Harvard Medical School scientists report they have successfully restored vision in mice by turning back the clock on aged eye cells in the retina to recapture youthful gene function.The team’s work, described Dec. 2 in the publication Nature, represents the first demonstration that it may be possible to safely reprogram complex tissues, such as the nerve cells of the eye, to an earlier age. In addition to resetting the cells’ aging clock, the researchers successfully reversed vision loss in animals with a condition mimicking human glaucoma, a leading cause of blindness around the world. The achievement represents the first successful attempt to reverse glaucoma-induced vision loss, rather than merely stem its progression, the team said. If replicated through further studies, the approach could pave the way for therapies to promote tissue repair across various organs and reverse aging and age-related diseases in humans.“Our study demonstrates that it’s possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function,” said senior author David Sinclair, professor of genetics in the Blavatnik Institute at Harvard Medical School, co-director of the Paul F. Glenn Center for Biology of Aging Research at HMS and an expert on aging. Sinclair and colleagues caution that the findings remain to be replicated in further studies, including in different animal models, before any human experiments. Nonetheless, they add, the results offer a proof of concept and a pathway to designing treatments for a range of age-related human diseases.“If affirmed through further studies, these findings could be transformative for the care of age-related vision diseases like glaucoma and to the fields of biology and medical therapeutics for disease at large,” Sinclair said. “At the beginning of this project, many of our colleagues said our approach would fail or would be too dangerous to ever be used. Our results suggest this method is safe and could potentially revolutionize the treatment of the eye and many other organs affected by aging.” — Yuancheng Lu, lead study author Making sense of how the blind ‘see’ color Related Focusing on the fovea First cellular atlas could prove valuable resource in study of blinding diseases Study suggests that blind and sighted experience visual phenomena differently, but share a common understanding of them For their work, the team used an adeno-associated virus (AAV) as a vehicle to deliver into the retinas of mice three youth-restoring genes — Oct4, Sox2, and Klf4 — that are normally switched on during embryonic development. The three genes, together with a fourth one, which was not used in this work, are collectively known as Yamanaka factors.The treatment had multiple beneficial effects on the eye. First, it promoted nerve regeneration following optic-nerve injury in mice with damaged optic nerves. Second, it reversed vision loss in animals with a condition mimicking human glaucoma. And third, it reversed vision loss in aging animals without glaucoma.The team’s approach is based on a new theory about why we age. Most cells in the body contain the same DNA molecules but have widely diverse functions. To achieve this degree of specialization, these cells must read only genes specific to their type. This regulatory function is the purview of the epigenome, a system of turning genes on and off in specific patterns without altering the basic underlying DNA sequence of the gene. This theory postulates that changes to the epigenome over time cause cells to read the wrong genes and malfunction — giving rise to diseases of aging. One of the most important changes to the epigenome is DNA methylation, a process by which methyl groups are tacked onto DNA. Patterns of DNA methylation are laid down during embryonic development to produce the various cell types. Over time, youthful patterns of DNA methylation are lost, and genes inside cells that should be switched on get turned off and vice versa, resulting in impaired cellular function. Some of these DNA methylation changes are predictable and have been used to determine the biologic age of a cell or tissue.Yet, whether DNA methylation drives age-related changes inside cells has remained unclear. In the current study, the researchers hypothesized that if DNA methylation does, indeed, control aging, then erasing some of its footprints might reverse the age of cells inside living organisms and restore them to their earlier, more youthful state.Past work had achieved this feat in cells grown in laboratory dishes but fell short of demonstrating the effect in living organisms.The new findings demonstrate that the approach could be used in animals as well. Overcoming an important hurdle Lead study author, Yuancheng Lu, research fellow in genetics at HMS and a former doctoral student in Sinclair’s lab, developed a gene therapy that could safely reverse the age of cells in a living animal. Lu’s work builds on the Nobel Prize winning discovery of Shinya Yamanaka, who identified the four transcription factors, Oct4, Sox2, Klf4, c-Myc, that could erase epigenetics markers on cells and return these cells to their primitive embryonic state from which they can develop into any other type of cell. Subsequent studies, however, showed two important setbacks. First, when used in adult mice, the four Yamanaka factors could also induce tumor growth, rendering the approach unsafe. Second, the factors could reset the cellular state to the most primitive cell state, thus completely erasing a cell’s identity.Lu and colleagues circumvented these hurdles by slightly modifying the approach. They dropped the gene c-Myc and delivered only the remaining three Yamanaka genes, Oct4, Sox2, and Klf4. The modified approach successfully reversed cellular aging without fueling tumor growth or losing their identity. Gene therapy applied to optic nerve regeneration In the current study, the researchers targeted cells in the central nervous system because it is the first part of the body affected by aging. After birth, the ability of the central nervous system to regenerate declines rapidly. To test whether the regenerative capacity of young animals could be imparted to adult mice, the researchers delivered the modified three-gene combination via an AAV into retinal ganglion cells of adult mice with optic nerve injury. For the work, Lu and Sinclair partnered with Zhigang He, HMS professor of neurology and of ophthalmology at Boston Children’s Hospital, who studies optic nerve and spinal cord neuro-regeneration.The treatment resulted in a two-fold increase in the number of surviving retinal ganglion cells after the injury and a five-fold increase in nerve regrowth. “At the beginning of this project, many of our colleagues said our approach would fail or would be too dangerous to ever be used,” said Lu. “Our results suggest this method is safe and could potentially revolutionize the treatment of the eye and many other organs affected by aging.”Reversal of glaucoma and age-related vision loss Following the encouraging findings in mice with optic nerve injuries, the team partnered with colleagues at Schepens Eye Research Institute of Massachusetts Eye and Ear Bruce Ksander, HMS associate professor of ophthalmology, and Meredith Gregory-Ksander, HMS assistant professor of ophthalmology. They planned two sets of experiments: one to test whether the three-gene cocktail could restore vision loss due to glaucoma and another to see whether the approach could reverse vision loss stemming from normal aging.In a mouse model of glaucoma, the treatment led to increased nerve cell electrical activity and a notable increase in visual acuity, as measured by the animals’ ability to see moving vertical lines on a screen. Remarkably, it did so after the glaucoma-induced vision loss had already occurred.“Regaining visual function after the injury occurred has rarely been demonstrated by scientists,” Ksander said. “This new approach, which successfully reverses multiple causes of vision loss in mice without the need for a retinal transplant, represents a new treatment modality in regenerative medicine.” The treatment worked similarly well in elderly, 12-month-old mice with diminishing vision due to normal aging. Following treatment of the elderly mice, the gene expression patterns and electrical signals of the optic nerve cells were similar to young mice, and vision was restored. When the researchers analyzed molecular changes in treated cells, they found reversed patterns of DNA methylation — an observation suggesting that DNA methylation is not a mere marker or a bystander in the aging process, but rather an active agent driving it.“What this tells us is the clock doesn’t just represent time — it is time,” said Sinclair. “If you wind the hands of the clock back, time also goes backward.” The researchers said that if their findings are confirmed in further animal work, they could initiate clinical trials within two years to test the efficacy of the approach in people with glaucoma. Thus far, the findings are encouraging, researchers said. In the current study, a one-year, whole-body treatment of mice with the three-gene approach showed no negative side effects. Linking sight and movement Researchers key in on finding that can help self-driving cars ‘see’ Other authors on the paper include Benedikt Brommer, Xiao Tian, Anitha Krishnan, Margarita Meer, Chen Wang, Daniel Vera, Qiurui Zeng, Doudou Yu, Michael Bonkowski, Jae-Hyun Yang, Songlin Zhou, Emma Hoffmann, Margarete Karg, Michael Schultz, Alice Kane, Noah Davidsohn, Ekaterina Korobkina, Karolina Chwalek, Luis Rajman, George Church, Konrad Hochedlinger, Vadim Gladyshev, Steve Horvath, and Morgan Levine.This work was supported in part by a Harvard Medical School Epigenetics Seed Grant and Development Grant, The Glenn Foundation for Medical Research, Edward Schulak, the National Institutes of Health (grants R01AG019719,R37AG028730, R01EY026939, R01EY021526, R01AG067782, R01GM065204, R01AG065403, R01EY025794, R24EY028767 and R21EY030276), and the St. Vincent de Paul Foundation.
“The game is in good health in many ways, but we know we are in an ever more crowded leisure sector, and their expertise will be invaluable as we look to get even more people into the game, across the whole country, and to build on the game’s significant contribution to society, to public health, the environment and tourism.” The Board of England Golf has appointed its first independent directors. Martha Brass and Michael Pask will join Nic Coward, who was appointed as first independent chairman earlier this year, and representatives from the men’s and women’s amateur game. Nic Coward commented: “We are absolutely delighted to be joined by directors of the calibre of Martha and Michael. “There are a number of opportunities, and challenges that face golf at the moment, not just in England. This is therefore a great time to be joining an increasingly dynamic governing body, to help build on the positive work I have seen going on around the country.” “They are both leaders in their fields. Their knowledge and insight will be a huge asset as we implement our strategic plan, Growing the Game of Golf in England, to get more people playing more golf. Martha Brass has held many top-level roles in media businesses, most recently as Chief Executive Officer, International Operations, of the Endemol Shine Group, working with hit programmes such as Big Brother, Broadchurch, Deal or No Deal, MasterChef, and Mr. Bean. In addition to her executive career, she has held a number of non-executive roles including with the British Olympic Commercial Counsel and the English Golf Partnership. Martha has stepped down from her role at Endemol Shine and is developing a portfolio of non-executive roles. Martha said: “I am delighted to be able to bring my business experience in the media and entertainment world to the England Golf Board. I know from personal experience how much fun this game is for people of all ages, and I also am well aware of its positive impact on physical and mental fitness and its ability to build a sense of community. My time on the England Golf Partnership Board has also shown me that there is so much more potential and that is incredibly exciting.” During his time at WME IMG, Michael created the Golf Advisory Business with global clients including HSBC and the successful French and Italian Ryder Cup bids. He also led the Olympic Management Group, guiding the careers of athletes including Sir Steve Redgrave, Michael Johnson, Ian Thorpe and Katherine Grainger. Michael now has a number of senior advisory roles in sport and leisure including with the Golf Environment Organisation, Urban Adventure and SMG Insight. 30 Aug 2017 Martha Brass and Michael Pask join England Golf as independent directors Michael Pask has 25 years’ experience working for WME IMG, the world’s largest sports, entertainment and media business, latterly as a Senior Vice President. His roles have covered event planning and management, brand development, sales, business development and relationship building. Michael said: “I am really honoured to be joining the England Golf board. I love the game, as a player, and having been lucky to have worked at the highest levels of the professional game and I am excited to support its growth in my home country. Tags: Board, Director, England Golf
Someone once advised me to set my expectations low so I would never be disappointed. Not being one to subscribe to that theory, I often imagine that holidays, vacations and birthdays will be family events full of laughter, appreciation, thankfulness and peace. So when I recently celebrated a milestone birthday, I expected it to be a day filled with kind words, no tears, no fighting and no complaining. Of course, being a parent now for eight years I should have known better.The morning started off perfectly, the kids quickly got ready for school and we had an enjoyable pancake breakfast prepared by my husband. Then the kids decided that they wanted to give me my presents before they left for school because they couldn’t wait to see what I got … and this is where the day took a turn for the worse.Present number one was a bottle of sunscreen … wait I promise the gifts do get better. Present number two was skimpy bikini (picked out by my husband) that I immediately thought I would never have the courage to wear outside of my bathroom. Still, the fact that he thought I could pull off the look got me wondering if I could and so I contemplated for a moment keeping the bathing suit. But, quickly my daughter brought me back to reality. After looking at the swimsuit and the catalog that came with it she says, “Mommy you don’t look like the models in the catalog.” My judgment clouded by my high expectations for a feel-good day, I asked why. “Because those models are sexy,” she replied. From that moment I knew the bathing suit was going back to the store.Nevertheless, with the sunscreen and bikini as clues, I had an idea where this birthday gift theme was going. Next, I unwrapped a brochure that revealed a sandy beach, palm trees and crystal clear ocean. It was a five-day trip to Aruba. In order to keep this gift a surprise to me, my husband hadn’t told my kids about it. So, when my 5-year-old son realized what it was, his face quickly lit up and he let out a big “YEESSS, we are ALL going to Aruba!” Unfortunately, the real surprise for him (and my daughter) was that Mom would be taking this trip with three of her friends – no children (and no husband) were included. Tears and cries of agony quickly followed this revelation, making it very hard for me to jump up and down and celebrate my soon-to be-had five days of freedom … that would have to wait till they went to school.Once off to school, I did enjoy a nice quiet day. I can’t even remember exactly what I did, but I know it did not involve laundry, food shopping, cleaning or work. I do remember that the time went too quickly. That evening we celebrated with a family dinner out that included the usual bickering, a spilled drink and two unfinished kids meals.Once in bed, my daughter looked up at me and sweetly said, “Mommy at least you don’t have to worry about being old anymore because the day is almost over.” Sadly, I told her that tomorrow I would be even older. Comfortingly she replied, “But you only think about how old you are on your birthday and I don’t think you look old at all.” I’m not sure if she said it to make me feel good or if she really meant it, but it was the perfect ending to a day that ultimately met my high expectations.
PERTH, Australia (CMC):West Indies Women’s star Deandra Dottin experienced mixed fortunes on her debut in the Women’s Big Bash on Boxing Day, as her Perth Scorchers beat Melbourne Stars by six wickets.The 24-year-old snared two for 27 from four overs of medium pacer as Stars, opting to bat first at the Western Australia Cricket Association ground, stumbled to 102 for six off their 20 overs.Fast bowler Katherine Brunt had the best figures of two for 11.Katie Mack struck 32 from 30 balls while opening partner and captain Meg Lanning got 27 from 31 deliveries in a 56-run stand for the first wicket.In reply, Scorchers reached their target in the final over, with veteran opener Charlotte Edwards stroking an unbeaten 61 off 56 deliveries.Dottin suffered the indignity of a fourth-ball ‘duck’, falling leg before wicket to leg-spinner Kristen Beams in the tenth over with the score on 50 as Scorchers lost three quick wickets for 12 runs.However, Edwards combined with Brunt (11 not out) in an unbroken fifth wicket stand of 45 to see the hosts to victory.
SAN JOSE — Sharks forward Evander Kane shared Thursday that he and his wife recently lost a child during pregnancy.In a statement released via his Twitter account, Kane said, “I would like to thank everyone who has reached out to my wife and I during this extremely difficult time. Over the weekend, our daughter, Eva, at 26 weeks, passed away. As expecting parents, this past week has broken us.“We’ve received a ton of support from family and friends, and we truly want to thank them. We would …
OAKLAND — The A’s appear to have found a power bat to fill the absence of Matt Olson.The club announced the acquisition of slugger Kendrys Morales in a trade with the Toronto Blue Jays Wednesday in exchange for minor league infielder Jesús Lopez and international slot money.Morales, 35, hit .249 with 21 home runs and 57 RBI last year with the Blue Jays and is a career .268 hitter with 211 home runs over 12 big league seasons. He was primarily their designated hitter, only playing 18 of 130 …
The McKinleyville High baseball team did it by committee on Wednesday at home as three pitchers combined to shut out visiting St. Bernard’s, 3-0, marking the team’s eighth shutout victory of the season.Lance Lally, Kyler Carr and Cameron Saso each picked a couple innings of work in the win. Lally started the day off on the bump and went three innings, giving up one run while recording four strikeouts. Carr handled the middle of the game and controlled innings four and five, allowing three hits …
Des galeries d’art modernes aux centres d’art rocheux, des musees dernier cri aux villages culturels eloignes, des clubs de jazz en ville aux festivals en plein air, il existe d’innombrables façons de faire l’experience de la richesse de la culture et du patrimoine de l’Afrique du Sud par vous-meme.Le rythme de l’Afrique du SudLa scene de la musique, de la danse et du theatre en direct est dynamique en Afrique du Sud dans des lieux allant des festivals dans le Bushveld et les jardins botaniques aux boites de nuit sombres et aux complexes theatraux huppes.Nous avons la musique dans le sang. Acheter un CD, se rendre dans un club, ecouter des musiciens de rue, visiter un village culturel ou se promener pres d’une eglise un dimanche matin; quelle que soit la maniere dont vous faites l’experience de la musique sud-africaine, vous aurez du mal a empecher vos pieds de battre la mesure.Passer du temps avec les sud-africainsRien ne peut remplacer une vraie rencontre avec des gens. Les nombreux villages culturels d’Afrique du Sud offre un bon aperçu des cultures traditionnelles du pays. Dans les principaux centres, les visites des townships, organisees avec sensibilite et fierte, vous mettront en contact avec de vrais sud-africains et leur histoire.Dans les zones rurales, les visites de communautes vous aideront a connaitre le pays a travers le regard de ceux qui y vivent. Vous pourrez decouvrir l’ancienne astronomie du Setswana a travers l’objectif d’une grand-mere possedant une connaissance approfondie des traditions anciennes. Et que penseriez-vous d’apprendre a cuisiner du poisson peche a la ligne de façon traditionnelle avec la communaute de pecheurs de Kalk Bay ?Le berceau de l’humaniteEt rappelez-vous, quel que soit l’endroit d’ou vous venez, vos racines sont ici. Il est reconnu que la vie humaine trouve son origine en Afrique du Sud. La plupart des gens regardent le monde differemment apres une visite du Berceau de l’Humanite pres de Johannesburg, un des sites de fossiles d’hominides les plus riches du monde.Les empreintes de pas fossilisees pres du Cap et la richesse des peintures rupestres et des abris qui ont survecu dans les montagnes de Drakensberg au Kwazulu-Natal et ailleurs dans le pays temoignent tous des origines de l’humanite de cet ancien continent.Les guerres, l’apartheid et la reconciliationPlus recemment l’histoire de l’Afrique du Sud a ete celle de la confrontation mais aussi de la reconciliation. Vous pouvez visiter les lieux de combat ou se sont deroules les evenements sanglants qui ont façonne le pays.D’Isandlwana ou Talana au Kwazulu-Natal jusqu’a Soweto a Johannesburg ou Langa au Cap, notre terre raconte une histoire, mais elle est difficile a interpreter et il vaut la peine de faire une visite guidee.Nous montrons les blessures de notre passe : visitez le Women’s Monument a Bloemfontein ou le Musee de l’Apartheid a Johannesburg.Mais nous affichons egalement notre recente unite. Un voyage sur l’ile de Robben vous montrera combien cette attitude peut etre puissante. Nous avons prix un lieu d’oppression, d’isolement et de desespoir et l’avons transforme en un symbole de pardon et d’espoir. C’est ce que font les sud-africains avec le pays entier.SAinfo reporter, incluant des documents de l’Office du Tourisme d’Afrique du Sud
The freedom we now enjoy and celebrate was achieved through the selfless sacrifice of patriots who were prepared to pay the ultimate price, says the GCIS’ acting director-general Donald Liphoko. (Image: Shamin Chibba)By Donald Liphoko, acting director-general of GCISOn Freedom Day millions of South Africans will celebrate the day that marks the occasion of our first democratic elections in 1994 and gave birth to our freedom and constitutional democracy.Some will choose to spend the day at home surrounded by family and friends, others may gather at the national Freedom Day celebrations in Manguzi, Umhlabuyalingana Municipality, KwaZulu-Natal, which will be led by President Jacob Zuma. There are also those who may choose to use the national Freedom Day celebrations as a platform to raise their concerns.Whatever South Africans choose they will be free to do so. Our Constitution, our democracy, and our freedom have ensured that all people across our land are free to celebrate in the manner of their choosing.At face value, this seems utterly obvious, but we must never forget that before 1994, what now seems so utterly normal was denied to the majority of our fellow countrymen and women.The freedom we now enjoy and celebrate was achieved through the selfless sacrifice of patriots who were prepared to pay the ultimate price. They lived and died for the dream of a free and democratic South Africa that would be truly united, non-racial, non-sexist and prosperous. A country where everyone no matter their present circumstances would be free to strive for a better and more prosperous tomorrow.Since 1994 our country, and successive democratic administrations have worked to make this vision a reality. South Africa is undeniably a better place today than it was at the birth of our freedom, but much work still remains to undo the apartheid legacy of poverty, inequality and unemployment.The administration of President Jacob Zuma has continued this work since 2009. As a caring government, we continue to push for a society that is more equal, both socially and economically. Sadly, some have sought to push back against this vision by advocating that the status quo should remain in place.Such a call is both untenable and deeply worrying. We cannot and will not allow the continued existence of two parallel countries, and economies. It cannot be that our freedom dividend should only benefit some in our society, while the majority remain trapped in an existence of poverty, inequality and unemployment.Therefore government will continue its push for meaningful and inclusive economic transformation, that not only benefits some but all in our country. Our priority is to ensure greater participation in the economy by historically disadvantaged communities.We have already begun to implement this through our Medium-Term Strategic Framework 2014 to 2019. It sets out 14 outcomes around which we will mobilise all sectors of our society and it aims to ensure more equitable growth of the economy.These interventions should be seen as part of government’s long-term economic plan as guided by the National Development Plan, and immediate interventions such as the Nine-Point Plan, and Operation Phakisa.We are aware that many would argue that our immediate challenges cannot be resolved by the NDP, which is a long-term plan. However, the NDP is more than just a plan; it is the overarching vision for South Africa. Therefore it includes all key policy instruments aimed at growing the economy and creating jobs.These include the New Growth Path, which sets the trajectory of economic development; the National Infrastructure Plan, which guides the roll-out of infrastructure to improve people’s lives and enable economic growth; and the Industrial Policy Action Plan, which focuses on promoting investment and competitiveness in leading sectors and industries.Together these interventions are a potent driver for inclusive and far-reaching economic growth. However, our nation faces strong headwinds in the form of a slowing economy and global economic weakness. Therefore we need all South African onboard to tackle both our economic and social challenges.Let us, therefore, move away from the rhetoric and grandstanding. It is a luxury our country cannot afford. We must ensure that our dialogues are fair, less acrimonious and more constructive.As a caring government we will continue to lead the way by providing hope to all South Africans. Our social assistance programmes have lifted millions of people out of despair, and have planted the seeds of hope.The structural changes we are implementing will spur economic growth and ultimately lead to an economy and society that is more equitable. However, we cannot do it alone and need every sector of society to partner with us in this endeavour.Many South African companies have reaped the fruits of our freedom and have over the years have grown into strong multi-national corporations.As pillars in industry, we encourage them to use their success to move the country forward as we create the nation we all envisioned at the start of democracy. When South Africa benefits we all stand to benefit. Equally, we call on society to put aside narrow self-interest. Together we can build the country of our dreams; a nation which is prosperous, equitable and provides space for everyone to shine.The patriots who lived and died for our freedom have paved the way for this future, now it’s our turn to move South Africa forward.
Cardiff boss Warnock explains his fury against Liverpool and Clyneby Paul Vegas9 months agoSend to a friendShare the loveCardiff City boss Neil Warnock has explained his furious blast at Liverpool and Nathaniel Clyne after they sent him on-loan to Bournemouth.Warnock claimed he was “promised” the right-back on loan by the Reds, but his attitude over Clyne has softened in the week after the shock FA Cup defeat to Gillingham.”I know I got criticised for saying that about Liverpool and Clyne, but all I needed was a phone call to say he is going to Bournemouth,” Warnock said.”If I had a choice of going to Bournemouth and Cardiff, I’d snap their hand off to work for the manager (Eddie Howe) there.”I don’t blame Nathaniel for going there at all, they are a great club and they are established.”You can’t blame the fans (for wanting signings), but all of us have to be patient. If nothing happens, so what? I won’t be losing any sleep with the squad I’ve got.”We’ve done it before and we’ve had a great time. I’ve got to give them a team that’s got to scrap and get enough points to stay up. They can help me with that.” TagsTransfersAbout the authorPaul VegasShare the loveHave your say