Hope against disease targeting children

first_imgHarvard Stem Cell Institute (HSCI) researchers studying spinal muscular atrophy (SMA) have found what they term “surprising similarities” between this childhood disorder that attacks motor neurons and amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig’s disease.The findings have been published online by the journal Cell Stem Cell.The research team led by HSCI principal faculty member Lee Rubin uncovered molecular changes that explain, at least in part, why motor neurons rather than others are affected by the illness. Unlike ALS and other neurodegenerative diseases, which tend to manifest later in life, SMA strikes infants. Unlike ALS, SMA is a genetic disorder that causes a range of outcomes, with the milder form leaving some children confined to wheelchairs, and the more severe form causing paralysis and death before the second birthday.Though not as well-known as ALS, SMA is “the most frequent fatal genetic disease of young children,” said Rubin, a professor in Harvard’s Department of Stem Cell and Regenerative Biology (HSCRB). About one in 50 people are carriers of SMA and about one in 5,000 children are born with the disease.Rubin said researchers are still working to determine the mechanisms of SMA. “It has never been clear why motor neurons — which relay signals from the brain to the muscles via the spinal column — die selectively,” Rubin said. “It is clear motor neurons die well before other kinds of cells, even other kinds of spinal-cord neurons, and the mystery has been trying to understand that.”A research team composed of HSCI investigators at the Broad Institute of Harvard and MIT and HSCRB, including HSCI principal faculty member John Rinn, worked in collaboration with the SMA Foundation’s Pediatric Neuromuscular Clinical Research Network and Wendy Chung from Columbia University College of Physicians and Surgeons to make neurons from donors with SMA of varying degrees of severity.The researchers first determined that the neurons in a dish behaved similarly to the way neurons would behave in an SMA patient. Not only did motor neurons die before other types of neurons, but motor neurons derived from patients with severe SMA died very quickly in comparison to those made from patients with a milder form of the disease.Then, using a method of intracellular cell labeling developed in HSCI co-director Doug Melton’s lab, the researchers separated motor neurons from other types of neurons in the dish, carried out an RNA sequencing analysis, and compared SMA motor neurons to those from healthy individuals.Healthy cells have mechanisms that help maintain an appropriate quantity of protein made by genes that are turned on within a given cell. There is a balance between protein production and protein degradation. Over time, neural cells targeted by late-onset neurodegenerative diseases — Parkinson’s, Alzheimer’s, Huntington’s, even ALS — lose their ability to maintain that balance. Proteins build up, and the clutter stresses the cell. If cells cannot resolve the issue, they shut down and die. After a number of cells have died, patients start to experience the effects of their disease.SMA, however, appears to work in the opposite way. There isn’t too much but too little of a specific protein, called survival of motor neuron (SMN), because the gene that codes that protein is broken. The researchers learned that a reduction in this protein affects the cells’ ability to process other proteins normally, leading to a motor neuron stress response. In particular, reduction in SMN causes a reduction in the levels of a chaperone protein that, Rubin said, acts like a protein traffic guard inside motor neurons. When other proteins are not folding correctly, the chaperone will hold up the stop sign, giving the other protein time to fold correctly before moving through the rest of the cell. If there are too few functional chaperones, it causes a protein traffic jam inside the cell. The buildup of these other proteins activates a stress response.When the research team shut off the stress response in the SMA-affected cells, both in culture and in a mouse model, they were able to keep the motor neuron cells from dying. “You could say that ALS and SMA converge on a pathway that causes motor neurons to be stressed,” Rubin said.Even though the two diseases have different origins — one with too much of the disease protein in the cells and the other with too little­­ — the point of convergence may be important, said Rubin. Because they both involve a stress response in motor neurons specifically, it is possible that the two diseases could eventually be treated by one drug.last_img read more

Drive By Truckers Still Rolling

first_imgPhoto by David McClisterAs Patterson Hood sings the chorus in “The Righteous Path,” a hard-hitting standout from the Drive-By Truckers’ new sprawling 35-track live album, his gravelly voice sounds a little more weathered than usual. Not that the wear and tear hasn’t been well earned. Hood is now 51 and he’s been fronting the Truckers alongside his main songwriting foil Mike Cooley for just shy of 20 years. In the two decades since the band emerged from Athens, Ga., it has played approximately 2,000 shows, released 10 studio albums, and had 14 different members. Impossible to calculate but no less relevant to the experience are the number of relentless road miles between gigs, Jack Daniels bottles killed onstage, or the eardrums permanently damaged at the band’s rowdy, deafeningly loud rock shows.DBTcover_Its-Great-To-Be-AliveIt’s Great to Be Alive!, which will be released on October 30, comes across as a grand retrospective that celebrates the Truckers’ scrappy longevity, despite some turmoil. Culled from a three-night stand at the legendary Fillmore Auditorium in San Francisco, the effort finds Hood and Cooley trading tunes that touch every part of the band’s impressively prolific discography.Through the years various line-ups have adjusted the band’s Southern rock sound—a mix of big distorted anthems, twangy thought-provoking ballads and even some of the dusty soul from Hood’s upbringing in Alabama as the son of the bassist of the famed Muscle Shoals Rhythm Section. The common thread, however, has always been Hood and Cooley’s vivid lyrics, which illustrate with brutal honesty many hard-to-swallow aspects of life in the South.That’s on full display in the new live set, as Hood revisits “The Living Bubba,” a tragic story song about a bar musician with AIDS who finds the will to live through his nightly shows that first surfaced on the Truckers’ primitive 1998 debut Gangstabilly. Cooley shines on the band’s more recent material, particularly the politically charged “English Oceans,” where he tells the crowd a story about growing up in Alabama and remembering being embarrassed when a visit from then-President Jimmy Carter to his hometown was interrupted by the KKK.Make no mistake: the Truckers’ lead songwriters are both proud of where they come from. You can hear it when Hood gets personal looking back at his 1999 song “Box of Spiders,” written for his grandparents. But they’ve also never been willing to sugarcoat the region’s shortcomings. The Truckers’ critical breakout came after the 2001 release of Southern Rock Opera, a two-disc concept album about growing up in the South, creatively filtered through reverence for Lynyrd Skynyrd. Hood referenced the album in July when he wrote a poignant op-ed in the New York Times Magazine about the Confederate Flag controversy that followed the tragic mass shooting at the Emanuel African Methodist Episcopal Church in Charleston, S.C.“The album wrestled with how to be proud of where we came from while acknowledging and condemning the worst parts of our region’s history,” he wrote, while also elaborating on his craft. “As a songwriter, I’ve spent the better part of my career trying to capture both the Southern storytelling tradition and the details the tall tales left out, putting this dialectical narrative into the context of rock songs.”That sums up what’s destined to be the band’s cemented legacy, something worth noting at a time when the group finally seems to have a comfortable roster. The band has admitted to internal discord as notable members have come and gone through the years, including Americana tunesmith Jason Isbell, who wrote some of the band’s most popular songs during his six-year tenure.These days, though, the Truckers play as a lean five-piece outfit that is arguably its tightest incarnation. Hood and Cooley handle the guitars with steadfast drummer Brad Morgan behind the kit. Spunky bassist Matt Patton holds down the low end, and the unsung hero is keyboardist Jay Gonzalez, who shines on It’s Great to Be Alive! by easing the intensity of the distortion with gospel-hued organ accents, funky vamps, and airy piano fills.The new album closes with “Grand Canyon.” The song is a moving elegy for Craig Lieske, a band crew member who passed away suddenly of a heart attack in 2013. It’s meditative and melodic, persisting for more than 13 minutes before patiently reaching a crashing peak that tapers off into piercing single note of feedback. When Hood sings the line, “Lug our sorrows, pains and angers and turn them into play,” it’s a reminder that even with some age on the wheels, his band is still finding creative ways to roll with the punches.last_img read more

Dzeko and Kompany join injury list

first_imgManchester City could face Christmas without any senior strikers and their captain following a costly 1-0 victory at Leicester. Press Association Forward Edin Dzeko suffered a calf injury in the warm-up at the King Power Stadium and skipper Vincent Kompany suffered a recurrence of a hamstring problem 77 minutes into his comeback. Dzeko joins fellow strikers Sergio Aguero and Stevan Jovetic on the sidelines and there is little chance of any of them being fit in the next fortnight. The problems forced Pellegrini to draft 18-year-old forward Jose Angel Pozo into his starting line-up at Leicester and the youngster could now get further chances. Pellegrini said: “We will see with Jose Pozo. We have other young players in the squad Patrick Vieira manages. We will see also another way to play but we are not going to complain about injuries.” The injuries marred City’s latest victory in their Barclays Premier League title defence, although their performance was far from a convincing one. Pellegrini’s men looked lethargic after their Champions League exertions and only another goal from on-loan former England midfielder Frank Lampard separated the sides. Lampard has now scored six goals since joining the club on a short-term loan from sister outfit New York City and his latest display is likely to increase Pellegrini’s desire to extend the deal beyond December. Pellegrini said: “There have been no serious discussions, but we know exactly what we must do. “Frank wants to stay, we want to keep him. Now we must resolve the problem with New York City and MLS. “He is very important. One of the reasons why he played today was because he has scored for me. Frank has been very useful for us in this moment.” Bottom side Leicester made life difficult for the champions in the early stages and City were generally below par. Pellegrini said: “It was not a beautiful game for the fans, but I don’t remember Joe Hart had any problems in our goal. “Leicester did not really have any chances because we defended well. I don’t think we played well, but it was not the target to play well in this game because it is very difficult to play with Leicester with 72 hours to recover from the last game and also after we had to fly back from Italy.” Leicester boss Nigel Pearson was pleased with the efforts of his side, even if they counted for little. He said: “It was a disappointing result for us, one that I don’t think we necessarily deserved, but we have got to deal with it – move on. There is not a lot we can do about it now. “I was very pleased with the performance, but what we are looking for is results. “Unfortunately we have been unable to break them down. Games like that when you can’t break teams down, you have got to keep a clean sheet. “We were undone just before half-time and that remains a frustration for us.” Pearson, who was recently involved in an exchange with a disgruntled fan, received some good backing from supporters. He said: “I am not dismissing that, it is positive, but the important thing is the supporters stay behind the players. My philosophy is always to continue working in the way I feel is right. “It is clear people have been frustrated with how things have gone in the last couple of months but I think it is too easy to over-emphasise the negatives. The performance today is something to be encouraged by.” Pearson was puzzled by and played down the significance of a picture of a fan apparently being ushered away from him by a steward early in the game. He said: “I think that was David Nugent’s dad. People may be trying to exploit potential situations to expand on something that happened last week. Quite frankly, I’m not interested.” Kompany might also be out of action until the new year. Manager Manuel Pellegrini said: “It is difficult immediately after the game to know what happened to both of them. “Vincent Kompany has the same problem in his hamstring he had a few weeks ago, that is one of the reasons he didn’t play on Wednesday in Rome. “Edin Dzeko felt a muscle injury in his calf. Maybe he will also be a couple of weeks out. I think it is impossible (for him to return) before the new year. “We will see with Vincent how hard his injury is but I think it will be very difficult for them to play before the next year.” Dzeko had made only two appearances since returning from another calf injury while Jovetic, who was a substitute in Wednesday’s Champions League win at Roma, has had niggly hamstring issues in recent weeks. Pellegrini said: “Jovetic also has a problem in his hamstring after the game against Rome. It is not a very important injury but I think he will also need a couple of weeks.” Top scorer Aguero damaged knee ligaments in last weekend’s victory over Everton and could be sidelined for up to eight weeks. last_img read more

Hearn Rules Out Joshua/Fury Possible Fight in UK

first_imgAnthony Joshua’s promoter Eddie Hearn has suggested a potential fight with British rival Tyson Fury would not go ahead in the UK.There is massive demand for the two British heavyweights to battle it out in the near future but Hearn has ruled out the UK hosting the fight because the government doesn’t ‘invest’ in mega events.When asked whether the possible British showdown would take place in the UK, he told iFL TV: ‘No it won’t. I can’t see how it does. ‘For me, it should happen in the UK and if there’s a way to do it, we’ll do it. But the problem is the money that could be generated.‘Because the government here don’t invest in bringing mega events to the UK, they don’t necessarily need to.‘They’ve got Premier League football games every weekend selling 50,000, 60,000, 80,000.‘But other countries whether it’s Nigeria, Congo, China, Saudi, Qatar, Abu Dhabi, their government, their tourism department, has a huge pot of money that they’re looking to bring major events to showcase their country to the world as a tourism destination.’The decision to hold Joshua’s rematch with Andy Ruiz in Saudi Arabia came in for plenty of criticism from human rights groups, accusing Hearn of helping the state with ‘sportswashing’, the practice of using a big event to improve reputation and change perception of a country with a poor human rights record.The promoter argues that the discrepancy in money available to his fighters makes it a simple decision, saying it comes down to getting the best payday possible.‘Someone messaged me and said, “For f***’s sake Eddie, Saudi Arabia, who cares about the money? You’re so greedy, just do it in England”.‘Do you think I go up to the guys and say, “You can make £150m each to do it in Saudi or £40m in the UK, but Dave on Twitter from Rochdale says you’re a c*** and you gotta do it in England”.‘It doesn’t work like that, have a brain.‘If it was the difference of £10m each… but it’s not, it’s double to go somewhere else. And it can’t be ignored. Especially a fight like that, it’s a one-off.’Share this:FacebookRedditTwitterPrintPinterestEmailWhatsAppSkypeLinkedInTumblrPocketTelegramlast_img read more

NBA: How Russell Westbrook, D’Angelo Russell fared in their debuts

first_img 10 months ago NBA: Watch Giannis Antetokounmpo score first triple-double of season 10 months ago NBA anti drug: Deandre Ayton and other times when players were banned SUBSCRIBE TO US Westbrook scored 24 points, 16 rebounds, seven assists, and two steals during their match against the Milwaukee Bucks. Though Rockets lost the match 111-117, Westbrook was the top scorer for his team. The 2017 NBA MVP was just three assists away from scoring a triple-double during his debut match. During Q4, Westbrook scored 16 of the 24 points by Rockets. He received ‘Brodie chants’ by the audience at the Toyota Center while he was at the free-throw line towards the end of the game. If not for Westbrook, Rockets would have lost the game with a much larger margin. Also read | NBA 2019-20: Boston Celtics vs Toronto Raptors player ratingsNBA 2019: D’Angelo Russell’s debut with the Golden State Warriors WATCH US LIVE Written By #DubNation @Dloading scores 20 PTS and hands out 8 AST in his @warriors debut. #KiaTipOff19 pic.twitter.com/0JICkM3bTj— NBA (@NBA) October 25, 2019 Russell dished out 20 points and eight assists for the Warriors during their season opener against the LA Clippers. Even though Stephen Curry was the top scorer, Russell managed to score 20 points. However, Warriors lost the 122-141 encounter. He went on a 10-0 run for the Warriors’ first points to bring the team back in the game. However, the latter part of his debut was forgettable due to the Warriors losing the match. Also read | NBA 2019-20: Brooklyn Nets vs New York Knicks player ratingsALso read | NBA 2019-20: Los Angeles Lakers vs Utah Jazz player ratings and result First Published: 28th October, 2019 17:21 IST WE RECOMMEND Devika Pawar center_img 10 months ago NBA: Draymond Green regrets fight with ex-GSW teammate Kevin Durant LIVE TV FOLLOW US Last Updated: 28th October, 2019 17:21 IST NBA: How Russell Westbrook, D’Angelo Russell Fared In Their Debuts Russell Westbrook debuted with the Houston Rockets and D’Angelo Russell debuted with the Golden State Warriors. Let us look at how they have performed. 10 months ago NBA: Player ratings from Clippers’ dominating win over the Warriors Strong debut for @russwest44 🚀🏀 24 PTS💪 16 REB➡️ 7 AST pic.twitter.com/9AuoNFR4CR— Houston Rockets (@HoustonRockets) October 25, 2019 Russell Westbrook and D’Angelo Russell were two of the many NBA players who have changed their team this offseason. Westbrook and Russell made their debut in front of their home crowd with just three games on the slate. Westbrook now plays for the Houston Rockets while Russell plays for the Golden State Warriors. Let us take a look at how both of them fared during their debuts.Also read | NBA anti drug: Deandre Ayton and other times when players were bannedNBA 2019-20: Russell Westbrook’s debut with the Houston Rockets 10 months ago NBA 2019-20: Boston Celtics vs Toronto Raptors player ratings COMMENTlast_img read more