to describe the model in terms of a generic loop-extruding factor. But the paper didn't shy away from speculating as to its identity: cohesin was the driving force behind the looping process for cells not in the middle of dividing, when chromosomes are loosely packed6. Condensin, they argued in a later paper, served this role during cell division, when the chromosomes are tightly wound7.
A key clue was the protein CTCF, which was known to interact with cohesin at the base of each loop of uncondensed chromosomes. For a long time, researchers had assumed that loops form on DNA when these CTCF proteins bump into one another at random and lock together. But if any two CTCF proteins could pair, why did loops form only locally, and not between distant sites?
Mirny's model assumes that CTCFs act as stop signs for cohesin. If cohesin stops extruding DNA only when it hits CTCFs on each side of a growing loop, it will naturally bring the proteins together.
But singling out cohesin was a big leap of faith, says biophysicist Geoff Fudenberg, who did his PhD in Mirny's lab and is now at the University of California, San Francisco. No one has seen these motors doing these things in living cells or even in vitro, he says. But we see all of these different features of the data that line up and can be unified under this principle.
Experiments had shown, for example, that reducing the amount of cohesin in a cell results in the formation of fewer loops8. Overactive cohesin creates so many loops that chromosomes smush up into structures that resemble tiny worms9.
The authors of these studies had trouble making sense of their results. Then came Mirny's paper on bioRxiv. It was the first time that a preprint has really changed the way people were thinking about stuff in this field, says Matthias Merkenschlager, a cell biologist at the MRC London Institute of Medical Sciences. (Mirny's team eventually published the work in May 2016, in Cell Reports6.)
Lieberman Aiden says that the idea of loop extrusion first dawned on him during a conference call in March 2015. He and his former mentor, geneticist Eric Lander of the Broad Institute in Cambridge, Massachusetts, had published some of the most detailed, high-resolution Hi-C maps of the human genome available at the time10.
During his conference call, Lieberman Aiden was trying to explain a curious phenomenon in his data. Almost all the CTCF landing sites that anchored loops had the same orientation. What he realized was that CTCF, as a stop sign for extrusion, had inherent directionality. And just as motorists race through intersections with stop signs facing away from them, so a loop-extruding factor goes through CTCF sites unless the stop sign is facing the right way.
His lab tested the model by systematically deleting and flipping CTCF-binding sites, and remapping the chromosomes with Hi-C. Time and again, the data fitted the model. The team sent its paper for review in July 2015 and published the findings three months later11.
Mirny's August 2015 bioRxiv paper didn't have the same level of experimental validation, but it did include computer simulations to explain the directional bias of CTCF. In fact, both models make essentially the same predictions, leading some onlookers to speculate on whether Mirny seeded the idea. Lieberman Aiden insists that he came up with his model independently. We submitted our paper before I ever saw their manuscript, he says.
There are some tiny differences. The cartoons Mirny uses to describe his model seem to suggest that one cohesin ring does the extruding, whereas Lieberman Aiden's contains two rings, connected like a pair of handcuffs (see 'The taming of the tangles'). Suzana Hadjur, a cell biologist at University College London, calls this mechanistic nuance absolutely fundamental to determining cohesin's role in the extrusion process.
Nik Spencer/Nature
Neither Lieberman Aiden nor Mirny say they have a strong opinion on whether the system uses one ring or two, but they do differ on cohesin's central contribution to loop formation. Mirny maintains that the protein is the power source for looping, whereas Lieberman Aiden summarily dismisses this idea. Cohesin is a big doughnut, he says. It doesn't do that much. It can open and close, but we are very, very confident that cohesin itself is not a motor.
Instead, he suspects that some other factor is pushing cohesin around, and many in the field agree. Claire Wyman, a molecular biophysicist at Erasmus University Medical Centre in Rotterdam, the Netherlands, points out that cohesin is only known to consume small amounts of energy for clasping and releasing DNA, so it's a stretch to think of it motoring along the chromosome at the speeds required for Mirny's model to work. I'm willing to concede that it's possible, she says. But the Magic 8-Ball would say that, 'All signs point to no'.
One group of proteins that might be doing the pushing is the RNA polymerases, the enzymes that create RNA from a DNA template. In a study online in Nature this week12, Jan-Michael Peters, a chromosome biologist at the Research Institute of Molecular Pathology in Vienna, and his colleagues show that RNA polymerases can move cohesin over long distances on the genome as they transcribe genes into RNA. RNA polymerases are one type of motor that could contribute to loop extrusion, Peters says. But, he adds, the data indicate that it cannot be the only force at play.
Frank Uhlmann, a biochemist at the Francis Crick Institute in London, offers an alternative that doesn't require a motor protein at all. In his view, a cohesin complex might slide along DNA randomly until it hits a CTCF site and creates a loop. This model requires only nearby strands of DNA to interact randomly which is much more probable, Uhlmann says. We do not need to make any assumptions about activities that we don't have experimental evidence for.
Researchers are trying to gather experimental evidence for one model or another. At the Lawrence Livermore National Laboratory in California, for example, biophysicist Aleksandr Noy is attempting to watch loop extrusion in action in a test tube. He throws in just three ingredients: DNA, some ATP to provide energy, and the bacterial equivalent of cohesin and condensin, a protein complex known as SMC.
We see evidence of DNA being compacted into these kinds of flowers with loops, says Noy, who is collaborating with Mirny on the project. That suggests that SMC and by extension cohesin might have a motor function. But then again, it might not. The truth is that we just don't know at this point, Noy says.
The experiment that perhaps comes the closest to showing cohesin acting as a motor was published in February13. David Rudner, a bacterial cell biologist at Harvard Medical School in Boston, Massachusetts, and his colleagues made time-lapse Hi-C maps of the bacterium Bacillus subtilis that reveal SMC zipping along the chromosome and creating a loop at a rate of more than 50,000 DNA letters per minute. This tempo is on par with what researchers estimate would be necessary for Mirny's model to work in human cells as well.
Rudner hasn't yet proved that SMC uses ATP to make that happen. But, he says, he's close and he would be shocked if cohesin worked differently in human cells.
For now, the debate rages about what cohesin is, or is not, doing inside the cell and many researchers, including Doug Koshland, a cell biologist at the University of California, Berkeley, insist that a healthy dose of scepticism is still warranted when it comes to Mirny's idea. I am worried that the simplicity and elegance of the loop-extrusion model is already filling textbooks, coronated long before its time, he says.
And although it may seem an academic dispute among specialists, Mirny notes that if it his model is correct, it will have real-world implications. In cancer, for instance, cohesin is frequently mutated and CTCF sites altered. Defective versions of cohesin have also been implicated in several rare human developmental disorders. If the loop-extruding process is to blame, says Mirny, then perhaps a better understanding of the motor could help fix the problem.
But his main interest remains more fundamental. He just wants to understand why DNA is configured in the way it is. And although his model assumes a lot of things about cohesin, Mirny says, The problem is that I don't know any other way to explain the formation of these loops.
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Judge allows new DNA testing in murder of NC college student – WNCN
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GASTONIA, N.C. (WBTV) Attorneys for convicted murderer Mark Carver got some good news from a judge in Gaston County Thursday after he ordered new DNA testing in the case.
Carver, convicted in the death of UNC Charlotte student Ira Yarmolenko, did not appear in court.
Judge David Lee requested five law enforcement officers who were involved in the case be contacted and asked to give DNA samples. Carvers defense team has argued that several investigators may have contaminated the crime scene.
We believe that all the evidence used against Mr. Carver has been discredited, said Chris Mumma, Executive Director of North Carolina Center on Actual Innocence. I would like to see those officers voluntarily give their DNA because there is no harm in giving it.
Judge Lee did not order the DNA be taken from the officers but did state that if the officers did not want to give the samples, additional hearings may be required.
Gaston County District Attorney Locke Bell argues that several of the law enforcement officials brought up in court had no connection or contact with Carver. Therefore, he said that contamination would be nearly impossible.
There has to be some sort of connection, or it just keeps going and going, said Bell in court. If that is not the case, what we would have to do is go back to where Carver had breakfast and take the DNA of the waitress.
The judge also ordered that the state must re-test the electronic DNA evidence used in the trial under the current protocol. Mumma says that protocol was available during the trial.
I am expecting to see exactly what our experts have seen. They have submitted reports that say it never would have been reported that Mark Carvers DNA was on that car, said Mumma.
Bell argued that the test that was done was accurate.
The new way of doing it does not say the old way was wrong, said Bell.
Both attorneys promised to share their complete files in the case before any hearing concerning a new trial.
He is innocent. We know that he is innocent. Everyone that knows him knows Mark is a great guy, said one of Carvers family members. The truth will come out, he will be found innocent.
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Mesa police use DNA technology to create composite sketch of man wanted in sex assault – AZCentral.com
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Paragon NanoLabs specializes in DNA phenotyping, which is the process of predicting physical appearance and ancestry from unidentified DNA evidence. The result is called a Snapshot prediction of what a person is likely to look like.(Photo: Mesa Police Department)
UsingDNA technology, Mesa police investigators have come up with a composite of a man in a Mesa sexual assault who has been at large since early January, police said.
On Jan. 9, a man entered a home in the 500 block of EastBroadway between 2 and 4 a.m., Mesa police said.
The man then sexually assaulted a 4-year-old in the home while the child's family was asleep, police said.
The man was described by witnesses as Hispanic, 18-30 years old, short build, with short brown curly hair, police said.
Using DNA evidence that was collected at the scene, investigatorssought the services of Paragon NanoLabs.
The companyspecializes in DNA phenotyping, which isthe process of predicting physical appearance and ancestry from unidentified DNA evidence.The result is called a Snapshot prediction of what a person is likely to look like.
An artist's sketch of a man wanted in a Mesa sexual assault.(Photo: Mesa Police Department)
Through using DNA evidence from this investigation, a Snapshot composite was produced depicting what the manmay have looked like at 25 years old with an average body-mass indexof 22, police said.His genomic ancestry matched a Latino with some African-American mixture, police said.
Snapshot composites are scientific approximations of appearance based on DNA and are not likely to be exact replicas of appearance, police said.
Silent Witness is rewarding up to $5,000 for information leading to the arrest and/orindictment of the suspect.
Anyone with information is asked to call the Mesa Police Department at 480-644-2211 or Silent Witness at 480-WITNESS.
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