a drug tetrathiomolybdate (TM), which mops copper in the body, which had already failed in a series of clinical trials on the previous cancer, is to get a second chance. A Phase II clinical trial of the drug in women who had been successfully treated for breast cancer but are at high risk of recurrence suggests that it can inhibit the growth of new tumors. Yet the promise of this copper depletion strategy appears not tarnished by clinical results, but the company strategy. The oncologist who led the Phase II clinical trial will now proceed to a, III TM largest phase of trial. But by TM Cancer Treatment rights are held by a Swedish biotechnology company developing the drug in place of Wilson's disease, a rare inherited disorder of copper accumulation. The company, Wilson Therapeutics, has no immediate plans to test TM in cancer patients, its CEO acknowledged, and for now will not sublicense the drug.
↵ * Ken Garber is a writer based in Ann Arbor, Michigan.
"Molecular microscope" is hidden AIDS virus in the body -
Researchers have developed a new sophisticated sensor that detects HIV hiding places inside and outside the cells. "It is a fantastic new technology that will allow us to visualize the virus in tissues that we have never been able to before," says immunologist Richard Koup, deputy director of the Vaccine Research Center at the National Institute of allergy and infectious diseases (NIAID) in Bethesda, Maryland, who was not involved in the research. Insights of this molecular microscope high power, revealed at an international AIDS conference last week, may clarify critical questions about the persistence of HIV and ultimately on how to rid the body of the virus.
To date, HIV assessments in the fabric known as in situ-analysis was hampered by a major difficulty. The most common sensors, which use fluorescent labels or radioactive markers to pinpoint the location of the virus in a tissue sample, sometimes have difficulty distinguishing the target RNA and HIV DNA from surrounding cell components . In essence, a marker can mislabel tissue the virus, creating a background that throws the analysis. The new technique has "very little noise," says immunologist Jake Estes National Frederick of the National Cancer Institute Laboratory (sister of NIAID) in Frederick, Maryland, used to produce highly detailed images of the AIDS virus in various tissues monkey (above) submitted to the conference.
Estes developed the technique in collaboration with Advanced Cell Diagnostics Hayward, California, modifying the existing product RNAscope of the company to detect HIV RNA, DNA or both the same time. RNA and DNA are composed of nucleotides that complement pair with a guanine, for example, binds to cytosine. Traditional methods for long strings of HIV use mapping the genetic material of these nucleotides, called oligomers, to find and bind to complementary strands of DNA or RNA in the sample tissue. These oligomers are labeled with a marker so they send a signal when they have reached their target, allowing the researchers to create an accurate picture of where the viral genetic material is dispersed in the tissue sample. But the oligomers are molecules large and somewhat clumsy, and they sometimes bind to cellular components other than the target sequence.
new technique Estes, however, uses a more complex sensor system that all but eliminates such errors. In essence, the approach chops in a two oligomer and sends the two halves in search of the target sequence. Their markers on if an additional oligomer which connects the two halves binds to time, which occurs only when they are parked next to each other on the target. The probability is extremely low that the two probes would land next to each other on something other than HIV.
HIV is an RNA virus, but it also converts to a form of DNA that allows it to build its genes in a human chromosome. Estes, who works with the virologist Jeffrey Lifson, also developed a DNAscope to view this DNA HIV-called provirus, which becomes embedded in human cells and can persist for decades without being attacked by the immune or antiretroviral system (ARV) . "Reservoirs" of infected cells that hold latent proviral are a major reason powerful combinations of ARVs can not eliminate infection and heal people.
Estes, Lifson and colleagues monkeys infected with the simian version of the AIDS virus and analyzed the tissues from many parts of their bodies. And RNAscope DNAscope were able to distinguish cells that harbor the provirus, the viral RNA, or even viruses outside cells much more clearly than any in situ prior art. "We are convinced that we can see individual virions, and it has an exquisite sensitivity and specificity," said Estes. To check their work, they counted HIV virions by the eye in one of their new images, and then compared the total to a validated measure of viral levels. "We see a good correlation," said Estes.
HIV / AIDS researchers working to heal the face of infection several obstacles that these new fields could help to overcome. The first is the absence of detectable virus in the blood plasma of patients on effective ART, making it difficult for researchers to assess whether an intervention to cure the infection works. Several techniques exist to measure changes in the tanks, but each has shortcomings that new tracts would be able to complete. Another obstacle is to not know where in the body the provirus prefers to hide. If the new sensor can help solve this longstanding puzzle, they could refine the retraction attempts viral reservoirs. "If we can go and see what happens to the virus in these tissues with this kind of sensitivity and specificity, it will answer a lot of questions," says NIAID Koup.
Breakthrough cancer therapy gives hope President Carter -
Former US President Jimmy Carter appeared relaxed and even made the joke from time to time when he publicly announced yesterday he melanoma that has spread to his liver and brain. The 0-year-old hoped it had advantages, as many are these days, advanced therapies that help the immune system to destroy cancer cells. (These treatments have exceeded Science 'Breakthrough of the year in 2013) Melanoma in some patients, was the first cancers to succumb to any of these immunotherapies, and specific treatment Carter takes has many oncologists excited: There is a monoclonal antibody called pembrolizumab Keytruda and sold under the brand name. Approved in the US there is a year for advanced melanoma, pembrolizumab belongs to a class of drugs called hot PD-1 inhibitors. By blocking PD-1 protein, the therapy enables the body to produce T cells that can chase after cancer.
Yet researchers have much to learn about pembrolizumab and other PD-1 therapies in development. Keytruda is also extremely expensive, about $ 150,000 per year. In clinical trials, PD-1 blockers generally work in less than half of the participants (see here and here). A study published earlier this year suggested that PD-1 inhibitors may work better in tumors with many mutations, and a small pembrolizumab clinical trial supported this. It found that people with advanced cancer were much more likely to respond if they had supposedly mismatch repair mutations in their tumors. This could also help explain why, so far, PD-1 inhibitors have produced the best results in people with lung cancer and melanoma, both are often heavy mutation of tumors.
What does all this mean for individual patients such as cancer Carter is still uncertain. "I had a wonderful life," he said in a conference television news from the Carter Center in Atlanta, with a grin. "I'll be ready for whatever comes."
Nearly 20 years ago, researchers have made of nucleic acids in the third dimension. Normally, DNA extracts and RNA resemble small chains. But the researchers found that when they have linked dozens of identical nucleic acid strands to a tiny metal nanoparticle, they formed nucleic acid particles that resembled tiny Koosh balls, with a solid core and flexible strands who exit. The particles with complementary nucleic acids bonded together, forming 3D materials. But what was more surprising was that the cells took the particles easily. Once inside the cells, spherical nucleic acids (SNA) can bind to RNA and DNA within cells, disabling the production of specific proteins. It has since been used to treat everything from cancer to psoriasis. Now a center at Northwestern University in Evanston, Illinois, received $ 11.7 million to continue SNA therapies, and human clinical trials with the particles should begin this fall.
dirty diapers are the most unlikely of crystal balls, but they could not hold the answer to why some children develop asthma . Only four types of intestinal bacteria in the stools seem to do all the difference, predict who will get the disease and who will not, researchers say. The discovery could help identify children at high risk of asthma and could also lead to the development of probiotic mixtures that prevent disease.
The new study "puts a lot of epidemiological observations from over the years into a new perspective," says researcher Marsha Wills-Karp asthma Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, who was not involved in the latest work.
a growing body of research has led to a new appreciation during the past decade to how the microbiome-collecting bacteria and viruses that live in the human health of those body shapes . And studies have suggested that the differences between microbiomes young babies, caused by biological methods, diet, environment and exposure to antibiotics could affect their chances of developing diseases such as asthma and allergies.
"There are all these smoking guns to indicate that the microbiota may be involved [in asthma], but there was no experience to prove it," says microbiologist Brett Finlay of the University of British Columbia (UBC) in Vancouver, Canada, lead author on the paper.
as part of the Child in Canadian Longitudinal Health Development (CHILD) Study, Finlay and his colleagues collected fecal and urine samples of more than 300 babies at 3 months and 1 year, as well as information on their health 1, 3 and 5 years. They then used the genetic high-throughput sequencing to detect levels of the intestine of microbes in each stool sample. Babies who had low or undetectable levels of four [1945003auxbactéries] Lachnospira Veillonella Faecalibacterium and old Rothia -at 3 months are all went to show the first signs of asthma wheezing and skin-allergies in one year. Babies who develop these symptoms still had high levels of the four bacteria in their stool samples to 3 months.
The Association held "fairly regularly" and "very" statistically significant, Finlay said. In addition to differences in bacteria stool, the team found differences in the urine of babies who developed asthma. Some bacterial byproducts were at higher or lower levels, suggesting that these chemicals produced in the gut, but distributed throughout the body could act on the immune system to make it more susceptible to disease.
, a group of Finlay
Next stool samples used from the asthmatic 3-month-olds subject to colonize the intestines of mice that had been raised in a bacteria-free environment. The animals continued to develop indicative inflamed lungs of asthma. But when the researchers added a mixture of the four missing microbes in the digestive tract of mice and feces, the mice had more increased risk of developing asthma, scientists report online today in Science Translational Medicine .
discovery has immediate application: identifying children at high risk of asthma in their first 100 days of life, said pediatrician Stuart Turvey University of British Columbia in Vancouver, a co-author on the paper. "These children could be followed or processed faster if they end up with asthma". But it also suggests he adds that providing this group with the unique mix of four bacterial combination not found in current commercial probiotics could prevent the occurrence of asthma.
But the development of therapies will be more difficult than a simple mixture of microbes together in pill form, Wills-Karp said, because babies have guts that are teeming with other bacteria. These "early settlers" can prevent new strains easily take over. and another study suggested various protective bacteria. "it is unclear at present exists for it means induce growth of these particular bacteria in children, "she said. "But it certainly begins to open the door to that possibility."
Finlay team Turvey and continues to monitor the health of the first group of children, the study will develop the real-asthma to date, more than a third of those who developed the first signs of the disease have the full version. In addition, since the microbiomes of people in different cultures are known to vary: they repeat the experience in a wider range, more diverse children, including some of Ecuador, to see if the four strains bacteria are universally important.
Feature: Giving sight to the blind illuminates the secrets of the brain -
NEW Delhi- Manoj Kumar Yadav came into this world with cataracts. In developed countries, a simple surgery heals this disabling eye disease in the first months of life. But as the vast majority of people in India, Yadav was born in a village, with limited access to health care. His parents are poor and uneducated. They do not even realize their infant son was blind until he starts banging crawling. Years later, when regional doctors examined Yadav, they told him he would never see. "We have given up," recalls Yadav, now 22. "We thought it was useless to run over trying to find a cure."
Then, in 2011, a team of specialists to New Delhi Yadav visited village in Uttar Pradesh. They he and other blind children examined and kindled hope that Yadav could one day be able to see after all. This August, he and his father took a train trip 13 hours in the capital of India. Here at the Hospital Dr Shroff Charity Eye, a surgeon excised his cataract lenses mounted and slid in synthetic for them.
When doctors removed the bandages a day later, the world Yadav was filled with light, and shapes that were impenetrable to him. He could not tell people objects, or if something has ended and another began. His brain, private information of his eyes for 18 years, did not know what to do with the flood of visual stimuli. But over the next few months, his brain gradually learned to interpret the signals he was getting from his eyes, and blurred and confused world began to come into focus.
Yadav is among hundreds of blind children, adolescents, and young adults who are now able to see through a project called Prakash, which means "light" in Sanskrit. India may have the largest number of blind children in the world. Estimates range from 360,000 to nearly 1.2 million. The vast majority live in rural areas, their quality of life worsened by poverty, lack of access to health care, and a lack of facilities for the disabled. Almost 40% of these children are considered preventable or curable blindness, caused by congenital cataracts, damaged corneas, and eye infections.
Led by neuroscientist Pawan Sinha, Prakash project began in 04 as a humanitarian effort to address this problem. But there was also a scientific purpose. Sinha, based at the Massachusetts Institute of Technology in Cambridge, speculated that the newly observed children could help answer a question that had long intrigued him: How the brain learns to see? Initially funded by the US National Institutes of Health as an exploratory grant, Prakash has since become a revolutionary effort in neuroscience. For years, doctors assumed that once a blind person passed a critical age in infancy, without vision, their brain would never be able to make sense of the visual world. With patients like Yadav, Prakash demolished this hypothesis.
Mr. Atarod / SCIENCE
"It took me years about a year and a half before I could see everything clearly," said Yadav. Light and short Yadav is polite and soft-spoken, his eyes darting nervously back and forth. The condition, nystagmus, is a relic of his congenital blindness. But disappeared with the cataracts, it does not stop to see. "Now I can even ride a bicycle through a crowded market," he said.
Prakash "beautifully demonstrates that there is still room for plasticity and recovery" in patients who have grown blind, said Collignon, a neuroscientist at the University of Trento in Italy. This does not mean the new psychic will be able to see as well as those born seers, he warns. "Not supported by the data."
Yet the surprising ability of Prakash patients to obtain an important vision is rewriting visual neuroscience. As the medical gain their efforts became clear, the project leaders have launched a series of studies, low-tech patient responses tests to visual illusions functional MRI (fMRI) imaging of their brain reorganization in response to visual input. While the survey how the newly preview process visual cues, project scientists are peeling away layers of mystery about aspects of the view that come pre-programmed and are shaped by experience.
OPHTHALMOLOGY MANUALS have long suggested that trying to give sight to adolescents who have been blind from birth is unlikely to succeed. In a series of groundbreaking studies in cats and monkeys who won the Nobel Prize in Physiology or Medicine in 1981, Torsten Wiesel and David Hubel have shown that if the brain is deprived of visual signals during a critical period shortly after the birth, vision is impaired for life. There was no similar experiments in humans for ethical reasons, but scientists took our slams critics windows closed between 6 and 8. This belief guided surgeons Shroff, who turned away the blind children over 8 years.
However, Sinha unearthed some studies it decades ago that suggested congenitally blind adults could earn at least some vision after cataract surgery. Then in 02 and 03, while traveling across India to understand the extent and causes of blindness, Sinha met four people who all had cataracts removed as teenagers and had gained some vision. Anecdotal evidence was enough to convince Sinha that, given recent advances in medicine, Prakash project was worth pursuing, and it convinced the Shroff surgeons to give it a try.
The eye specialists and team of health workers set up screening camps in rural areas to identify children who might benefit from surgery and nonsurgical interventions such as eyeglasses, drops eyes, and medications. So far, more than 1,400 children received nonsurgical care and nearly 500 children and young adults have undergone cataract surgery. About half of these patients-those that scientists believe blind research topics-birth became.
Their recent studies show that the experience is not critical for certain visual functions. Instead, the brain seems to be wired to interpret at least some simple aspects of the visual world. The evidence comes from tests of visual illusions that also help settle a longstanding debate about why the brain misinterprets particular types of images.
When our perception of an image differs from reality, we experience a visual illusion. Some neuroscientists believe that the innate wiring of our brain is responsible illusions; others think they are a product of learning. The resolution of this debate has been difficult, said Susana Martinez-Conde, a neuroscientist at the State University of New York Downstate Medical Center who studies delusions. "Babies can not realize the visual experience," she said. "And it would be unethical to deprive a baby of visual experience to test." The answer was "anybody's guess," said up Prakash this project began studying newly observed children whose vision it at the first acquisition, is close to.
in 2010 and 2011, the team Sinha took newborn nine children of those about to undergo surgery for cataracts. the subjects had been blind since birth, according to parents and surgeons Shroff Charity Hospital Eye. Shortly after their bandages were removed, scientists have shown their Ponzo illusion. first shown there is more than a century, this illusion usually involves converging lines on the horizon (such as railroads) and two short parallel lines cut through them. Although the lines horizontal are identical, one near the horizon is more like.
The prevailing explanation of the Ponzo illusion is that it is the result of brain experience interpreting 2D images as 3D scenes, with the individual elements of the images perceived as different depths and distances. "This learning brings us to combine these two identical rows in this illusion as being at two different distances from us," says Sinha. The brain interprets the line closer to the apparent horizon further and thus longer than the other identical line.
functional MRI shows activity in the visual cortex of a newly overview Prakash patient begins to perceive human faces. Prakash children gradually learn to use the same region of the cortex that supports face perception in people normally observed.
Project Prakash
If the Ponzo illusion were the result of visual learning, Prakash children would not fall for it. But to the surprise of the team, the children were equally sensitive to Ponzo illusion as were the control subjects with normal vision. They consistently found the line near the horizon addition, the team reported in Current Biology May
children also fell for the illusion Müller-Lyer, a pair of lines with arrows on both ends; a tip assembly arrowheads outwardly, the other inwardly toward the line. The line with the arrows inwards seems. "All we can say on the basis of these results is that this is not the experience," says Sinha. "It's something else. It is probably driven by very simple factors in the image that the brain is probably naturally programmed to respond to. "
Martinez-Conde is willing to hazard a guess on how the Müller-Lyer illusion works. His previous research has shown that our eyes tend to notice more corners than straights. Maybe be, she said, our brain focuses on the corners arrows outward, making the line between watching shorter than the arrow line inward. "But this should be taken with a large grain of salt because I have no data to prove it. "
Whatever the mechanism, the new study adds to the evidence increasingly" that we are not blank slates when we born, "says Martinez-Conde. other evidence comes from a recent study by Amir Amedi, a neuroscientist at the Hebrew University, and his colleagues in which they have used fMRI to compare the visual cortex congenitally blind individuals with that of those normally observed. They found that the basic organization of the visual cortex of blind people of birth is similar to that of normal vision, and both have similar connections between different parts of the cortex. This means that "we are born with this machinery to see that in a sense does not require visual experience to emerge," said Amedi. "The visual system comes with some connections and means of calculation."
SUCH cabling May HELP children acquire Prakash functional vision in the months following surgery, Amedi speculates. But experience and learning seem to play a more important role in the visual acquisition. "This n 'there is more evidence that [even] adult brain can change in the structure and function, "says Brigitte Roeder, a neuropsychologist at the University of Hamburg in Germany. for example, studies have shown that adults who regularly play video action games are better at certain visual tasks, such as reading the fine print on a bottle of prescription or monitoring several friends who are moving through a crowd.
More relevant to Prakash children is the ability to create a mental image of a 3D space. "Satellite imagery is very important in our lives," said team member Prakash Tapan Gandhi, a neuroscientist at the Indian Institute of Technology, Delhi, New Delhi. "If I ask you, think of your kitchen where you kept that, you can visualize it. This is very important for our daily lives. "But blind people are not able to imagine spaces. When tested for this ability using a die and moving ankles, Prakash children before the poor results of surgery compared with people normally seen, said Gandhi. Few after surgery, however, they begin to get better at spatial imaging tasks. the vision must be crucial to help the brain create mental maps of the areas, he said. and the brain is not no critical window for this ability, or the window remains open until much later in life, Gandhi and colleagues reported in 2014 12 March issue of Psychological Science.
the team . found similar adaptability in the ability to distinguish a human face from pictures facelike Shortly after surgery, Prakash patients can not differentiate it also contradicts the dogma. Homing on the faces is an ability visual scientists think is innate. But after a few weeks, the new seer can recognize a human face and begin to recognize different faces. The team also found that their patients quickly learn to connect contacts view. In other words, they are soon able to recognize objects they have touched blindfolded when they see these remote objects.
But plasticity has its limits. Collignon and his colleagues studied a group of adults in Canada who were born with cataracts, but underwent corrective surgery before turning 1. Despite at least two decades of sight restored, each individual had slightly blurred vision. Their 3D perception and their ability to detect motion has also been compromised, according to unpublished results. The researchers found that the brains of these people seem to be wired differently. Unlike people normally seen, their visual cortexes also sound process, they reported in August in Current Biology
"What is really striking here is that we're talking about people who are deprived [of sight] for a few weeks a few months, but it leads to a reorganization longtime brain to better respond to sound, "says Collignon. Prakash patients who are blind for years, are also likely to have them reorganized visual cortex, he said, which could hamper the recovery. "They have a record of their past [in their brains], and their past is blindness," he said. "These people will never be able to recover the vision as one who has seen before."
The findings from Sinha confirmed. The Prakash patients do not develop a vision as sharp as normally seen others. "Despite following these children for many years, we do not find an increase in the acuity to normal," says Sinha. This suggests a critical window of acuity that closes some time before they turn 8 young age Prakash to this Treaty.
Yadav's experiences are typical. "I can read the headlines with my glasses," he said. But 4 years since his operation, he still has trouble reading the fine print in newspapers and books
The window also appears close early for contrast sensitivity :. The ability to discern contrasts, shades and patterns, one of the most basic functions of vision. In one test, the team of Prakash Sinha shows children four models-a house, a square, an apple, and a circle and asks them to identify patterns as they change size and contrast. Normally sighted people can detect these patterns for a range of sizes, if the contrast is above a certain threshold. Prakash for children, their contrast sensitivity significantly improves until several months after the surgery, but never reached normal levels. They remain blocked in the detection of a limited number of sizes, and only when the contrast is quite high.
Manoj Yadav bicycles to work in Gorakhpur, India. "I can ride a bike, even in a crowded market," he said.
Graham Crouch
Taken together, the results demonstrate that no single critical period governing vision says Amy Kalia, a postdoctoral fellow with Sinha. "is recoverable vision or not," she said, "is a more complex story."
The training could help children recover Prakash most visual function, said Uri Polat, a neuroscientist at the University of Tel Aviv in Israel. "The window did not close," he said. "It becomes less sensitive."
In 04, Polat was the first to show that training can restore vision in adults with amblyopia, or lazy eye. A lazy eye prevents the normal development of the visual cortex in infancy. Patients have a binocular visual impairment and low acuity and contrast sensitivity; the diminished view was considered irreversible after age 10. Patients Polat was watching a computer screen with variations of an image Gabor Patch, who fuzzy patterns in black and white that change size and contrast . After only a month of training, patients had greater acuity and contrast sensitivity.
Amedi agreed that training is the key, but think it should involve touch and sound, too, meaning that blind people rely on to navigate the world. His research showed that her interpreting or touch, they rely on some of their visual cortex normally devoted to vision. For example, they use the same part of the brain that use of sighted Braille for reading. Project Prakash plans to open a boarding school the next year for the rehabilitation and education of children after cataract surgery using physical exercises and multisensory experiences.
FINALLY , the team will reveal how Prakash restore vision changes the visual cortex. They begin to fathom the changes in the brain with fMRI.
When the image of the visual cortex of a patient before and 2 days after surgery, different areas of the cortex appear to work in synchrony. "So if you have high activity in a part of the cortex, you will have a similar activity in another part of the cortex," says Sinha. "It is as if a large part of the visual cortex is pulsating together."
However, only a few months after surgery, fMRI picture begins to change. Different regions of the visual cortex light up differently, suggesting a division of labor. Pictures of human faces presented to patients, for example, activate a zone the cortex known to meet the faces of people normally observed.
"It makes a lot of sense," said Amedi. "When they begin to process visual information, they can not perform tasks. They can not identify an object, a person. It is all the same nonsense for them." But as time passes, and the brain learns to distinguish objects, shapes and faces, different areas of the visual cortex begin to specialize.
Sinha, for one, do not expect these changes in the brain. "I'm amazed by how much, how massive change is and how it happens quickly, and how the end of life, it can happen, "he said. He did not wait for the geyser of project results generated. "I was afraid of having to work with children old enough, we were ourselves up for failure." Instead, the project has brought hundreds of young people like Yadav in light while keeping the field visual neuroscience in a new light well.
See our slide show Project Prakash.
Listen to a podcast with the author Rhitu Chatterjee.
More than half of Americans over the age of 70 have cataracts caused by masses of collection of proteins in the lens of the eye. The only way to remove them is surgery, an option unavailable or unaffordable for many of the 20 million people worldwide who are blinded by the condition. Now a new study in mice suggests eye drops made with a natural steroid could reverse cataracts by teasing apart the protein clusters.
"This is a game changer in the treatment of cataracts," says Roy Quinlan, a molecular biologist at the University of Durham in the UK, who was not part of the study. " it takes decades for cataracts to get to this point, so if you can reverse that in a few drops into the eye over a couple of weeks, which is amazing. "
the proteins that make up the lens human are among the oldest in the body, forming about 4 weeks after fertilization. the majority are crystalline, a family of proteins that allow the eye to focus and keep a clear lens. Two of the most abundant crystalline , CRYAA and CRYAB are produced in response to stress or injury. They act as chaperones, identifying and binding to misfolded or damaged proteins in the lens, preventing aggregation. But over the years, such as damaged proteins accumulate in the lens, these chaperones become overwhelmed. The mutated proteins clump together and blocking the light and producing cloudiness revealing cataract.
To treat the disease without surgery, which is out of reach for many patients in developing nations, researchers studied the drug treatments. While strengthening the function and CRYAA CRYAB seems a good target, the development of a therapeutic has been difficult. Most drugs that act on proteins associated with the disease work by changing the way the protein functions, scientists can measure something by monitoring the enzyme activity of the protein. CRYAA, CRYAB and similar proteins are known as "undruggable" because their activity can not be measured, said Jason Gestwicki, a biochemist at the University of California (UC), San Francisco, and lead author of the new study, published in online today science .
Gestwicki team decided to use a technology called differential scanning fluorimetry, allowing scientists to measure the temperature at which a target protein begins to melt. They analyzed CRYAA and CRYAB and found that, in a type of hereditary cataract CRYAB takes a mutant form having a melting temperature much higher than the normal version. If we could find a molecule that bind to the mutant protein CRYAB and lower its return melting temperature than that of a healthy CRYAB, they speculated, CRYAB should function normally and prevent lumps damaged proteins in the lens . The researchers turned to a bank of 2450 molecules that had similar properties and CRYAA CRYAB. They added molecules mutant CRYAB, seeking a which stabilize their target. They are installed on the compound 29, a naturally occurring steroid in the blood, but not in the lens, which has no blood supply. Mice with cataracts and age-related hereditary received drops in his right eye while the left eye went untreated. After only a few weeks, the treated eye was visibly clearer, said Gestwicki, who led the work while at the University of Michigan. Cataract gravity is measured on a scale of zero to four, with four being the worst case. On average, the mice in the study had an improvement of one grade in serious cataracts after 4 weeks of treatment.
This is the second study this year to find that eye drops made from a class of steroids called sterols can successfully reverse cataracts. In July, the UC San Diego researchers reported that lanosterol, a steroid found in the human eye, inverted dogs cataracts.
"There is a me-too document in the sense that this new study also dealt with a sterol cataract," says Quinlan. "But they came to the same conclusion in completely different ways. This is how scientific excellence is done, and [it’s] something that should get philanthropists and pharma excited."
An essential difference between the two studies is how different steroids were administered. The dog study drug administered both by injection into the eye drops and eyes. The new study only used eye drops.
There is still a lot to discover before the two studies can move into clinical trials, Quinlan notes. The lens of the human eye is very different from those mice or dogs, and neither study explains how steroids work on cataract. "Mechanically, we do not really know what is going on here. It is a black box."
Understanding how the reverse cataract treatment is the next task of the team, a key step towards clinical trials which Gestwicki hopes to launch in the next year. ViewPoint Therapeutics, a biotechnology company he co-founded in San Francisco, California, holds the license for the technology and launch additional animal studies soon.
Progress, but still much to do, AIDS, the report found -
Of the estimated 36.9 million people infected with HIV worldwide, 70% live in sub -saharienne. Of these, 49% do not know their HIV status and about 57% do not receive antiretroviral drugs, according to a report released today by the Joint United Nations Programme on HIV / AIDS.
The report, which arrives on the eve of World AIDS Day on December 1st, celebrates the progress that has been made in getting antiretrovirals to 15.8 million people in June 2015. But he also notes how many countries are to meet the World health Organization guidelines health issued in September, calling for each infected person to receive treatment.
huge ongoing push to start all infected people on antiretroviral emerged from recent evidence that early initiation of treatment benefits the health of infected people, and also makes it very unlikely that they will transmit the virus (if fully suppress their own infection). But in sub-Saharan Africa, the report notes, it is estimated that 68% of those infected have not removed their HIV levels
Other statistical highlights from the report :.
About 36.9 million people living with HIV at the end of 2014. (This is the medium in an estimated range of 34.3 to 41.4 million people ).
2 million (from 1.9 to 2.2 million) people were infected with HIV at the end of 2014. New HIV infections have fallen by 35% since 00.
1.2 million (980,000-1.6 million) people died of AIDS-related illnesses in 2014.
as of June 2015, 15.8 million people living with HIV had access to antiretroviral therapy, against 13.6 million in June 2014.
US monitoring of the pathogens in risk could be better, the draft report -
concludes Just a "small subset" of studies that handle dangerous pathogens for their provide new capabilities pose potentially serious risk to the public, an advisory panel to the US government concluded in a new draft report released today. But the current patchwork of US policies to regulate such risky experiments "not enough," and "may require supplementation," concludes the report. He said there are a few so-called gain of function (GOF) of experiences that can never justify the risk.
Some outside scientists, however, say the apparent approval of the report for greater government oversight of these studies may not be sufficient to ensure public safety. "as usual, the devil is in the details," Harvard University epidemiologist Marc Lipsitch wrote in an email to Science Insider. "I'm glad to see some recognition experiences should not be doing, but I fear the exaggerated perception of the benefits and shortcomings in existing processes to weigh the risks and benefits, would thus neutralize this recognition anything de facto "will approach. "
The 70-page document, released today by a working group of the National Scientific Advisory Board for Biosecurity (NSABB), is the latest contribution to a long -Operation debate on how best to regulate potentially risky research with infectious agents. such studies are needed to develop treatments and vaccines, but the accidental or intentional release of pathogens changed is always a risk.
this debate gained prominence in 2011 when two groups of researchers announced that in experiments that seek to understand what makes influenza viruses spread, they had changed the deadly H5N1 bird flu for to transfer more easily between mammals. Some scholars have objected to the publication of results, fearing that they could help bioterrorism, while others fear the risks of a pandemic if the new virus escaped from a laboratory. The controversy eventually led researchers around the world to voluntarily declare a 1 year moratorium on these experiences GOF.
The work of GOF finally resumed, but the debate has taken a new turn in late 2014 when the US government made the unprecedented decision to end 18 GOF US studies funded involving making virus responsible for the flu and new diseases such as respiratory syndrome Middle East (MERS) or SARS pathogen or more likely to spread in mammals. The National Institutes of Health (NIH) later exempted some of the studies to the prohibition of funding, but government officials said it would remain in place while NSABB and the National Research Council (NRC) reviewed risks and rewards of GOF studies.
This discussion began with a meeting of the NRC in December 2014 where all sides have broadcast issues. And earlier this year the NIH has commissioned a private firm to conduct a risk analysis GOF-benefit studies; some documents of 1000 pages was published earlier this month and should be discussed at a meeting on 7-8 January NSABB in Bethesda, Maryland.
Risks and benefits
The draft report released today aims to inform and guide this discussion. He concluded that the benefit-risk, conducted by scientific Gryphon Takoma Park, Maryland, is "[o] ... GLOBAL complete, objective and reasonable and generally well documented." The Gryphon report includes a review of the probability both laboratory accidents and security breaches, the draft report notes. After examining a number of scenarios, it concluded that "[o] nly a small fraction of laboratory accidents would result in a loss of containment; of these, only a small fraction would result acquired laboratory infection, and of those, only a fraction would spread throughout the surrounding community (or of the world population) "
the. Gryphon report also suggests that certain types of GOF experiences are not likely to present significant risk to the public, the report notes NSABB. This includes experiments to improve the growth of influenza viruses for vaccines and efforts to adapt human stem in animal models.
Yet Gryphon analysis "has some weaknesses and limitations," the NSABB working group concludes. Data on GOF risks are often scarce, he notes, and some tests can "obscure material risks associated with GOF studies." For example, some scenarios have compared the risks of potential manipulations of certain strains of human influenza with influenza virus that caused a pandemic in 1918 and killed millions of people. But the use of the 1918 flu as a criterion could even relatively new deadly flu strains seem tame by comparison, the report notes.
The risk-benefit study also identified potential gaps in the current patchwork US regulatory systems that have evolved over the past decades to oversee risky research. Some pathogens are regulated as "agents selected" for example, with work restricted to laboratories with certain security and safety systems. But others are covered by less stringent systems and GOF studies involving a small number - , including the MERS virus and virus seasonal influenza - do not seem to fall easily into any single regulatory system. "Control Policies vary in scope and applicability, therefore, the current monitoring is not enough for all GOF studies of concern," the draft concludes NSABB.
Is it "of concern?"
to reduce risk, the draft report proposes a phased approach to the assessment of GOF studies before they are financed. in the first step, the evaluators will determine whether a study of GOF three criteria that would "concern" and in need of a special assessment. the pathogenic agent is to create researcher should be "highly communicable" and "significantly virulent" in a model mammal concerned, "probably resistant" to existing treatments, and more "able" to spread in human populations that existing strains.
GOF studies considered potentially problematic would be subject to a review that considers seven criteria. The reviewers would determine whether the study was "scientifically meritorious," for example, and if the benefits outweigh the risks. They also examine whether the sponsoring institution could achieve safely study, and if there are safer alternatives to achieve the same knowledge. "Proposals that do not meet these criteria will not be financed," the proposal of NSABB States. In a last step, the funded studies would be systematically reviewed and considered by the nominating institution and federal funding agencies.
This framework, and the many other issues raised in the draft report, are likely to attract many comments NSABB next meeting. Lipsitch, which helped catalyze the current moratorium on research funded by GOF US because of concerns about biosecurity, said he is still absorbing the document. But his first catch is that NSABB and Gryphon "agree very credulous statements not approved by those who make and fund GOF concern studies that these studies offer unique practical advantages ... [T] he NSABB draft report seems to show much more optimism than I think is justified that existing structures can take care of the matter. If that were the case, there would not have needed the funding break. "
With reporting by Jon Cohen. Reference materials from reports before by Jocelyn Kaiser.
There was a brief celebration. Hours after the World Health Organisation (WHO) declared the Ebola outbreak in West Africa on Thursday, Sierra Leone has reported a new case of the disease at WHO. At 22, the woman, who had died earlier in the week, had tested positive for the virus. WHO confirmed the case Friday. "A joint team of local authorities, WHO and partners are studying the origin of the case, identifying contacts, and initiate control measures to prevent transmission," WHO said in a statement .
The details of the case are troubling. The young woman was a student at Lunsar, a town in the district of Port Loko, said Christopher Dye of the WHO. Around Christmas, she traveled from there to the Kambia district, near the border with Guinea, and stayed there until January 6. "We suspect that was the time of onset of the disease," said Dye. "He became ill, she decided to go home, and the family home is in Tonkalili." The young woman went to the hospital, but was not recognized as a case of Ebola. "It gets progressively worse and died. The body preparation process for the funeral and the burial itself were done unsafely," said Dye. "This is of course not what we would have liked to see happen in the light of all the Ebola cases we had."
Accordingly, there are a number of people who came in contact with women who are at high risk of being infected by the Ebola virus. There were 27 contacts listed Thursday night, said Dye. "But I would certainly expect that figure to be revised upwards." A vaccine produced by Merck that protected people from the deadly virus in a trial in Guinea last year may be granted to such persons and their contacts. "The plan is to ring vaccination with this vaccine," said Dye. "Obviously, it must be done very quickly. There is vaccine available and there is support for vaccination teams in Guinea, some will cross the border to assist health authorities in Sierra Leone perform the vaccinations. "
Even as leaders of WHO said Thursday that for the first time in 2 years, West Africa was free of Ebola transmission, they had warned against the risk of outbreaks. Because ebolavirus can persist in some tissues and body fluids surviving for months, there is a risk they can transmit the virus to others, for example, through unprotected sex. it also seems a likely explanation in the new case, said Vincent Munster, a virologist at Rocky Mountain Laboratories of the uS National Institute of allergy and infectious diseases in Hamilton, Montana. "I think we must remain vigilant for a while."
The new case was discovered because the authorities in Sierra Leone Swab regularly corpses for Ebola. This case was not recognized earlier and women had a hazardous landfill point of weaknesses in the system, however, says Dye. "We are really concerned about these things and it is a huge disappointment." possible Ebola patients testing should be done just as effectively as the unclogging of the bodies, he said.
Sierra Leone was declared free of Ebola, November 7, 2015, and was in a 0-day period of increased surveillance. media reports that the woman who died of Ebola had gone to the hospital and sent the call to the house in question the way hospitals are ready in West Africa to treat the virus, even after the largest Ebola outbreak on record.