Since its discovery, researchers have hailed Cas9 — a protein “machine” that can be programmed by a strand of RNA to target specific DNA sequences and to precisely cut, paste, and turn on or turn off genes — as a potential key to unlocking a host of new treatments and therapies for genetic conditions, but only if they fully understand how it works.That’s where David R. Liu and his students Vikram Pattanayak and John Guilinger come in.Liu, a Harvard professor of chemistry and chemical biology and an investigator with the Howard Hughes Medical Institute, joined with Professor Jennifer Doudna of the University of California, Berkeley, to lead an effort to develop a detailed “specificity profile” for Cas9 — data to reveal how accurately Cas9 can home in on the DNA sequence it is programmed to target, and how susceptible the protein/RNA complex is to acting on decoy off-target sequences instead. The work was described in a paper published last month in Nature Biotechnology.“A major issue that will determine the extent to which technologies like Cas9 are useful research tools, especially for human therapeutics, is how specific they are,” Liu said.“It’s widely understood that the ability to manipulate the structure of our genomes has the potential to have a profound impact on human health,” he added. “But before you give a patient some treatment that will change their genes, you need to be very confident that it’s not going to have unintended effects elsewhere, because the difference between cutting an on-target site and an off-target site could mean treating a disease or triggering the development of cancer.”The Cas9 research is just the latest effort by Liu and colleagues to characterize such tools. A paper published last year outlined the specificity profile for a similar genetic tool, called a zinc finger nuclease, and the lab has also submitted for publication a third paper — on a genome-engineering technique called TALEs (transcription activator-like effectors).While it holds promise for manipulating the human genome, the Cas9 system originated as the basis for the immune system in bacteria.Unlike the human immune system, which produces antibodies to protect against disease, bacteria incorporate a small part of a pathogen’s DNA into their own genome. Using that segment of foreign DNA to program the Cas9 machine, bacteria can fight off later infections.Using Cas9 in the lab begins with researchers identifying a unique site of interest, typically between 20 and 23 base pairs in length from the billions that make up the genome.Researchers then design a single strand of “guide” RNA that matches only the target segment of DNA. When the Cas9 machine and the guide RNA encounter the target DNA site, Cas9 performs its function. Cas9 cuts DNA naturally, but researchers have engineered Cas9 variants that instead turn on or turn off the expression of targeted genes.The problem, Liu explained, is that although the Cas9/RNA complex in theory can bind only to a specific location in the genome, its accuracy had never been fully studied.“We can design RNA that is a perfect match for a specific DNA locus, but your genome is huge,” he said. “Somewhere else in your genome there will be a sequence that might be very similar. The question is: If there is another site in your genome that differs from the target sequence by just a single base, or two bases, or four bases, will Cas9 still cut these off-target sites?”Researchers also addressed a number of other questions, including whether multiple mismatches at various locations in the targeted DNA were tolerated, whether mismatches of the 20-base pair sequence mattered more or less based on their position across the guide RNA, and how the architecture of the guide RNA might affect the system’s accuracy.They found that while the entire RNA sequence is important in delivering Cas9 to the proper location, the tolerance for errors can change depending on what site in the genome is targeted and where the mismatches occur across the guide RNA sequence.Perhaps most importantly, he said, researchers found that both increasing the concentration of Cas9 and changing the architecture of the guide RNA to increase its activity led to a decrease in accuracy.“A key message is that there is a tradeoff between activity and specificity,” Liu said. “That’s an important lesson, because when scientists develop these tools into — hopefully — therapeutics, they need to make sure that as they improve the activity they’re not introducing new off-target cleavage effects.”To avoid those problems going forward, Liu and other researchers are working to engineer versions of Cas9 — as well as zinc fingers and TALEs — that are even more accurate than the system evolved by nature.If Cas9 becomes a valuable tool for research and future therapies, Liu said, a detailed understanding of the principles that determine its DNA targeting specificity will play a key role.“For obvious reasons, scientists and doctors are very wary of manipulating our genome in ways that are unknown to us,” Liu said. “This data highlights the need to be very careful because some sequences with several mismatches can still be targeted by Cas9.”
Sign up for our COVID-19 newsletter to stay up-to-date on the latest coronavirus news throughout New York A celebrity food critic’s husband is discovered slain in their multi-million-dollar Upper East Side townhouse, his throat slashed, butt cheek missing and naked corpse garnished in parsley, garlic and Parmesan cheese. The couple’s husky, Skippy, is guarding the body.Enter F.X. Shepherd, pet columnist for the daily tabloid New York Mail, mistakenly sent to cover the murder by his Australian overlords/editors instead of the real cops reporter, who’s out on “holiday” and has the same last name. The request interrupts Shepherd’s chicken souvlaki lunch and kicks off a quest for the truth that transports readers on an inside tour of the salaciously cutthroat-bloodlust world of tabloid journalism and the grisly, backbreaking, raw shoeleather work of crime and court reporting in New York City.Kieran Crowley, a bestselling author and award-winning investigative journalist formerly of the New York Post, knows the subject matter inside-out, having covered countless murders and trials and making it his personal hobby along the way to find evidence overlooked by NYPD crime scene detectives.The man is a legend, a master of his craft, and Hack is a seamlessly flowing, imaginative translation of these realms, blended together in exciting, suspenseful and oftentimes hilariously moving prose that reads like a conversation while serving as engrossing fiction, compelling insight and eye-opening commentary. It’s a joy to read and captures the imagination from the start.Crowley is not just a monster journalist, he’s also one hell of a storyteller. Nails it.
Sign up for our COVID-19 newsletter to stay up-to-date on the latest coronavirus news throughout New York A record-breaking storm that pounded Long Island early Wednesday and paralyzed local roadways is being blamed for at least one death, Suffolk County police said. The driver of a Jeep Liberty lost control of his vehicle in Melville near Route 110 on the Long Island Expressway around 5 a.m. and was struck by a tractor trailer, police said. The SUV slammed into a guardrail and then became engulfed in flames, police said. The driver was pronounced dead at the scene. The man’s name is being withheld pending positive identification by the Suffolk County Medical Examiner’s office, police said. The 52-year-old driver of the tractor trailer, owned by JVB Transport, sustained minor injuries, police said. The trailer was carrying waste oil. Officials said the crash was weather related. More than a foot of rain fell on Long Island early Wednesday morning. Tim Morrin, a meteorologist with the National Weather Service, said 5 inches of rain fell in some areas between 3 a.m. and 4 a.m.The powerful storm submerged dozens of vehicles and left countless others abandoned.
West Java governor Ridwan Kamil says his administration plans to conduct rapid tests to detect COVID-19 in sports stadiums as soon as his area receives testing kits from the central government. For now, the testing will be prioritized for people in Greater Jakarta and Greater Bandung since both areas have the most COVID-19 cases based on data from the Health Ministry. Out of 55 positive cases in West Java, 41 are from Bogor, Depok and Bekasi. “The rest of them are not from Bogor, Depok, or Bekasi. Their places of origin have been confirmed through their identity cards,” Ridwan said during a coordination meeting on Sunday. The West Java administration is reportedly to receive 8,000 to 10,000 rapid test kits from Jakarta.The administration is to distribute the test kits in three venues, namely the Patriot Candrabaga stadium in Bekasi, the Pakansari stadium in Bogor and the Si Jalak Harupat stadium in Bandung. Each location is to receive 2,000.The Candrabaga stadium is to be used to test those from Bekasi, Bekasi regency and Karawang. The Pakansari stadium is to be used to test those from Bogor city, Bogor regency and Depok, while the Si Jalak Harupat stadium is to be used to test those from the Greater Bandung area. Read also: Some 70,000 Indonesians could be infected with COVID-19 before Ramadan, scientists sayRidwan stated that the stadiums were chosen as the testing venues after learning from the experiences of other countries in conducting mass testing. The governor was convinced of the use of sports stadiums as the most effective way to conduct testing because it minimizes close-ranged physical interaction among people throughout the event.Ridwan added that the testing would be conducted with a drive-through scheme, by which individuals are to be tested while they are inside their cars. “The rapid test will use blood samples. It can be detected within minutes. If the result is negative, they are allowed to go home. But if the result is positive, they have to move to another location in the stadium,” Ridwan said. Ridwan had asked each regional government to assign at least 30 officers to prepare for the test. They will be tasked to greet the public, conduct the test, manage the incoming vehicles and send the people off. He suggested that people who wished to be tested should register online. If there is an individual who wants to participate but they do not possess a car, Ridwan said he would ask the community unit head to give them a ride. He said he hopes many people would be able to get tested within a short time. “I already consulted with the National Disaster Mitigation Agency [over the testing procedure]. “We will manage the distance between each vehicle. Hopefully we will be able to receive the results within days,” Ridwan said.The mass testing mechanism in West Java is to be different from Jakarta as each regional administration was welcome to create its own model, added the governor.The rapid test would prioritize people who have had contact with COVID-19 patients, those who are under COVID-19 monitoring and those who have contact with people under COVID-19 monitoring.The next batch of the test is aimed at medical workers who have direct interaction with COVID-19 patients. “The third is [for those working in] transportation, such as in terminals and gates. And the next test is for those whose line of work requires them to interact with a lot of people, such as ulema,” Ridwan said. (dpk)Topics :
French energy giant Total has closed the acquisition of Engie’s portfolio of upstream liquefied natural gas (LNG) assets for an overall enterprise value of USD 1.5 billion.Should the oil market mark a major improvement in the coming years, Total’s bill could be increased by additional USD 550 million.The takeover, revealed back in November 2017, has secured Total the second place on global scale of LNG players.The portfolio includes participating interests in an LNG tanker fleet, liquefaction plants, notably the Cameron LNG project in the US, long term LNG sales and purchase agreements, as well as access to regasification capacities in Europe.The move will see the company’s fleet increase to 18 LNG carriers, of which 2 are floating storage and regasification units (FSRUs).“Acquiring Engie’s LNG business is a real step change for Total allowing us to leverage size and flexibility in the fast growing and increasingly commoditized LNG market. This transaction makes Total the second largest global LNG player among the majors with a worldwide market share of 10% and the group will manage an overall LNG portfolio of around 40 Mt per year by 2020. It also helps us to build a position in the US LNG market, with the 16.6% stake in the Cameron LNG project,” commented Patrick Pouyanné, Chairman & Chief Executive Officer of Total.Following the transaction, Total takes over the teams in charge of the upstream LNG activities at Engie.The move is in line with Engie’s strategy to reduce its exposure to commodity prices. The French utility company said it would keep its downstream activities, including the regasification infrastructures and LNG retail end-customer sales. The company is refocusing on three key businesses: low carbon power generation, infrastructures – notably gas, and integrated downstream customer solutions.
By Greg AregoniSTURGEON BAY, Wis. (July 26) – Billy Lemieux was a star-studded Man in Door County over the weekend.Not only did he rank in 135th place out of 160 players at the M.A.C softball tournament, he decided to double up on feature wins at Thunderhill Raceway on Sunday night. Lemieux earned wins in both the IMCA Sunoco Stock Car and local street stock events.A lone caution would fly on lap 11 of the Stock Car main and allowed LeMieux to come into play. He rode around Suchocki on top and cruised over the final laps.Other winners included Tyler Hackett in the Xtreme Motor Sports IMCA Modifieds, Jarred VanLaanen in the Karl Chevrolet Northern SportMods and Dave Schmidt in the IMCA Sunoco Hobby Stocks.
President of the Guyana Boxing Association (GBA) yesterday commenced a 100-mile walk in order to raise finds to send a team to the Caribbean Development Tournament.Up to last evening Ninvalle and his group were closing in on New Amsterdam, having started at Number 43 Village, Corentyne.Here the GBA president (second from left) pose with a part of his team which includes Ursula Parris, wife of Guyana’s only Olympic medallist Michael Parris.
Facebook Twitter Google+ The Syracuse women’s lacrosse team fell to Georgetown 12-8 on Saturday, snapping its two-game winning streak. The loss also ended SU’s undefeated start to Big East play, dropping it to 3-1 in conference games and 5-7 overall.Alyssa Murray, Sarah Holden and Katie Webster had two goals apiece for the Orange in the loss. But it wasn’t enough against a Georgetown team that simply dominated SU in the second half. Despite holding a 6-5 halftime lead, the Orange could not convert in the second half and was outscored 7-2.Down 8-5 after SU scored the first two goals of the second half, the Hoyas went on a 7-0 run to close the game. The Orange, which had scored two goals in less than five minutes to start the half, was held scoreless for the final 25-plus minutes of the game.The freshman Murray led SU with four points in the game. Attack Michelle Tumolo had zero goals on three shots but had two assists. Goaltender Liz Hogan had nine saves.SU won more draw controls than the Hoyas but was dominated in the groundball battle, losing 18-5. The Orange also committed 16 turnovers, five more than Georgetown.AdvertisementThis is placeholder textWith the win, the Hoyas stayed perfect in Big East play. SU, meanwhile, has two straight Big East games ahead on its schedule, starting with Louisville on Thursday at 5 p.m. in the Carrier Dome.Track and fieldThe Syracuse track and field team traveled to two different meets this weekend, adding even more Big East championship qualifiers to an already lengthy list.The long distance team went back to head coach Chris Fox’s early coaching roots, running in the Kent Taylor-Joe Hilton Carolina Invitational. Fox’s first coaching job was at North Carolina.Andrew Nelson became SU’s most recent qualifier for the Big East championship, with a time of 3:53.85 in the 1,500-meter run. Overall, he finished 27th.Other long distance runners who posted solid times were Robert Molke and Lauren Penney. The sophomore Molke finished third in the 3,000-meter steeplechase. Penney, a junior, finished third in the 1,500-meter run.As for the other meet, the Auburn War Eagle Invitational, 12 athletes met qualifying times for the Big East. Four athletes met times for the conference championship.Hurdlers Donald Pollitt and Matthew Callanan both recorded personal-best times, finishing sixth and seventh. Pollitt ran his heat in 14.51. Callanan ran his in 14.56.SaDe Lewis nabbed an 18th-place finish in the 100-meter hurdles with a personal-best time of 14.44.In the field, junior Ieva Staponkute placed fifth, meeting Big East and ECAC qualifying marks.Senior Kelsey Rubeor met her personal best in the long jump and shot put.Frank Taylor finished eighth in the long jump with a leap of 6.97 meters.On the outdoor season, Syracuse has 33 players who have qualified for the Big East championship that takes place in early May.— Compiled by The Daily Orange Sports staff Published on April 17, 2011 at 12:00 pm Comments
Published on September 28, 2015 at 9:07 pm Contact Connor: [email protected] | @connorgrossman Less than a month into life as an American soccer player, Andreas Jenssen has found himself in the wrong spot at the wrong time.Minutes after substituting into Friday’s game, he tried to get open downfield but slipped and fell on his back. He stood up and wiped off his muddy hand, blankly staring at the fresh divot in the ground.As Syracuse formed its customary running-in-place circle before the second-half kickoff, Jenssen blindly turned around to sprint to his position and immediately bumped into the passing referee.The bumbling 5-foot-7 Jenssen has very much played the part of a freshman displaced across the Atlantic Ocean from his home in Lommendalen, Norway.But with snapshots of clumsiness has come a learning curve that he’s adapted to, already garnering appreciation from his teammates for his relentless, cerebral style of play.AdvertisementThis is placeholder text“I like to call him a little bulldog,” midfielder Liam Callahan said.Jenssen is one of a select few head coach Ian McIntyre has called upon to enter games off the bench, usually slotting him into the center midfield. It’s a role he’s comfortably settled into after a “culture shock” admittedly got the best of him as an initial starter for SU who was playing in Norway two weeks prior to his first game.The second shortest player on the Orange isn’t trying to fool opponents with overbearing strength — he acknowledged he can’t contribute so much on long balls.But he’s been able to lean back on his short, simple passing game to help the ball flow through the midfield.It was the only thing he could focus on in his debut against Georgetown — a game he hardly remembers.“I was nervous, so I just wanted to make secure passes,” Jenssen said. “I wanted to impress and show a good first impression. I just remember running a lot.”He’s had to come to grips with a faster-paced American style of soccer — a product of unlimited substitutions allowing coaches to enter and re-enter rested players who come at you “100 miles per hour.”Emphasis on tempo of the game has forced Jenssen to rethink how elaborate he can be with his technique, and instead focus on the quickest move he can make. When receiving a throw-in against Pittsburgh on Friday, Jenssen immediately settled the ball to his feet.Instead of turning and attempting a play in the box, he quickly dished it off to midfielder Oyvind Alseth. He used his superior angle to the goal and launched a cross to the center of the box that resulted in a Noah Rhynhart goal.“You kind of need to be thrown into (the game),” Jenssen said. “You can only learn so much from practice, you really need to experience the game.“It’s totally different.”In the Orange’s 5-0 win over the Panthers, Jenssen was subbed in for midfielder Korab Syla with 15 minutes remaining in the first half. Immediately, Jenssen took over duties commanding the central midfield, pushing Alseth out wide to cover the territory Syla once was.The result was offensive fireworks — a season-high five goals for the Orange and three assists from Alseth in his newfound spot on the wing. Jenssen didn’t get his name on the scoresheet, but the domino effect of the scoring was rooted in his entrance into the game.He’s the unexpected trump card McIntyre has been able to play this season to maintain fluidity in his offense, despite the slippery ground or errant referees in his way.“He’s a player we talk about joining the dots — a smart guy that can keep the ball moving,” McIntyre said. “He’s sees the next pass.” Comments Facebook Twitter Google+