29 abr. 2018

Epstein-Barr virus linked to seven serious diseases




A far-reaching study conducted by scientists at Cincinnati Children's reports that the Epstein-Barr virus (EBV)—best known for causing mononucleosis—also increases the risks for some people of developing seven other major diseases.
Those diseases are:  (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel  (IBD), celiac disease, and type 1 diabetes. Combined, these seven diseases affect nearly 8 million people in the U.S.
Study results published April 12 in the journal Nature Genetics. The project was led by three scientists: John Harley, MD, PhD, Director of the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children's and a faculty member of the Cincinnati VA Medical Center; Leah Kottyan, PhD, an immunobiology expert with CAGE; and Matthew Weirauch, PhD, a computational biologist with the center. Critical contributions were provided by Xiaoting Chen, PhD, and Mario Pujato, PhD, both also in CAGE.
The study shows that a protein produced by the Epstein-Barr virus, called EBNA2, binds to multiple locations along the human genome that are associated with these seven diseases.
Overall, the study sheds new light on how environmental factors, such as viral or bacterial infections, poor diet, pollution or other hazardous exposures, can interact with the human genetic blueprint and have disease-influencing consequences.
"Now, using genomic methods that were not available 10 years ago, it appears that components made by the virus interact with human DNA in the places where the genetic risk of disease is increased," Harley says. "And not just for lupus, but all these other diseases, too."
The full impact of this study could take years to explore. Here are some of the initial implications:
New concern about the 'kissing disease'
EBV is a strikingly common virus. In the US and other developed nations, more than 90 percent of the population becomes infected by age 20. In less-developed nations, 90 percent of people become infected by age 2. Once infected, the virus remains in people for their entire lives.
Mononucleosis, which causes weeks of extreme fatigue, is the most common illness caused by EBV. Mono was nicknamed the "kissing disease" years ago because the virus spreads primarily via contact with saliva.
Over the years, scientists have linked EBV to a few other rare conditions, including certain cancers of the lymphatic system. Harley, who has devoted much of his career to studying lupus, found possible connections between lupus and EBV years ago. That work includes proposing mechanisms that the immune system uses in response to the virus that lead to lupus, and showing that children with lupus almost always are infected with EBV.
Today's study adds weight to those lupus findings and adds six more well-known diseases to the list.
"This discovery is probably fundamental enough that it will spur many other scientists around the world to reconsider this virus in these disorders," Harley says. "As a consequence, and assuming that others can replicate our findings, that could lead to therapies, ways of prevention, and ways of anticipating disease that don't now exist."So far, no vaccine exists that will prevent EBV infection.
"I think we've come up with a really strong rationale for encouraging people to come up with more of an effort," Kottyan says. "Some EBV vaccines are under development. I think this study might well encourage them to push forward faster and with rededicated effort."
How EBV hijacks our immune system
When viral and bacterial infections strike, our bodies respond by commanding B cells within our immune systems to crank out antibodies to battle the invaders. However, when EBV infections occur, something unusual happens.
The EBV virus invades the B cells themselves, re-programs them, and takes over control of their functions. The Cincinnati Children's research team has discovered a new clue about how the virus does this, a process that involves tiny proteins called .
Our bodies have about 1,600 known transcription factors at work within our genome. Each cell uses a subset of these to become what they are and to respond to their environment. These proteins constantly move along the strands of our DNA, turning specific genes on and off to make sure cells function as expected.
Credit: Cincinnati Children's
However, when the transcription factors change what they do, the normal functions of the cell can also change, and that can lead to disease. The Cincinnati Children's team suspects that the EBNA2 transcription factor from EBV is helping change how infected B cells operate, and how the body responds to those infected cells.
The new paper shows that seven seemingly unrelated disease states actually share a common set of abnormal transcription factors, each affected by the EBNA2 protein from the Epstein-Barr virus. When these EBNA2-related clusters of transcription factors attach themselves to one portion of the genetic code, the risk of lupus appears to rise. When those same transcription factors land on another part of the code, the risk of multiple sclerosis appears to rise. And so on.
"Normally, we think of the transcription factors that regulate human gene expression as being human," Kottyan says. "But in this case, when this virus infects cells, the virus makes its own transcription factors, and those sit on the human genome at lupus risk variants (and at the variants for other diseases) and that's what we suspect is increasing risk for the disease."
New leads emerge for improving treatment
It remains unclear how many cases of the seven diseases listed in the study can be traced to prior EBV infection. More genomic analyses involving many more patients with these diseases will be required to make reliable estimates.
"The impact of the virus is likely to vary across the diseases," Harley says. "In lupus and MS, for example, the virus could account for a large percentage of those cases. We do not have a sense of the proportion in which the virus could be important in the other EBNA2-associated diseases."
However, the breakthrough identification of specific transcription factors connected to EBV infections opens new lines of study that could accelerate efforts to find cures.
"This same cast of characters is a villain in multiple immune-related diseases," Weirauch says. "They're playing that role through different ways, and doing it at different places in your genome, but it's the same sinister characters. So if we could develop therapies to stop them from doing this, then it would help multiple diseases."
A number of compounds—some experimental, some approved as medications for other conditions—already are known to be capable of blocking some of the high-risk transcription factors listed in the paper, Weirauch says. Teams at Cincinnati Children's have begun deeper studies of some of these compounds.
Findings go far, far beyond EBV
While the EBV-related findings involved more than 60 human proteins linked to seven diseases, the Cincinnati Children's research team already has taken a huge next step. They applied the same analytic techniques to tease out connections between all 1,600 known transcription factors and the known gene variants associated with more than 200 diseases.
The results of that massive cross-analysis also appear in today's study. Intriguing associations were documented involving 94 conditions.
"Our study has uncovered potential leads for many other diseases, including breast cancer," Harley says. "We cannot possibly follow up on all of these, but we are hoping that other scientists will."
After devoting decades of research to hunting down the causes of lupus, Harley says this study represents the most important discovery of his career. "I've been a co-author in almost 500 papers. This one is more important than all of the rest put together. It is a capstone to a career in medical research," he says.
Software behind discoveries to be made public
Detecting and tracking the activities of these transcription factors took years of work involving dozens of laboratory and computational experts.
The project required gathering massive sets of genetic data, then analyzing every genetic change affecting the activity of the . Doing this required creating two new algorithms, called RELI and MARIO, which were developed at Cincinnati Children's by Weirauch and colleagues.
Both software tools and a related website will be made publicly available.
"We are going to great lengths to not only make the computer code available, but all of the data and all of the results," Weirauch says. "We think it's an interesting approach that could have implications for many diseases, so we're contacting experts on the various diseases and sharing the results and seeing if they want to collaborate to follow up on them."
More information: John B. Harley et al, Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity, Nature Genetics (2018).  DOI: 10.1038/s41588-018-0102-3 











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The Worlds First Marijuana Mall Opened in Colorado






History is being made in Trinidad, Colorado, as the world’s first marijuana mall is scheduled to open this upcoming April.
Developers Chris Elkins and Sean Sheridan deemed Trinidad as the perfect location to build their dream project given Trinidad’s views on law and tourism.
In an interview with local news station KRDO, Elkins said, “This town has a zero-foot setback, which allows us to put five dispensaries here right next to one another. As far as we know, we are the only town in Colorado that can do this.”

Elkins and Sheridan have received city permits and have already purchased a building in downtown Trinidad on Commercial Street. Their next step is waiting for City Council to give their approval.
According to Elkins, four of the five spaces have already been leased to marijuana-based businesses, and if the City Council gives their approval, they are hoping to open their doors to the public in April.

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24 abr. 2018

Motor neurone disease sufferer calls for right to die with dignity - video


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Paul Chamberlain, a 66-year-old chartered accountant, has motor neurone disease, a terminal illness that affects the nervous system. Here, he explains why he has decided to take his own life - and why he is campaigning in favour of the assisted dying bill, which would legalise assisted suicide for terminally ill people

Stephen Hawking, science's brightest star, dies aged 76


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 Cosmology's brightest star Stephen Hawking dies aged 76 – video
I first encountered Stephen Hawking on the cover of the New York Times magazine. Inside, its pages told a story we all know today, but at the time it was a revelation: a Cambridge astrophysicist sought to solve the great mysteries of the universe, while he himself was trapped in a wheelchair by a progressive neurogenerative disease. I remember being struck by writer Timothy Ferris’s description of Professor’s Hawking’s shoes, their soles pristine, having never touched the ground. I tucked the article in my knapsack, and a few days later I finished reading it on my way to lunch with a literary agent.
In one of those remarkable moments of serendipity, during lunch I mentioned the article to agent Al Zuckerman, who told me he was already trying to reach Professor Hawking to see if he might be interested in writing a popular book. Some months later I received a submission from Al — a short manuscript and an invitation to participate in an auction for the publishing rights to A Brief History of Time.
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At the time I was a senior editor at Bantam Books, which was an unlikely home for Prof Hawking’s book, given the number of prestigious, traditional publishing houses in the hunt to acquire it. However, Bantam’s experience selling popular paperbacks meant that its distribution went far beyond bookstores into drugstores, supermarkets, and airport shops. I sent a letter to Professor Hawking along with our financial offer, making the case that Bantam could get his book in the hands of the widest possible readership. It turned out that he was the rare academic who wanted just that — to bring his esoteric scholarly work to the attention of the masses. He chose us.
A few months later Stephen Hawking came to the US from Cambridge to give a lecture at Chicago’s Fermi Institute, so I arranged to meet him afterwards at the Holiday Inn, where Stephen was staying. As I turned into the parking lot, another car pulled up nearby. A young man got out, opened the trunk, unfolded a wheelchair, and placed a large battery underneath it. Then he opened the passenger door and gently scooped up a thin figure, and arranged him in the wheelchair. As I got out of my car he shouted, “Is that Peter Guzzardi? This is Professor Hawking,” just as the wheelchair spun a full 360 degrees and rocketed in the direction of the hotel lobby, with Stephen’s assistant and me in full pursuit.
When we convened in Prof Hawking’s room, I introduced myself, and asked politely if his flight from London had been comfortable. Stephen responded with a brief series of undecipherable sounds, which his assistant, a physics graduate student named Brian Whitt, translated. “Prof Hawking wants to know if you brought the contract.” So much for small talk. I produced the legal document, and Brian held it up, page by page, for Stephen to read, which he did at breathtaking speed. His body might be largely beyond his control, but his mind was obviously in hyper-drive.
Since Stephen didn’t yet have a publisher in the UK, the job of editing the English language edition of A Brief History of Time fell to me. I won’t pretend that it wasn’t a challenge. The manuscript was a slender but extremely dense 100 pages, describing the quest for the holy grail of science – one theory that could unite two separate fields that worked individually but wholly independent of each other. Particle physics explained the ghostly forces at work within atoms, whereas astrophysics made sense of massive effects like gravity that operated at the level of galaxies and star systems. As Stephen would so poetically put it, if scientists could come up a grand unified theory that explained both these fields we would truly understand everything: we would finally “know the mind of God.”
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The rest, as they say, is history. A Brief History of Time sold out its first US printing in a matter of days, became a #1 bestseller around the world, was translated into more than 35 languages, and went on to sell more than 10 million copies. More importantly, it continues to make generations of readers aware of the ongoing quest to come up with the Grand Unified Theory of Everything. I’m honoured to have played a role in the publication of A Brief History of Time, and to have known, worked with, and befriended the brilliant, inspiring man who wrote it.

Since you’re here …

… we have a small favour to ask. More people are reading the Guardian than ever but advertising revenues across the media are falling fast. And unlike many news organisations, we haven’t put up a paywall – we want to keep our journalism as open as we can. So you can see why we need to ask for your help. The Guardian’s independent, investigative journalism takes a lot of time, money and hard work to produce. But we do it because we believe our perspective matters – because it might well be your perspective, too.
I appreciate there not being a paywall: it is more democratic for the media to be available for all and not a commodity to be purchased by a few. I’m happy to make a contribution so others with less means still have access to information.Thomasine, Sweden

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Paralympics in the Spotlight



The opening ceremonies of the Pyeongchang Paralympics, photo courtesy of the Republic of Korea
For winter sports enthusiasts going through Olympic withdrawal syndrome, fear not — the Paralympic Games are just getting started.
The opening ceremonies of the 2018 Paralympics in Pyeongchang, South Korea, took place on March 9. The games run through March 18 and have made huge strides in media recognition. Case in point, if you log on to Google today, you see a cool animation showing a seated cross-country skier, sled hockey player, curler in a wheelchair, below-the-knee amputee snowboarder and one-armed snowboarder.  Even better, there is a write-up on the “Google doodle” in Time magazine.
The games are also gaining television coverage, specifically on NBC and NBC Sports Network, as well as the Olympic Channel and livestreaming on nbcolympics.com.  The full schedule of coverage can be seen here.
The winter Paralympics have also captured interest on tech and edgy sites like BuzzFeed, which features a catchy and easy-to-understand write up and animation of the six sports and explanation of disability classifications — paraplegic, amputee, vision-impaired, etc. — as well as a look at adaptations and techniques that the 650 participants use to compete.
And last but not least, unlike after past Olympics, where sponsors “rolled up the carpet and went home” before the start of the Paralympics, Toyota remains a strong partner — perhaps this means we might catch more glimpses of the new iBot in their commercial coverage.
Let the games begin!
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19 abr. 2018

SOOKE HISTORY: 1953 polio epidemic took Sooke by storm







Elida Peers
Contributed
Not long ago I was chatting with David McClimon, seeking help with a 1953 photograph. David said, “Sorry I can’t help you with that – I was in an iron lung in 1953.”
His words brought it all back.
Today the scourge of polio seems all but forgotten, but it was a dreadful infectious illness that commonly caused muscle atrophy, until Dr. Jonas Salk created a vaccine to prevent its occurrence, in 1953.
Two years later the vaccine was perfected to the point that a massive vaccination program against this frightening disease was established throughout the Western world.
The greatest polio epidemic to hit Victoria was in 1953, the Victoria Daily Colonist recorded, with 80 patients treated at Royal Jubilee Hospital.
The news that four Sooke boys were hospitalized in the epidemic took the community by storm.
As these photos show, our local high school boys were Jim Baker, Bob Hodges, Dan Lajeunesse and David McClimon. Members of a Sooke team competing for the BC Juvenile Softball championships, they travelled to Vancouver together on the CPR ferry. It remains a puzzle how they had each fallen ill to the crippling disease one after the other.
Bob Hodges was treated in a rocking bed while David McClimon’s case required his confinement to an iron lung. Thankfully, each boy did recover use of their limbs, though not entirely without long-lasting effects.
Another name for poliomyelitis was “infantile paralysis,” though its victims were certainly not limited to youngsters.
One of the most famous victims diagnosed with polio, at age 39, was the remarkable Franklin Delano Roosevelt, who, despite that he’d lost the use of his legs, went on to become a four-term elected president of the United States.
David McClimon, the most seriously affected, has allowed us to include an account he wrote years ago: “The summer of 1953 saw me in an iron lung – the first one, a terribly old contraption made mostly of wood. Later, I was upgraded to a more modern model … If I learned anything from my polio experience, it’s to avoid iron lungs if at all possible!
“Other things very much worth mentioning have to do with the compassion, help, and love that come from family, nurses, doctors and friends.
“My memories include nurses wrapping hot steaming cloths around my limbs, the crunching sound as doctors (despite my advice not to do so) cut a hole in my throat, my favourite uncle from the Yukon looking down at me with obvious concern, my favourite mom and dad gazing at their favourite (only) son with tears in their eyes, my two fine sisters so worried, the ceaseless noise from the lungs, the incessant drip from the damn intravenous and the stomach tube poked through my nose all the way to what must have been my toes.
“Finally, following all this, I can so easily recall my first real taste of food (a poached egg) after not able to eat for so long. And such memories must also include my joy in realizing as time went by that I was slowly getting back some control of my young body.”
Today David McClimon is a member of a post-polio support society. Experience has shown that many polio survivors find that, years later, they are affected by symptoms relating to the earlier illness.
While the breakthrough in preventing polio was made by Dr. Jonas Salk, we are reminded that it was Dr. Albert Sabin, who perfected an easy-to-take oral vaccine a few years later.
While this 1953 episode was the most dramatic in our area, we are aware of a number of others who suffered with polio as well, including Karl Linell, Ray Vowles, Karen Longland, and Adele Lewis. Lydia Van Ek was another youngster stricken.
The Van Eks were a Dutch family who had come to stay at the Woodside farm with the Wilfords after the war, and Pete Wilford recalls that his dad Phil made Lydia her first crutches. Lydia continues to require a leg brace all these years later.
The Sooke Rotary Club is part of an international effort to see that polio is eradicated in all corners of the globe, and we can only be thankful, that our younger generations today are so fortunate that, thanks to the vaccine, polio has not crossed their paths.
•••
Elida Peers is the historian of the Sooke Region Museum.

Polio victims Jim Baker, Bob Hodges, Dan Lajeunesse and David McClimon are shown along with their teammates. Standing: coach Buster Monk, Bob George, George Pedneault, Dennis Hird, Norm Essery, Pat George, and manager Wally Butler. Front: Sidney Morton, Gordie Eve, Paul Morton, Howard Monk. (Contributed by Sooke Region Museum)

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