Biomedical Research News

Protein not sugar stimulates cells keeping us thin and awake, new study suggests.

2012-02-09T20:35:00.000+05:30

A new study has found that protein and not sugar activates the cells responsible for keeping us awake and burning calories. The research, published today in the 17 November issue of the scientific journal Neuron, has implications for understanding obesity and sleep disorders.

Wakefulness and energy expenditure rely on “orexin cells”, which secrete a stimulant called orexin/hypocretin in the brain. Reduced activity in these unique cells results in narcolepsy and has been linked to weight gain.

Scientists at the University of Cambridge compared actions of different nutrients on orexin cells. They found that amino acids – nutrients found in proteins such as egg whites – stimulate orexin neurons much more than other nutrients.

“Sleep patterns, health, and body weight are intertwined. Shift work, as well as poor diet, can lead to obesity,” said lead researcher Dr Denis Burdakov of the Department of Pharmacology and Institute of Metabolic Science. “Electrical impulses emitted by orexin cells stimulate wakefulness and tell the body to burn calories. We wondered whether dietary nutrients alter those impulses.”

To explore this, the scientists highlighted the orexin cells (which are scarce and difficult to find) with genetically targeted fluorescence in mouse brains. They then introduced different nutrients, such as amino acid mixtures similar to egg whites, while tracking orexin cell impulses.

They discovered that amino acids stimulate orexin cells. Previous work by the group found that glucose blocks orexin cells (which was cited as a reason for after-meal sleepiness), and so the researchers also looked at interactions between sugar and protein. They found that amino acids stop glucose from blocking orexin cells (in other words, protein negated the effects of sugar on the cells).

These findings may shed light on previously unexplained observations showing that protein meals can make people feel less calm and more alert than carbohydrate meals.

“What is exciting is to have a rational way to ‘tune’ select brain cells to be more or less active by deciding what food to eat,” Dr Burdakov said. “Not all brain cells are simply turned on by all nutrients, dietary composition is critical.

“To combat obesity and insomnia in today’s society, we need more information on how diet affects sleep and appetite cells. For now, research suggests that if you have a choice between jam on toast, or egg whites on toast, go for the latter! Even though the two may contain the same number of calories, having a bit of protein will tell the body to burn more calories out of those consumed.”

http://www.cam.ac.uk/research/news/3pm-slump-why-a-sugar-rush-may-not-be-the-answer/#

A Doctor in Your Pocket

2012-01-19T18:41:00.000+05:30

What does the future of medicine hold? Tiny health monitors, tailored therapies—and the end of illness

Take a moment to imagine what it would be like to live robustly to the ripe old age of 100 or more. You wouldn't die of any particular illness, and you wouldn't gradually waste away under the spell of some awful, enfeebling disease that began years or decades earlier.

It may sound far-fetched, but it is possible to live a long, disease-free life. Most of the conditions that kill us, including cancer and heart disease, could be prevented or delayed by a new way of looking at and treating health. The end of illness is near.

Today, we mostly wait for the body to break before we treat it. When I picture what it will be like for my two children to stay in good health as independent adults in 10 or 20 years, I see a big shift from our current model.

I see them being able to monitor and adjust their health in real time with the help of smartphones, wearable gadgets—perhaps like small, invisible stickers—to track the inner workings of their cells, and virtual replicas of their bodies that they will play much like videogames, allowing them to know exactly what they can do to optimize every aspect of their health. What happens when I take drug x at dosage y? How can I change the expression of my genes to stop cancer? Would eating more salmon and dark chocolate boost my metabolism and burn fat? Can red wine really lower my risk of heart attack?

From a drop of their blood, they will be able to upload information onto a personal biochip that can help to create an individualized plan of action, including both preventive measures and therapies for identified ailments or signs of "unhealthiness." (Other body fluids—like tears and saliva—might be routinely tested, too.) They would be on the lookout for problems like imbalances in blood-sugar control, a risk factor for diabetes, and uncontrolled cell growth, which could signal cancer. Their doctors won't just examine them once a year; they will continually monitor the next generation of patients, offering advice along the way.

What is equally exciting is that this patient data will be added to a universal database that can be aggregated by powerful search engines like Google and constantly fed into new trials and experiments—speeding up our understanding of which drugs work best for which people. The database might show, for example, that people with a particular genetic profile respond to one type of cancer treatment but not another. As more people anonymously add their health data, this database would become more and more effective as a tool for preventive medicine.

Today, most people who are concerned about their health follow sweeping, general guidelines. If you want to lose weight, you are likely to pick a diet that advises eating more fibrous vegetables and cutting back on processed sugar. If you want to reduce your risk for cancer, you avoid tobacco smoke, exercise regularly and take early detection seriously.

The problem with health care today is that we don't know enough about the body to practice preventive medicine actively. With limited knowledge, diagnostic medicine makes sense. If we don't know what we're trying to prevent or how best to do it, we have to wait for an obvious symptom to emerge in order to take action. At that point, we're usually treating a disease that has had ample opportunity to progress.

We can do better. To start, we need to appreciate the body for what it is: a very complex network, much of which we don't yet fully understand. When you look at the body from this systemic point of view, you begin to see that a lot of what we know about health is gravely misunderstood.

In 2009, my colleague Danny Hillis—a former Disney engineer who pioneered the development of so-called parallel supercomputers—and I set up a way to measure 100,000 different types of proteins from a single drop of blood. The goal is to evaluate and make sense of the body's intricate inner workings in a way that's much more dynamic and insightful than what DNA alone can provide. Proteins change in your body every minute, depending on what's going on internally. Our ultimate plan is to develop tests, based on protein levels, for illnesses like cancer. Such tests could take the place of invasive techniques like biopsies.

With each passing year, the technology necessary for this revolution in medicine is growing less expensive. Last week, Life Technologies of Carlsbad, Calif., announced that it will be able to map an individual's entire genetic sequence in one day, for $1,000. Similar tests today cost many thousands of dollars. The ability to follow day-to-day changes in your body's proteins and metabolites is not far behind.

So how do we get to this future?

It has to start with data collection. In 2004, Dell launched a company program called Well at Dell to encourage healthy lifestyles. Employees receive alerts and information customized to their health issues, incorporating their latest test results and treatments and allowing them to make more informed decisions. A newly diagnosed diabetic, for example, might get information about how to monitor blood sugar and watch out for the circulatory problems that often accompany the disease.

Not surprisingly, these corporate health-management tools have come under fire, with most critics worrying about privacy. But we can't expect the health-care industry to continue to innovate and grow if we continue to hoard health information.

The federal agency that administers Medicare pays over half of the medical bills in the U.S., but it doesn't retrieve, organize or mine that data. Imagine how much better the Medicare system could be if all this data were analyzed to improve public health. Or imagine databases from many different sources, private and public, coming together in a centralized network that would look for patterns and try to translate them into new ideas for anticipating and preventing health problems.

Personalized medicine isn't as far away as you might think. Consider what's already happening in genetic profiling for individuals, which is available today for several hundred dollars. I co-founded a genetic screening company and am a big proponent of the technology. It allows us to take a broad look at DNA variations and to assess your risk for certain ailments and what medications, at what dosages, might work best, based on your metabolism. Just because you have one or two markers of genetic risk does not mean that you will definitely develop a particular condition, but the outcome can be affected by changes in lifestyle, or in some cases, by taking medication.

As these and other technologies advance, it will become progressively easier to monitor and maintain our overall health. Then it will be up to us. The promise of personalized medicine depends, finally, not on the tools that become available but on our determination to be informed and willing patients.

http://online.wsj.com/article/SB10001424052970204124204577155162382326848.html?mod=djemWMPIndia_h

A Gut Check for Many Ailments

2012-01-19T17:42:00.000+05:30

What you think is going on in your head may be caused in part by what's happening in your gut.

A growing body of research shows the gut affects bodily functions far beyond digestion. Studies have shown intriguing links from the gut's health to bone formation, learning and memory and even conditions including Parkinson's disease. Recent research found disruptions to the stomach or intestinal bacteria can prompt depression and anxiety—at least in lab rats.

Better understanding the communication between the gut and the brain could help reveal the causes of and treatments for a range of ailments, and provide diagnostic clues for doctors.

"The gut is important in medical research, not just for problems pertaining to the digestive system but also problems pertaining to the rest of the body," says Pankaj J. Pasricha, chief of the division of gastroenterology and hepatology at Stanford University School of Medicine.

The gut—considered as a single digestive organ that includes the esophagus, stomach and intestines—has its own nervous system that allows it to operate independently from the brain.

This enteric nervous system is known among researchers as the "gut brain." It controls organs including the pancreas and gall bladder via nerve connections. Hormones and neurotransmitters generated in the gut interact with organs such as the lungs and heart.

Like the brain and spinal cord, the gut is filled with nerve cells. The small intestine alone has 100 million neurons, roughly equal to the amount found in the spinal cord, says Michael Gershon, a professor at Columbia University.

The vagus nerve, which stretches down from the brainstem, is the main conduit between the brain and gut. But the gut doesn't just take orders from the brain.

"The brain is a CEO that doesn't like to micromanage," says Dr. Gershon. The brain receives much more information from the gut than it sends down, he adds.

Many people with psychiatric and brain conditions also report gastrointestinal issues. New research indicates problems in the gut may cause problems in the brain, just as a mental ailment, such as anxiety, can upset the stomach.

Stanford's Dr. Pasricha and colleagues examined this question in the lab by irritating the stomachs of newborn rats. By the time the animals were eight to 10 weeks old, the physical disturbance had healed, but these animals displayed more depressed and anxious behaviors, such as giving up more quickly in a swimming task, than rats whose stomachs weren't irritated.

Compared to controls, the rats also showed increased sensitivity to stress and produced more of a stress hormone, in a study published in May in a Public Library of Science journal, PLoS One.

Other work, such as that of researchers from McMaster University in Hamilton, Ontario, demonstrated that bacteria in the gut—known as gut flora—play a role in how the body responds to stress. The exact mechanism is unknown, but certain bacteria are thought to facilitate important interactions between the gut and the brain.

Electrically stimulating the vagus nerve has been shown to reduce the symptoms of epilepsy and depression. (One treatment approved by the Food and Drug Administration, made by Cyberonics Inc., is already on the market.)

Exactly why such stimulation works isn't known, experts say, but a similar procedure has been shown in animal studies to help improve learning and memory.

Earlier this month, researchers made a small step toward understanding a gastrointestinal ailment that typically affects children with autism.

In a study of 23 autistic children and nine typically developing kids, a bacterium unique to the intestines of those with autism called Sutterella was discovered.

The results, published online in the journal mBio by researchers at Columbia's school of public health, need to be studied further, but suggest Sutterella may be important in understanding the link between autism and digestive ailments, the authors wrote.

Dr. Gershon, professor of pathology and cell biology at Columbia, has been studying how the gut controls its behavior and that of other organs by investigating the neurotransmitter serotonin.

Low serotonin levels in the brain are known to affect mood and sleep. Several common antidepressants work by raising levels of serotonin in the brain.

Yet about 95% of the serotonin in the body is made in the gut, not in the brain, says Dr. Gershon. Serotonin and other neurotransmitters produced by gut neurons help the digestive track push food through the gut.

Work by Dr. Gershon and others has shown that serotonin is necessary for the repair of cells in the liver and lungs, and plays a role in normal heart development and bone-mass accumulation.

Studying the neurons in the gut also may also help shed light on Parkinson's disease. Some of the damage the disease causes to brain neurons that make the neurotransmitter dopamine also occur in the gut neurons, researchers say.

Researchers are now studying whether gut neurons, which can be sampled through a routine colonoscopy, may help clinicians diagnose and track the disease without invasive brain biopsies, says Pascal Derkinderen, a professor of neurology at Inserm, France's national institute of health.

http://online.wsj.com/article/SB10001424052970204468004577164732944974356.html?mod=djemWMPAsia_h

Omelets: The Ultimate Fast Food

2012-01-18T18:33:00.004+05:30

For some time now the medical literature has been countering the myth that the cholesterol in eggs goes straight to the arteries and that eggs should be shunned by anybody committed to healthy eating. Studies have shown that only a small amount of dietary cholesterol passes into the blood and that saturated fats and trans fats have much bigger effects on cholesterol levels. In fact, according to the Harvard School of Public Health, the only large study that looked at the effect of egg consumption on heart disease found no correlation between the two, except among people with diabetes, who were a bit more likely to develop heart disease if they ate an egg a day.

That’s great news, because eggs are an excellent and delicious source of nutrients, rated by some nutritionists as the gold standard for protein, as one egg has only 75 calories but 7 grams of protein. They are also a great source of the carotenoids lutein and zeaxanthin, which have been associated with protection against vision loss.

It’s also great news because eggs cook quickly. Make an omelet if you need a quick, utterly satisfying meal. Omelets are my response to people who tell me that they’d like to eat a healthier diet but that it’s too time-consuming. In addition to the fillings in this week’s recipes, think of using up leftovers or little hunks of cheese that are lingering in your refrigerator, or search through your pantry for something that looks delicious.

Beet Green and Feta Omelet

At this time of year I don’t let a week go by without buying beets at the farmers’ market. I cook up the greens when I get home so that I can make meals like this one in minutes.

For each omelet:

1/3 cup chopped blanched or steamed beet greens (about 1 ounce; see below)

1 garlic clove, minced

1/2 teaspoon red wine vinegar or sherry vinegar

Salt and freshly ground pepper

2 eggs

2 to 3 teaspoons low-fat milk

2 teaspoons extra virgin olive oil

1/2 ounce feta cheese, crumbled

1. In a bowl, toss the chopped blanched beet greens with the garlic, vinegar and salt and pepper to taste.

2. Break the eggs into another bowl and beat with a fork or a whisk until eggs are frothy. Whisk in salt and pepper to taste and 2 to 3 teaspoons milk.

3. Heat an 8-inch nonstick omelet pan over medium-high heat. Add 2 teaspoons olive oil. Hold your hand an inch or two above the pan, and when it feels hot, pour the eggs into the middle of the pan, scraping every last bit into the pan with a rubber spatula. Swirl the pan to distribute the eggs evenly over the surface. Shake the pan gently, tilting it slightly with one hand while lifting up the edges of the omelet with the spatula in your other hand, to let the eggs run underneath during the first minute or two of cooking.

4. As soon as the eggs are set on the bottom, sprinkle the beet greens over the middle of the egg “pancake” and top with the feta. Next, jerk the pan quickly away from you then back toward you so that the omelet folds over onto itself. If you don’t like your omelet runny in the middle (I do), jerk the pan again so that the omelet folds over once more. Cook for a minute or two longer. Tilt the pan and roll the omelet out onto a plate.

Another way to make a 2-egg omelet is to flip it over before adding the filling. Do this with the same motion, jerking the pan quickly away from you and then back toward you, but lift your hand slightly as you begin to jerk the pan back toward you. The omelet will flip over onto the other side, like a pancake. Place the filling in the middle. Use your spatula to fold one side over, then the other side, and roll the omelet out of the pan.

To blanch beet greens: Bring a pot of water to a boil while you wash and stem the beet greens. Rinse in 2 changes of water to rid the leaves of sand. When the water comes to a boil, salt generously and add the greens. Blanch for 1 to 2 minutes, until just tender, and transfer to a bowl of cold water. Drain, squeeze out excess water, and chop. To steam the greens, place them in a steamer basket above 1 inch of boiling water. Cover and steam for 2 minutes or until wilted. Rinse and squeeze out excess water.

Yield: Serves 1

Advance preparation: The blanched beet greens will keep for 4 to 5 days in a covered bowl in the refrigerator.

Nutritional information per serving: 275 calories; 7 grams saturated fat; 3 grams polyunsaturated fat; 11 grams monounsaturated fat; 385 milligrams cholesterol; 4 grams carbohydrates; 1 gram dietary fiber; 369 milligrams sodium (does not include salt to taste); 16 grams protein.

http://www.nytimes.com/2012/01/16/health/nutrition/omelets-the-ultimate-fast-food-recipes-for-health.html?src=me&ref=general

It Could Be Old Age, or It Could Be Low B12

2012-01-18T18:32:00.001+05:30

Ilsa Katz was 85 when her daughter, Vivian Atkins, first noticed that her mother was becoming increasingly confused.

“She couldn’t remember names, where she’d been or what she’d done that day,” Ms. Atkins recalled in an interview. “Initially, I was not too worried. I thought it was part of normal aging. But over time, the confusion and memory problems became more severe and more frequent.”

Her mother couldn’t remember the names of close relatives or what day it was. She thought she was going to work or needed to go downtown, which she never did. And she was often agitated.

A workup at a memory clinic resulted in a diagnosis of early Alzheimer’s disease, and Ms. Katz was prescribed Aricept, which Ms. Atkins said seemed to make matters worse. But the clinic also tested Ms. Katz’s blood level of vitamin B12. It was well below normal, and her doctor thought that could be contributing to her symptoms.

Weekly B12 injections were begun. “Soon afterward, she became less agitated, less confused and her memory was much better,” said Ms. Atkins. “I felt I had my mother back, and she feels a lot better, too.”

Now 87, Ms. Katz still lives alone in Manhattan and feels well enough to refuse outside assistance.

Still, her daughter wondered, “Why aren’t B12 levels checked routinely, particularly in older people?”

It is an important question. As we age, our ability to absorb B12 from food declines, and often so does our consumption of foods rich in this vitamin. A B12 deficiency can creep up without warning and cause a host of confusing symptoms that are likely to be misdiagnosed or ascribed to aging.

A Vital Nutrient

B12 is an essential vitamin with roles throughout the body. It is needed for the development and maintenance of a healthy nervous system, the production of DNA and formation of red blood cells.

A severe B12 deficiency results in anemia, which can be picked up by an ordinary blood test. But the less dramatic symptoms of a B12 deficiency may include muscle weakness, fatigue, shakiness, unsteady gait, incontinence, low blood pressure, depression and other mood disorders, and cognitive problems like poor memory.

Labs differ in what they consider normal, but most authorities say a deficiency occurs when B12 levels in adults fall below 250 picograms per milliliter of blood serum. Like all Bvitamins, B12 is water-soluble, but the body stores extra B12 in the liver and other tissues. Even if dietary sources are inadequate for some time, a serum deficiency may not show up for years.

If the amount of B12 in storage is low to begin with, a deficiency can develop within a year, even more quickly in infants.

Recommended dietary amounts of B12 vary: 2.4 micrograms daily for those age 14 and older, 2.6 micrograms for pregnant women and 2.8 micrograms for nursing women. Barring circumstances that impair B12 absorption, these are levels easily obtained from awell-balanced diet containing animal protein.

In its natural form, B12 is present in significant amounts only in animal foods, most prominently in liver (83 micrograms in a 3.5-ounce serving). Good food sources include other red meats, turkey, fish and shellfish. Lesser amounts of the vitamin are present in dairy products, eggs and chicken.

Those at Risk

Natural plant sources are meager at best in B12, and the vitamin is poorly absorbed from them. Many strict vegetarians and all vegans, as well as infants they breast-feed, must consume supplements or fortified breakfast cereals to get adequate amounts.

Certain organisms, like the bacterium Spirulina and some algae, contain a pseudo-B12 that the body cannot use but may result in a false reading of a normal B12 level on a blood test. Despite claims to the contrary, laver, a seaweed, and barley grass are not reliable sources of B12.

In animal foods, B12 is combined with protein and must be released by stomach acid and an enzyme to be absorbed. Thus, chronic users of acid-suppressing drugs like Prilosec, Prevacid and Nexium, as well as ulcer medications like Pepcid and Tagamet, are at risk of developing a B12 deficiency and often require a daily B12 supplement.

Stomach acid levels decline with age. As many as 30 percent of older people may lack sufficient stomach acid to absorb adequate amounts of B12 from natural sources. Therefore, regular consumption of fortified foods or supplementation with 25 to 100 micrograms of B12 daily is recommended for people over 50.

Synthetic B12, found in supplements and fortified foods, does not depend on stomach acid to be absorbed. But whether natural or synthetic, only some of the B12 consumed gets into the body. Treatment to correct a B12 deficiency typically involves much larger doses than the body actually requires.

Free B12 from both natural and synthetic sources must be combined with a substance in the stomach called intrinsic factor to be absorbed through the gut. This factor is lacking in people with an autoimmune disorder called pernicious anemia; the resulting vitamin deficiency is commonly treated with injections of B12.

Although most doctors are quick to recommend injections to correct a B12 deficiency, considerable evidence indicates that, in large enough doses, sublingual (under-the-tongue) tablets or skin patches of B12 may work as well as injections for people with absorption problems, even for those with pernicious anemia.

Most often, a daily supplement of 2,000 micrograms is recommended for about a month, then lowered to 1,000 micrograms daily for another month, then lowered again to 1,000 micrograms weekly. Sublingual B12 or B12 patches, or even B12 lollipops, can be helpful for people who require a supplement but cannot swallow pills.

Others at risk of developing a B12 deficiency include heavy drinkers (alcohol diminishes B12 absorption), those who have had stomach surgery for weight loss or ulcers, and people who take aminosalicylic acid (for inflammatory bowel disease or tuberculosis) or thediabetes drug metformin (sold as Glucophage and other brands). Patients who take the anticonvulsants phenytoin, phenobarbital or primidone are also at risk.

Large doses of folic acid can mask a B12 deficiency and cause permanent neurological damage if normal levels of B12 are not maintained. Supplements of potassium impair B12 absorption in some people.

Although a B12 deficiency can raise blood levels of the amino acid homocysteine, a risk factor for heart disease and stroke, supplements of B12 have not reduced cardiovascular risk.

And while high homocysteine levels are linked to Alzheimer’s disease and dementia, lowering them with B12 supplements has not been shown to improve cognitive function. However, in one study, among women with a poor dietary intake of B12, supplements of the vitamin significantly slowed the rate of cognitive decline.

http://www.nytimes.com/2011/11/29/health/vitamin-b12-deficiency-can-cause-symptoms-that-mimic-aging.html?_r=1&WT.mc_id=NYT-E-I-NYT-E-AT-1207-L23&nl=el

Depression Defies the Rush to Find an Evolutionary Upside

2012-01-18T18:31:00.001+05:30

In certain quarters of academia, it’s all the rage these days to view human behavior through the lens of evolutionary biology. What survival advantages, researchers ask, may lie hidden in our actions, even in our pathologies?

Depression has come in for particular scrutiny. Some evolutionarypsychologists think this painful and often disabling disease conceals something positive. Most of us who treat patients vehemently disagree.

Consider a patient I saw not long ago, a 30-year-old woman whose husband had had an affair and left her. Within several weeks, she became despondent and socially isolated. She developed insomnia and started to ruminate constantly about what she might have done wrong.

An evolutionary psychologist might posit that my patient’s response has a certain logic. After all, she broke off her normal routine, isolated herself and tried to understand her abandonment and plan for the future. You might see a survival advantage in the ability of depressed people like her to rigidly and obsessively fix their attention on one problem, tuning out just about everything and everyone else around them.

Certain studies might seem to support this perspective. Paul W. Andrews, a psychologist at Virginia Commonwealth University, reported that normal subjects get sadder while trying to solve a demanding spatial pattern recognition test, suggesting that something about sadness might improve analytical reasoning.

In a similar vein, Joseph P. Forgas, a psychologist at the University of New South Wales in Australia, found that sad subjects were better judges of deception than happy ones. After subjects were shown a video intended to induce a happy or a sad mood, Dr. Forgas had them view deceptive or truthful interviews with people who denied committing a theft.Subjects in a sad mood were more skeptical and more accurate in detecting deceptive communication, while subjects in a positive mood were far more trusting and gullible.

Findings like these may suggest some benefits to sadness, but lately they have been generalized to patients with full-blown depression. For example, Dr. Andrews and Dr. J. Anderson Thomson Jr., a psychiatrist at the University of Virginia, have proposed that the rumination of depressives is an adaptive strategy to solve a painful problem. Clinicians, on the other hand, continue to maintain that the grim outlook of depressives is evidence that their thought process is distorted and erroneous. It must be fixed, not embraced.

There is strong evidence from neuropsychological and brain imaging studies that clinical depression is linked with various types of memory impairments in all age groups and at all levels of depressive severity. Challenging and changing the dysfunctional thoughts of depression are the exact aims of cognitive-behavioral therapy, one of the most empirically validated and popular forms of psychotherapy.

So who’s right about depression, the evolutionary biologists or the clinicians?

To start, the subjects in the above studies were normal controls whose moods were manipulated to be transiently sad. They do not really resemble people with clinical depression, whose condition can last months or even years.

Indeed, as Dr. Forgas said by e-mail, “I never worked with depressives, and I do not think that the experiments we have done looking at mood effects on cognitive processes in normal populations experiencing minor, everyday mood differences can be readily generalized to depressive cognition.”

Under close scrutiny, the case for depression’s adaptive benefits has problems — big ones. For one thing, the ruminative thinking of depression is often not particularly effective in solving problems. As another patient of mine once said: “I would think the same things over and over and could never decide what to do. It’s not a creative way of thinking.”

More critically, depression can arise without any psychosocial stressor at all, which makes it hard to argue that depression is a response to a difficult situation or problem. Dr. David J. Kupfer, a psychiatrist at the University of Pittsburgh, has found that a major life stressor almost always precedes a first episode of depression, but that episodes recur with milder stressors, or even none at all.

If depression conferred a problem-solving benefit, it should not become a chronic or autonomous condition — which it is for about half the patients.

According to the World Health Organization, depression is the leading cause of disability and the fourth leading contributor to the global burden of disease, projected to reach second place by 2020. There is also strong evidence that it is an independent risk factor for heart disease, and several studies show that prolonged depression is associated with selective and possibly permanent damage to the hippocampus, a region of the brain critical to memory and learning.

Add the fact that 2 percent to 12 percent of depressed people eventually commit suicide, and the “advantages” of depression suddenly don’t look so good.

Why, then, does the notion persist that depression confers special insights and benefits?

I got a clue recently from one depressed patient. He was an educated and articulate young man, unhappy because the world was such an awful place, he said. Because he had so many other symptoms of depression — insomnia, fatigue, low libido and poor self-esteem — I told him that he was clinically depressed and that his Hobbesian worldview was probably a result of depression, not its cause.

He scoffed, but he was willing to try a course of cognitive-behavioral therapy and antidepressant medication, if only to feel better. Months later, when he had recovered, I asked him again about his worldview.

The world was just as dire, he said, but he felt better. Still, he speculated wistfully that his newfound cheerfulness was not his authentic self, which he described as brooding and creative.

This cuts to the heart of why depression is increasingly romanticized. What is natural, the thinking goes, is best. If we are designed to suffer depression in response to life’s ills, there must be a good reason for it, and we should allow it to take its painful and natural course.

But unlike ordinary sadness, the natural course of depression can be devastating and lethal. And while sadness is useful, clinical depression signals a failure to adapt to stress or loss, because it impairs a person’s ability to solve the very dilemmas that triggered it.

Even if depression is “natural” and evolved from an emotional state that might once have given us some advantage, that doesn’t make it any more desirable than other maladies. Nature offers us cancer, infections and heart disease, which we happily avoid and do our best to treat. Depression is no different.

http://www.nytimes.com/2012/01/17/health/depression-defies-rush-to-find-evolutionary-upside.html?src=me&ref=general

Cracking Open the Scientific Process

2012-01-18T18:29:00.000+05:30

The New England Journal of Medicine marks its 200th anniversary this year with a timeline celebrating the scientific advances first described in its pages: the stethoscope (1816), the use of ether foranesthesia (1846), and disinfecting hands and instruments before surgery (1867), among others.

For centuries, this is how science has operated — through research done in private, then submitted to science and medical journals to be reviewed by peers and published for the benefit of other researchers and the public at large. But to many scientists, the longevity of that process is nothing to celebrate.

The system is hidebound, expensive and elitist, they say. Peer review can take months, journal subscriptions can be prohibitively costly, and a handful of gatekeepers limit the flow of information. It is an ideal system for sharing knowledge, said the quantum physicist Michael Nielsen, only “if you’re stuck with 17th-century technology.”

Dr. Nielsen and other advocates for “open science” say science can accomplish much more, much faster, in an environment of friction-free collaboration over the Internet. And despite a host of obstacles, including the skepticism of many established scientists, their ideas are gaining traction.

Open-access archives and journals like arXiv and thePublic Library of Science (PLoS) have sprung up in recent years. GalaxyZoo, a citizen-science site, has classified millions of objects in space, discovering characteristics that have led to a raft of scientific papers.

On the collaborative blog MathOverflow, mathematicians earn reputation points for contributing to solutions; in another math experiment dubbed the Polymath Project, mathematicians commenting on the Fields medalistTimothy Gower’s blog in 2009 found a new proof for a particularly complicated theorem in just six weeks.

And a social networking site called ResearchGate — where scientists can answer one another’s questions, share papers and find collaborators — is rapidly gaining popularity.

Editors of traditional journals say open science sounds good, in theory. In practice, “the scientific community itself is quite conservative,” said Maxine Clarke, executive editor of the commercial journal Nature, who added that the traditional published paper is still viewed as “a unit to award grants or assess jobs and tenure.”

Dr. Nielsen, 38, who left a successful science career to write “Reinventing Discovery: The New Era of Networked Science,” agreed that scientists have been “very inhibited and slow to adopt a lot of online tools.” But he added that open science was coalescing into “a bit of a movement.”

On Thursday, 450 bloggers, journalists, students, scientists, librarians and programmers will converge on North Carolina State University (and thousands more will join in online) for the sixth annual ScienceOnline conference. Science is moving to a collaborative model, said Bora Zivkovic, a chronobiology blogger who is a founder of the conference, “because it works better in the current ecosystem, in the Web-connected world.”

Indeed, he said, scientists who attend the conference should not be seen as competing with one another. “Lindsay Lohan is our competitor,” he continued. “We have to get her off the screen and get science there instead.”

Facebook for Scientists?

“I want to make science more open. I want to change this,” said Ijad Madisch, 31, the Harvard-trained virologist and computer scientist behind ResearchGate, the social networking site for scientists.

Started in 2008 with few features, it was reshaped with feedback from scientists. Its membership has mushroomed to more than 1.3 million, Dr. Madisch said, and it has attracted several million dollars inventure capital from some of the original investors of Twitter, eBay and Facebook.

A year ago, ResearchGate had 12 employees. Now it has 70 and is hiring. The company, based in Berlin, is modeled after Silicon Valley startups. Lunch, drinks and fruit are free, and every employee owns part of the company.

The Web site is a sort of mash-up of Facebook, Twitter and LinkedIn, with profile pages, comments, groups, job listings, and “like” and “follow” buttons (but without baby photos, cat videos and thinly veiled self-praise). Only scientists are invited to pose and answer questions — a rule that should not be hard to enforce, with discussion threads about topics like polymerase chain reactions that only a scientist could love.

Scientists populate their ResearchGate profiles with their real names, professional details and publications — data that the site uses to suggest connections with other members. Users can create public or private discussion groups, and share papers and lecture materials. ResearchGate is also developing a “reputation score” to reward members for online contributions.

ResearchGate offers a simple yet effective end run around restrictive journal access with its “self-archiving repository.” Since most journals allow scientists to link to their submitted papers on their own Web sites, Dr. Madisch encourages his users to do so on their ResearchGate profiles. In addition to housing 350,000 papers (and counting), the platform provides a way to search 40 million abstracts and papers from other science databases.

In 2011, ResearchGate reports, 1,620,849 connections were made, 12,342 questions answered and 842,179 publications shared. Greg Phelan, chairman of the chemistry department at the State University of New York, Cortland, used it to find new collaborators, get expert advice and read journal articles not available through his small university. Now he spends up to two hours a day, five days a week, on the site.

Dr. Rajiv Gupta, a radiology instructor who supervised Dr. Madisch at Harvard and was one of ResearchGate’s first investors, called it “a great site for serious research and research collaboration,” adding that he hoped it would never be contaminated “with pop culture and chit-chat.”

Dr. Gupta called Dr. Madisch the “quintessential networking guy — if there’s a Bill Clinton of the science world, it would be him.”

The Paper Trade

Dr. Sönke H. Bartling, a researcher at the German Cancer Research Center who is editing a book on “Science 2.0,” wrote that for scientists to move away from what is currently “a highly integrated and controlled process,” a new system for assessing the value of research is needed. If open access is to be achieved through blogs, what good is it, he asked, “if one does not get reputation and money from them?”

Changing the status quo — opening data, papers, research ideas and partial solutions to anyone and everyone — is still far more idea than reality. As the established journals argue, they provide a critical service that does not come cheap.

“I would love for it to be free,” said Alan Leshner, executive publisher of the journalScience, but “we have to cover the costs.” Those costs hover around $40 million a year to produce his nonprofit flagship journal, with its more than 25 editors and writers, sales and production staff, and offices in North America, Europe and Asia, not to mention print and distribution expenses. (Like other media organizations, Science has responded to the decline in advertising revenue by enhancing its Web offerings, and most of its growth comes from online subscriptions.)

Similarly, Nature employs a large editorial staff to manage the peer-review process and to select and polish “startling and new” papers for publication, said Dr. Clarke, its editor. And it costs money to screen for plagiarism and spot-check data “to make sure they haven’t been manipulated.”

Peer-reviewed open-access journals, like Nature Communications and PLoS One, charge their authors publication fees — $5,000 and $1,350, respectively — to defray their more modest expenses.

The largest journal publisher, Elsevier, whose products include The Lancet, Cell and the subscription-based online archive ScienceDirect, has drawn considerable criticism from open-access advocates and librarians, who are especially incensed by its support for theResearch Works Act, introduced in Congress last month, which seeks to protect publishers’ rights by effectively restricting access to research papers and data.

In an Op-Ed article in The New York Times last week, Michael B. Eisen, a molecular biologist at the University of California, Berkeley, and a founder of the Public Library of Science, wrote that if the bill passes, “taxpayers who already paid for the research would have to pay again to read the results.”

In an e-mail interview, Alicia Wise, director of universal access at Elsevier, wrote that “professional curation and preservation of data is, like professional publishing, neither easy nor inexpensive.” And Tom Reller, a spokesman for Elsevier, commented on Dr. Eisen’s blog, “Government mandates that require private-sector information products to be made freely available undermine the industry’s ability to recoup these investments.”

Mr. Zivkovic, the ScienceOnline co-founder and a blog editor for Scientific American, which is owned by Nature, was somewhat sympathetic to the big journals’ plight. “They have shareholders,” he said. “They have to move the ship slowly.”

Still, he added: “Nature is not digging in. They know it’s happening. They’re preparing for it.”

Science 2.0

Scott Aaronson, a quantum computing theorist at the Massachusetts Institute of Technology, has refused to conduct peer review for or submit papers to commercial journals. “I got tired of giving free labor,” he said, to “these very rich for-profit companies.”

Dr. Aaronson is also an active member of online science communities like MathOverflow, where he has earned enough reputation points to edit others’ posts. “We’re not talking about new technologies that have to be invented,” he said. “Things are moving in that direction. Journals seem noticeably less important than 10 years ago.”

Dr. Leshner, the publisher of Science, agrees that things are moving. “Will the model of science magazines be the same 10 years from now? I highly doubt it,” he said. “I believe in evolution.

“When a better system comes into being that has quality and trustability, it will happen. That’s how science progresses, by doing scientific experiments. We should be doing that with scientific publishing as well.”

Matt Cohler, the former vice president of product management at Facebook who now represents Benchmark Capital on ResearchGate’s board, sees a vast untapped market in online science.

“It’s one of the last areas on the Internet where there really isn’t anything yet that addresses core needs for this group of people,” he said, adding that “trillions” are spent each year on global scientific research. Investors are betting that a successful site catering to scientists could shave at least a sliver off that enormous pie.

Dr. Madisch, of ResearchGate, acknowledged that he might never reach many of the established scientists for whom social networking can seem like a foreign language or a waste of time. But wait, he said, until younger scientists weaned on social media and open-source collaboration start running their own labs.

“If you said years ago, ‘One day you will be on Facebook sharing all your photos and personal information with people,’ they wouldn’t believe you,” he said. “We’re just at the beginning. The change is coming.”

http://www.nytimes.com/2012/01/17/science/open-science-challenges-journal-tradition-with-web-collaboration.html?ref=general&src=me&pagewanted=all

A Drug That Wakes the Near Dead

2012-01-18T18:25:00.002+05:30

The moment she saw him, Judy Cox knew her son was dead. It was an October morning in 2008, and she had just stepped out the door to run an errand when she found him lying faceup in the driveway, ghost white, covered in purple splotches. He wasn’t breathing, and when she couldn’t revive him, she ran screaming into the house where her husband, Wayne, was still asleep. “Chris is dead,” she cried. “Call 911!”

Wayne jumped out of bed and raced down to the driveway, where he knelt over his son’s limp frame and tried frantically to elicit a breath or a heartbeat. As he pumped Chris’s chest and scooped out the vomit that had collected in his mouth, Judy ran to the kitchen and steadied herself long enough to call for an ambulance.

Chris was 26. He had not been well. An A.T.V. accident the previous August left him with debilitating back pain that physical therapy did nothing to alleviate. His doctor had recently prescribed Oxycontin. His parents learned later that he had taken too much.

By the time the ambulance arrived, Chris’s heart had been still for at least 15 minutes. It took the paramedics another 15 to get it pumping again; even then, doctors had little hope he would survive. Brain cells begin dying off just five minutes after blood stops delivering oxygen. After 30 minutes, there is likely to be more dead tissue than living.

Nonetheless, the emergency-room staff members at the local hospital did their best. They hooked Chris up to a tangle of tubes and machines and injected him with drugs to stabilize his heart rate. Wayne and Judy watched helplessly from the hallway. After four hours, a doctor finally summoned them to a secluded corridor.

Chris was in a coma, the doctor said, and in all likelihood had suffered severe, irreversible brain damage. He was breathing only with the help of a ventilator and would probably have a series of heart attacks in the night.

“First they asked us to let them pull the plug,” Judy recalled one recent afternoon, as we sat in the living room of the Coxes’ house in a Memphis suburb. “Then they tried getting us to sign a do-not-resuscitate order.” Without one, the doctor explained, hospital staff would be forced to revive Chris each time he started slipping away, which could mean cracking his ribs and shocking him with electricity. Even if they managed to keep his body alive, what was left of his brain would surely die in the days ahead.

Wayne and Judy refused to sign. “This is not some dog we’re talking about putting down,” Wayne shouted. “This is our son.” Chris still lived with his parents. He was a good kid, a joker, but bashful, especially around girls. He liked playing basketball and fishing in the pond near his house. He was planning to take over the family repo business when Wayne retired in a few years. Before the A.T.V. accident, he’d never given them much trouble at all. He deserved every chance the hospital could give him.

The heart attacks never came. Four days later, Chris woke up.

It was not the awakening of Hollywood movies in which the patient comes to, just as he was, speaking full sentences and completely mobile. Three years later, Chris still cannot talk. Although he breathes on his own, his lungs battle a steady barrage of infections; a feeding tube provides all his sustenance, and his muscles have contracted into short, twisted knots. He can move only the slightest bit — his fingers and eyelids twitch, but his arms and legs remain mostly immobile — and his neck is not quite strong enough to hold up his head, which leans against a crescent-shaped support around his wheelchair headrest.

Still, Wayne and Judy say that his cognition is improving. On good days, they say, he can respond to basic commands — blink his eyes for yes, wiggle his finger for no, give a thumbs up when asked. Doctors agree that Chris has progressed beyond a vegetative state, to a hazy realm known as minimal consciousness. What that means — what it says about his experience of the world around him or his prospects for further recovery — is something they are still trying to figure out.

Convinced that the son they know and love is still “in there,” Chris’s parents have spent the past three years searching for a way to bring him back out. So far, their best hope has come from an unlikely source: Ambien. A growing body of case reports suggests that the popular sleep aid can have a profound — and paradoxical — effect on patients like Chris. Rather than put them to sleep, both Ambien and its generic twin, zolpidem, appear to awaken at least some of them. The early reports were so pronounced that until recently, doctors had a hard time believing them. Only now, more than a decade after the initial discovery, are they taking a closer look.

The first report of a zolpidem awakening came from South Africa, in 1999. A patient named Louis Viljoen, who, three years before, was declared vegetative after he was hit by a truck, had taken to clawing at his mattress during the night. Thinking he was suffering from insomnia, his family doctor suggested zolpidem to help him sleep. But 20 minutes after his mother ground the tablet up and fed it to him through a straw, Viljoen began to stir. His eyes, which normally wandered the room, vacant and unfocused, flickered with the light of consciousness. And then he began to talk (his first words were “Hello, Mummy”), and move (he could control his limbs and facial muscles). A few hours later he became unresponsive. But the next day, and for many days after that, zolpidem revived him, a few hours at a time.

Here was a case worthy of Hollywood: three years was well past the point at which doctors would expect any sort of spontaneous recovery. Viljoen awoke with the ability to speak in complete sentences. Not only did he recognize his mother, but he also recognized the voices of people who had spoken to him only when he was apparently vegetative. He remembered nothing of the mysterious realm he kept receding back into. When doctors asked him what it was like to slip away, he said he felt no changes at all. But he could recall conversations from the previous day’s awakening, along with bits and pieces of his former life: his favorite rugby team, specific matches he attended, players that he rooted for and against. As time passed, his cognition improved. He could laugh at jokes, and his awakenings stretched from a few hours to entire days. Eventually, he no longer needed zolpidem.

In the years that followed, a steady trickle of similar reports emerged — some from doctors who tried zolpidem after hearing about the Viljoen case, others from those who discovered its benefits accidentally, as Viljoen’s doctor had. The drug did not work for everyone, and even when it did, its effects typically wore off after an hour or two. But for a lucky few, those effects were profound. People who seemed vegetative for years were waking up.

There are roughly 200,000 patients in the United States trapped in the borderlands between consciousness and oblivion. Until recently, most doctors believed that recovering from this condition was not possible. Vegetative states were considered permanent after three months if the injury was caused by oxygen deprivation, or one year if it was caused by blunt trauma. And since minimally conscious patients did not fare much better than those who were vegetative, most doctors did not bother to draw the distinction.

But in the past decade, a series of developments have coalesced into a far more complicated picture than previously imagined. In 2003, an Arkansas man named Terry Wallis emerged, after 19 years, from a minimally conscious state. Neuroimaging suggested that his brain had essentially reconfigured itself — surviving neurons bypassed dead ones and forged new connections to one another. In a 2007 Nature paper, Nicholas Schiff, a neurologist from Weill Cornell Medical College, and his colleagues showed that deep brain stimulation — surgically implanting a “brain pacemaker” that sends electrical impulses to specific regions of the brain — can help some severely injured patients recover the ability to speak and eat, years after the injury. And just this month, Adrian Owen, a British neuroscientist, reported in the journal The Lancet that the brains of some patients who seemed vegetative responded to basic commands: their bodies didn’t move, but distinct patterns of neuronal firing were detected on EEG scans when these patients were told to make a fist (which triggered one region of the premotor cortex) or wiggle their toes (which triggered another).

This year, scientists at Moss Rehabilitation Research Institute and at the University of Pennsylvania, both in the Philadelphia area, began the first large-scale clinical study of zolpidem as a treatment for disorders of consciousness. (Amantadine, a drug used to treat Parkinson’s disease, and the anti-anxiety medication Ativan also show promise in increasing awareness in minimally conscious patients.) So far, the evidence suggests that less than 10 percent of brain-injured patients will experience the drug’s paradoxical effects, and that among those, only a few will respond as profoundly as Viljoen did. For families like the Coxes, such odds provide a tortured kind of hope. For doctors, they bring questions. Why does a sleeping pill induce awareness in some patients but not others? And what can these bizarre awakenings tell us about the brain’s ability to heal?

Two weeks after Chris first emerged from the coma, he began tracking objects with his eyes. At one month, he could follow simple commands. “His friends would come in the room, and there’d be two or three on each side of the bed,” Judy recalled. “And eventually, when they’d say, ‘Look at Jim,’ or ‘Look at Bob,’ he’d fix his eyes on the right guy.” Wayne and Judy asked for a follow-up M.R.I., but their neurologist said it would be pointless. Chris’s behaviors were entirely reflexive, he said; they were produced by his brainstem, which regulates basic functions like breathing and body temperature, not by his cortex, the region responsible for higher-order thinking. That Chris’s friends and family saw him following commands was proof of their denial, not of Chris’s recovery.

“Every couple days, the doc would stop in the doorway and shout Chris’s name to see if Chris responded,” Judy said. “But he wouldn’t come in the room and look at Chris up close. So one day, I practically grabbed his arm and dragged him into the room, over to Chris’s bed.” She told Chris to blink his eyes. He did. Then she made the doctor walk across the room and told Chris to keep his eyes on the doctor. He did. Finally, with the doctor standing across the room, eyes fixed on Chris, she asked Chris to give her a thumbs up. When he wiggled his thumb, just the tiniest bit, the doctor’s jaw dropped. Chris was not in a vegetative state after all. He was minimally conscious.

Still, there was little that the community hospital could do for him. It had neither the resources nor the expertise to tease out a prognosis or chart a course of therapy. The same was true of local nursing homes, which is where many patients like Chris end up.

So Wayne and Judy took over their son’s care, bringing him first to a premier brain-injury center in Atlanta (where Chris had a device implanted in his spine, which releases drugs to help with spasticity) and then to a clinic in Destin, Fla. (where he tried an experimental treatment known as hyperbaric oxygen therapy). They had just made their way back home to Tennessee when a friend told them about the Ambien paradox and the clinical trial in Philadelphia.

One hallmark of the minimally conscious state is a rapid fluctuation between levels of awareness. Spend 10 or 20 minutes with Chris Cox, and you might conclude that there is nothing going on upstairs. But spend a full hour, and at some point you’ll see his puppy-dog eyes come into focus. They will appear to search for one of his parents, or to settle quizzically on the new person in the room. Ask him to say something, and he’ll smack his lips frantically before leaning forward and tapping his feet in apparent frustration. You’ll swear that he is there with you and that only his physical infirmities (he cannot quite swallow or control his jaw) prevent him from describing the netherworld from which he has just emerged.

And then, a few minutes later, he’ll slip away again.

This fluidity makes diagnosis a challenge. “If a patient follows every command you give them, you know that,” says Dr. John Whyte, director of the Moss Institute and lead investigator on the zolpidem trial. “If a patient has never, ever followed a command, you know that too. But if you tell a patient to wiggle their finger, and they do it occasionally — which is the case for most of these folks — how do you figure out if that ‘occasionally’ means something or not?”

Whyte has spent his entire career trying to answer this question. His first job after his residency was at a facility with a large number of vegetative patients. While working there, he was struck by the amount of contention over diagnoses. For all their experience with this population, clinicians could not seem to agree on whether any given patient was actually conscious. Family members also argued, with one another and with staff, over the meaning of every wince, twitch and eye flutter.

It turned out that a lot of people — staff members included — were drawing their conclusions from pure coincidence. Whyte told me about one mother who insisted that her son would point down toward his feeding tube to indicate that fluid was leaking onto his stomach, causing irritation. “He did it while I was there,” Whyte says. “And she lifted his shirt and said: ‘See, doctor, there’s the liquid. He’s communicating with us.’ And I said: ‘How often do you look under there when he isn’t pointing like this? Never? Not even once?’ ” It was possible that the pointing corresponded to the leak, Whyte explained. But it was also possible that the leaking was constant and the pointing was random. There were countless other examples. “Behaviors would be exceptions if they happened at the wrong time, and evidence if they happened at the right time,” Whyte says.

To help eliminate this bias, Whyte developed what he calls the single-subject assessment, in which doctors design a set of tests specific to each patient’s idiosyncrasies to determine whether the patient is vegetative or minimally conscious. It is painstaking work, but the information it yields is significant. “Patients who achieve minimal consciousness early tend to have a better prognosis,” Whyte says. “And you can at least try to build a communication system with them, because you have a foundation to work from.”

With a reliable assessment method in place, he began searching for ways to build on that foundation. Then the curious Ambien awakenings caught his attention.

It’s not entirely surprising that Ambien would arouse instead of sedate. The pill has long been linked to reports of bizarre sleepwalking behavior (not to mention sleepeating, sleeptalking, even sleepdriving). Some scientists call this phenomenon “paradoxical excitation.” So far, none of the accepted determinants of prognosis — age, overall health, the nature of the initial injury or the extent of brain damage as determined by an M.R.I. — have proved useful in predicting which brain-injured patients will experience it and which won’t. To begin answering that question, Whyte says, you need to study both responders and nonresponders in an unmedicated state.

One morning this past March, I met Chris, Wayne and Judy at the University of Pennsylvania’s main hospital, where they had been flown in from Tennessee, at the study’s expense, so that Chris could be tested in an unmedicated state. From the corner of a small hospital room, we watched as Whyte’s research assistant, Andras Szeles, attached dozens of tiny electrodes to Chris’s face and scalp, then fitted him with a large headset. The electrodes would measure Chris’s brain activity as Szeles administered a series of cognitive tests.

For one test, Szeles placed a rubber glove on Chris’s right hand. A voice coming through the headset told Chris to either “squeeze glove” or “squeeze bare,” several times over. Chris did not seem to be responding at all, but Szeles explained that the electrodes would measure what the naked eye could not. “We’re not so interested in whether or not Chris can squeeze,” he said. “We just want to know if he’s trying to squeeze.” Different neurons fire when you move your left hand versus your right hand. They also fire if you imagine moving it, prepare to move it or start to move it but stop, all of which the electrodes would detect.

“The term ‘consciousness’ can be a real can of worms,” Szeles said. “There are degrees of awareness, and it’s not always clear what the threshold should be. What we’re really looking for here is evidence of comprehension and will.” If Chris understood the words “squeeze” and “glove,” knew that this very specific thing was being asked of him, and possessed, at the most basic level, the will to respond, a distinct pattern of brain waves would show up in the results.

After Whyte and his team have tested 80 patients, they will compare the results of zolpidem responders to those of nonresponders and look for clues that might help explain the difference — maybe a specific brain region that lights up unexpectedly, or a pattern of neuronal firing common to one group but not the other. Any such discovery could light a path not only through the labyrinths of Chris’s fractured mind but to a better understanding of consciousness itself.

Wayne and Judy have a more immediate question: they want to know their son’s long-term prognosis. Has he reached the pinnacle of his cognitive recovery? Or is it a launching pad from which greater heights might be reached?

“Once a patient progresses to minimal consciousness, we can’t predict what’s going to happen,” says Dr. Joseph J. Fins, chief of medical ethics at Weill Cornell Medical College and author of a coming book, “Rights Come to Mind: Brain Injury, Ethics and the Struggle for Consciousness.” Some patients have recovered full consciousness, but many more remain stuck in limbo. The only way to know the outcome is to give the patient time.

But offering time is a complex proposition. “Early on, when families have the option to pull the plug, it’s almost impossible to tell what the long-term prognosis will be,” says Dr. Soojin Park, a neurointensivist at the University of Pennsylvania Hospital, and an investigator on the zolpidem trial. “And then later, when we have the certainty — that this is as good as it’s going to get — that option is gone. Because by then, the patient is breathing on their own. There’s no more plug to pull.” At that point, families who want to end a loved one’s suffering must either have the feeding tube removed, or agree to let the next bacterial infection win out, unhindered by antibiotics. Many families find choosing these deaths much more difficult than turning off a ventilator. It’s an instinct reinforced by religious edicts that forbid the withholding of basic sustenance but allow, for example, unplugging artificial respirators.

It is not uncommon for doctors to assume the worst and advise family members to withdraw care early. They do so in part because they see their duty as helping loved ones face reality. But Fins argues that this is a cop-out. “It’s glossing over all the unknowns for the sake of a quicker, cleaner solution,” he says. “It’s wrong to be so uniformly fatalistic so early on, especially with all the data emerging about the prospects for later-stage recovery.”

According to several studies, about 40 percent of patients who have been declared vegetative are actually minimally conscious. Other studies have shown that a surprising number of vegetative and minimally conscious patients made huge strides toward recovery much later than conventional wisdom would predict.

Park says that more doctors are trying drug therapy on vegetative and minimally conscious patients, but for the most part, they are groping in the dark. “We still don’t understand which drugs should work on which patients, or at what dosage, or at what point in their recovery,” she says. “And that makes it tough for families to know when they should fight and when they should give up.”

There is also the matter of cost. Treating and monitoring patients like Chris — designing and performing single-subject assessments that can discern random twitches from deliberate behavior, managing the host of medical complications that can stymie brain recovery and continually evaluating progress — is significantly more expensive than placing them in nursing homes, where they receive basic care but have no access to brain-injury specialists. Proponents argue that the measures will save money in the long run — if the patient is able to go home, for instance. Still, it’s unclear whether even the most aggressive care will make much difference for many patients. “The payers need a better sense of what the likely outcome is for any given patient,” says Tom Smith, program director at Moss, “so that they can say with confidence which patients are likely to benefit from treatment, and how significant that benefit is likely to be. And I hate to sound this way, but then it’s basically: ‘Am I going to invest this amount of money to get this outcome? Is that worth it?’ And that is a tough, tough question to answer.”

When Chris first returned from the hospital, the Coxes’ house was flooded with well-wishers. A former teacher brought a quilt that Chris and his classmates made in grade school. Old girlfriends, acquaintances and childhood pals visited regularly. His high-school friends even held a fund-raiser to help pay for some of his therapy. But as time wore on, and it became clear that he would neither die nor fully recover, the guests dwindled. Besides Chris’s sister, Amber, who visits often, Wayne and Judy are now mostly on their own.

The couple surrendered their bedroom, which is on the ground floor of their split-level house, to Chris. They take turns sleeping there, on a small cot in the corner of the room, surrounded by medical equipment: a hospital bed with a queen-size air mattress that helps prevent bed sores, a special chair called a “sit-stand,” which can be cranked into an upright position and is supposed to help ease muscle contractions. A mechanical lift. A breathing machine.

Judy is especially keen to show me Chris’s latest gadget, a device called an Eyegaze, that looks a bit like an iPad, and which Chris is learning to use to communicate. She mounts it to a handlebar on Chris’s wheelchair. At first, Chris’s eyes move rapidly across several rows of icons — words with pictures, partial sentences like “I want” or “I like,” and cartoon images of friends and family members with their names in bold. Tracking his eyes, the computer reads: “Green. Brit. I want.” And then, “Brit–Brit–Brit–Brit–Brit.” Brit is his cousin. It’s unclear if he’s asking for her, or if his eyes are just not cooperating.

Judy puts the computer away. He still needs practice, she says. When they first tried it, in February, during outpatient rehab, the therapist asked Chris what color went with Valentine’s Day, and he was able to look at the “red” icon. But so far, “I want a drink,” is the only full sentence he has managed.

Each day begins with the same routine: Judy helps Chris up, forcing him to sit on the edge of the bed, without neck or back support, for several minutes. The goal is to strengthen his neck muscles so that one day he can hold his own head up. A nurse helps her bathe him and then lift him into his chair, so that he can be wheeled into the living room or taken outside. Three times a week, a van delivers mother and son to a rehab center, where a therapist works to stretch and stimulate Chris’s contracted muscles. And almost as often, either Wayne or Judy spends several hours on the phone, battling Chris’s insurance company, which they say has covered private nursing and weekly therapy but denied an extended stay at a brain-injury rehab center. The couple arrange their schedules so that their son is never without at least one parent.

The Coxes have surrounded themselves with a new group of friends — other parents with children like Chris. The families in this informal group share strategies and trade information on emerging research and experimental treatments. They also talk of weariness and isolation. “At the end of the day, you feel like you’re a thousand years old,” Judy says. “And you have no idea how you’re going to get up and do it all over again tomorrow.” Both Wayne and Judy admit to being frustrated by the slow pace of Chris’s progress. But he’s come this far; they can’t help hoping that he might come further still. “I know that some people, even people who loved Chris, think maybe he should have just died,” Wayne says. “But he didn’t die. He lived. And as long as he’s still breathing, we have to do the absolute best we can for him.”

The reports on zolpidem are still mixed. Viljoen and a few others have improved steadily over time; some of them are now fully conscious on their own, without medication. (Viljoen is confined to a wheelchair and has cognitive disabilities but has improved over the years.) But such improvement is rare. According to Whyte, most responders fall into one of two categories: those who can take zolpidem daily, with no appreciable loss of efficacy, and those for whom the “awakenings” wane with continued use. The latter type, he says, may be the most common.

With no way of knowing which type of responder Chris might be, the Coxes play it safe. They give Chris Ativan every day; it has a similar though less profound effect on his behavior. But zolpidem they hoard like pixie dust, giving it only on special occasions, when friends and family can be there.

They gave him some when I visited, so I could see how it works.

A few minutes after receiving the zolpidem, Chris opened his eyes and smiled. Judy sat on the bed, facing him. “Hey, buddy!” she said. “Can I have a kiss?” She leaned in, cheekward, but he turned his head up in what looked like a deliberate slight. “Chris!” she admonished, playfully. He smiled and grunted. He was teasing her. Just as she pulled away, he thrust forward and grazed her cheek with puckered lips. Confident that he was there with us, Judy took out a marker and some paper and wrote one command after another, each of which Chris followed: Stick out your tongue, give me five, give me a thumbs up. And then, “Show us your Elvis grin.” Chris curled his upper lip into a sneer. When Judy ran out of commands, Chris began smacking his lips and moving his tongue. “Talk to us, buddy,” Wayne said. “Say, ‘Mom,’ ” Judy said. After several moments, Chris managed a loud, slow “Maaaa.”

http://www.nytimes.com/2011/12/04/magazine/can-ambien-wake-minimally-conscious.html?_r=1&nl=el&pagewanted=all

Before DNA, before RNA: Life in the hodge-podge world

2012-01-16T09:57:00.002+05:30

Take note, DNA and RNA: it's not all about you. Life on Earth may have begun with a splash of TNA – a different kind of genetic material altogether.

Because RNA can do many things at once, those studying the origins of life have long thought that it was the first genetic material. But the discovery that a chemical relative called TNA can perform one of RNA's defining functions calls this into question. Instead, the very first forms of life may have used a mix of genetic materials.

RNA, DNA… TNA

Today, most life bar some viruses uses DNA to store information, and RNA to execute the instructions encoded by that DNA. However, many biologists think that the earliest forms of life used RNA for everything, with little or no help from DNA.

A key piece of evidence for this "RNA world" hypothesis is that RNA is a jack of all trades. It can both store genetic information and act as an enzyme, seemingly making it the ideal molecule to start life from scratch.

Now it seems TNA might have been just as capable, although it is not found in nature today.

It differs from RNA and DNA in its sugar backbone: TNA uses threose where RNA uses ribose and DNA deoxyribose. That gives TNA a key advantage, says John Chaput of Arizona State University in Tempe: it is a smaller molecule than ribose or deoxyribose, possibly making TNA easier to form.

Chaput and his colleagues have now created a TNA molecule that folds into a three-dimensional shape and clamps onto a specific protein. These are key steps towards creating a TNA enzyme that can control a chemical reaction, just like RNA.

The team took a library of TNAs and evolved them in the presence of a protein. After three generations, a TNA turned up that had a complex folded shape like an enzyme and could bind to the protein.

No TNA world

That doesn't mean TNA was the original genetic material, though. Chaput thinks it probably wasn't, if only because the chemistry of early Earth was so messy that TNA would not have arisen on its own. Rather, many different kinds of genetic material probably formed in a genetic hodge-podge. "The most likely scenario is that nature sampled lots of different things," says Chaput.

That's in line with a recent study by Nobel prizewinner Jack Szostak of Harvard University and colleagues. He created mosaic nucleic acids that were half DNA, half RNA. Like Chaput's TNA, some of these could bind to target molecules (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1107113108).

However, there are problems with the hodge-podge world hypothesis. For one thing, there is no trace of TNA or its cousins in modern organisms. For another, although TNA looks simpler than RNA, we can't be sure it was easier to make some 4 billion years ago because no one has actually made it in the conditions that existed on Earth before life began, says John Sutherland of the MRC Laboratory of Molecular Biology in Cambridge, UK.

Chaput points out that we still know very little about what TNA can do, because the technology to evolve the molecules in the lab is so new. The research, he says, is just getting going.

Journal reference: Nature Chemistry, DOI: 10.1038/nchem.1241

Cousins of DNA

TNA is just one of many nucleic acids that may have been important in the first life on Earth. Here are three others.

PNA (peptide nucleic acid) ditches the sugar in its backbone and inserts a peptide instead, so it is more closely related to proteins. Like DNA, it can form double strands with itself, as well as with DNA or RNA, making it a promising genetic system (Science, DOI: 10.1126/science.1174577). It is also easy to make long PNA molecules in the conditions of prebiotic Earth, even at temperatures of 100 °C (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.97.8.3868).

GNA (glycol nucleic acid) is even simpler than TNA, with just three carbon atoms in its backbone, yet can still form helical molecules, much like DNA (The Journal of Organic Chemistry, DOI: 10.1021/jo201469b).

ANA (amyloid nucleic acid) consists of nucleic acids attached to amyloid proteins, infamous for their role in Alzheimer's disease. ANA fibres have been suggested as the first organisms (PLoS One, DOI: 10.1371/journal.pone.0019125), because the amyloid could protect genetic material contained within.

Totally drug-resistant TB emerges in India

2012-01-16T09:52:00.002+05:30

Discovery of a deadly form of TB highlights crisis of 'mismanagement'.

Physicians in India have identified a form of incurable tuberculosis there, raising further concerns over increasing drug resistance to the disease¹. Although reports call this latest form a “new entity”, researchers suggest that it is instead another development in a long-standing problem.

The discovery makes India the third country in which a completely drug-resistant form of the disease has emerged, following cases documented in Italy in 2007² and Iran in 2009³.

However, data on the disease, dubbed totally drug-resistant tuberculosis (TDR-TB), are sparse, and official accounts may not provide an adequate indication of its prevalence. Giovanni Migliori, director of the World Health Organization (WHO) Collaborating Centre for Tuberculosis and Lung Diseases in Tradate, Italy, suggests that TDR-TB is a deadlier iteration of the highly resistant forms of TB that have been increasingly reported over the past decade. “Totally resistant TB is not new at all,” he says.

Since the 1960s, two drugs — isoniazid and rifampicin — have been the standard TB treatment. Although episodes of resistance cropped up periodically, during the 1990s the incidence of multiple drug resistance grew significantly, leading researchers in 2006 to refer to it as extensively drug-resistant tuberculosis (XDR-TB). Surveillance data from the WHO indicate that XDR-TB is present in at least in 58 countries, with an estimated 25,000 cases occurring each year.

Epidemiologist Carole Mitnick of Harvard Medical School in Boston, Massachusetts, agrees that TDR-TB is not new, and points to the history of XDR-TB. “When XDR-TB was first named, it was a phenomenon that had existed but hadn’t gotten much attention before. TB in general doesn’t receive a lot of attention,” she says.

Inadequate care

Part of the increase in drug resistance is related to complications that arise in treating patients who are also infected with HIV — 13% of TB cases, according to the WHO. However, the greatest part of the problem results from the management of the disease.

Although the WHO describes TB as a “disease of poverty”, drug-resistant varieties might best be understood as resulting from poor treatment. According to a 2011 WHO report, fewer than 5% of newly diagnosed or previously treated patients are tested for drug resistance. And it is estimated that just 16% of patients with drug-resistant TB are receiving appropriate treatment.

“The cases are a story of mismanagement,” says Migliori. “Resistance is man-made, caused by exposure to the wrong treatment, the wrong regimen, the wrong treatment duration.”

In the management of TB, many factors affect whether the disease is cured or becomes resistant to treatment. Drug misuse or mismanagement can result if a patient does not follow a full course of treatment, or if the correct drugs are not available or patients with undiagnosed resistant TB receive inappropriate therapies.

Part of the problem also relates to TB testing. The WHO recommends sputum smear microscopy, a test developed more than one hundred years ago, as the standard diagnosis. Although inexpensive, this method is prone to false negatives, does not provide information on drug susceptibility, and test results can take several weeks — a large window of time for a patient to potentially receive the wrong drugs or transmit the infection. However in 2010, the WHO approved a new rapid and fully automated test, known as Xpert, which assesses resistance to the first-line drug rifampicin. As of July 2011, 26 countries are using Xpert and 145 are eligible to purchase kits at a reduced price.

Drug dearth

The fact that no new first-line TB drugs have been developed for half a century has probably contributed to the emergence of strains that are unresponsive to treatment, says Mitnick. “If you keep using the same drugs for that long, resistance is inevitable.”

Tuberculosis trails behind only HIV as the world’s leading cause of death from infectious disease. But in spite of its impact on human health and economic growth, it has not ranked among the pharmaceutical industry's priorities.

“The pharmaceutical industry had scant interest in TB for decades,” says Richard Chaisson, director of the Center for TB Research at the Johns Hopkins School of Public Health in Baltimore, Maryland. “The industry pretty much concluded it wasn’t an attractive market, there was not enough potential profit.”

But with a growing number of public–private partnerships in research, Chaisson says, industry interest is “an order of magnitude greater than it was a decade ago”.

As of 2011, there were 10 new or repurposed TB drugs in clinical trials that have the potential to either shorten treatment duration or improve therapy for resistant TB. Late-stage studies include a phase III trial by Bayer to assess whether its antibiotic moxifloxacin can help to reduce the duration of standard therapy from 6 months to 2. And both Tibotec and Novartis are in phase II trials for products that may be useful in treating drug-resistant forms.

Nature

doi:10.1038/nature.2012.9797

DNA Hackers

2012-01-03T19:34:00.001+05:30

DNA Hackers: Synthetic biology weaponized virus, zero-day exploit to infect your brain?

From the let's get futuristically freaky department, future hacking crimes could take a decidedly sinister twist; not hacking to breach systems but brains, bodies and behaviors. This DNA hacking goes way beyond potentially using police bees to bust biohackers, or even storing unhackable data in box of bio-encrypted bacteria. It's not science fiction to hack insulin pumps or to use jamming signals to stop hackers from lethal pacemaker attacks, but now bioengineers and security futurists are warning that the day is coming when criminals and bioterrorists hunt for vulnerabilities that will give a new meaning to zero-day exploits. In the future, a weaponized virus will aim to infect you, your brain and body biology, and not just your computer or mobile device.

While some people resist the idea of needing antivirus or other security software defenses for their smartphones, in the world of synthetic biology, a world where bits, bytes, atoms and biology mix dreams with nightmare realities, it could be lethal to lag behind in patching potential vulnerabilities. Some day, when you hear about something going 'viral,' it will not apply to an idea or video but to a DNA hack going viral to infect the masses. When a computer is infected with malware or a virus, you can reformat a hard drive, but will a future security scenario include needing to worry about BSOD and reformatting your brain?

Just as you can personalize your computer and mobile devices, advances in synthetic biology are allowing DNA hackers to personalize biology so that we will be able to use a DNA printer that will allow us "to print out our own treatments." Think of it as a patch you need to close a vulnerability on a system. In this case, you would download it, print it, and swallow the "cure." You will be able to search for a flu or cold vaccine and then print out the genetic designs or download the "cure" via a smartphone app, reported Genomeweb. Cures for horrific diseases could spread quickly through social media, but with all good so too comes the bad. Just as a tainted app, poisoned link, phishing email, or malicious drive-by-download can target individuals to infect computers for espionage or cybercrime, computer-designed viruses like biologically engineered biotoxins could target groups to try to wipe them out.

Bioengineer Andrew Hessel, co-chair of Biotechnology at Singularity University, has talked extensively about the Internet of Living Things and how synthetic biology will be the next big IT industry. Hessel likes to play with molecules, DNA and computers, and explained "synthetic biology as computer-assisted genetic design will go 'from an idea to printing DNA to ultimately booting DNA'." SmartPlanet reported, "Mobile phones equipped with genome decoders are coming. DIY fabricators that work with cells are already here...The cost barriers around genetic engineering are, in fact, falling, and what are essentially life-form design tools are increasingly accessible."

When Aldith Hunkar interviewed Hessel at TEDx Amsterdam, Hessel said the barriers to engineering bacteria, viruses and much higher forms of life are falling away to create a "parallel biology, one that is moving at about 100 million years of evolutionary time for every calendar year." Synthetic biology "will grow faster than some computer technology" and then almost anyone can play God; the stuff of dreams and nightmares will become real. Hessel looks at cells as computers and viruses as software. To describe his biggest synthetic biology nightmare, he said, "When I look at the world of computing today, I see all of these hacks, all of these little exploits, whether it's spam or whether it's literally hacking into different systems and manipulating them in different ways. And I see the potential for biology to be used in very similar ways."

At Techonomy 2011, Hessel discussed the emerging field of synthetic biology and bioengineering. He said in this video that the engineering of life is like software engineering and computer-assisted genetic design will give us the ability to make viruses and vaccines. He asked, "What happens when we can make a vaccine as easily as we can make a tweet?"

Hessel explained that living systems can be programmed with new functions to do commercially or intellectually useful tasks. That could be great, so long as the people who are creating the bacteria are not out to wreak havoc. At TedXm, Hessel said our bodies have a relationship with bacteria which is constantly sending chemicals into our brains. However an evil bacteria or virus has no borders and hypothetically there might be a bacteria that strikes like a drive-by-download, made to appear like an innocent or helpful cure which we might print out on a DNA printer. But after we "ingest" it into our systems, it might trigger chemicals in the brain that change behavior. The security landscape will change if we have "to learn how to counterattack" such weaponized viruses.

Now consider when we will have the ability to "boot DNA" in the same way as booting up a PC, but the data wirelessly transmits into us to perhaps keep us "healthy." Another scary example from Hessel was if two companies were business competitors and one company infected the other with a virus or bacteria that made the company employees lazy or unhappy. If viruses are like biological spam, we could be infected with bacteria that manipulates our behavior and we might not even know it's happening.

Synthetic biology, when tweaked by bioterrorists, could be used for exploitation and "not only to drive large-scale outbreaks. They will also be able to create targeted attacks against a single individual based on his or her own unique biology," reported The Washington Post. "We will need anti-virus software and defenses just as we have for computer software. But although we can reformat our hard disks to remove a computer virus, we can't reformat our genomes ... yet."

If DNA becomes the next big hacking frontier, it would open a plethora of "Pandora's Box problems." The Washington Post quoted security futurist Marc Goodman, the founder of Future Crimes:

Synthetic biology will lead to new forms of bioterrorism - opportunities for the bad guys to create never-before-seen forms of bio-toxins. These bio-threats might be nearly impossible to detect because they can be customized to the genome of a certain person or groups of people. Goodman, who has long worked on cyber crime and terrorism with organizations such as Interpol and the United Nations, believes the potential bio-threat is greatly underestimated. "Bio-crime today is akin to computer crime in the early 1980s. Few initially recognized the problem, but one need only observe how the threat grew exponentially over time."

The more I read about the topic, and the more synthetic biology videos I watched, the possibilities blew my mind. There would be so many ways to 'save the world' or to destroy it. It's a fictional story waiting to be written. I know people who can't even keep their computers protected, updated and patched . . . I wonder if they will be become more security-minded when the hacking could be literally lethal?

http://blogs.computerworld.com/19409/dna_hackers_synthetic_biology_weaponized_virus_0day_exploit_to_infect_your_brain?source=CTWNLE_nlt_networking_2011-12-14

New Way to Ensure Effectiveness of TB Treatment?

2011-12-31T16:47:00.001+05:30

ScienceDaily (Dec. 28, 2011) — A UT Southwestern Medical Center study using a sophisticated "glass mouse" research model has found that multidrug-resistant tuberculosis (TB) is more likely caused in patients by speedy drug metabolism rather than inconsistent doses, as is widely believed.

If the study published in The Journal of Infectious Diseases is borne out in future investigations, it may lead to better ways to treat one of the world's major infectious diseases. Health workers worldwide currently are required to witness each administration of the combination of drugs during months of therapy.

"Tuberculosis is a common ailment, accounting for up to 3 percent of all deaths in many countries. Although effective therapy exists, there are still cases of treatment failure and drug resistance remains a threat," said Dr. Tawanda Gumbo, associate professor of internal medicine and senior author of the study.

The results seem to challenge the current approach endorsed by the World Health Organization.

Under that method, directly observed therapy-short-course strategy (DOTS), TB that responds to medication is treated with a cocktail of drugs under the supervision of health care workers, who in many countries must travel to isolated villages -- a costly and time-consuming process.

"Every TB patient is supposed to be watched as they swallow their pills in order to increase adherence and decrease emergence of drug resistance. This is the most expensive part of the program, but has been felt to be cost-effective since it improves compliance," said Dr. Gumbo, administrative director of research programs for the Office of Global Health at UT Southwestern.

In this study, UT Southwestern researchers created a sophisticated system of high-tech test tubes, which they called a "glass mouse," that mimicked standard therapy being given daily for 28 to 56 days, with dosing adherence varying between 0 percent and 100 percent. The threshold for defined non-adherence (failure to take a required dose of medication) was reached at 60 percent of the time or more.

"The first main finding in our laboratory model was that in fact non-adherence did not lead to multidrug resistance or emergence of any drug resistance in repeated studies, even when therapy failed. In fact, even when we started with a bacterial population that had been spiked with drug-resistant bacteria, non-adherence still did not lead to drug resistance," he said.

In fact, using computer simulations based on 10,000 TB patients in Cape Town, South Africa, the researchers discovered that approximately 1 percent of all TB patients with perfect adherence still developed drug resistance because they cleared the drugs from their bodies more quickly.

The body sees drugs as foreign chemicals and tries to rid itself of them, Dr. Gumbo said. A population of individuals with a genetic trait that speeds the process has been found in one area of South Africa that has a high rate of multidrug-resistant TB. In that population, patients who receive standard doses of drugs end up with concentrations in their bodies that are too low to kill the TB bacillus and drug resistance develops, he said.

A Journal of Infectious Diseases editorial that accompanies the study suggests that monitoring the levels of TB drugs in a patient's blood could be as important as monitoring compliance with therapy -- in contrast to current WHO guidelines.

"These data, based on our preclinical model, show that non-adherence alone is insufficient for the emergence of multidrug-resistant TB," Dr. Gumbo said. "It might be more cost-effective to measure patients' drug concentrations during treatment and intervene with dosage increases in those who quickly clear the drugs from their systems."

http://www.sciencedaily.com/releases/2011/12/111228111724.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29

multiple sclerosis is not a disease of the immune system

2011-12-25T08:11:00.001+05:30

An article to be published Friday (Dec. 23) in the December 2011 issue of The Quarterly Review of Biology argues that multiple sclerosis, long viewed as primarily an autoimmune disease, is not actually a disease of the immune system. Dr. Angelique Corthals, a forensic anthropologist and professor at the John Jay College of Criminal Justice in New York, suggests instead that MS is caused by faulty lipid metabolism, in many ways more similar to coronary atherosclerosis (hardening of the arteries) than to other autoimmune diseases.

Framing MS as a metabolic disorder helps to explain many puzzling aspects of the disease, particularly why it strikes women more than men and why cases are on the rise worldwide, Corthals says. She believes this new framework could help guide researchers toward new treatments and ultimately a cure for the disease.

Multiple sclerosis affects at least 1.3 million people worldwide. Its main characteristic is inflammation followed by scarring of tissue called myelin, which insulates nerve tissue in the brain and spinal cord. Over time, this scarring can lead to profound neurological damage. Medical researchers have theorized that a runaway immune system is at fault, but no one has been able to fully explain what triggers the onset of the disease. Genes, diet, pathogens, and vitamin D deficiency have all been linked to MS, but evidence for these risk factors is inconsistent and even contradictory, frustrating researchers in their search for effective treatment.

"Each time a genetic risk factor has shown a significant increase in MS risk in one population, it has been found to be unimportant in another," Corthals said. "Pathogens like Epstein-Barr virus have been implicated, but there's no explanation for why genetically similar populations with similar pathogen loads have drastically different rates of disease. The search for MS triggers in the context of autoimmunity simply hasn't led to any unifying conclusions about the etiology of the disease."

However, understanding MS as metabolic rather than an autoimmune begins to bring the disease and its causes into focus.

THE LIPID HYPOTHESIS

Corthals believes that the primary cause of MS can be traced to transcription factors in cell nuclei that control the uptake, breakdown, and release of lipids (fats and similar compounds) throughout the body. Disruption of these proteins, known as peroxisome proliferator-activated receptors (PPARs), causes a toxic byproduct of "bad" cholesterol called oxidized LDL to form plaques on the affected tissue. The accumulation of plaque in turn triggers an immune response, which ultimately leads to scarring. This is essentially the same mechanism involved in atherosclerosis, in which PPAR failure causes plaque accumulation, immune response, and scarring in coronary arteries.

"When lipid metabolism fails in the arteries, you get atherosclerosis," Corthals explains. "When it happens in the central nervous system, you get MS. But the underlying etiology is the same."

A major risk factor for disruption of lipid homeostasis is having high LDL cholesterol. So if PPARs are at the root of MS, it would explain why cases of the disease have been on the rise in recent decades. "In general people around the world are increasing their intake of sugars and animal fats, which often leads to high LDL cholesterol," Corthals said. "So we would expect to see higher rates of disease related to lipid metabolism—like heart disease and, in this case, MS." This also explains why statin drugs, which are used to treat high cholesterol, have shown promise as an MS treatment.

The lipid hypothesis also sheds light on the link between MS and vitamin D deficiency. Vitamin D helps to lower LDL cholesterol, so it makes sense that a lack of vitamin D increases the likelihood of the disease—especially in the context of a diet high in fats and carbohydrates.

Corthals's framework also explains why MS is more prevalent in women.

"Men and women metabolize fats differently," Corthals said. "In men, PPAR problems are more likely to occur in vascular tissue, which is why atherosclerosis is more prevalent in men. But women metabolize fat differently in relation to their reproductive role. Disruption of lipid metabolism in women is more likely to affect the production of myelin and the central nervous system. In this way, MS is to women what atherosclerosis is to men, while excluding neither sex from developing the other disease."

In addition to high cholesterol, there are several other risk factors for reduced PPAR function, including pathogens like Epstein-Barr virus, trauma that requires massive cell repair, and certain genetic profiles. In many cases, Corthals says, having just one of these risk factors isn't enough to trigger a collapse of lipid metabolism. But more than one risk factor could cause problems. For example, a genetically weakened PPAR system on its own might not cause disease, but combining that with a pathogen or with a poor diet can cause disease. This helps to explain why different MS triggers seem to be important for some people and populations but not others.

"In the context of autoimmunity, the various risk factors for MS are frustratingly incoherent," Corthals said. "But in the context of lipid metabolism, they make perfect sense."

Much more research is necessary to fully understand the role of PPARs in MS, but Corthals hopes that this new understanding of the disease could eventually lead to new treatments and prevention measures.

"This new framework makes a cure for MS closer than ever," Corthals said.

http://www.eurekalert.org/pub_releases/2011-12/uocp-rcm122211.php

Septin proteins take bacterial prisoners

2011-12-23T19:40:00.001+05:30

Cellular proteins called septins might play an important part in the human body’s ability to fight off bacterial infections, according to a study.

Septins are found in many organisms, and are best known for building scaffolding to provide structural support during cell division and to rope off parts of the cell. However, most studies of septins, or guanosine-5′-triphosphate (GTP) binding proteins, have been confined to yeast cells. The latest research in human cells suggests that septins build 'cages' around bacterial pathogens, immobilizing the harmful microbes and preventing them from invading other healthy cells.

Septin proteins build cages (red) to trap bacteria (blue) that invade human cells.

S. Mostowy

This cellular defence system could help researchers to create therapies for dysentery and other illnesses, the researchers say. “This is a new way for cells to control an infection,” says Pascale Cossart, a cell biologist at the Pasteur Institute in Paris, who presented the findings in a poster session on Sunday at the annual meeting of the American Society for Cell Biology in Denver, Colorado.

The researchers discovered the caging behaviour with Shigella, a bacterium that causes sometimes lethal diarrhoea in humans and other primates. To propagate from cell to cell, Shigella bacteria develop actin-polymer 'tails', which propel the microbes around and allow them to force their way into neighbouring host cells. To counterattack, human cells produce a cell-signalling protein called TNF-α. The researchers found that when TNF-α is present, thick bundles of septin filaments encircle the microbes. This, in turn, interferes with tail formation and stops Shigella in its tracks1, 2.

Microbes that become trapped in septin cages are broken down in a stage of the cell's life cycle called autophagy. “Autophagy is more efficient because of the septin cage, and the septin cage does not occur if you do not have the autophagy,” says Cossart.

Joining the dots

The work “implies that septins are more dynamic than originally thought”, says Alexis Gautreau, a cell biologist at the French National Research Agency in Gif-sur-Yvette. Until now, he says, the function of septins in helping yeast cells to divide was well known, “but no one could relate that to mammalian cell physiology”.

“Septin’s role is pretty mysterious,” agrees Harry Higgs, a biochemist at Dartmouth Medical School in Hanover, New Hampshire. “The cool thing to me is that pathogenic bacteria have been so instrumental in figuring out how actin works, and this is the first sign that they will help to figure out how septins work.”

The researchers are now working to better understand the link between septins and autophagy, and to determine how important septins are in humans in vivo.

Previous studies have suggested that disruptions in septins and mutations in the genes that code for them could be involved in causing leukaemia, colon cancer and neurodegenerative conditions such as Parkinson’s disease and Alzheimer’s disease. Potential therapies for these, as well as for bacterial conditions such as dysentery caused by Shigella, might bolster the body’s immune system with drugs that mimic the behaviour of TNF-α and allow the septin cages to proliferate, says Cossart. “If you have a way to increase the number of cages, you have a new way to fight against infection,” she adds.

http://www.nature.com/news/septin-proteins-take-bacterial-prisoners-1.9540?WT.ec_id=NEWS-20111206

Why Tuberculosis Is So Hard to Cure

2011-12-17T08:13:00.001+05:30

When microbes divide, you usually get more of the same: A cell splits up and creates two identical copies of itself. But a new study shows that's not true for mycobacteria, which cause tuberculosis (TB) in humans—and that may explain why the disease is so difficult to treat. Mycobacteria divide asymmetrically, generating a population of cells that grow at different rates, have different sizes, and differ in how susceptible they are to antibiotics, increasing the chances that at least some will survive. Researchers hope the findings will help them develop drugs against those cells that are especially hard to kill.

"It is incredible that we are finding such basic things out only now," says immunologist Sarah Fortune of at the Harvard School of Public Health in Boston, the paper's lead author. "But it reflects the fact that mycobacteria are relatively understudied."

More than a third of the world's population is estimated to be infected with Mycobacterium tuberculosis. Most people's immune system can keep the bacteria in check, but there is a lifetime chance of 1 in 10 that the dormant infection will progress to TB; the disease still kills 4000 people every day. Tuberculosis treatment is a combination of antibiotics taken for half a year or more—a major drawback, because patients often quit therapy prematurely, increasing the risk of drug-resistant strains emerging. Scientists have assumed that mycobacteria are so hard to kill because dormant cells exist even in patients with active disease and these cells are far less susceptible to antibiotics than metabolically active bacteria.

But Fortune and her colleagues found a second, more surprising mechanism. They cultured M. smegmatis, which is closely related to M. tuberculosis but faster growing, in a tiny chamber with a constant flow of nutrients, allowing them to watch single live cells growing and replicating. Unlike other rod-shaped bacteria, such as E. coli, mycobacterial cells divided asymmetrically, creating a tapestry of cell types with widely different sizes and growth rates, the team reports online today in Science.

By labeling the cell wall of the mycobacteria with a fluorescent dye and observing the new, unstained cell wall growing at the poles, the researchers found that daughter cells mainly grow at their "old" pole. As the new end, created by the cell division, grows older, it matures and the cell elongates faster. And as the cells go through numerous divisions, cells with poles of many different "ages" emerge, leading to the wide variety in growth rates.

Importantly, the cells also differed in their susceptibility to antibiotics: While "older," fast-growing cells were more susceptible to the drugs isoniazid and cycloserine; younger, slower-growing cells were more susceptible to rifampicin. "When I started working on mycobacteria, the assumption was that all the bacteria are indistinguishable. This is the first mechanistic insight into why the cells are phenotypically different," says Fortune. The asymmetry is a way for mycobacteria to keep their population diverse, she says, just like viruses create diversity by mutating frenetically.

"This is an important study, because it shows that our way of thinking that populations are the sum of equal organisms is incorrect," says immunologist Stefan Kaufmann of the Max Planck Institute for Infection Biology in Berlin. "As we look at individual microbes, we find diversity." Kaufmann cautions, however, that most of the experiments were done with M. smegmatis and need to be verified with M. tuberculosis. "But this could explain, at least in part, why tuberculosis is so hard to treat," he says. "And it could pave the way for a rational search for new combination therapies composed of drugs that attack the different types of bacteria."

http://news.sciencemag.org/sciencenow/2011/12/why-tuberculosis-is-so-hard-to.html?ref=em&elq=d661ccc382b64524836cc194d7243fc5

Red-type Rubiscos

2011-12-16T21:31:00.001+05:30

Structural analyses of the first identified activase for red-type Rubiscos reveal key insights into Rubisco activation.

The authors propose that Cbbx (left) releases RuBP from Rubisco (right) through transient interactions with the C-terminal tail of the Rubisco large subunit (red wire). Figure courtesy of Andreas Bracher.

Red-type Rubiscos, present in photosynthetic bacteria, red algae, and phytoplankton, are responsible for most of the oceanic carbon uptake. Understanding the catalytic cycle of red-type Rubiscos could therefore aid in improving the CO2 uptake and biomass productions of photosynthetic organisms.

Rubiscos catalyze the carboxylation of Ribulose-1,5-bisphosphate (RuBP) by CO2 in the first step of carbon fixation in photosynthesis. Binding of Rubisco to RuBP in the absence of active site carbamylation creates an inactive complex that must be reactivated by Rubisco activase (Rca), which catalyzes the release of RuBP from Rubisco in an ATP-dependent manner. While Rca has been identified in green algae and plants, no Rca homolog has been identified in organisms containing red-type Rubiscos.

Mueller-Cajar and colleagues have now identified and characterized the Rubisco activase CbbX from the proteobacterium Rhodobacter sphaeroides. Like Rca, CbbX is an AAA+ protein with ATPase activity and is able to activate inhibited Rubisco in the presence of ATP. Unlike Rca, CbbX has no inherent ATPase activity in the absence of RuBP. Therefore, RuBP acts as an allosteric regulator of CbbX and ensures that the enzyme is only active during photosynthesis, when levels of RuBP are high.

Analysis of CbbX by negative stain electron microscopy revealed that CbbX forms ring-like structures similar to other AAA+ proteins in the presence of ATP and RuBP. The crystal structure of CbbX reveals a typical AAA+ fold with an N-terminal α/β domain and a C-terminal α-helical domain. The α/β domain contains the canonical Walker A and B motifs, which are important for binding ATP, and a conserved pore loop. The position of two bound sulfate ions in the α-helical domain reveals the likely binding site for RuBP.

Based on structural analyses, the authors proposed a model for Rubisco activation in which the C-terminal extension present in red-type Rubiscos, but not green-type Rubiscos, is pulled into the core of CbbX by the conserved pore loop. This pulling force opens up the active site of Rubisco and enables the inhibitory RuBP molecule to leave.

Jennifer Cable

References:

O. Mueller-Cajar et al. Structure and function of the AAA+ protein CbbX, a red-type Rubisco activase.
Nature. 479, 194-199 (2011). doi:10.1038/nature10568

Children with HIV in Asia Suffer Resistance to AIDS Drugs

2011-12-10T17:10:00.001+05:30

Researchers with the HIV/AIDS network TREAT Asia are calling for improved access to advanced pediatric HIV drugs. The collaboration of clinics, hospitals, and research institutions has released a new long-term study of 4,000 patients under age 23 in six Asian countries: It finds growing evidence of drug resistance and loss of bone density among the youths.

“In our cohort, about 14 percent of the children have failed first-line drugs ... . Some of the children who are already on second-line [drugs] are under the age of five,” said TREAT Asia Director Annette Sohn, a pediatric HIV/AIDS specialist.

Drug resistance can be caused by poor adherence to AIDS drug regimens, though in Asia it also is due to a lack of formulations for children. “We all made some mistakes on how we managed patients with HIV in the beginning of the epidemic,” said Sohn. “We used adult tablets, we had no pediatric formulations in our countries.”

“Unless we develop access to third-line drugs, we are going to find ourselves in a clinic room with a patient that there is nothing left and we have no other drug to give them,” Sohn said.

The study - carried out in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam - found a high percentage of teenage patients with low bone mineral density, a precursor to osteoporosis. “We did a special X-ray on these teenagers, who are about 16 years old, and found that 15 percent of them had low bone mass,” Sohn said. “This is not normal. Kids are not supposed to have low bone mass when they’re 16 years old and that’s because of the effect of HIV on their bodies ... brain, bone, immune system.”

Though she noted this may also be due to toxic effects that some AIDS drugs, such tenofovir, have on bone, Sohn added, “It is not so much about avoiding one drug or another but being aware of these side effects, studying what drug doses will suppress the virus while not being toxic, having the resources to monitor side effects, and having access to alternative drugs if they do arise.”

Reuters (12.01.11):: Tan Ee Lyn

Simple blood test diagnoses Parkinson's disease long before symptoms appear

2011-12-03T15:45:00.001+05:30

New research in the FASEB Journal suggests that phosphorylated alpha-synuclein, a substance found in the blood of Parkinson's patients, could lead to definitive diagnostic tool

Bethesda, MD—A new research report appearing in the December issue of the FASEB Journal (http://www.fasebj.org) shows how scientists from the United Kingdom have developed a simple blood test to detect Parkinson's disease even at the earliest stages. The test is possible because scientists found a substance in the blood, called "phosphorylated alpha-synuclein," which is common in people with Parkinson's disease, and then developed a way to identify its presence in our blood.

"A blood test for Parkinson's disease would mean you could find out if a person was in danger of getting the disease, before the symptoms started," said David Allsop, Ph.D., a researcher involved in the work from the Division of Biomedical and Life Sciences and the School of Health and Medicine at the University of Lancaster, in Lancaster, UK. "This would help the development of medicines that could protect the brain, which would be better for the quality of life and future health of older people."

To develop the blood test for Parkinson's disease, Allsop and colleagues studied a group of people diagnosed with the disease and a second group of healthy people of a similar age. Blood samples from each group were analyzed to determine the levels of phosphorylated alpha-synuclein present. They found those with Parkinson's disease had increased levels of the substance. Based upon these findings, researchers developed a blood test that detects the presence of phosphorylated alpha-synuclein, which could allow for diagnosis of the disease well before symptoms appear but when brain damage has already begun to occur.

"When most people think of Parkinson's disease, they think of the outward symptoms, such as involuntary movements," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "but many people with Parkinson's also develop neurological problems that may be more difficult to detect right away. Having a blood test not only helps doctors rule out other possible causes of the outward symptoms, but it also allows for early detection which can help patients and their caregivers prepare for the possibility of the mental, emotional, and behavioral problems that the disease can cause."

http://www.eurekalert.org/pub_releases/2011-11/foas-sbt113011.php

Medical researchers in Canada and the US discover hidden side of prion diseases

2011-12-03T15:37:00.001+05:30

Medical researchers in Canada and the United States recently published their joint findings that fatal prion diseases, which include BSE or "mad cow disease," have a hidden signature.

Findings published this month in the peer-reviewed journal, Public Library of Science (PLoS) Pathogens, demonstrate that up to seven months before an animal shows physical signs of having a prion infection, a particular prion protein in the brain was being eradicated. This member of the prion family is known as shadoo protein.

"What we discovered is that as the early prion disease process unfolds in an infected brain, that the shadoo protein is simultaneously disappearing," said lead author and co-principal investigator, David Westaway, a researcher in the Faculty of Medicine & Dentistry at the University of Alberta.

"This is telling us there is a process within the disease that we were previously unaware of, a process that is happening before the infected animals are getting sick. It's telling us that the brain cells are more active in defending themselves than what we thought they were. The brain cells are in fact trying to get rid of the prion protein and as a consequence, this bystander shadoo protein is being destroyed unintentionally.

"This finding suggests that prion diseases are dynamic and not necessarily unstoppable, that there could be a cellular process trying to destroy the infectious prions as they appear. And if we could help that process a little bit more, that might be an avenue to attenuate the disease."

Westaway, who works in both the Division of Neurology of the Faculty of Medicine & Dentistry, and the Centre for Prions and Protein Folding Diseases at the U of A, collaborated with a team of researchers from Ontario, the University of California, the Institute for Systems Biology in Washington, the McLaughlin Research Institute in Montana and a researcher in Germany, on this discovery.

The same day this paper was published, very similar findings were published by a team of researchers from the University of California, which demonstrates "these new chemical changes are a concrete and reproducible hallmark of prion disease," says Westaway.

Co-principal investigator George Carlson, from the McLaughlin Research Institute, added: "Given that shadoo may be destroyed by a process that actually targets infectious prions, it was surprising that when we increased the amount of shadoo in laboratory models that the course of disease was not changed. We need to understand why."

The next step for Westaway's research team is to determine why this shadoo protein is disappearing.

The finding opens up a new window of research opportunities.

"We need to better understand this. We want to solve this mystery," he says.

http://www.eurekalert.org/pub_releases/2011-11/uoaf-mri112811.php

lack of tenure creates a dynamic lab environment

2011-11-18T12:56:00.001+05:30

Sean Eddy has his dream job: he is a group leader in computational genomics at the Janelia Farm Research Campus of the Howard Hughes Medical Institute (HHMI), in Ashburn, Virginia. Yet, as he approaches his first cyclical review next year, he faces the prospect of being asked to leave if his work is not deemed worthy of the institute's mission.

Eddy was one of ten scientists who, aiming to energize their research and forge multidisciplinary ties, decided in 2006 to join a newly opened research institute with unconventional operating and funding models. Although he was once a tenured researcher at the Washington University School of Medicine in St Louis, Missouri, Eddy is unruffled by the lack of tenure at Janelia. In July 2012, Eddy will undergo a review, required for all Janelia group leaders — there are now 26 — after their initial six years. If an external review panel finds his work deserving, he will be offered the chance to renew for five years. If his work doesn't measure up, he has to be out by July 2014. But the uncertainty of his future never keeps him up at night.

OCEAN/CORBIS

Eddy is “wonderfully stressed” about the review. “I like knowing they can kick me out to the street,” he says. But he isn't revealing a masochistic streak. Remove the security blanket of tenure, says Eddy, and he is driven to work harder, and to assess his research programme more frequently to make sure that it is still on the right track. Furthermore, he says, tenure, which is especially coveted in the United States, brings its own job-related anxieties. “If I'm tenured at Washington University or anywhere, they can't fire me, but they can put me in a closet and take away my space,” he says. “I prefer it this way — I think it's appropriate to have a little fire under you.”

Top model?

As Janelia reaches its fifth anniversary, its research and culture continue to draw notice, and the question of whether its approach is effective remains unanswered (see page 284). Its operating model was a head-turner in 2000, when the HHMI announced plans to create the research campus; and when Janelia opened in 2006, it sparked articles in the academic, scientific and mainstream press that noted its 'radical' departure from the conventional US academic approach (see Nature 443, 128–129; 2006).

But executive director Gerry Rubin, a former academic, emphasizes that Janelia's cyclical-review model is not new. It is based in large part on similar models at established institutes that offer fixed-term contracts with reviews and opportunities to renew, such as the Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge, UK, and the former basic-research model at Bell Laboratories in Murray Hill, New Jersey, which is now the research arm of French telecommunications company Alcatel-Lucent. Similar models at Cold Spring Harbor Laboratory, a biological sciences institute in New York, and the Carnegie Institution for Science, based in Washington DC, also helped to inspire Janelia. The European Molecular Biology Laboratory, which has five sites across Europe, offers rotating contracts too (see Nature 478, 547–548; 2011).

Scientists at Janelia and similar institutions don't baulk at giving up the comfort and protection of a longer-term job — and in many cases, tenure. On the contrary, they're eager to abandon the academic prototype in favour of a workplace culture in which research is the focus and high-risk, inventive projects are the norm. They are also generally less worried about grants, teaching, committee service and other off-the-bench activities. Indeed, despite the job security and intellectual freedom that tenure confers, it is hardly universally relevant or obligatory, argue administrators and some bench scientists. Limited-term, research-focused contracts, they say, sharpen research programmes by ensuring that scientists are actively involved in day-to-day experiments.

Still, only researchers with an appetite for high-risk work and a willingness to change institutions and lab environments should embrace such a model. Young scientists should also keep in mind that labs at these institutions tend to be far smaller than those in academia, which could create logistical problems if people leave. Researchers who enjoy teaching or the university setting are also more likely to find career satisfaction elsewhere.

Tenure time-out

From the start, Rubin felt sure that Janelia held promise. “We looked at the LMB and Bell and Cold Spring and Carnegie and we saw that you did not have to offer tenure to get the highest quality of scientists,” he says.

Tenure can be antithetical to good science, says Eric Betzig, a group leader in physics at Janelia, who spent six years at Bell. “The chase for tenure enforces a certain conservatism — you learn not to stick your neck out,” says Betzig. “Then, once you have it, it's possible to get stale. And it's small enough around here that we can't afford to have a bunch of stale people.”

Limited-contract institutions typically provide generous funding packages, with a salary for four to five years and enough money to buy equipment and supplies, and hire a postdoc and lab technician. The publish-or-perish imperative of academia is greatly reduced, because such institutions focus more on the researcher's overall scientific programme than on his or her publication rate.

M. STALEY/JANELIA FARM

At Janelia Farm Research Campus, scientists forgo tenure for short-term contracts and cutting-edge labs.

And, because few of these institutions, at least in the United States, offer classes for students, scientists working at them typically don't have to teach; instead, researchers spend a lot of time in the lab. At some facilities, such as Janelia and Bell, scientists have virtually no obligations outside their research; Janelia, in fact, requires its scientists to spend 75% of their time at the bench. Other organizations require a nominal level of non-research commitment, such as service on a committee. “The postdocs here are ticked off because the principal investigators are having so much fun,” says Eddy. “At Janelia, we're all saying, 'Yeah, I guess I should let the postdoc do an experiment'.” Harald Hess, a group leader doing high-resolution microscopy at Janelia, who also spent 11 years at Bell, says that there are few time-sinks to keep scientists away from the bench at either institution. Rubin agrees. “If you want to work in the lab with your own hands, you have to come here,” he says. “That's not going to happen at most academic institutions.”

In return for the right to concentrate so closely on their research, scientists tend to be reviewed on how innovative their programmes are, and on the likelihood of field-changing discoveries, rather than on more conventional metrics. “You may not succeed, and you may not have anything to show for your five or seven years,” says Karel Svoboda, a neurobiologist and biophysicist at Janelia who has worked at both Bell and Cold Spring Harbor. “But in this environment, you may still be viewed as successful, even if you don't have the big paper.”

Judgement day

Review committees at non-tenure institutions examine investigators' work at set intervals, usually every four or five years; researchers who don't make the cut generally have between six months and two years to find a new position. Panels can be internal, external or a combination of both. For example, when the first reviews start happening at Janelia, the committee will consist of about 20 scientists, half from the group that reviews HHMI-funded investigators at other institutions, and half from the field of the person being reviewed. The reviewees will give 45-minute presentations on their work to the full panel.

Review criteria vary, but institutions strive to ensure that their researchers' science is original and creative, and will have an impact. “We don't just count papers or citations, we make a judgement about whether people are doing something that's worth doing,” says Hugh Pelham, director of the LMB. Carnegie asks whether the reviewees are taking advantage of the opportunities provided by the institution, notes president Richard Meserve — in particular, that they are effectively using the time freed up by not having to teach or chase grants. Institutions may consider how much collaboration principal investigators have been involved in and how active they have been on committees; Rubin says he will also provide input on reviewees' performance as lab colleagues and mentors to junior scientists. At the LMB, Pelham and others who regularly interact with reviewees can step in and disagree with the panel's comments; Pelham can even override a recommendation to dismiss, if he thinks the reviewee is on the cusp of a big breakthrough.

At Janelia, investigators aren't allowed to seek external funding, so grant success is irrelevant in reviews. But this is not true everywhere: for example, Cold Spring Harbor does take grant success, and indeed publication rate, into account. Its internal review panel uses both to gauge whether investigators have developed independent research programmes and have the potential to become leaders in their fields. Ideally, the lab would like investigators who are renewed in their fourth-year reviews to earn enough external funding to support 80% of their work by their fifth year.

Meserve declines to reveal Carnegie's staff-retention rates, but says that “very few” of the scientists hired as permanent staff members have left in the past two cycles. Rubin expects about 80% retention at Janelia.

Risky business

E. GRINNELL/HARVARD UNIV.

Cherry Murray: "It was an incredibly highly competitive atmosphere."

A limited-contract system is not for the faint of heart. “There are risks,” says Sydney Brenner, a Nobel-prizewinning molecular biologist and senior resident fellow at Janelia, who was once a senior researcher at the LMB. He notes that doses of uncertainty are par for the course. “But if you're passionate enough about doing science, and you have confidence in yourself, you'll be willing to take them,” he adds.

The pressures of such models are clear. Working at Bell “was an incredibly highly competitive atmosphere”, says Cherry Murray, a physicist who spent 26 years at the lab in research and management positions, including research vice-president, and is now dean of the Harvard School of Engineering and Applied Sciences in Cambridge, Massachusetts. “You were given some leeway, say for a few years after your arrival, to build up your research programme,” she says. But those who consistently stayed in the bottom 10% after that — who weren't exploring imaginative, original ideas as assessed by their managers, and whose research never led to an invention or the possibility of one — were politely asked to leave. Evelyn Hu, an electrical engineer at Harvard who spent nine years as a Bell researcher, recalls a chilling prophecy from company management early on. “I remember attending an orientation for new hires and being told, 'Look to your right, look to your left — in five years, only one of you will be here',” she says.

Those willing to embrace the pressure may face other constraints. The small size of labs in limited-contract institutes can be inhibiting, says Chris Field, director of global ecology at Carnegie and a biologist and environmental Earth systems scientist at Stanford University in California, where he conducts his research but gets no financial or other benefits. “There are some people for whom Carnegie becomes a stage that's not the right size,” he says. “Some people find that as they move through their programme, they're more interested in building a bigger lab group.”

Those running small labs can risk losing a critical mass of personnel, says Douglas Koshland, a geneticist who spent a long time at Carnegie but accepted a tenured position at the University of California, Berkeley, last year. “If you have four people and two leave, then you've got two left, and that can be painful,” he says. But Koshland is still a proponent of small labs, pointing out that the same reduced lab size also enables principal investigators to actually do research, rather than just supervise a dozen or more junior researchers.

Jim Broach is a molecular biologist at Princeton University in New Jersey, but he began his career at Cold Spring Harbor. It was lack of teaching, not of tenure, that drove him into academia. “Postdocs aren't as eager to explore new ideas as graduate students,” he says, noting that Cold Spring Harbor does now have an on-campus graduate programme, the Watson School of Biological Sciences, founded in 1999. “Teaching benefits your research — you learn to formulate your questions more precisely and you learn how to organize and present your ideas in a very powerful way,” he says.

Soft landing

Being asked to leave a place such as Janelia does not usually spell disaster. Murray notes that any researcher who, voluntarily or otherwise, left Bell while she was there had no problem finding an industrial or tenured academic research position elsewhere. For some, that is a fair exchange. Joanna Aizenberg, a materials scientist at Harvard, spent nine years at Bell, where she loved her work. But when the company began to move away from a basic-research focus to concentrate more on applied, product-driven research, she decided to resign. Shortly after Aizenberg left the company in 2007, she accepted an offer at Harvard. “It's obviously wonderful to have tenure,” says Aizenberg, “and to think that whatever happens, I have it.”

At Janelia, group leaders who don't receive a renewal offer for a second term will get transitional funding of up to US$1 million a year for two years, a bonus that significantly boosts their recruitment value. Those who get a renewal offer but decide to leave anyway can take their HHMI investigator status, and they get the same transitional funding. “You show up with a really big cheque in your pocket — that's really valuable in academia,” says Tim Harris, director of the applied physics and instrumentation group at Janelia. At the LMB, those who are asked to leave are given a month's pay for each year they've worked at the Medical Research Council, up to a maximum of 21 months, and get about a year's notice before they actually have to leave. At Cold Spring Harbor, researchers are reviewed four years into their five-year contracts, so if they are asked to leave, they still have a year to find a job, and may have some money left over from their start-up packages. At Carnegie, departures are often based on mutual agreement. Scientists who go elsewhere receive a lump sum representing their unused annual leave.

Supporters of the short-term model note that tenured academic positions are tough to find — and, in any case, few jobs have long-term guarantees. “Having any job in research, especially now, is such a gift,” says Hess. He says researchers should focus on their innovations, rather than on how long their jobs will last. “For me, the reward has always been on the positive side — what's exciting, what's new, and to not be fear-driven about when my job might end,” he says. “It's really a blessing to have this kind of opportunity — where people pay you to do what you love doing.”
http://www.nature.com/naturejobs/science/articles/10.1038%2Fnj7373-433a?WT.ec_id=NATUREjobs-20111103

Mitochondria Can’t Be Cleared out When Damaged

2011-11-14T16:09:00.001+05:30

ScienceDaily (Nov. 10, 2011) — Current thinking about Parkinson's disease is that it's a disorder of mitochondria, the energy-producing organelles inside cells, causing neurons in the brain's substantia nigra to die or become impaired. A study from Children's Hospital Boston now shows that genetic mutations causing a hereditary form of Parkinson's disease cause mitochondria to run amok inside the cell, leaving the cell without a brake to stop them.

Findings appear in the Nov. 11 issue of Cell.

Mitochondrial movement is often a good thing, especially in neurons, which need to get mitochondria to cells' periphery in order to fuel the axons and dendrites that send and receive signals. However, arresting this movement is equally important, says senior investigator Thomas Schwarz, PhD, of Children's F.M. Kirby Neurobiology Center, since it allows mitochondria to be quarantined and destroyed when they go bad.

"Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too," Schwarz says. "It's the equivalent of an environmental disaster in the cell."

Studying neurons from fruit flies, rats and mice, as well as cultured human cells, Schwarz and colleagues provide the most detailed understanding to date of the effects of the gene mutations, which encode the proteins Parkin and PINK1. They demonstrate how these proteins interact with proteins responsible for mitochondrial movement -- in particular Miro, which literally hitches a molecular motor onto the organelle.

Normally, when mitochondria go bad, PINK1 tags Miro to be destroyed by Parkin and enzymes in the cell, the researchers showed. When Miro is destroyed, the motor detaches from the mitochondrion. The organelle, unable to move, can then be disposed of: The cell literally digests it.

But when either PINK1 or Parkin is mutated, this containment system fails, leaving the damaged mitochondria free to move about the cell, spewing toxic compounds and fusing to otherwise healthy mitochondria and introducing damaged components.

The study's findings are consistent with observed changes in mitochondrial distribution, transport and dynamics in other neurodegenerative diseases such as Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), and Charcot-Marie-Tooth disease, the researchers note.

Although the team studied a rare hereditary form of Parkinson's, the findings may shed light on what's going on in the more common sporadic form of the disease, Schwarz says.

"Whether it's clearing out damaged mitochondria, or preventing mitochondrial damage, the common thread is that there's too much damage in mitochondria in a particular brain region," he says.

While Schwarz sees potential in gene therapy to restore normal PINK1 or Parkin to neurons, he is more interested in the possibility of helping neurons flush out bad mitochondria or make enough new, healthy mitochondria to keep them viable. "We may need to do both," he says.

The study was funded by the Ellison Medical Foundation, the Hartman Foundation for Parkinson's Research, the National Institutes of Health and a LSRF Novartis Fellowship. Xinnan Wang, PhD, of the F.M. Kirby Neurobiology Center at Children's, was first author.

Weird Cases Point Up Allergists' Weird World

2011-11-14T10:04:00.001+05:30

BOSTON -- If there's a limit to the range of ways in which the human body can fail, medical science has yet to find it, and allergists may be more aware of that fact than clinicians in other specialties.

Poster presentations at the American College of Allergy, Asthma, and Immunology's annual meeting here highlighted the bizarre and every-expanding number of substances that the immune system can regard as noxious, ranging from Mom's breast milk to a man's own semen.

Some of these case reports were the first ever to describe such allergies, according to the physicians presenting them. That raises the question of their importance to the allergist community -- what is the value of knowing about a possible allergy that most clinicians will never encounter in their entire careers?

John Oppenheimer, MD, who headed the ACAAI's abstract selection committee for the meeting, had a ready answer. "It may be one in a million, but if it's you [with the allergy], it's 100%," he told MedPage Today.

He also noted that allergies now recognized as common were initially noticed in a single patient, with latex allergy being an example.

"When latex was first reported as an allergy, it was an abstract and it was forgotten for years. All of a sudden it became a signal when HIV came and this was a big issue. Having had that as a prior report allowed us to move forward," Oppenheimer said.

"What might be wacky today might be an epidemic tomorrow," he added.

With that in mind, here's a sample of some of the more unusual reports presented at this year's meeting.

Semen Allergy Explains Flu-Like Symptoms

Againdra Bewtra, MBBS, of Creighton University in Omaha, Neb., and colleagues described the case of a man who complained of head and body aches, accompanied by what he called "brain fog," within a day after ejaculation irrespective of the circumstances.

Bewtra's group had previously identified semen allergy in a series of female patients and, since there was no ready explanation of the man's symptoms, they tested him with a sample of his semen.

Skin prick testing with the sample yielded "mildly positive" results and a follow-up with intradermal testing showed a large reaction, the researchers reported.

They recommended that the man try prednisone and/or high doses of antihistamines before having sexual activity, but they did not indicate whether or not it worked.

Peanut Allergy in an Exclusively Breastfed Infant

Researchers at the University of Michigan in Ann Arbor reported what they believed to be the first case of enterocolitis triggered by peanut allergy in an infant whose only exposure appeared to be breast milk from his mother.

The case involved a 7-month-old who would vomit copiously after breastfeeding, but only when his mother had recently eaten peanut products. As far as could be determined, the baby boy was exclusively breastfed and had never eaten any peanut products directly.

Patch testing indicated peanut sensitivity, although skin prick and serum IgE results were negative for peanut. Oral challenge testing was not performed.

When peanut products were eliminated from the mother's diet, the baby's symptoms disappeared, according to David Robertson, MD, MPH, and Matthew Greenhawt, MD.

Although development of peanut allergy in this way appeared unprecedented, the researchers noted that previous studies had shown that breast milk can contain peanut protein and that other types of food allergies have been induced in exclusively breastfed infants.

Another Way Alcohol Can Be Bad for You

Alcohol not only ruins the liver and causes accidents, it also can be an allergen, according to researchers at Walter Reed National Military Medical Center in Bethesda, Md.

They described a case involving a 25-year-old woman who would develop hives on her back whenever she had alcoholic beverages, including wine, beer, and distilled spirits.

An oral challenge test at Walter Reed reproduced the syndrome, reported Wayne Wolverton, DO, and colleagues, and no recurrence was reported after they recommended strict avoidance.

The researchers said this was only the second reported case of systemic dermatitis attributed to ethanol allergy.

Anaphylaxis in an Allergy Clinic Worker

Needlesticks are hazardous even in the absence of contamination with infectious pathogens, according to another group of military doctors, who reported a case of anaphylaxis in a careless allergy clinic worker.

The worker was preparing syringes to be used for routine immunotherapy injections. She accidentally pricked herself with one containing Timothy grass allergens.

She was known to be mildly allergic to Timothy grass and had previously taken loratadine for it, but severe hypersensitivity had not been suspected.

Within five minutes of the needlestick, she developed a systemic reaction. It took five doses of epinephrine to bring her hypotension, tachycardia, and breathing difficulties under control, according to Capt. Michelle Bandino, MD, and Michael Tankersley, MD, of Lackland Air Force Base in San Antonio.

Post hoc review disclosed that the worker was also taking a beta-blocker, which is known to increase the risk of severe allergic reactions in sensitive individuals.

The Lackland physicians suggested that healthcare workers be screened for such risk factors before being assigned to duties that could expose them to potential anaphylaxis triggers.

Pork-Cat Syndrome: No Longer the French Disease

An odd co-allergy to pork meat and to cats previously reported only in France has now been detected in the U.S., according to a report from researchers at the University of Virginia.

In a platform presentation at the ACAAI meeting, Jonathon Posthumus, MD, said his clinic had confirmed "pork-cat" syndrome in six patients.

The condition appears to involve cross-reactive sensitivity to serum albumin from pigs and cats. In the case of cats, the protein is contained in skin and saliva, so the exposure is similar to that responsible for the more common cat allergy related to the Fel d1 protein.

Objective testing in the six patients showed that they were sensitive to cat and pork serum albumins.

Posthumus said a complicating factor in diagnosing the condition was that patients reported that reactions were inconsistent following pork ingestion. However, albumin proteins can be broken down by heating, so that different cooking methods could explain the variability.

About That Runny Nose ...

Two case reports here described patients whose rhinitis turned out not to be allergic, but something potentially far more serious.

Both patients complained of runny noses that did not appear correlated with any known allergen, either temporally or in objective testing.

Finally, physicians examined the nasal discharge itself and found that it was not the normal type, but in fact was cerebrospinal fluid. Follow-up imaging exams revealed fistulas through which CSF was leaking into the nasosinus cavity.

The two reports offered different tips on how to distinguish the condition from allergic rhinitis.

Richard Harris, MD, in private practice in Beverly Hills, Calif., noted that CSF contains glucose whereas normal nasal secretions do not. He suggested that urinary glucose test strips meant for monitoring diabetic patients can be used to determine that a nasal discharge is likely to be CSF.

The other group, led by Rohit Divekar, MD, PhD, of the University of Texas Medical Branch in Galveston, said that cranial CT findings were reliably diagnostic.

"An empty sella is a robust radiographic marker and is almost universally present in this group of patients, but not in patients with nonspontaneous leaks," they indicated.

http://www.medpagetoday.com/MeetingCoverage/ACAAI/29563?utm_source=WC&utm_medium=email&utm_campaign=Meeting_Roundup_ACAAI

Food Sheath

2011-11-11T12:32:00.001+05:30

Consciousness: What You Don't Know Might Kill You

Ever ask yourself, "Where does consciousness come from?" Or, "Can consciousness come from an absence of consciousness?" Albeit, not the subject of your everyday discourse, these are still interesting and relevant questions. When inquiring about consciousness a valid qualifying question might be, "What type of consciousness are we talking about?" For example, dreaming consciousness comes from the REM cycle. A medical coma consciousness comes from pharmaceutical drugs. Enlightenment consciousness comes from meditation or some other practiced ability to observe and focus attention. However, when it comes to your physical consciousness, such as how emotional and mentally astute you are and how healthy you are on a cellular level, the answer might surprise you.

The Eastern sciences, such as Indian or Tibetan Ayurveda and Chinese medicine, have a very clear-cut and direct answer to this last aspect of consciousness. These ancient sources of wisdom say that the food you eat is the foundation upon which your emotional, mental and physical well-being is based upon. Ayurveda has a very succinct term for the physical body. It is referred to as the "Food Sheath." They call the physical body that because it requires a myriad of different types of food. It requires oxygen food, light food, physical "tactile" food, hydrating water food and solid alimentary food, all as sources of nourishment. The "Food Sheath" term eliminates all the "judgment" issues from the physical -- no charges about the butt being too big or small, no painful comparisons or emphasis on beauty of any kind. The body is simply the "Food Sheath."

The physical body or "Food Sheath" receives its quality of intelligence from the food you eat. We're not talking brain science or rocket surgery here. If you start your morning by drinking nothing but coffee and eating a donut, then you run around all day, some time in the afternoon you are going to start tanking. You will find it increasingly difficult to focus and concentrate. You will find yourself becoming more and more agitated and impatient when life's daily dose of obstacles smacks you right on your... food sheath. You may experience shaking of the extremities or a headache. You may find your mind easily distracted and unable to remember simple details: Where are my glasses, keys or cell phone?

As stated in age-old philosophy and co-opted by the high-tech world, "garbage in; garbage out." That's because a calorie is not a calorie. The quality of your energy comes directly from the quality of the food/fuel you take in. Now Ayurveda goes deeper with this understanding than may initially seem self-evident. For example, if you eat a lot of foods that have been grown to produce no seeds, such as some types of oranges or watermelon, over time, that could compromise your body's fertility. After all what are seeds? They are highly concentrated forms of fertility consciousness/energy. Bear in mind these types of food would have to be pervasive in your diet and you would have to be exposed to these fertility-sterilized forms of foods consistently for prolonged periods of time. It is unlikely anyone is going to eat that much seedless fruits with no diversity. But what if all crop seeds were sterile? Would that change the dynamics?

With that in mind, let's now look at a pervasive form of food that we have all been exposed to for a prolonged period of time: GMOs. Genetically modified food organisms. Even though GMOs are foods that have been genetically injected with extremely poisonous material, the FDA in its infinite wisdom has declared that these foods do not require any testing whatsoever. In fact, the FDA has never done any testing on them! Monsanto has been legally, genetically poisoning our food supply for decades. It's no surprise that wildlife such as migrating birds will not touch a single kernel of GMO corn when growing side by side a crop of non-GMO corn. In fact no animal, other than humans, when given a choice, will consume a GMO food.

These animals intuitively know what Ayurveda and Chinese Medicine teach: Food is your first wave of either medicine or poison. When you eat foods that are packed with Chi, life force energy, your mind, body and emotions are energized. When you eat foods that are packed with antioxidants, your immune system becomes stronger and empowered to destroy free radicals, because that is where the consciousness that directs the body comes from. Conversely, when you eat foods that have been genetically altered to contain chemicals that are designed to kill and destroy life, how can that have a positive affect on your energy?

In addition to the GMO nightmare, Monsanto has produced "terminator seeds." These are seeds especially designed to die after one crop. They carry a sterilized energy that does not allow another generation of plants to grow. Why? Money. The farmer has to go back to Monsanto each and every growing season for more seeds, so Monsanto's profits have increased accordingly. It is pure and simple greed, even though the planet destroying consequences of this greed are neither pure nor simple.

How can Monsanto get away with poisoning our food supply? You may find it interesting to know that many high level FDA people are former Monsanto employees. And, that's right; you guessed it. Incestuously many of the upper level Monsanto employees are former FDA staff. Well, maybe it isn't interesting. Pathetic may be closer to the truth. We have the best politicians money can buy.

Most people are unaware of these healing sciences that have survived scrutiny for thousand of years. What they have to say about the quality of consciousness that feeds your health or disease is still relevant in today's world. You need to look no further than cancers, both common and exotic, which are on the rise, or that the rate of obesity and insulin resistant disorders like diabetes have been increasing exponentially. Attention deficit disorders and autism cases seem omnipresent. Isn't it interesting that the expansion of all of these diseases happens to magically correspond to the ever-increasing presence of GMO's in the American diet.

If you are thinking, "Oh, but I'm not eating GMOs," think again. You probably are; you just don't know it. Since the FDA has declared that foods containing GMOs do not have to be labeled as such, you are not informed that the food you are consuming is toxic. If you are not eating organic foods exclusively, if you are eating or drinking anything with high fructose corn syrup (sodas, ketchup, fruit juices), corn, soybeans, cottonseed, sugar beets, canola oil, most fast food meals or pre-packaged processed foods from large food corporations, you are most likely eating GMOs. For more information please visit: http://www.nongmoshoppingguide.com/tips-for-avoiding-gmos.html.

What you may have become painfully aware of is that you are fatigued all the time. You may have noticed that you having a harder time concentrating or remembering things. You may have observed an increase in health issues or poor sleep. You may have sensed that the consciousness of the body is off in some way but have not yet connected all the dots. All of these are profound reasons to examine what you are consuming that is feeding the quality of consciousness that governs your human experience.

Socrates once commented, "The unexamined life is not worth living." If he were alive today, his consciousness cry might be, "The unexamined diet is not worth eating."

http://www.huffingtonpost.com/vaishali/gmo-seeds-food_b_1031515.html

AIDS-free generation

2011-11-11T05:29:00.001+05:30

Hillary Clinton Says U.S. Aims to Wipe Out AIDS

WASHINGTON -- The United States will, for the first time, make it a policy goal to have an "AIDS-free generation" in the near future, Secretary of State Hillary Clinton announced.

The administration's new AIDS-free generation goal will focus on "combination prevention strategy," combining three interventions that have been proven to slow the spread of the disease: ending mother-to-child transmissions; expanding voluntary male circumcision; and making greater use of antiretroviral medications.

Scientist now have a better understanding of the virus that has infected 60 million people and killed nearly 30 million since the first case of HIV was reported in 1981. And that better understanding of a once-mysterious virus makes it an achievable goal to eradicate AIDS, Clinton said during an event at National Institutes of Health (NIH) on Tuesday.

"HIV may be with us well into the future, but the disease that it causes need not be," Clinton said.

She outlined the three main areas of focus for the government's AIDS-free generation plan.

Prevention of mother-to-child transmissions, which are responsible for one in seven new infections worldwide -- it's already a global goal of the President's Emergency Plan For AIDS Relief (PEPFAR) to eliminate new infections in babies by 2015
Increase rates of voluntary male circumcision -- the procedure has been shown to reduce the risk of female-to-male transmission by more than 60%
Use treatment to prevent new infections -- recent studies show that treating HIV-positive patients with anti-retroviral drugs helps reduce transmission of the virus to a non-infected partner by 96%
Clinton said the U.S. government would commit an additional $60 million beyond the $50 million it's already spent to explore which prevention tactics work best in sub-Saharan Africa, where AIDS is the leading cause of death.

In 2003, when President George W. Bush signed the PEPFAR legislation, only 50,000 people in sub-Saharan Africa were receiving anti-retroviral drugs. Today, more than five million sub-Saharan Africans receive the drugs, along with another one million people in other regions of the world. Most of those drugs are paid for by the U.S., either through PEPFAR or through the Global Fund to Fight AIDS, Tuberculosis, and Malaria.

Speaking with MedPage Today after Clinton's speech, Anthony Fauci, MD, director of the NIH's National Institute of Allergy and Infectious Diseases, said he thought an AIDS-free generation was an achievable goal, especially in light of the relatively recent findings from the HPTN 052 trial that, in heterosexual discordant couples, if the HIV-positive partner is treated with antiretrovirals it "remarkably diminishes" the likelihood of infecting the HIV-negative partner.

"Within a reasonable amount of time, we could have an AIDS-free generation," he said.

Another physician in the audience, Thomas Quinn, MD, director of the Johns Hopkins Center for Global Health, said that science achieved a "home run" with the HPTN 052 trial, but the challenge is convincing policymakers to fund scientifically-proven interventions. But Clinton's message convinced him that at least one policymaker is sure that ramping up the nation's effort to combat HIV is something that needs to be done.

"Science here has led to a policy change," he said.

By Emily P. Walker, Washington Correspondent, MedPage Today
Published: November 09, 2011

Ten tips on getting recruited abroad

2011-11-06T07:05:00.000+05:30

At the recent Naturejobs Career Expo in London, Michael Schneider from Imperial College London spoke about how to maximise your chances of getting recruited overseas. Schneider, currently director of Imperial's British Heart Foundation Centre of Research Excellence, studied at Harvard, the University of Pennsylvania, and Duke, followed by research training at the US National Institutes of Health (NIH). In our final follow-up to the Expo we present a summary of his advice - if you have any tips to share, please add them below.

If you're at an early stage of your science career, be aware that a strong academic record is not enough to secure a position abroad. "Posts go to those with something more [than excellent qualifications]," says Schneider.

Early research experience is the key discriminator - and it should be sustained or unusually intensive.

If you're still studying, find high-impact summer and winter research opportunities - examples that Schneider highlighted include the Erasmus student exchange programme in Europe and the Cold Spring Harbor Undergraduate Research Program (URP) in the United States.

You'll need to make personal contacts with overseas scientists - and email is generally the best way to make initial speculative enquiries with overseas labs.

Don't focus exclusively on the usual suspects - in the United States for example, Schneider says there are at least a dozen universities where mentors are as good as at prestigious institutes such as Harvard, MIT, University of California and Stanford - but there is less competition because they are less well-known.

Try to have complete research 'stories' - and be aware that for this reason completing a three-year PhD can put you at a disadvantage against those whose PhDs typically last longer, such as in the United States.

Fund yourself if possible.

Carefully check the eligibility criteria of funding opportunities - for example the US NIH only offers postdoc fellowships to US citizens, with one exception, says Schneider - the Pathway to Independence Award (K99-R00) is open to overseas applicants.

When considering a career move, vertical promotion - where you move up within the same institution - can be counter-productive, says Schneider: "Research funders typically prefer to see relocation as proof of independence."

When considering who to apply to, make sure you check where your potential superior publishes, and also where their trainees have gone afterwards.

http://blogs.nature.com/naturejobs/2011/11/02/ten-tips-on-getting-recruited-abroad?WT.ec_id=NATUREjobs-20111103