Normally, the lining of blood vessels, or endothelium, acts like Teflon when at rest, ignoring the many cells and other factors rushing by in the bloodstream.But in response to inflammatory signals, as well as other stimuli, endothelial cells change suddenly and dramatically — sending out beacons to attract inflammatory cells, changing their surface so those cells can stick to and enter tissues, and initiating a complex cascade of responses essential to fighting infection and dealing with injury.Unfortunately, these same endothelial responses also promote atherosclerosis, the build-up of plaque in arteries that cause heart attacks, strokes, and other inflammatory diseases.A study led by researchers at two Harvard affiliates, Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, is the first to demonstrate that BET bromodomain-containing proteins help execute inflammation in the endothelium while inhibition of BET bromodomain can significantly decrease atherosclerosis in vivo.The study was published online Sept. 25 in Molecular Cell.‘We have identified a set of compounds we developed initially for cancer that halt the progression of coronary disease.’ — James E. Bradner“By using tools that interrogate the entire genome, it has been exciting to uncover how inflammatory signals known to promote atherosclerosis employ BET bromodomain-containing proteins as an epigenetic means of directing entire programs of endothelial gene expression,” said co-corresponding senior author Jorge Plutzky of BWH Preventive Cardiology, an associate professor of medicine at Harvard Medical School (HMS). “BET bromodomain-containing proteins have been studied in cancer for some time, where they are in therapeutic trials, but now we have mechanistic evidence for how BETs and their inhibition can impact endothelial inflammation and atherosclerosis.”Looking at the epigenome of endothelial cells, researchers sought to get a better understanding of the inflammatory response responsible for the initiation of atherosclerosis by characterizing the dynamics, structure, and function of the elements that regulate the response. This work involved harnessing the expertise of different teams of researchers, including James E. Bradner of Dana-Farber Cancer Institute, who developed one of the first BET inhibitors.“This research demonstrates how environmental influences lead to dynamic changes in genome structure leading to disease states, here the inflammation associated with heart disease,” said Bradner, an associate professor of medicine at HMS. “Further, we have identified a set of compounds we developed initially for cancer that halt the progression of coronary disease. These unexpected findings exemplify the very best outcome of open, interdisciplinary science.”In preclinical models, the researchers found that activating NF-kB, a canonical mediator of inflammation, rapidly redistributed the BET protein known as BRD4 to chromosomal sites where super enhancers driving expression of nearby inflammatory genes are located. Bromodomains are amino acid regions that bind to specifically modified sites on histones, the proteins around which DNA is coiled. By binding to these amino acid regions, BET bromodomain inhibitors block the assembly of protein complexes that drive expression of certain genes. In these studies, inhibiting BET bromodomains turned off an inflammatory program in human endothelial cells, decreased white blood cells adhering to endothelial cells, and decreased atherosclerosis in mice.“By offering new perspectives on transcriptional programs in inflammation and atherosclerosis and how to identify previously unrecognized players in those responses, these studies can offer new therapeutic approaches for atherosclerosis and other inflammatory conditions,” said Plutzky. “It also shows what collaborative teams thinking about completely different disease states can uncover by working together.”
– Advertisement – – Advertisement – Traders work on the floor of the New York Stock Exchange on Nov. 4th. 2020.NYSE (This story is for CNBC Pro subscribers only).The stock market was roaring on Monday after Pfizer announced that its Covid-19 vaccine candidate appeared to be more than 90% effective in its phase-three trial, creating a rush of money into Wall Street’s favorite plays that stand to benefit from a vaccine that works.As several vaccine candidates worked their way through the regulatory process in recent months, Wall Street strategists and analysts put together lists and recommendations of the stocks most likely to bounce on positive vaccine news. Pfizer said Monday that it plans to apply for emergency use authorization for its vaccine by the end of the month. – Advertisement –
Officials in Miami have issued a community notice about the second round of King Tides that is said to take place on select dates through October 3rd. While the flooding from King tides is a reoccurring event, officials are reporting that the tides this year has been extremely high and are causing more flooding than usual, especially in low laying areas and areas with poor drainage systems.Rising water levels at the Pelican Harbor Marina have already been reported.Some reports state that water levels are expected to be 3 feet higher than normal in some areas.The City of Miami says they are making preparations for the coming floods including putting temporary water pumps and generators in place to reduce the effects of flooding.They have also created a webpage with tips on how you can keep your family and your property safe during this time.
Carolina Panthers’ Kelvin Benjamin (13) is tackled by Pittsburgh Steelers’ Ike Taylor (24) during the second half of an NFL football game in Charlotte, N.C., Sunday, Sept. 21, 2014. (AP Photo/Bob Leverone)CHARLOTTE, N.C. (AP) – Pittsburgh cornerback Ike Taylor broke his right forearm in the Steelers’ 37-19 victory over the Carolina Panthers on Sunday night.Steelers coach Mike Tomlin said it was unclear how long Taylor will be out.Tomlin said linebackers Ryan Shazier and Jarvis Jones, who also left the game with injuries, will be evaluated Monday.Taylor was injured in the third quarter when he made a break on a pass play and was hit on his right arm by teammate Lawrence Timmons, who was converging on the tackle. Trainers immediately rushed to Taylor’s side and put an air cast on his arm.He was seen wearing a hard cast after the game.Earlier, Shazier left with a right knee injury. Jones left with a right wrist injury in the second half and will not return.For the Panthers, running back Jonathan Stewart was taken to the locker room with a right knee contusion and did not return and will be reevaluated on Monday. He started in place of DeAngelo Williams, who did not play because of a hamstring injury.Fullback Mike Tolbert also left with a leg injury.___AP NFL website: www.pro32.ap.org and www.twitter.com/AP_NFL
“SALLY” IS A single mother who had been working as a caseworker for a mental health counseling facility for adults, until she became a victim of downsizing and has spent the last two years unemployed. Things were tough for her while collecting unemployment insurance, but that has ended and Sally has had to do what she could to provide food for herself and her 6-year-old daughter. And that meant getting what has traditionally been called food stamps, public assistance to help her stretch her exceedingly meager budget.Sally is not the real name of the 40-year-old Neptune resident and college graduate, but she asked that her name be withheld. Sally’s story has become more common here in Monmouth County.“You just feel so helpless; sometimes it feels so hopeless,” she said recently.Kathleen Weir, the deputy director of the Monmouth County Division of Social Services, shared the startling news that her offices has seen an 83 percent increase since Oct. 2009 in active case loads for the Supplemental Nutritional Assistance Program, or SNAP, previously known as food stamps, a federally funded public assistance program. According to Weir the current number of active cases as of last month stands at 16,585. By active case, Weir explained that the number of those applying has remained fairly consistent since 2009, but this indicates more are meeting the eligibility requirements.On the state level, enrollment has increased by more than 24 percent, by about 150,000 individuals, from March 2010 to March 2011, according to information provided by Nicole Brossoie, assistant commissioner of public affairs for the New Jersey Department of Human Services.During that same time period, according to Brossoie, the number of households on the program grew by a little more than 25 percent or about 80,000 additional homes.When money gets tight, when people try to live on less as they lose their jobs or find themselves in difficult straits, they will make changes, cut expenses. But “Food is not a discretionary expense. You need it to live,” this week said Arti Sinha, a Monmouth County human services specialist.Sinha said the makeup of the clients has been changing in these last few economically difficult years. “I’ve seen more retirees then I did in the past,” as those on fixed incomes try to address the rising cost of groceries. “I’m seeing younger families who in the past were able to make it,” but now can’t, she said.“I had people in the past say, ‘There are people who need it more than me. I’m not going to apply. But now I need it,’” Sinha said of her experiences. “That is the phrase I keep hearing over and over, that people are coming because they must, it’s imperative.”“It’s very said.”There has also been a change in some of the geography. There are traditional pockets within the county, most of them in the eastern portion, where clients would live. Now, though, “We’ve seen a lot of clients that we would never have seen in the past,” from some of the western and affluent communities, such as Manalapan and Marlboro, Allentown, Millstone, she said.“We’ve definitely seen quite an influx,” she said.A family of four would qualify for SNAP if their gross income level doesn’t exceed $3,447 per month. And families can include children up to age 22. “If you live together and eat together you are considered part of the same household,” according to Sinha. There are other deductions available for housing, utilities and medical expenses. At that income level a family would be eligible for $668 a month from the program for food. And “the bigger the household size, the higher the income threshold,” she said.But for some that allowance isn’t enough to carry them through the month, forcing them to go to food pantries.One woman told Sinha how she buys mac and cheese and frozen hot dogs for her three young children. “’I buy things based on how long I can make them last,’” she told Sinha.“You’re buying based on that it’s filling, rather than maybe nutritional, and you look for what’s on sale,” Sinha said, relating her clients’ experience.Sinha and her colleagues have seen their caseloads triple, which has its impact on them as well. “Everyone’s story is so compelling,” and she and her co-workers worry about suffering from compassion fatigue. “You wake up at 3 o’clock [a.m.] thinking about finishing a case,” she said.“I truly feel for families with children and the elderly,” Sinha said. “They are the most vulnerable of our population.”Sally in her work sometimes would have to assist other vulnerable populations, those emotionally and mentally challenged, to maneuver the system to get them benefits, never thinking she would be in a similar situation she said.“I’ve heard a lot of complaints,” from those that had been her clients. Some lived in single room occupancy hotels, under housing vouchers. But those facilities usually don’t allow hot plates or refrigerators, and the food program doesn’t allow clients to purchase prepared foods, making it difficult for them, she said.SNAP also doesn’t cover paper products, which can be another problem for people, Sally said.Sally has been surviving on intermittent work in her field and some help from her family. But looking for work has been “horrible” and she and her daughter will have to move in with her parents.For now the food stamps provide a necessary lifeline, but “It’s limited, it’s once a month and it’s never enough,” she said.
Tony Award-winner Alice Ripley stars in the one-woman play “The Pink Unicorn” at Holmdel Theatre Jan. 30-31. Photo courtesy Holmdel Theatre Co. Cook is also a producer for “The Pink Unicorn.” Amy E. Jones is director and Tina Scariano is stage manager. Ripley is looking forward to spreading a message of love, hope and understanding with the Holmdel audience. “There’s no doubt thisreally rocks Trisha’s world,”said Ripley. “It blindsides her.I don’t have any kids, but I’mhonored to be chosen as thevoice for this character. WhatTrisha is going through, a lotof people are facing.” “I can’t wait to tell this important and timely story with the brilliant Alice Ripley and this incredible team again,” she said. Arts and entertainment reporter Mary Ann Bourbeau can be reached at [email protected] Ripley won critical acclaim for her performance as Diana Goodman in the Pulitzer Prize-winning show, “Next to Normal,” for which she took home the 2009 Tony Award for Best Actress in a Musical. She also appeared on Broadway in “Side Show” (Tony nomination), “American Psycho,” “The Rocky Horror Show,” “Sunset Boulevard,” “The Who’s Tommy” and “Les Miserables.” “The Pink Unicorn” was originally produced in 2013 by DogTown Theatre in Washington, D.C. and has since been performed throughout the U.S. and Canada, including a run at United Solo Theatre Festival in New York, where Elise Forier Edie won Best Storyteller. The show was produced Off-Broadway in 2018 by Out of the Box Theatrics and starred Ripley. HOLMDEL – What does a Christian widow living in a conservative Texas town do when her teenage daughter announces she is gender queer and is starting a chapter of the Gay Straight Alliance in her high school? Tickets for “The Pink Unicorn” are $50 and can be purchased at holmdeltheatrecompany.org or by calling the box office at 732-946-0427. “I took one look at the script and it didn’t take me long to say yes,” she said. Liz Flemming, producing consultant and artistic director for Out of the Box Theatrics, is excited to revisit “The Pink Unicorn” with Ripley at the Holmdel Theatre Company’s Duncan Smith Theater. “It’s OK to make mistakes along the way,” she said. “Nobody’s perfect. But if Trisha has to choose between the church and her daughter, it’s no contest.” By Mary Ann Bourbeau “A lot of people are dealing with this issue and it’s important to feel like you can talk about it,” she said. “It’s a happy ending, but it’s not easy getting there. Hopefully, seeing Trisha going through what she goes through will give the audience courage.” This crisis of gender issues is one that Trisha Lee never saw coming. Tony Award winner Alice Ripley brings Trisha to life in a one-woman play called “The Pink Unicorn,” which will be presented as part of Broadway at the Barn at the Holmdel Theatre Jan. 30 and 31. The story begins as amonologue and turns intoan immersive play in whichTrisha makes a lot of wrongchoices, but also a lot ofright choices, said Ripley. “It really hits people in theheart,” she said. “It’s hardfor a kid to say somethinglike that to their parent. Thishelps people understand thatit’s important to keep talkingabout it, and maybe it willhelp give them an idea of thekind of language to use. Wesee this as an introductionto the conversation. If you’recoming from a place of love,that’s a good place to start.” “We are thrilled to have Alice Ripley back in the Barn,” said Colleen Cook, Holmdel Theatre Company’s executive director. In June 2019, she kickedoff Holmdel Theatre’s“Broadway at the Barn”series with her solo show,“Ripley Prescription,” whichwas recently named BestCabaret Performance in the2019 BroadwayWorld NewJersey Awards. Ripley said the humor inflected in Elise Forier Edie’s script helps Trisha get through this situation and come to a place of understanding and acceptance. This article originally appeared in the Jan. 23, 2020 print edition of The Two River Times.
SANTA ANITA HOSTS BREEDERS’ CUP NOV. 4 & 5CHAMPION STELLAR WIND WORKS FOR HIRSCHSMITH BACK HOME FOLLOWING BELMONT SCORESECURITY’S MIKE JACOBELLIS RETIRES TODAYDERBY WINNER NYQUIST BREEZES TOMORROW Brandon Boulanger5861510%21%$159,199 SANTA ANITA STATISTICS Mike Smith45158133%53%$1,014,947 Richard Baltas6410121416%56%$477,060 Doug O’Neill10512222111%52%$872,676 Richard Mandella4195722%51%$724,512 Brayan Pena676589%28%$154,340 James Cassidy4574616%38%$427,845 Rafael Bejarano19044423123%62%$2,523,132 Kent Desormeaux61119618%43%$484,775 FINISH LINES: Kentucky Derby king Nyquist will work five furlongs at 6:30 tomorrow morning under Mario Gutierrez, trainer Doug O’Neill reported Sunday. A decision on his next race is expected in the next few days . . . Coppa, who remained unbeaten in three starts with her win in Belmont Park’s Grade III Victory Ride at 6 ½ furlongs Saturday under Joe Talamo for Phil D’Amato, is being considered for Saratoga’s Grade I, $500,000 Test Stakes for three-year-old fillies at seven furlongs Aug. 6, the trainer said . . . Santa Anita Derby winner Dortmund, a candidate for Del Mar’s San Diego Handicap July 23, worked six furlongs in company Sunday for Bob Baffert in 1:13.20 from the gate. Stablemate Vale Dori got 1:13.40 . . .GOOD LUCK TO TRACK ANNOUNCER MICHAEL WRONA, AS HE AND FIANCE’ KATHY KENNEDY WILL MARRY NEXT SUNDAY IN LAKE TAHOE . . . There are mandatory payouts in the Pick Six and Super High Five today. The total Pick Six pool is expected to exceed $500,000. Tiago Pereira11012161711%41%$539,967 CHAMP STELLAR WIND IN ‘EXCELLENT’ DRILLStellar Wind, champion three-year-old filly of 2015, worked six furlongs in company under Victor Espinoza Sunday in 1:14.20 as she prepares for a rematch with three-time Eclipse Award winner Beholder in the Grade I Clement L. Hirsch Stakes at Del Mar July 30.Beholder and Stellar Wind ran one-two in the Grade I Vanity Mile at Santa Anita June 4.John Sadler, who trains Stellar Wind for the Hronis brothers, Kosta and Peter, had Carnival Lights as her workmate. She was clocked in 1:15.80.“It was an excellent work,” Espinoza said of Stellar Wind. “She was brilliant today. Now she’s ready to go. The Vanity got her fit for the next race and even though it’s against Beholder who’s a champ, too, you never know what will happen. Stellar Wind is doing great.”The Vanity was Stellar Wind’s first race since last Oct. 30, when she finished a troubled second by a neck in the Breeders’ Cup Distaff at Keeneland. (Current Through Saturday, July 9) TrainerSts1st2nd3rdWin%ITM%Money Won Mark Glatt7314151119%55%$503,651 MIKE JACOBELLIS TURNS IN BADGE TODAY After serving for 10 years with Santa Anita Security, which was preceded by a 32-year run with LAPD, Mike Jacobellis will retire from The Great Race Place today and be honored in a Winner’s Circle ceremony following the fourth race.A graduate of Alhambra High School, Jacobellis, who is currently an Area Manager overseeing plain-clothed personnel, leaves a legacy of good will with fans, jockeys, horsemen and fellow employees.“We are very fortunate to have had Mike on staff for the past 10 years,” said Santa Anita Chief of Security, Lou Scalera. “Mike gets along with everyone and he’s an outstanding cop. He retired from LAPD as a Detective Sergeant and he pays attention and follows up on things in a very professional manner.“Although he’s leaving us to spend more time with his family, we will have him here for the Breeders’ Cup in November and we hope to have him next year on big days, like the Santa Anita Derby and the Big ‘Cap.“Given the fact that he’s met so many owners, trainers and jockeys over the years, I’d be surprised if we didn’t see him every now again as a fan. It’s hard not to develop a love for this game when you’re so close to everyone involved in it.” Chad Lindsay731381218%45%$315,100 Martin Pedroza831391216%41%$403,100 Flavien Prat15840272325%57%$1,946,640 Edwin Maldonado15627231717%43%$1,094,450 Bob Baffert561612629%61%$862,103 Stewart Elliott979879%25%$395,200 Tyler Baze19631403816%56%$1,573,731 Peter Eurton4796519%43%$500,660 Simon Callaghan3173223%39%$316,965 JockeyMts1st2nd3rdWin%ITM%Money Won Philip D’Amato992520925%55%$1,606,938 Mario Gutierrez78916612%40%$695,300 Joseph Talamo13926192019%47%$1,527,073 Alonso Quinonez56610711%41%$266,730 HOME COURSE ADVANTAGE FOR BREEDERS’ CUP?Santa Anita hosts the Breeders’ Cup World championships for an unprecedented ninth time come Nov. 4 and 5.Whether it can be a home course advantage or not depends on who you talk to. Trainer Ron Ellis, for one, says there is a benefit in not shipping and running on a track just a hundred yards away in your own back yard.“I think it’s similar to a football team that doesn’t have to play on the road,” said Ellis, who hopes to have his crack sprinter, Masochistic, ready for either the Dirt Mile or the Sprint.“While they’re not necessarily creatures of habit, athletes and horses seem more comfortable in familiar surroundings. The home teams don’t have to travel, nor do horses based at Santa Anita, and that can reduce intangibles such as stress, which doesn’t help.”Bob Baffert, whose horses have flown worldwide, says it makes no never mind to him and his stock.“It’s more of an economic advantage than anything,” said the Hall of Fame trainer who has made Santa Anita his base of operations for more than two decades. “You don’t have to spend any extra money shipping because the horses are here.“There might be a horse or two that wouldn’t have shipped well, but otherwise, I don’t think it’s a big deal. If you have good horses, they’ll come through. All my horses ship well. I ship a lot and they’re used to it. My success rate is pretty high.” Martin Garcia811361416%41%$712,434 Peter Miller591015717%54%$485,955 Mike Puype54117620%44%$360,850 John Sadler65971414%46%$750,278 Fernando Perez10113111113%35%$557,713 Jerry Hollendorfer771581519%49%$1,050,183 SMITH RETURNS FOLLOWING SUBURBAN WIN AT BELMONT PARK Mike Smith, who joined fellow Hall of Famer Gary Stevens for a special Beholder/Songbird poster signing prior to Sunday’s races, was still “feeling it” following his big win aboard Effinex in Saturday’s Grade I, mile and a quarter Suburban Handicap yesterday at Belmont Park.“When he puts it all together, he’s a serious horse. He can run with the best of the best,” said Smith of the Jimmy Jerkins trainee who is pointing to an eventual engagement in the $6 million Breeders’ Cup Classic at Santa Anita on Nov. 5. “He can beat ’em when he puts his mind to it; he’s just not always in a stable frame of mind (jokingly).”Yesterday he was on and ran brilliant . . . Belmont’s a funny track. The size of the track, the turns . . . You can pull the trigger way too soon there and it can play tricks on you . . . but I’ve been there since the ’80s, so it helps to know it. I love going, but I love coming back!” Santiago Gonzalez18323253113%43%$1,138,703 Patrick Gallagher2972224%38%$266,100