Tuesday, 9 October 2012

Cell Re-Programmers Take the Nobel

John B. Gurdon of the Gurdon Institute in Cambridge and Shinya Yamanaka of Kyoto University in Japan have won the 2012 Nobel Prize for Physiology or Medicine for finding that cells of an adult organism—once thought be terminally locked into their developed state—can start anew. The discoveries, awarded the prize this morning (October 8) by The Nobel Assembly at Karolinska Institute in Stockholm, have ignited research in areas ranging from cloning to cancer treatment.
“Gurdon and Yamanaka fundamentally changed the way we all think about the specialized state of cells,” George Daley, director of the Stem Cell Transplantation Program at the Harvard Medical School, wrote in an email to The Scientist. “Collectively they taught us that the identity of a cell can be re-engineered—that an adult cell can be reverted to its embryonic state. This paradigm-shifting concept has opened up whole new avenues of research.” 
Gurdon, sometimes referred to as the “the godfather of cloning,” published a landmark study in the Journal of Embryology and Experimental Morphology in 1962, showing that implanting the nucleus of an adult frog cell into a frog egg that had had its nucleus removed could result in a functional, cloned tadpole. Though widely scrutinized at the time, Gurdon’s reprogrammed frog paved the way for breakthroughs in cloning, eventually leading to the creation of the now famous sheep, Dolly, in 1996.
Gurdon’s first nuclear-transfer experiment raised the possibility that adult cells maintain the ability to orchestrate embryonic development, despite having already reached their developmental fate. But a question remained about whether intact cells could be reprogrammed to a pluripotent state, capable of giving rise to other cell types of the body.
The answer came more than 40 years after Gurdon’s frog experiment, when Shinya Yamanaka discovered that four genes are capable of reprogramming an adult mouse cell to a cell with embryonic-like flexibility. In the first few days of development, pluripotent embryonic stem cells give rise to all the cells of the body, including those of the skin, intestines, and brain. Yamanaka’s finding showed that intact, adult cells can be rebooted into what are now known as induced pluripotent (iPS) cells, which, like embryonic stem cells, can give rise to many different cell types. The 2006 finding, published in Cell, provides researchers with the genetic recipe to generate iPS cells from mature cells in mice and humans.
Since the discovery, other scientists have generated iPS cells from humans—a feat which some argue reduces the need for controversial and difficult to acquire embryonic stem cells. These iPS cells allow researchers to study disease and development in the lab by, for example, generating disease models from the skin of patients with neurodegenerative disorders. The cells are also showing promise for cell replacement therapies to treat various illnesses.
“Induced pluripotent stem cells have already begun to revolutionize medicine,” Paul Fairchild, director of the Oxford Stem Cell Institute, said in an email. They provide “much-needed models of rare and complex disease states while providing sources of cells that may one day be used to replace those that are either worn out or compromised by degenerative diseases.”
The award is a long-time coming, said Magdalena Zernicka-Goetz, of the The Gurdon Institute of Cambridge. “I think we were all expecting it for quite a while,” she said.

Monday, 8 October 2012

Neurons Made From Adult Cells In The Brain

The researchers write about their work in the 5 October online issue of Cell Stem Cell.

Much of the stem cell research that is going on into making new brain cells focuses on using stem and adult cells from other parts of the body and reprogramming them to form new brain cells and then implanting them into the brain. 

For example, earlier this year, Stanford researchers in the US reported how they converted mouse skin cells directly into neural precursor cells, the cells that go on to form the three main types of cell in the brain and nervous system.

But corresponding author of this latest study, Benedikt Berninger, now at the Johannes Gutenberg University Mainz, says they are looking at ways of making new neurons out of cells that are already in the brain.

"The ultimate goal we have in mind is that this may one day enable us to induce such conversion within the brain itself and thus provide a novel strategy for repairing the injured or diseased brain," says Berninger in a press release.

A major challenge of finding cells already in the brain that can be coaxed into forming new neurons, is whether they will respond to reprogramming.

The cells that Berninger and colleagues are focusing on are called pericytes. These cells are found close to blood vessels in the brain and help maintain the blood-brain barrier that stops bacteria and other unwanted material crossing from the bloodstream into the brain. 

In other parts of the body, pericytes help with wound healing, which is what drew the team's attention:

"Now, we reason, if we could target these cells and entice them to make nerve cells, we could take advantage of this injury response," says Berninger.

They managed to coax adult human brain pericytes into neuron-like cells with the help of two genes, Sox2 and Mash1:

"Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1," write the researchers.

They used a method called "genetic fate mapping" in mice to confirm that the new brain cells had come from pericytes.

When they tested the new cells to see how closely they resembled neurons, they found they could produce electrical pulses and reach out to other neurons, two important features for being able to integrate into neural networks.

There is still a long way to go before what works in the test tube can be made to work in living tissue, but nonetheless, this is an important step in the search for a new way to make brain cells, say the researchers in their conclusions:

"While much needs to be learnt about adapting a direct neuronal reprogramming strategy to meaningful repair in vivo, our data provide strong support for the notion that neuronal reprogramming of cells of pericytic origin within the damaged brain may become a viable approach to replace degenerated neurons."

"Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates," they write.

"Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells"; Marisa Karow, Rodrigo Sánchez, Christian Schichor, Giacomo Masserdotti, Felipe Ortega, Christophe Heinrich, Sergio Gascón, Muhammad A. Khan, D. Chichung Lie, Arianna Dellavalle, and others; Cell Stem Cell, 11(4) pp. 471 - 476, published online 5 Oct 2012; DOI:10.1016/j.stem.2012.07.007; Link to Abstract
Additional Source: Cell Press.

Dating Between Modern Humans and Neandertals

When the Neandertal genome was sequenced in 2010 it revealed that people outside Africa share slightly more genetic variants with Neandertals than Africans do. One scenario that could explain this observation is that modern humans mixed with Neandertals when they came out of Africa. An alternative, but more complex, scenario is that African populations ancestral to both Neandertals and modern humans remained subdivided over a few hundred thousand years and that those more related to Neandertals subsequently left Africa.
Gene flow less than 100,000 years ago. In the case of recent gene flow from Neandertals (NEA) into the ancestors of non-Africans (CEU) but not into the ancestors of Africans (YRI), we expect long range LD at sites where Neandertal has the derived allele, and this expectation of admixture generated LD is verified by computer simulation as shown in the right of the panel along with a fitted exponential decay curve. (Credit: Sankararaman S, Patterson N, Li H, Pääbo S, Reich D (2012) The Date of Interbreeding between Neandertals and Modern Humans. PLoS Genet 8(10): e1002947. doi:10.1371/journal.pgen.1002947)

Dr. Sriram Sankararaman and colleagues measured the length of DNA pieces in the genomes of Europeans that are similar to Neandertals. Since recombination between chromosomes when egg and sperm cells are formed reduces the size of such pieces in each generation, the Neandertal-related pieces will be smaller the longer they have spent in the genomes of present-day people.
The team estimate that Neandertals and modern humans last exchanged genes between 37,000 and 86,000 years ago, well after modern humans appeared outside Africa but potentially before they started spreading across Eurasia. This suggests that Neandertals (or their close relatives) had children with the direct ancestors of present-day people outside Africa.

Sleeping Brain Behaves as If It's Remembering Something

The research team simultaneously measured the activity of single neurons from multiple parts of the brain involved in memory formation. The technique allowed them to determine which brain region was activating other areas of the brain and how that activation was spreading, said study senior author Mayank R. Mehta, a professor of neurophysics in UCLA's departments of neurology, neurobiology, physics and astronomy.
In particular, Mehta and his team looked at three connected brain regions in mice -- the new brain or the neocortex, the old brain or the hippocampus, and the entorhinal cortex, an intermediate brain that connects the new and the old brains. While previous studies have suggested that the dialogue between the old and the new brain during sleep was critical for memory formation, researchers had not investigated the contribution of the entorhinal cortex to this conversation, which turned out to be a game changer, Mehta said. His team found that the entorhinal cortex showed what is called persistent activity, which is thought to mediate working memory during waking life, for example when people pay close attention to remember things temporarily, such as recalling a phone number or following directions.
"The big surprise here is that this kind of persistent activity is happening during sleep, pretty much all the time." Mehta said. "These results are entirely novel and surprising. In fact, this working memory-like persistent activity occurred in the entorhinal cortex even under anesthesia."
The study appears Oct. 7, 2012 in the early online edition of the journal Nature Neuroscience.
The findings are important, Mehta said, because humans spend one-third of their lives sleeping and a lack of sleep results in adverse effects on health, including learning and memory problems.
It had been shown previously that the neocortex and the hippocampus "talk" to each other during sleep, and it is believed that this conversation plays a critical role in establishing memories, or memory consolidation. However, no one was able to interpret the conversation.
"When you go to sleep, you can make the room dark and quiet and although there is no sensory input, the brain is still very active," Mehta said. "We wanted to know why this was happening and what different parts of the brain were saying to each other."
Mehta and his team developed an extremely sensitive monitoring system that allowed them to follow the activities of neurons from each of three targeted portions of the brain simultaneously, including the activity of a single neuron. This allowed them to decipher the precise communications, even when the neurons were seemingly quiet. They then developed a sophisticated mathematical analysis to decipher the complex conversation.
During sleep, the neocortex goes into a slow wave pattern for about 90 percent of that time. During this period, its activity slowly fluctuates between active and inactive states about once every second. Mehta and his team focused on the entorhinal cortex, which has many parts.
The outer part of the entorhinal cortex mirrored the neocortical activity. However, the inner part behaved differently. When the neocortex became inactive, the neurons in the inner entorhinal cortex persisted in the active state, as if they were remembering something the neocortex had recently "said," a phenomenon called spontaneous persistent activity. Further, they found that when the inner part of the entorhinal cortex became spontaneously persistent, it prompted the hippocampus neurons to become very active. On the other hand, when the neocortex was active, the hippocampus became quieter. This data provided a clear interpretation of the conversation.
"During sleep the three parts of the brain are talking to each other in a very complex way," he said. "The entorhinal neurons showed persistent activity, behaving as if they were remembering something even under anesthesia when the mice could not feel or smell or hear anything. Remarkably, this persistent activity sometimes lasted for more than a minute, a huge timescale in brain activity, which generally changes on a scale of one thousandth of a second."
The findings challenge theories of brain communication during sleep, in which the hippocampus is expected to talk to, or drive, the neocortex. Mehta's findings instead indicate that there is a third key actor in this complex dialogue, the entorhinal cortex, and that the neocortex is driving the entorhinal cortex, which in turn behaves as if it is remembering something. That, in turn, drives the hippocampus, while other activity patterns shut it down.
"This is a whole new way of thinking about memory consolidation theory. We found there is a new player involved in this process and it's having an enormous impact," Mehta said. "And what that third player is doing is being driven by the neocortex, not the hippocampus. This suggests that whatever is happening during sleep is not happening the way we thought it was. There are more players involved so the dialogue is far more complex, and the direction of the communication is the opposite of what was thought."
Mehta theorizes that this process occurs during sleep as a way to unclutter memories and delete information that was processed during the day but is irrelevant. This results in the important memories becoming more salient and readily accessible. Notably, Alzheimer's disease starts in the entorhinal cortex and patients have impaired sleep, so Mehta's findings may have implications in that arena.
For this study, Mehta teamed with Thomas Hahn and Sven Berberich of Heidelberg University in Germany and the Max Planck Institute for Medical Research and James McFarland of Brown University and the UCLA Department of Physics. Going forward, the team will further study this brain activity to uncover the mechanisms behind it and determine if it influences subsequent behavioral performance.
"These results provide the first direct evidence for persistent activity in medial entorhinal cortex layer neurons in vivo, and reveal its contribution to cortico-hippocampal interactions, which could be involved in working memory and learning of long behavioral sequences during behavior, and memory consolidation during sleep," the study states.
The study was funded by the Whitehall Foundation, the National Institutes of Health, the National Science Foundation, the W. M. Keck Foundation, the German Ministry of Education and Research and the Max Planck Society.

Sunday, 7 October 2012

The £90,000 'robolegs' that got me out of my wheelchair: How one woman stood on her own feet nine years after she was paralysed

It is an extraordinary sight. From the waist up, 27-year-old Sophie Morgan is every inch the pretty blonde girl-next-door. But from the waist down, with her legs encased in £90,000 of motorised carbon-fibre, she is RoboCop.
Sophie’s thumb manipulates a joystick built into the armrests of her suit, causing the legs to hiss and whirr into life, before she takes three slow but sure steps. Her face breaks into a broad grin.
Five minutes earlier, Sophie was in her wheelchair. She was left paralysed from the chest down in a car crash nine years ago that shattered her spine. Over the years, Sophie, an aspiring television presenter who appeared in Channel 4’s Paralympics coverage, had come to accept that she would never walk again.
Positive step: Sophie in the robotic exoskeleton Rex, with her wheelchair in the background
Positive step: Sophie in the robotic exoskeleton Rex, with her wheelchair in the background
Today, though, she is one of the first people in the world to benefit from a robotic exoskeleton called Rex, the first major advance in the treatment of paralysis in decades.
Powered exoskeletons – metal and carbon-fibre frameworks that encase part of the body – allow paralysed patients (even those who have no movement from the neck down) to walk. It is this technology that will, arguably, mark the end of the wheelchair.
In recent years, stem-cell therapy (injections that would regrow spinal-cord tissue) had been seen as the great hope for spinal injury, but although research is continuing in this field, no magic bullet looks likely to appear soon. Instead exoskeletons appear to offer the greatest hope for those who have lost the use of their limbs.

Sophie first tried Rex in May. ‘I was in a hotel room in London and my family and friends were with me,’ she recalls. ‘It was a bizarre feeling. I’m 5ft 10in and the floor looked so far away. I felt safe but it was all an emotional blur. Afterwards I couldn’t believe that I had been walking around, and wanted to do it all over again.’
Her boyfriend Tom, 28, a chef, whom she met five years ago, says: ‘It was the first time I’ve seen her standing up.’
Sophie adds: ‘It was wonderful to be eye to eye with each other. We just hugged and hugged.’
The user is held firmly within the carapace of Rex with straps running from torso to toes.
Family bond: Sophie, centre, with, from left, mother Carol, brother Tom, boyfriend Tom and father John
Family bond: Sophie, centre, with, from left, mother Carol, brother Tom, boyfriend Tom and father John
Once in, the only movement needed is the strength to operate a small joystick, which instructs 29 micro-controllers within the machine to react within milliseconds. The user can move in all directions, sit down, and ascend and descend stairs. There are currently ten in existence around the world and only 30 people have tried Rex.
It is completely self-supporting, unlike the ReWalk suit used by 32-year-old Claire Lomas in this year’s London Marathon which uses crutches for balance.
Rex weighs nearly 6st – about the same as an 11-year-old child – and is relatively bulky, yet experts say that within the next few decades the devices will be small and light enough to slip on under a pair of jeans. For Sophie, her greatest achievement so far with Rex was a walk along the beach at Brighton. ‘I thought people would stare but I think I was such an odd sight that they avoided looking at me,’ she says.
Standing up for the first time was so bizarre... the floor seemed miles away
Sophie was given the opportunity to use Rex, made by New Zealand-based Rex Bionics, while filming a news story for Channel 4. She was told about the device by her friend, BBC security correspondent Frank Gardner, who was left partly paralysed after being shot in Saudi Arabia in 2004.
‘Until you have been in a wheelchair for years you cannot understand what it’s like to stand up, physically or emotionally,’ says Sophie. ‘When Frank first told me about Rex, I was hesitant. I’d been through a lot emotionally and had come to accept my wheelchair. I didn’t want to regress.’
Sophie was just 18 and celebrating excellent A-level results from Gordonstoun School in Scotland when she had the accident that would rob her of the ability to walk. Driving home from a party with four friends, she took a corner too fast and the car overturned.
Her back was broken on impact and she also suffered a broken nose and fractured skull.
In common with many who have been severely injured, Sophie found life most difficult when she returned home. ‘I should have been reading law at Manchester,’ she says. ‘Instead I was relearning everything – how to wash, how to dress. It was very frustrating.’
Carefree: Sophie prepares for a camping trip a month before her accident
Carefree: Sophie prepares for a camping trip a month before her accident
Sophie later enrolled in an art foundation course in Brighton before moving to London to start a degree at Goldsmiths College, but then suffered a serious setback. 
‘I felt as if I was getting my life back, but then I sat on a splinter on a pub bench. Because I couldn’t feel anything, I didn’t realise there was a problem until I developed an ulcer. It was so serious I ended up requiring bed rest for two years.’
Lying on her stomach waiting for her body to heal was, she admits, her darkest period. 
Eventually, though, Sophie threw herself into every opportunity available, including modelling for Stella McCartney. ‘Coming to terms with being in a wheelchair isn’t a linear process,’ she says. ‘There are fluctuations. Something difficult happens and then something amazing like Rex comes along. But I am very happy with my life and situation.’
The benefits of exoskeletons go far beyond the simple act of walking or standing. Robotics expert Faisal Almesfer, one of the developers of Rex, explains: ‘When you are in a wheelchair, the muscles in the lower half of the body relax and shrink. Organs rely on being in a vertical position, so the digestive system is less efficient and the bowels can’t move as they should.’
Being in a wheelchair also puts patients at a higher risk of blood clots in the legs, which can cause fatal pulmonary embolisms.
I watch as Faisal picks Sophie up and lowers her carefully into Rex. ‘Most users are able to ease themselves in, but the level of Sophie’s paralysis means that she isn’t able to,’ he says.
She pulls the straps tightly across her legs and tummy and then, using the joystick, she rises into a standing position. Sophie would probably berate me for being patronising, but my eyes well up. ‘I have seen all 30 users at the moment they first stood up,’ reassures Faisal. ‘It is incredibly emotional every time.’
Moving is slow, but Sophie is able to walk. If you look carefully, you can see that it is the machine moving her legs, rather than the other way around.
While Rex and ReWalk exoskeletons are available to buy, a third company that make suits offers the technology only in a rehabilitation environment.
‘It’s not a case of just stepping into them and walking,’ says Andy Hayes, managing director of Ekso Bionics Europe. ‘People need training in their use and we’re focusing on the clinical world first.’
There are 20 Ekso units around the world but just one in the UK – at Prime Physio, a sports injury centre in Melbourn, Cambridgeshire. The company also has an exoskeleton in pre-production for  the US Army, enabling the wearer to carry more than 15st in addition to their  normal load.
So what’s next? In two months Rex Bionics is launching a new model called Rehab Rex. This will allow ten wheelchair users a day to use it for rehabilitation purposes within specialised spinal clinics. The University of Houston is also investigating using the device with a brain interface. A cap on the head picks up brainwaves in the form of EEG signals and if the wearer thinks about going forwards, the frequency alters and the machine will move. This will enable complete quadriplegics to walk.
‘The ultimate goal is to connect the brain directly to the electrodes,’ says Kevin Warwick, Professor of Cybernetics (the meshing of technology and biology into one system) at Reading University.
As a test, he had electrodes implanted in his arm and, using just his brain and a wi-fi connection, moved objects on the other side of the world that he could see on a computer screen. ‘Within a decade, those with physical disabilities may be more able than those without,’ he says.
For the moment, the potential of exoskeletons is only just being realised. Sophie has had to hand her robo-legs back to the Rex research team and she says: ‘I would love to have my own, but don’t dismiss the wheelchair yet. Mine gets me around quickly and efficiently. If there were a robot that could do more than a chair, I’d be thrilled.’
Back at their house last week, Tom and Sophie (and Rex) cooked breakfast together. ‘I also did lots of boring menial tasks such as tidying up the sitting room. It was wonderful,’ says Sophie. ‘I can’t afford my own Rex but the experience has been amazing. In my dreams I can stand. Rex made that a reality.’

Deadly Black Mamba venom kills pain as well

The next time you come across a Black Mamba, you might want to think twice about your escape – the deadly African snake could be as much of a help as a threat.
French scientists have found that proteins – or peptides – isolated from Black Mamba venom can block pain as effectively as morphine, while at the same time being free of toxic side effects.
The researchers from the Institute of Molecular and Cellular Pharmacology in Valbonne, France, published their study on the venom's painkilling peptides, called mambalgins, in the journal Nature.
In experiments on mice, the peptides bypassed receptors in the brain that are usually targeted by morphine.
The proteins acted on both the central and peripheral nervous systems, stopping pain in a different way from powerful opiates, which can be addictive. But as ever with new drugs, many challenges remain on the path from lab to lips, and it will likely be at least a decade before a drug is publicly available.
Pain pathway
Scientists isolated and purified the mambalgins from the venom of the African Black Mamba, which is among the deadliest snakes in the world.
The French researchers injected the compounds into mice and then measured the animals' response to scalding water on their paws and tails.
Mice that had been treated with the snake venom peptides were able to withstand the pain of the hot water for twice as long as untreated ones. The treatment was also effective after repeated dosage - unlike with morphine, to which users typically develop a tolerance.
Eric Lingueglia, a molecular physiologist and head of the research team at the Valbonne institute, says the researchers "were able to identify new channels for the pain pathway."
The mambalgins act on a different pain player than morphine, which until now has been the strongest pain reliever available.
black mamba snake on branch
The Black Mamba is among the world's deadliest snakes
While opiates such as morphine stimulate receptors in the brain, causing pleasure while stopping pain, mambalgins inhibit acid-sensing ion channels, cutting off pain in both neurons of the central nervous system - such as in the spinal cord - and those of the peripheral nervous system, like in the skin.
This also means that the newly discovered compounds are unlikely to cause dependency - a major problem with opiates.
Bryan Grieg Fry, a biochemist and venom expert at the University of Queensland in Australia says this is "the beauty of it - [this painkiller is] not habit-forming."
The mambalgins "block your pain, but don't give you pleasure," says Fry.
In addition to lower drug tolerance and reduced risk of dependency, the mambalgin treatment is also free of other negative opiate side effects, such as constipation and slowed breathing.
"It really has a broad range of potential protective applications," Lingueglia told DW.
But Fry adds that "there are lots of technological difficulties that must be overcome" before a product can be brought to market.
Obstacles to use
One open question is whether the peptide is stable enough to be effective. Lingueglia says he is confident, describing the peptides as "robust," with a "compact structure, usually very resistant to degradation."
Fibril peptide nanowire microscope image on screen in laboratory
Peptides, pictured here as a fibril nanowire, are large molecules of linked amino acids
Another issue is molecular size. With 57 amino acids, the mambalgins are quite large - perhaps even so big as to provoke an immune response when absorbed, as the body reacts to foreign material.
Fry says the larger molecule structure of mambalgins could "trigger a violent allergic reaction." He thinks the substance will likely have to be made smaller in order for the human immune system to be able to handle it.
Lingueglia concedes that molecule size may be an issue. He says the next step for the drug would be to develop a smaller, synthetic version of the molecule, which would eventually be clinically tested on people.
The isolated peptide has been patented and passed on to a company that will undertake the expensive work of replicating the molecular structure into a practical form. It's also a time-consuming process - Lingueglia says it could take 10 to 15 years for the company to achieve success.
And to develop a non-peptide version that can be taken as a pill, developers of the medication will "need to get in bed with some very, very clever organic chemists," says Fry.
Vicious venom
Fry says "millions of years of evolution have made venoms the ultimate smart weapons."
"Neurotoxins smash into the nerves really fast," Fry explains. Their "extreme potency and accurate targeting" makes them well-suited in the search for new painkillers.
Lingueglia says his team had not specifically looked for painkillers, but that they had focused on "identifying new channels in the pain pathway and figuring out how it works." The next step in their research will be to test mambalgins with different pain conditions on mice.
Fry, who has a passion for venomous animals and has worked extensively in the field, describes Black Mambas as "very formidable creatures, among the most dangerous animals" in the world.
"It's surprising," concludes Lingueglia, "to have a very good compound in a very bad venom."

Friday, 5 October 2012

Caffeinated Coffee Linked to Vision Loss

The study, The Relation between Caffeine and Coffee Consumption and Exfoliation Glaucoma or Glaucoma Suspect: A Prospective Study in Two Cohorts, is the first to examine the link between caffeinated coffee and exfoliation glaucoma in a U.S. -based population.
"Scandinavian populations have the highest frequencies of exfoliation syndrome and glaucoma," said author, Jae Hee Kang, ScD, of Channing Division of Network Medicine at Brigham and Women's Hospital in Boston, Mass. "Because Scandinavian populations also have the highest consumption of caffeinated coffee in the world, and our research group has previously found that greater caffeinated coffee intake was associated with increased risk of primary open-angle glaucoma, we conducted this study to evaluate whether the risk of exfoliation glaucoma or glaucoma suspect may be different by coffee consumption."
The study was composed of two cohorts: 78,977 women from the Nurses' Health Study (NHS) and 41,202 men from the Health Professionals Follow-up Study (HPFS) who were at least 40 years of age, did not have glaucoma and reported undergoing eye examinations from 1980 (for NHS participants) and 1986 (for HPFS participants) to 2008. The research team used questionnaires to obtain and validate the consumption of beverages containing caffeine and reviewed medical records to determine incident cases of exfoliation glaucoma, which contributes to elevated pressure sufficient enough to damage the optic nerve, or exfoliation glaucoma suspect that have milder or only suspect optic nerve damage.
A meta-analysis of the two cohorts showed that, compared to abstainers, participants who drank three cups or more of caffeinated coffee daily were at an increased risk of developing exfoliation glaucoma or glaucoma suspect. The researchers did not find associations with consumption of other caffeinated products, such as soda, tea, chocolate or decaffeinated coffee. The results also showed that women with a family history of glaucoma were at an increased risk.
Kang, along with his colleagues, report that this study represents a much needed effort to better understand the causes of exfoliation glaucoma, which are largely unknown.
"Because this is the first study to evaluate the association between caffeinated coffee and exfoliation glaucoma in a U.S. population, confirmation of these results in other populations would be needed to lend more credence to the possibility that caffeinated coffee might be a modifiable risk factor for glaucoma," said Kang. "It may also lead to research into other dietary or lifestyle factors as risk factors.

Artificial Cornea Could Help Save Vision, Make Up for Lack of Donor Corneas

Our eyes are our window to the world. Thousands of people have lost their eyesight due to damages to the cornea, such as trauma, absent limbal stem cells or diseases. Transplantation of a donor cornea is the therapy of choice for a great number of those patients. Let alone the issue of scarce donor material, a sub-group of patients do not tolerate transplanted corneas, necessitating the employment of an alternative means of restoring eye sight. In Germany alone, around 7,000 patients are waiting to be treated. In close cooperation with the Aachen Centre of Technology Transfer, Dr. Storsberg and his team from the Fraunhofer Institute for Applied Polymer research IAP in Potsdam, are attempting to improve the situation by developing an artificial cornea. Scientific partners in the "ART CORNEA" project include the Martin Luther University of Halle-Wittenberg, ACTO e. V. and the Ophthalmic Clinic Cologne-Merheim.
"We are in the process of developing two different types of artificial corneas. One of them can be used as an alternative to a donor cornea in cases where the patient would not tolerate a donor cornea, let alone the issue of donor material shortage," says IAP project manager Dr. Joachim Storsberg. The scientist has considerable expertise in developing and testing of next-generation biomaterials. Between 2005 and 2009 he collaborated with interdisciplinary teams and private companies to successfully develop an artificial cornea specifically for patients whose cornea had become clouded -- a condition that is extremely difficult to treat. Such patients are unable to accept a donor cornea either due to their illness or because they have already been through several unsuccessful transplantation attempts. Dr. Storsberg was awarded the Josef-von-Fraunhofer Prize 2010 for this achievement."A great many patients suffering from a range of conditions will be able to benefit from our new implant, which we've named ArtCornea®. We have already registered ArtCornea® as a trademark," reports Storsberg.
Ultima ratio patients regain vision
ArtCornea® is based on a polymer with high water-absorbent properties. Dr. Storsberg and his team have added a new surface coating to ensure anchorage in host tissue and functionality of the optic. The haptic edge was chemically altered to encourage local cell growth. These cells graft to the surrounding human tissue, which is essential for anchorage of the device in the host tissue. The researchers aimed to enlarge the optical surface area of the implant in order to improve light penetration beyond what had previously been possible -- a tall order. "Once ArtCornea® is in place, it is hardly visible, except perhaps for a few stitches. It's also easy to implant and doesn't provoke any immune response," says Storsberg, highlighting the merits of this new development.
The specialists have also managed to make a chemically and biologically inert base material biologically compatible for the second artificial cornea, ACTO-TexKpro. Dr. Storsberg achieved this by selectively altering the base material, polyvinylidene difluoride, by coating the fluoride synthetic tissue with a reactive molecule. This allows the patient's cornea to bond together naturally with the edge of the implant, while the implant's inner optics, made of silicon, remain free of cells and clear. The ACTO-TexKpro is par- ticularly suitable as a preliminary treatment, for instance if the cornea has been destroyed as a consequence of chronic inflammation, a serious accident, corrosion or burns.
The experiments were carried out in collaboration with Dr. Norbert Nass and Dr. Saadettin Sel, Senior consultant ophthalmologist at Martin-Luther-University Halle-Wittenberg. How well TexKpro and ArtCornea® are accepted by clinicians as an additional tool at their disposal was first tested by the doctors in the laboratory thereafter in vivo in several rabbits. After a six month healing process, the implanted prostheses were accepted by the rabbits without irritation, clearly and securely anchored within the eye. Tests carried out following the operation showed that the animals tolerated the artificial cornea well. Prof. Dr. Norbert Schrage will take charge of clinical trials that will soon commence at the Eye Clinic Cologne-Merheim. It is likely that the positive results of tests carried out thus far will be confirmed, and the co-operation partners rate the chances of success very highly.
Their optimism is well founded: As early as 2009, several Ultima-Ratio patients received implants of a Kerato prosthesis specially developed for them because they had previously rejected human corneas. These patients have not suffered any complications and are still wearing their artificial corneas today.

Universal Map of Vision in the Human Brain

The study appears in the latest issue of Current Biology, a Cell Press journal.
Scientists frequently use a brain imaging technique called functional MRI (fMRI) to measure the seemingly unique activation map of vision on an individual's brain. This fMRI test requires staring at a flashing screen for many minutes while brain activity is measured, which is an impossibility for people blinded by eye disease. The Penn team has solved this problem by finding a common mathematical description across people of the relationship between visual function and brain anatomy.
"By measuring brain anatomy and applying an algorithm, we can now accurately predict how the visual world for an individual should be arranged on the surface of the brain," said senior author Geoffrey Aguirre, MD, PhD, assistant professor of Neurology. "We are already using this advance to study how vision loss changes the organization of the brain."
The researchers combined traditional fMRI measures of brain activity from 25 people with normal vision. They then identified a precise statistical relationship between the structure of the folds of the brain and the representation of the visual world.
"At first, it seems like the visual area of the brain has a different shape and size in every person," said co-lead author Noah Benson, PhD, post-doctoral researcher in Psychology and Neurology. "Building upon prior studies of regularities in brain anatomy, we found that these individual differences go away when examined with our mathematical template."
A World War I neurologist, Gordon Holmes, is generally credited with creating the first schematic of this relationship. "He produced a remarkably accurate map in 1918 with only the crudest of techniques," said co-lead author Omar Butt, MD/PhD candidate in the Perelman School of Medicine at Penn. "We have now locked down the details, but it's taken 100 years and a lot of technology to get it right."
The research was funded by grants from the Pennsylvania State CURE fund and the National Institutes of Health (P30 EY001583, P30 NS045839-08, R01 EY020516-01A1).

Earthquake in a Lab

Scientists have simulated a moderate- to large-size earthquake in the laboratory. No, there's no shaking going on. Instead, researchers have developed a disc-brake-like device that can simulate motion along a fault line. The industrial-strength apparatus holds two disks of stone (the dotted line marks the right side of the interface between the two disks), each representing one side of a small patch of a fault zone. Sensors in the device (connected to the wires at center left) monitor the temperature of the stone disks as well as their acceleration and deceleration as they grind past each other. The energy needed to drive the faux quakes is stored in a 225-kilogram flywheel; once the flywheel is spinning at the appropriate speed for the test at hand-typically somewhere between 20 revolutions and 300 revolutions per minute-its energy is transferred to one of the stone disks, which then scrubs against the other disk with great pressure and at high speed until frictional forces bring the rotating disk to a halt. The device can simulate quakes measuring between magnitude 4 and 8, the researchers report online today in Science. Such tests may help scientists better identify how the energy released during an earthquake is distributed. At present, it's not well understood what proportion of the energy ends up in seismic waves, what portion is expended fracturing rocks in Earth's crust, and what fraction is spent heating the rocks along the fault zone due to friction. 

Wednesday, 3 October 2012

Smallpox virus may help treat deadly form of breast cancer Read more: http://www.dailymail.co.uk/health/article-2211631/Smallpox-virus-help-treat-deadly-form-breast-cancer.html#ixzz28E3eOqJz Follow us: @MailOnline on Twitter | DailyMail on Facebook

A relative of the small pox virus may be an effective weapon against one of the deadliest forms of breast cancer, researchers say.
Laboratory tests showed that more than 90 per cent of triple negative breast cancer (TNBC) cells treated with the vaccinia virus were destroyed within four days.
In mice with the disease, one strain of the virus cleared away 60 per cent of tumours while the extent of those left was dramatically reduced.
Vaccinia virus: The virus that helped eradicate smallpox could also combat a type of breast cancer resistant to current treatments
Vaccinia virus: The virus that helped eradicate smallpox could also combat a type of breast cancer resistant to current treatments
Vaccinia virus is best known as the basis of the vaccine that eradicated smallpox. Although closely related to the variola virus that causes smallpox, it is generally harmless to humans.
TBNC is difficult to treat because it lacks three types of molecular 'receptor' that can be targeted by existing hormonal and antibody treatments.
The disease mostly occurs in younger women and is responsible for 10% to 20 per cent of all breast cancer cases. TBNC tends to be aggressive and often recurs after chemotherapy.
The virus targets a signalling protein tumours use to promote the formation of blood vessels that support their growth.

TBNC has high levels of the protein, known as vascular endothelial growth factor (VEGF).
Lead researcher Dr Sepideh Gholami, from Stanford University in California, US, said: 'The reason we used the vaccinia virus is that it is a member of the small pox family, and, as we know, small pox vaccine has been given to millions of people to eradicate small pox. So we thought it would be safer and more promising in terms of a clinical trial and actual application.'
Screening: Mammograms can pick up breast cancer early in at-risk individuals
Screening: Mammograms can pick up breast cancer early in at-risk individuals
The findings were presented today at the American College of Surgeons' Annual Clinical Congress in Chicago.
Exposing mice with TNBC tumours to the virus led to "extensive destruction" of the cancer over a period of three weeks, said the scientists.
'Based upon pathology, we could see that at least 60 per cent of the tumours were completely regressed and the other 40 per cent  had very little areas of tumour cells present with a lot of necrosis (die off), which is a sign that the tumour was responding to therapy,' said Dr Gholami.
As well as infecting and breaking down cancer cells, the virus also blocked the growth of tumour blood vessels.
Ultrasound imaging revealed a 'significant reduction' in blood flow to tumours. The network of blood vessels supplying tumours with nutrients and oxygen shrank to half its normal size in treated animals.
The next step will be to design a clinical trial and assess the safety of the virus in patients, Dr Gholami added.
Baroness Delyth Morgan, chief executive of the Breast Cancer Campaign charity, said: 'This is one example of a new type of therapy using viruses to attack cancer cells. The research is currently at an early stage in mice so the findings should be treated with cautious optimism.'

How nuclear power works

Nuclear power
The world's first large-scale nuclear power plant opened at Calder Hall in Cumbria, England, in 1956 and produced electricity for 47 years.
Nuclear power is generated using uranium, a metal that is mined as an ore in large quantities, with Canada, Australia and Kazakhstan providing more than half of the world's supplies.
Nuclear reactors work in a similar way to other power plants, but instead of using coal or gas to generate heat, they use nuclear fission reactions. In most cases, heat from the nuclear reactions convert water into steam, which drives turbines that produce electricity.
There are different kinds, or isotopes, of uranium, and the type used in nuclear power plants is called uranium-235, because these atoms are easiest to split in two. Because uranium-235 is quite rare, making up less than 1% of natural uranium, it has to be enriched until the fuel contains 2-3%.
Inside a nuclear reactor, rods of uranium are arranged in bundles and immersed in a giant, pressurised water tank. When the reactor is running, high-speed particles called neutrons strike the uranium atoms and cause them to split in a process known as nuclear fission. The process releases a lot of energy and more neutrons, which go on to split other uranium atoms, triggering a chain reaction. The energy heats up the water, which is piped out to a steam generator.
To make sure the power plant does not overheat, control rods made of a material that absorbs neutrons are lowered into the reactor. The whole reactor is encased in a thick concrete shield, which prevents radiation escaping into the environment.
In Britain, nuclear power stations provide 19% of our electricity and account for 3.5% of our total energy use. All but one of those reactors are due to close down by 2023.
Some groups oppose nuclear power stations because they produce radioactive waste and could release radioactive material if there was an accident. But nuclear power plants do not release greenhouse gases, which cause coal and gas-fired power plants to contribute to global warming. Without nuclear power stations, UK's carbon emissions would be 5% to 12% higher than they are.
In 1957, the world's first nuclear power accident occurred at Windscale in west Cumbria. A fire in the reactor caused a release of radioactivity, which led to a ban on milk sales from nearby farms. The site was later renamed Sellafield. Modern reactors are designed to shut down automatically. The worst nuclear power accident in history took place in Chernobyl in 1986 when a reactor there exploded, killing tens of people instantly and exposing hundreds of thousands more to radiation.
In January, the government reaffirmed its plans to expand nuclear power in Britain to help it meet stringent targets to reduce carbon dioxide emissions.
Nuclear weapons
There are two main types of nuclear weapon: atomic bombs, which are powered by fission reactions similar to those in nuclear reactors, and hydrogen bombs, which derive their explosive power from fusion reactions.
The first atomic bomb was produced at Los Alamos National Laboratory in America under the Manhattan Project at the end of the second world war. An atomic bomb uses conventional explosives to slam together two lumps of fissionable material, usually uranium-235 or plutonium-239. This creates what is known as a critical mass of nuclear material, which releases its energy instantaneously as atoms inside it split in an uncontrolled chain reaction.
Atomic bombs unleash enormous shock waves and high levels of neutron and gamma radiation. In atomic bombs, uranium is enriched much more than fuel, to about 85% uranium-235.
On August 6 1945, an atomic bomb called Little Boy was dropped on the Japanese city of Hiroshima, followed three days later by another, called Fat Man, on Nagasaki.
Hydrogen, or thermonuclear bombs, work in almost the opposite way to atomic bombs. Much of their explosive power comes from fusing together hydrogen atoms to form heavier helium atoms, which releases far more energy than a fission bomb. Two types, or isotopes, of hydrogen are used - deuterium and tritium. A deuterium atom is the same as a hydrogen atom, except the former has an extra neutron in its nucleus. A tritium atom has two extra neutrons.
A hydrogen bomb has a built-in atomic bomb, which is needed to trigger the fusion reaction. Hydrogen bombs have never been used in war and are thousands of times more powerful than atomic bombs.
The first test of a hydrogen bomb was at Enewatak, an atoll in the Pacific Ocean. It released a three mile-wide fireball and a mushroom cloud that rose to nearly 60,000 feet, destroying an island in the process.
Nuclear waste
One of the biggest problems the nuclear industry faces is what to do with the radioactive waste it produces. Some of it will remain radioactive and hazardous for hundreds of thousands of years.
High-level waste is the most dangerous because it can melt through containers and is so radioactive it would be fatal if someone was near it for a few days. This type of waste makes up just 0.3% of Britain's total volume of nuclear waste, which is mostly waste from spent fuel rods. The largest amounts of radioactive waste are made up of nuclear fuel cases, reactor components and uranium.
Today, high-level waste is dealt with by cooling it in water for several years and then mixing it into a molten glass, which is poured into steel containers. These canisters are then stored in a concrete-lined building.
This is only a temporary measure, though. Scientists know that eventually they need to find a way of storing nuclear waste safely for thousands of years. Some countries, such as America and Finland, plan to store nuclear waste in deep underground bunkers. For this to be safe, scientists have to be sure the material could never leak out and contaminate water supplies or rise up to the surface.
Britain already has more than 100,000 tonnes of higher activity radioactive waste that needs to be stored. Large amounts of low-level waste are already stored in concrete vaults in Drigg in Cumbria. Other plans for disposing of nuclear waste have included dumping it at sea and blasting it into space.

White Finger Disease And Genetics

Vibration-induced white finger disease (VWF) is caused by continued use of vibrating hand held machinery (high frequency vibration >50 Hz), and affects tens of thousands of people. New research published in BioMed Central's open access journal Clinical Epigenetics finds that people with a genetic polymorphism (A2191G) in sirtuin1 (SIRT1), a protein involved in the regulation of endothelial NOS (eNOS), are more likely to suffer from vibration-induced white finger disease. 

VWF (also known as hand arm vibration syndrome (HAVS)) is a secondary form ofRaynaud's disease involving the blood vessels and nerves of arms, fingers and hands. Affected fingers feel stiff and cold and lose sensation for the duration of the attack, which can be very painful. Loss of sensation can make it difficult to carry out manual activities. Initially attacks are triggered by cold temperatures but as the disease progresses attacks can occur at any time. 

Little is known about what causes the restriction in blood flow, however researchers from Germany investigated the role of SIRT 1 by looking at polymorphisms (naturally occurring variations in DNA sequence) in people affected by VWF. 

SIRT1 regulates activation of other genes by controlling how tightly DNA is wound in the nucleus. Tightly wound DNA cannot be 'read' and consequently cannot be used to make new protein. SIRT1 is known to regulate vasodilation by targeting eNOS, a nitric oxide synthase within the cells lining the inside of blood vessels, which regulates smooth muscle contraction, and hence the diameter of the vessel, and the amount of blood that can flow through it. 

Of 113 polymorphisms tested, in the gene coding for SIRT1, only four actually affected the protein, the rest were non-coding or false positives. Of these four, only one was different between people with VWF and unaffected controls. A single nucleotide at position 2191 can either be an A or a G. In the unaffected population 99.7% had the A, but amongst the patients with VWF, almost a third had the G. 

Dr Susanne Voelter-Mahlknecht from the University of Tuebingen, who led this study, explained, "While this does not mean that only people with the G version of the gene for SIRT1 will get VWF, it can be used to identify a set of people who would be at risk of VWF if they used vibrating hand held tools. Testing for this variant before starting to work with vibrating machinery could prevent years of pain and disability." 

Sirtuin1 single nucleotide polymorphism (A2191G) is a diagnostic marker for vibration-induced white finger disease Susanne Voelter-Mahlknecht, Bernd Rossbach, Christina Schleithoff, Christian-Lars Dransfeld, Stephan Letzel and Ulrich Mahlknecht Clinical Epigenetics (in press) 
BioMed Central