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The genetics of regeneration

first_img Drawing inspiration from plants, animals to restore skin tissue Harvard researchers find mature cells revert back to stem cells to boost tissue regeneration and repair in mouse intestines Understanding how the intestine replaces and repairs itself Nanofiber dressings heal wounds, promote regenerationcenter_img When it comes to regeneration, some animals are capable of amazing feats. If you cut off a salamander’s leg, it will grow back. When threatened, some geckos drop their tails to distract their predator, only to regrow them later.Other animals take the process even further. Planarian worms, jellyfish, and sea anemones can actually regenerate their bodies after being cut in half.Led by Assistant Professor of Organismic and Evolutionary Biology Mansi Srivastava, a team of researchers is shedding new light on how animals pull off the feat, along the way uncovering a number of DNA switches that appear to control genes for whole-body regeneration. The study is described in a March 15 paper in Science. Using three-banded panther worms to test the process, Srivastava and Andrew Gehrke, a postdoctoral fellow working in her lab, found that a section of noncoding DNA controls the activation of a “master control gene” called early growth response, or EGR. Once active, EGR controls a number of other processes by switching other genes on or off.“What we found is that this one master gene comes on [and activates] genes that are turning on during regeneration,” Gehrke said. “Basically, what’s going on is the noncoding regions are telling the coding regions to turn on or off, so a good way to think of it is as though they are switches.”For that process to work, Gehrke said, the DNA in the worms’ cells, which normally is tightly folded and compacted, has to change, making new areas available for activation.“A lot of those very tightly packed portions of the genome actually physically become more open,” he said, “because there are regulatory switches in there that have to turn genes on or off. So one of the big findings in this paper is that the genome is very dynamic and really changes during regeneration as different parts are opening and closing.”Before Gehrke and Srivastava could understand the dynamic nature of the worm’s genome, they had to assemble its sequence — no simple feat in itself.“That’s a big part of this paper,” Srivastava said. “We’re releasing the genome of this species, which is important because it’s the first from this phylum. Until now there had been no full genome sequence available.”,It’s also noteworthy, she added, because the three-banded panther worm represents a new model system for studying regeneration.“Previous work on other species helped us learn many things about regeneration,” she said. “But there are some reasons to work with these new worms.” For one thing, they’re in an important phylogenetic position. “So the way they’re related to other animals … allows us to make statements about evolution.” The other reason, she said, is, “They’re really great lab rats. I collected them in the field in Bermuda a number of years ago during my postdoc, and since we’ve brought them into the lab they’re amenable to a lot more tools than some other systems.”While those tools can demonstrate the dynamic nature of the genome during regeneration — Gehrke was able to identify as many as 18,000 regions that change — what’s important, Srivastava said, is how much meaning he was able to derive from studying them. She said the results show that EGR acts like a power switch for regeneration — once it is turned on, other processes can take place, but without it, nothing happens.“We were able to decrease the activity of this gene and we found that if you don’t have EGR, nothing happens,” Srivastava said. “The animals just can’t regenerate. All those downstream genes won’t turn on, so the other switches don’t work, and the whole house goes dark, basically.”While the study reveals new information about how the process works in worms, it also may help explain why it doesn’t work in humans.“It turns out that EGR, the master gene, and the other genes that are being turned on and off downstream are present in other species, including humans,” Gehrke said.“The reason we called this gene in the worms EGR is because when you look at its sequence, it’s similar to a gene that’s already been studied in humans and other animals,” Srivastava said. “If you have human cells in a dish and stress them, whether it’s mechanically or you put toxins on them, they’ll express EGR right away.”The question is, Srivastava said, “If humans can turn on EGR, and not only turn it on, but do it when our cells are injured, why can’t we regenerate? The answer may be that if EGR is the power switch, we think the wiring is different. What EGR is talking to in human cells may be different than what it is talking to in the three-banded panther worm, and what Andrew has done with this study is come up with a way to get at this wiring. So we want to figure out what those connections are, and then apply that to other animals, including vertebrates that can only do more limited regeneration.”Going forward, Srivastava and Gehrke said they hope to investigate whether the genetic switches activated during regeneration are the same as those used during development, and to continue working to better understand the dynamic nature of the genome.,“Now that we know what the switches are for regeneration, we are looking at the switches involved in development, and whether they are the same,” Srivastava said. “Do you just do development over again, or is a different process involved?”The team is also working on understanding the precise ways that EGR and other genes activate the regeneration process, both for three-banded panther worms and for other species as well.In the end, Srivastava and Gehrke said, the study highlights the value of understanding not only the genome, but all of the genome — the noncoding as well as the coding portions.“Only about 2 percent of the genome makes things like proteins,” Gehrke said. “We wanted to know: What is the other 98 percent of the genome doing during whole-body regeneration? People have known for some time that many DNA changes that cause disease are in noncoding regions … but it has been underappreciated for a process like whole-body regeneration.“I think we’ve only just scratched the surface,” he continued. “We’ve looked at some of these switches, but there’s a whole other aspect of how the genome is interacting on a larger scale, not just how pieces open and close. And all of that is important for turning genes on and off, so I think there are multiple layers of this regulatory nature.”“It’s a very natural question to look at the natural world and think, if a gecko can do this, why can’t I?” Srivastava said. “There are many species that can regenerate, and others that can’t, but it turns out if you compare genomes across all animals, most of the genes that we have are also in the three-banded panther worm … so we think that some of these answers are probably not going to come from whether or not certain genes are present, but from how they are wired or networked together, and that answer can only come from the noncoding portion of the genome.”This research was supported with funding from the Milton Fund of Harvard University, the Searle Scholars Program, the Smith Family Foundation, the National Science Foundation, the Helen Hay Whitney Foundation, the Human Frontier Science Program, the National Institutes of Health, the Biomedical Big Training Program at UC Berkeley, the Marthella Foskett Brown Chair in Biological Sciences, and the Howard Hughes Medical Institute. 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Leadership on the front line

first_img Will inequality worsen the toll of the pandemic in the U.S.? Law School’s Food Law and Policy Clinic steps up its efforts in time of pandemic Hundreds of mayors and municipal leaders from across the United States and the world are turning to experts from Harvard for help in managing their cities’ response to the global coronavirus pandemic.In weekly sessions organized by the Bloomberg Harvard City Leadership Initiative and Bloomberg Philanthropies’ Coronavirus Local Response Initiative, nearly 400 mayors and hundreds more senior city officials and leaders are receiving real-time advice on everything from public health to crisis leadership.“The world is facing an unprecedented crisis right now and we haven’t seen the worst of it yet. We know that you, the mayors, are in it right now,” said Jorrit de Jong, faculty director of the Bloomberg Harvard City Leadership Initiative and a senior lecturer in public policy and management at Harvard Kennedy School.The sessions are designed to provide critical public health information and actionable insights on crisis leadership to busy mayors and city leaders who have been forced to redirect their focus in the face of the pandemic. “It’s wonderful we can maintain our learning community, a community of action, while maintaining social distancing,” de Jong said.Jorrit de Jong addressed the virtual gathering of city leaders from across the country.So far, two virtual gatherings have taken place, with special guests including former President Bill Clinton and Tom Frieden, former director of the Centers for Disease Control and Prevention, speaking at the second session. A third event in the series took place Thursday.During the first session, 60 of the participating mayors were displayed on the screen wall of Harvard Business School’s live online classroom, where they posed questions directly to the faculty members. Other participants sent in questions through the video conferencing chat function. While the sessions themselves are limited to mayors and public leaders, Bloomberg Harvard City Leadership Initiative is providing session slides and takeaways on their website so that lessons from the series are available to all.Former New York Mayor Michael Bloomberg addressed the virtually gathered mayors and expressed confidence in their ability to meet the challenge of the coronavirus crisis in their communities, underscoring their importance in moving beyond partisan politics. Josh Sharfstein, vice dean for public health practice and community engagement at Johns Hopkins Bloomberg School of Public Health, then outlined the basics of the coronavirus pandemic and public health guidance to help inform the mayors’ decisions. Sharfstein fielded questions from the city leaders about best practices for social distancing, misinformation about the coronavirus, and virus transmission.“This is going to be a matter of self-reliance, and that’s always true, actually, in large disasters,” Dutch Leonard said. “Almost all of the work comes from inside the community.”The second half of the session featured Kennedy School faculty members Dutch Leonard, the George F. Baker Jr. Professor of Public Management at HKS and Eliot I. Snider and Family Professor of Business Administration at HBS, and Juliette Kayyem, the Belfer Senior Lecturer in International Security. They focused on three areas: where we are in the crisis; how mayors can pivot and adapt; and what political challenges stand in the way.Where do we stand right now?Kayyem, who served as an assistant secretary at the Department of Homeland Security in the Obama administration, spoke about the stages of crisis response and observed that we are now in the response phase where public leaders must take quick and decisive action.Acknowledging the unprecedented nature of this pandemic, Kayyem said that “while the virus is new, crisis management is not. It is beginning to look familiar, and that should give you some hope.” She also noted that American states and cities have been ahead of the U.S. federal government in their response: “You saw these governors and a lot of mayors move forward because they knew time was of the essence.”How can we pivot and adapt?“A lot of this feels like it is coming to you on the local level, and in fact, I think that’s correct,” said Leonard, an expert on crisis management. “I think what is going to get us through this event as well as we possibly can, is local leadership.”Leonard emphasized that local leaders will be at the forefront of the response. “This is going to be a matter of self-reliance, and that’s always true, actually, in large disasters,” he said. “Almost all of the work comes from inside the community.” “While the virus is new, crisis management is not. It is beginning to look familiar, and that should give you some hope.” — Juliette Kayyem Waste not, want not But dealing with the complexity and uncertainty, Leonard said, would require “an ongoing iterative problem-solving process.” He suggested city leaders create an incident management team representing people with a range of interests, subject matter experts, and people familiar with the city and community. This team should then develop a process and iterate on it, treating decisions as part of “an experiment that is ongoing.”What are the hardest political choices?After the mayors shared some of the toughest political challenges they faced — including remaining aligned with state and federal leaders — Kayyem and Leonard offered insights. Drawing on her own experience with the U.S. federal government’s response to the 2010 Deepwater Horizon oil spill, Kayyem said that in crisis situations, leaders must handle the response as well as politics. “You can’t deny it; you can’t work your way around it,” she said. Kayyem suggested that mayors should figure out ways in which their incident command structures can absorb the politics, while offering data, information, and hope: “It’s just honest. That’s all you have got: numbers and hope.”Leonard added that local leadership is fundamentally political and that the purpose of politics is to resolve decisions about values. “Most people, when they really understand that we’ve got a crisis, are at their very best,” he said. “Enlist their help.” Like Kayyem, Leonard emphasized the need for hope: “We will turn out to be more resilient than we currently think.” Karen Dynan and Kenneth Rogoff say Fed and Congress are moving in the right direction Related Economists cheered by relief package but see long, tough slog ahead Chan’s Bassett warns that responses must include steps to ease the health and economic impacts on the poorlast_img read more

Katori Hall’s Our Lady of Kibeho Begins Performances Off-Broadway

first_img Our Lady of Kibeho Show Closed This production ended its run on Dec. 14, 2014 The cast will also include Jade Eshete, Danaya Esperanza, Niles Fitch, Kambi Gathesha, Brent Jennings, Joaquina Kalukango, Mandi Masden, Owiso Odera, Nneka Okafor, Stacey Sargeant, T. Ryder Smith, Irungu Mutu, Angel Uwamahoro and Bowman Wright. The world premiere of Katori Hall’s Our Lady of Kibeho begins previews off-Broadway on October 28. Directed by Michael Greif and starring Starla Benford, the production will run through December 7 in The Irene Diamond Stage at The Pershing Square Signature Center. Opening night is scheduled for November 16. Related Shows Our Lady of Kibeho is based on real events. Set in 1981, a village girl in Rwanda claims to see the Virgin Mary. Ostracized by her schoolmates and labeled disturbed, everyone refuses to believe, until the impossible starts happening again and again. Skepticism gives way to fear, faith, and fate, causing upheaval in the school community and beyond. View Commentslast_img read more

Congress convenes

first_imgBy Faith PeppersUniversity of GeorgiaWhen the National 4-H Congress convenes in Atlanta Nov. 25-29, participants will represent 46 U.S. states and Puerto Rico. This year’s congress, the 83rd annual national meeting for the 103-year-old organization, will also welcome international visitors from Ghana and Liberia.”Having international participants is a first for National 4-H Congress,” said Susan Stewart, executive director of National 4-H Congress. “We routinely have participants from the U.S. Virgin Islands, Puerto Rico and other U.S. territories, but never from other countries. This year, we got a letter from these two countries, asking if they could come and observe. And we were delighted to have them.”National 4-H Congress brings together representatives from states across the nation to participate in leadership, service learning and educational programs. Each state sets different criteria for being selected to attend the event.”Georgia’s representatives are the winners from our State 4-H Congress project achievement process,” said Bo Ryles, state leader for Georgia 4-H, a unit of the University of Georgia College of Agricultural and Environmental Sciences. “This year we will send 66 Georgia students to National Congress to represent our 198,000 Georgia 4-H’ers and to host the visiting 4-H’ers.”Living wellDuring their five days in Atlanta, the 1,100 delegates will hear from a variety of speakers, including Miss America Deidre Downs. They will attend educational workshops, too, on living healthy lifestyles.”The workshops will include leadership skills, facing eating disorders, teenage depression and how to avoid it, healthy foods with preventative properties, and sport nutrition,” Stewart said. “We will also have an Alpharetta, Ga., policeman on hand to teach a class on personal safety. And instructors will take the delegates through classes in Pilates and yoga.”Giving backService learning is a major part of what 4-H is all about. During this conference, the delegates will take a class in baking as a gift and learn how it can be used for community service. They will also get out and help Atlanta.”During the week, each teen participates in a community service activity,” Stewart said. “Some will assist at the Festival of Trees set up. Others will help record oral histories from senior citizens. Some will help clean up local parks and Zoo Atlanta as a part of the second-largest day of community service for Hands on Atlanta.”Since 4-H celebrated its centennial in 2003, the students began bringing a dime for each year 4-H has been in existence. “This year, each 4-H’er will bring 103 dimes,” Stewart explained. “The money goes to a savings account. And when we have enough, we will partner with Habitat for Humanity to build Clover House in Atlanta.”4-H is a program of the U.S. Department of Agriculture. It’s administered in every state by the land-grant university. The organization has more than 7 million members nationwide. It’s offered in every county in Georgia through the University of Georgia Cooperative Extension office. To find a 4-H program near you, call 1-800-ASK-UGA1, or visit on-line at ugaextension.com.last_img read more

Cricket News VB Chandrasekhar, former India opener, committed suicide over debts: Chennai Police

first_imgVB Chandrasekhar played seven games in 1988.VB was instrumental in getting MS Dhoni to Chennai Super Kings in IPL.Sachin Tendulkar and Anil Kumble also praised VB. The legendary Sachin Tendulkar and former India captain Anil Kumble also offered their condolences to Chandrasekhar’s family. “Very sad to hear of the passing away of VB Chandrasekhar. Have fond memories of him. My condolences to his family,” Tendulkar tweeted. Kumble wrote: “Terrible news…VB…too soon. Shocking! Heartfelt condolences to his family and friends.”  Former India captain Krish Srikkanth, who had opened several times in the past with VB, said he was shocked to learn about the death of his erstwhile batting partner, adding he was a very nice person. India and Chennai Super Kings player Suresh Raina also condoled the death of Chandrasekhar.  “Extremely sad & shocked to hear about the passing away of VB Chandrasekhar sir. His consistent efforts made it possible to set the right foundation of the CSK team. He always encouraged & believed in us since very beginning. My deepest condolences to the family,” Raina tweeted.India and CSK off-spinner Harbhajan Singh expressed sadness. “Very shocking to hear VB Chandrashekhar indian cricketer is no more.. very sad news .. very young to go..rest in peace VB.. Big lose. condolences to the family,” Harbhajan wrote on his twitter handle.   IPL team Chennai Super Kings, for which Chandrasekhar was director-operations and a selector, said  Chandrasekhar was “one of the main architects behind CSKs strong foundation and brand of cricket.” “V B Chandrasekhar’s contribution to TN cricket as a player, mentor and official is immeasurable. He was an integral part of the Super Kings family and it is truly a personal loss to all of us,” the CSK said on its twitter handle.  His mortal remains will be kept at his residence in  Mylapore and the final rites will take place from 9 AM on Saturday.  highlightscenter_img Chennai: Former India opener and national selector VB Chandrasekhar committed suicide over debts, the police said in Chennai on Friday, ruling out speculation that he died after suffering a cardiac arrest. According to a senior police official, Chandrasekhar ended his life by hanging himself at his house in the city on Thursday evening due to debts, a day after it was reported that his death was the result of a cardiac arrest. “He was under a lot of stress due to the debts incurred,” the police official added.  The former Indian opener owned a team (VB Kanchi Veerans) in the Tamil Nadu Premier League, the fourth edition of which concluded on Thursday. “He was under a lot of stress due to debts but it has also come to light that his health was deteriorating and he had become very frail,” a source said.  “The Tamil Nadu cricket fraternity is in a state of shock as he always shared a close relationship with former BCCI President N Srinivasan. He was instrumental in getting MS Dhoni to Srinivasan’s IPL franchise Chennai Super Kings,” the source added.   The right-hander, who was only six days short of his 58th birthday, is survived by his wife and two daughters. Chandrasekhar played seven ODIs between 1988 and 1990, scoring only 88 runs, but at the domestic level, he was prolific for a few seasons, aggregating 4,999 runs in 81 games with a highest score of 237 not out. A qualified engineer, VB, as he was popularly known in cricketing circles, was a member of the state team that won the Ranji Trophy in 1987-’88.  The cricketing fraternity across the country was shocked to learn about Chandrasekhar’s death. The Indian cricket board condoled his death and posted on its Twitter handle (@BCCI): “BCCI regrets to inform that former India opener VB Chandrasekhar is no more. Our heartfelt condolences to his family, friends and his fans.”  The Tamil Nadu Cricket Association on Friday condoled the death of the former India batsman. “The Members and cricket fraternity of the Tamil Nadu Cricket Association deeply condole the sudden and sad demise of former Indian Cricketer V B Chandrasekhar,” it said in a message.   For all the Latest Sports News News, Cricket News News, Download News Nation Android and iOS Mobile Apps.last_img read more