Scientists ID New Genetic Connection for Gout

The painful inflammatory condition affects about 2 percent of people worldwide
      
     To help explain why the debilitating arthritic condition known as gout strikes some people and not others, a new genetic analysis has identified 18 new mutations that appear to boost blood levels of uric acid, the key trigger for a gout attack.

The current effort involved an analysis of data concerning more than 140,000 people, gleaned from 70 independent studies conducted in Europe, the United States, Japan and Australia.

"Abnormal levels of uric acid have been associated with various common diseases and conditions, but causal relationships are not always clear," said study author Dr. Veronique Vitart of the Medical Research Council Human Genetics Unit at the University of Edinburgh, in Scotland, in a school news release. "Gaining insight into the genetic components of uric acid levels offers a very useful tool to tackle these issues and to further our understanding of these conditions."

The study appeared in the Dec. 23 issue of Nature Genetics.

The authors noted that gout has been called the "disease of kings," based on the belief that rich foods (consumed by rich people) are the principle culprit behind the onset of often immobilizing attacks.

Gout affects roughly 2 percent of the population. High levels of uric acid from a wide varietyTo of foods and alcohol accumulate and form into hard crystals, which then lodge themselves into joints and tissues. The result: extreme pain and swelling.

Researchers hope that any fresh insight into the role of genetics in gout incidence might pave the way for better treatment and prevention.

"Existing therapies to avoid attacks of gout sometimes cause side effects," study co-author Mark Caulfield, at the William Harvey Research Institute at Queen Mary University of London, said in the news release. "[So] our findings identify new potential mechanisms for gout and offer opportunities for new therapies which may improve prevention of this debilitating condition in the future."



SOURCE: University of Edinburgh, news release, Dec. 23, 2012
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Does looking at a computer damage your eyes?

          The old saying goes that watching too much TV will make your eyes go square. Nowadays, we seem to spend most of our time looking at screens: be it a computer screen at work, a mobile phone screen to make a call or a TV screen to relax. But how bad is looking at screens for our eyes? Is there really any truth behind the old saying?


        According to Dr Blakeney, an optometric adviser to the College of Optometrists, computers will not permanently damage the eyes; however, they can cause strain or exacerbate existing eye conditions. (1)
What problems do looking at computer screens cause?

      People who look at computers frequently, (in particular those that look at a computer for more than three hours a day), (2) may experience symptoms such as:
*Eye discomfort
*Headaches
*Itchy eyes
*Dry or watering eyes
*Burning sensations
*Changes in color perception
*Blurred vision
*Difficulty focussing (1, 2, 3)
*Eyestrain

*Eyestrain is a type of repetitive strain injury (RSI) that is caused by insufficient rest periods, incorrect working conditions and so forth. (2, 4)

*There are many causes of eyestrain. One of these is glare.

*There are two types of glare, direct and indirect. Direct glare is where light shines directly in your eyes; whereas indirect glare is caused by light reflecting off surfaces into your eyes. (3)

*Glare often results from computer screens being too dark or too bright. (2, 5)

*Glare leads to eye muscle fatigue, for the eyes have to struggle to make out the images on the screen. (2)

*Another major cause of eyestrain is the position of the computer screen.

Naturally, the eyes are positioned so that they look straight ahead and slightly down.

If the eyes have to look in a different direction, the muscles have to continually work to hold this position.

Thus, if your computer monitor is positioned incorrectly, the eye muscles must constantly work to hold the eyes in the correct position to view the monitor. (2)

In order to prevent the eyes becoming strained in this way, the top of your computer screen should be no higher than eye level. (3)
Dry eye syndrome
         According to the NHS, using your computer correctly can also help to prevent dry eye syndrome.

Dry eye syndrome is a condition in which the eyes become inflamed due to a lack of tears. This lack of tears is commonly due to a blockage of the oil secreting glands in the eyes.

Although this condition causes discomfort, it does not usually affect vision. (6)
Ways to minimise damage to your eyes caused by computer screens

There are several ways you can minimise the potential damage to your eyes caused by looking at computer screens.

Firstly, it is important to set up your computer screen so that it is in the correct position in relation to your eyes.

As previously mentioned, the top of the screen should be in line with your eye level. In addition, the screen should be placed approximately 18-30 inches from you.

The screen should also be tilted slightly back – between 10 to 15 degrees depending on the person’s particular preference. This is so that you do not receive glare from lights in the ceiling. (3, 7)

Glare can also be avoided by placing blinds over nearby windows, or using a glare screen. (2, 5)

In addition to adjusting the position of your screen, you can also minimise eye problems by simply blinking more frequently.

Many people don’t realise that they actually blink less when they look at a screen. (2)

Blinking is important, however, as it washes your eyes in their naturally therapeutic fluids. (5)

It is also important to take breaks from looking at your screen. One easy way to remember this is to think of 20-20-20. This reminds you that every 20 minutes you should try to look at something 20 feet away for a minimum of 20 seconds. (5)

It is also recommended to take breaks from your screen altogether, in particular every 2 hours. (2)
Can looking at screens improve eyesight?

Despite the potential eye problems caused by looking at a screen too frequently, research carried out in the US has actually found that some screen viewing can be of benefit to the eyes.

Specifically, they found that playing video games can improve vision.

This is because playing video games gives the users chance to improve their contrast sensitivity. (8)

Contrast sensitivity refers to how faded an object can be before it is impossible to differentiate it from the same field of view. It is something that is affected by ageing. (8, 9)

Contrast sensitivity is particularly important for activities such as driving in poor visibility, like in fog or at night. (8)
Overall does looking at computers damage your eyes?

Overall it seems that although looking at a computer may not cause permanent eye damage, it can cause some irritating problems, such as eye strain and dry eyes.

It is also important to remember, that there are many other potential problems associated with sitting down and staring at a computer for long periods of times, such as deep vein thrombosis (DVT). (10)

History of DNA Research

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit. Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However, Levene thought the chain was short and the bases repeated in a fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.

In 1928, Frederick Griffith discovered that traits of the "smooth" form of the ''Pneumococcus'' could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carried genetic information—the Avery-MacLeod-McCarty experiment—when Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943. DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the Hershey-Chase experiment showed that DNA is the genetic material of the T2 phage.

In 1953 James D. Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal ''Nature''. taken by Rosalind Franklin and Raymond Gosling in May 1952, as well as the information that the DNA bases were paired—also obtained through private communications from Erwin Chargaff in the previous years. Chargaff's rules played a very important role in establishing double-helix configurations for B-DNA as well as A-DNA.

Experimental evidence supporting the Watson and Crick model were published in a series of five articles in the same issue of ''Nature''. Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partially supported the Watson and Crick model; this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and ''in vivo'' B-DNA X-ray patterns also supported the presence ''in vivo'' of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the previous two pages of ''Nature''. In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. Unfortunately, Nobel rules of the time allowed only living recipients, but a vigorous debate continues on who should receive credit for the discovery.

In an influential presentation in 1957, Crick laid out the "Central Dogma" of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment. Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology.

MIGRAINE

A migraine is a common type of headache that may occur with symptoms such as nausea, vomiting, or sensitivity to light. In many people, a throbbing pain is felt only on one side of the head.

Some people who get migraines have warning symptoms, called an aura, before the actual headache begins. An aura is a group of symptoms, including vision disturbances, that are a warning sign that a bad headache is coming.

See also:


Cluster headache


Tension headache
Causes, incidence, and risk factors

Migraine headaches tend to first appear between the ages of 10 and 45. Sometimes they may begin later in life.


Migraines occur more often in women than men


Migraines may run in families


Some women, but not all, may have fewer migraines when they are pregnant

A migraine is caused by abnormal brain activity, which can be triggered by a number of factors. However, the exact chain of events remains unclear. Today, most medical experts believe the attack begins in the brain, and involves nerve pathways and chemicals. The changes affect blood flow in the brain and surrounding tissues.

Alcohol, stress and anxiety, certain odors or perfumes, loud noises or bright lights, and smoking may trigger a migraine. Migraine attacks may also be triggered by:


Caffeine withdrawal


Changes in hormone levels during a woman's menstrual cycle or with the use of birth control pills


Changes in sleep patterns


Exercise or other physical stress


Missed meals


Smoking or exposure to smoke

Migraine headaches can be triggered by certain foods. The most common are:


Any processed, fermented, pickled, or marinated foods, as well as foods that contain monosodium glutamate (MSG)


Baked goods, chocolate, nuts, peanut butter, and dairy products


Foods containing tyramine, which includes red wine, aged cheese, smoked fish, chicken livers, figs, and certain beans


Fruits (avocado, banana, citrus fruit)


Meats containing nitrates (bacon, hot dogs, salami, cured meats)


Onions

This list may not include all triggers.

True migraine headaches are not a result of a brain tumor or other serious medical problem. However, only an experienced health care provider can determine whether your symptoms are due to a migraine or another condition.
Symptoms

Vision disturbances, or aura, are considered a "warning sign" that a migraine is coming. The aura occurs in both eyes and may involve any or all of the following:


A temporary blind spot


Blurred vision


Eye pain


Seeing stars or zigzag lines


Tunnel vision

Other warning signs include yawning, difficulty concentrating, nausea, and trouble finding the right words.

Not every person with migraines has an aura. Those who do usually develop one about 10 - 15 minutes before the headache. However, an aura may occur just a few minutes to 24 hours beforehand. A headache may not always follow an aura.

Migraine headaches can be dull or severe. The pain may be felt behind the eye or in the back of the head and neck. For many patients, the headaches start on the same side each time. The headaches usually:


Feel throbbing, pounding, or pulsating


Are worse on one side of the head


Start as a dull ache and get worse within minutes to hours


Last 6 to 48 hours

Other symptoms that may occur with the headache include:


Chills


Increased urination


Fatigue


Loss of appetite


Nausea and vomiting


Numbness, tingling, or weakness


Problems concentrating, trouble finding words


Sensitivity to light or sound


Sweating

Symptoms may linger even after the migraine has gone away. Patients with migraine sometimes call this a migraine "hangover." Symptoms can include:


Feeling mentally dull, like your thinking is not clear or sharp


Increased need for sleep


Neck pain
Signs and tests

Your doctor can diagnose this type of headache by asking questions about your symptoms and family history of migraines. A complete physical exam will be done to determine if your headaches are due to muscle tension, sinus problems, or a serious brain disorder.

There is no specific test to prove that your headache is actually a migraine. However, your doctor may order a brain MRI or CT scan if you have never had one before or if you have unusual symptoms with your migraine, including weakness, memory problems, or loss of alertness.

An EEG may be needed to rule out seizures. A lumbar puncture (spinal tap) might be done.
Treatment

There is no specific cure for migraine headaches. The goal is to treat your migraine symptoms right away, and to prevent symptoms by avoiding or changing your triggers.

A key step involves learning how to manage your migraines at home. A headache diary can help you identify your headache triggers. Then you and your doctor can plan how to avoid these triggers.

If you have frequent migraines, your doctor may prescribe medicine to reduce the number of attacks. You need to take the medicine every day for it to be effective. Medications may include:


Antidepressants such as amitriptyline or venlafaxine


Blood pressure medicines such as beta blockers (propanolol) or calcium channel blockers (verapamil)


Seizure medicines such as valproic acid, gabapentin, and topiramate

Botulinum toxin (Botox) injections may also help reduce migraine attacks.

TREATING AN ATTACK

Other medicines are taken at the first sign of a migraine attack. Over-the-counter pain medications such as acetaminophen, ibuprofen, or aspirin are often helpful when your migraine is mild. Be aware, however, that:


Taking medicines more than 3 days a week may lead to rebound headaches -- headaches that keep coming back.


Taking too much acetaminophen can damage your liver. Too much ibuprofen or aspirin can irritate your stomach.

If these treatments don't help, ask your doctor about prescription medicines. These include nasal sprays, suppositories, or injections. Your doctor can select from several different types of medications, including:


Triptans -- prescribed most often for stopping migraine attacks


Ergots -- contain different forms of ergotamine


Isometheptene (Midrin)

Some migraine medicines narrow your blood vessels. If you are at risk for heart attacks or have heart disease, talk with your health care provider before using these medicines. Do not take ergots if you are pregnant or planning to become pregnant.

Other medications are given to treat the symptoms of migraine. They may be used alone or along with other drugs. Medications in this group include:


Nausea medicines


Sedatives such as butalbital


Narcotic pain relievers

Feverfew is a popular herb for migraines. Several studies, but not all, support using feverfew for treating migraines. If you are interested in trying feverfew, make sure your doctor approves. Also, know that herbal remedies sold in drugstores and health food stores are not regulated. Work with a trained herbalist when selecting herbs.
Support Groups

American Council for Headache Education - www.achenet.org

The National Migraine Association - www.migraines.org

National Headache Foundation - www.headaches.org
Expectations (prognosis)

Every person responds differently to treatment. Some people have rare headaches that need little to no treatment. Others need to take several medications or even go to the hospital sometimes.

Migraine headache is a risk factor for stroke in both men and women. The risk is higher in people who have migraines that occur with aura. People with migraines should avoid other risk factors for stroke, include smoking, taking birth control pills, and eating an unhealthy diet.
Calling your health care provider

Call 911 if:


You are experiencing "the worst headache of your life"


You have speech, vision, or movement problems or loss of balance, especially if you have not had these symptoms with a migraine before


Your headaches are more severe when lying down


The headache starts very suddenly

Also, call your doctor if:


Your headache patterns or pain change


Treatments that once worked are no longer helpful


You have side effects from medication, including irregular heartbeat, pale or blue skin, extreme sleepiness, persistent cough, depression, fatigue, nausea, vomiting, diarrhea, constipation, stomach pain, cramps, dry mouth, or extreme thirst


You are pregnant or could become pregnant -- some medications should not be taken when pregnant

See the general article on headaches for more information on emergency symptoms.

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001728/

Technique may reveal where it all began

BOSTON — Predicting the future is notoriously difficult, but uncovering the past can be just as tricky. Now researchers have developed a method that looks backward and may reveal where a widespread phenomenon originated, be it the outbreak of a disease or a new technology.
Typically techniques for deriving the origin of something rely on the notion that whatever is spreading will take a certain time to travel a certain distance. But with planes, trains and automobiles, geographic distance by itself is no longer a good predictor of arrival time, said Dirk Brockmann, who presented the new approach February 28 at a meeting of the American Physical Society. That population densities aren’t uniform across an area makes estimating spread using geography alone even more difficult.
The new method still relies on distance, but not one constrained by geography. Just as diagramming the relationships among friends can yield close or “coupled” people, even if they live far apart, diagrams of relationships among locations that consider the traffic between them can yield coupled locations. Using such relationships, Brockmann, of Northwestern University in Evanston, Ill., and his colleagues came up with a way to compute paths that are in effect the shortest between locations, even if they are far apart geographically.
Once that path diagram is in hand, the researchers can test whether various starting points might be the root of the branching, treelike spread of whatever phenomenon is being studied. A clean, circular diagram emerges when the correct root is identified, computer simulations reveal.
“Computer simulations are among the most useful tools in our armory,” says Bill Hanage, an epidemiologist at Harvard School of Public Health who has been tracing the origins of last year’s E. coli outbreak in Europe, which killed dozens of people. Such simulations are particularly helpful if they work even with poor or biased samples of data, he says.

4 New Genes Linked to Type 2 Diabetes

Four new genes associated with type 2 diabetes have been identified by researchers, who also pinpointed six independent diabetes-associated gene variants at previously known locations on chromosomes.
These findings, from an analysis of 50,000 genetic variants across 2,000 genes linked to heart and metabolic function, appear in the Feb. 9 issue of the American Journal of Human Genetics.
The results offer valuable insight into the genetic risk for type 2 diabetes in multiple ethnic groups and could help lead to new treatments, according to a journal news release.
A number of environmental and genetic factors are associated with type 2 diabetes.
"Together, known [type 2 diabetes] genetic variants explain only about 10 percent of the genetic variance, indicating that additional genetic factors are likely to contribute to disease risk," senior study co-author Dr. Brendan Keating, of The Children's Hospital of Philadelphia, said in the news release.
"Further, previous studies have been based almost exclusively on individuals of European ancestry, and genetic contributors to [type 2 diabetes] are less well understood in non-European populations," he added. "An important first step towards understanding genetic risk across populations is to establish whether known [diabetes-associated] genes span ethnicities or are population-specific."
Keating and an international team of colleagues analyzed 39 multiethnic studies on type 2 diabetes that included more than 17,000 people with diabetes and 70,000 people without the disease.
"As a result of our large-scale genetic analysis, we uncovered previously unknown European and multiethnic genetic variants and confirmed that, together, known genetic risk factors influence [type 2 diabetes] risk in multiethnic populations, including African-Americans, Hispanics and Asians," senior co-author Richa Saxena, of Massachusetts General Hospital and Harvard Medical School, said in the release.
Saxena said that identifying new genes associated with type 2 diabetes in diverse ethnic groups could eventually guide strategies for developing treatments.

Drug halts organ damage in inflammatory genetic disorder

A new study shows that Kineret (anakinra), a medication approved for the treatment of rheumatoid arthritis, is effective in stopping the progression of organ damage in people with neonatal-onset multisystem inflammatory disease (NOMID). This rare and debilitating genetic disorder causes persistent inflammation and ongoing tissue damage. The research was performed by scientists at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health.
NOMID affects numerous organs and body systems, including the skin, joints, eyes, and central nervous system. The first sign of the disease is often a rash that develops within the first weeks of life. Other problems, including fever, meningitis, joint damage, vision and hearing loss, and mental retardation, can follow. Kineret, one of a relatively new class of drugs known as biologic response modifiers or biologics, blocks the activity of interleukin-1 (IL-1), a protein made by cells of the immune system. IL-1 is overproduced in NOMID and a number of other diseases, leading to damaging inflammation. Previous work by the same NIAMS group showed that blocking IL-1 was effective in relieving symptoms of NOMID. However, this is the first study to show that Kineret works over the long-term and, at higher doses, can also control damage that often results in vision and hearing loss, and brain lesions.
“Inflammation prolonged over many years will eventually cause irreversible damage and loss of function,” said lead author Dr. Raphaela Goldbach-Mansky of the NIAMS Translational Autoinflammatory Disease Section.
For example, inflammation of the cochlea — a tiny structure of the inner ear — was found to be responsible for hearing loss in people with NOMID. Thinning of the optic nerve caused by inflammation-related pressure in the brain has been identified as a cause of vision loss.
“We knew we could effectively block inflammation in the inner ear and in the brain and eyes. The next step was to find out if we could sufficiently prevent the progression of hearing or vision loss,” said Goldbach-Mansky.
The group sought the answers to their questions in the study published online in Arthritis & Rheumatism. Study participants, who ranged in age from 10 months to 42 years, were treated with daily doses of Kineret based on body weight — 1 to 5 milligrams of Kineret per kilogram of body weight (1 to 5 mg/kg/day) — for at least 36 months and as long as 60 months. Disease activity was monitored with blood tests to measure C-reactive protein, a marker for inflammation in the body, and by daily diaries kept by the patients or their parents. The researchers also used sensitive MRI imaging methods to assess inflammation in the inner ear and brain.
Researchers found the initial Kineret doses used were insufficient to control organ inflammation, but by increasing the dose, they were able to do so. By preventing organ inflammation, scientists were able to preserve organ function in most patients. In addition, the scientists found ways to predict who is at greatest risk of hearing and vision loss.
“The few patients in the study who had hearing loss were also the ones who continued to have inflammation in the inner ear,” said the study's first author Dr. Cailin H. Sibley. “We also found that people who had thin optic nerves when we assessed their vision were more likely to lose vision than those who had thick optic nerves, simply because they had already lost fibers due to untreated disease and, therefore, started with a huge disadvantage.”
These findings point to the importance of early diagnosis and treatment to keep organ damage from developing. “We are continuing the study with an emphasis on enrolling very young children to prospectively show that we can prevent any organ damage from developing if we start treatment early in life,” Goldbach-Mansky said.
Because IL-1 is needed to fight infections, there has been concern that blocking it with high doses of Kineret might leave the body vulnerable to infections. But overall, the study drug was well tolerated. “While we have seen infections in the study, none were serious enough to discontinue the drug, and all healed well with appropriate treatment.”
While Kineret is not a cure for NOMID — its effects last only as long as the drug is taken — the study offers hope for people with the disease. “Without Kineret, people with NOMID are at risk of progressive organ damage that results in hearing and vision loss, cognitive impairment and, in many cases, early death. As many as 20 percent of children with this genetic disorder do not live to adulthood,” said Goldbach-Mansky. “This study shows that treatment over five years is safe and effective, and can prevent organ damage.”
In addition to funding from the NIAMS, portions of this work were also supported by the Intramural Research Programs of the National Cancer Institute, the National Institute on Deafness and Other Communication Disorders, the National Eye Institute, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the NIH Clinical Center.

Drugs activate dormant gene Chemotherapy agent may offer hope for treating Angelman syndrome

By kick-starting a gene that is naturally inactivated, chemotherapy drugs could help reverse a genetic brain disorder that is sometimes mistaken for autism or cerebral palsy. The unexpected finding may also spark a new avenue of research on a type of gene regulation known as imprinting.
The genetic disorder, Angelman syndrome, occurs in about one in 15,000 live births. It is caused when the copy of a gene called UBE3A inherited from the mother goes missing or is damaged by a mutation. That’s a problem because the copy of the gene inherited from the father is already turned off in brain cells, leaving no way to make UBE3A protein.
Genes such as UBE3A that turn off one parent’s copy are called imprinted genes. Until now, researchers knew of no way short of gene therapy to override the imprinting and restore gene activity.
Now, researchers from the University of North Carolina at Chapel Hill have discovered that a type of chemotherapy drug called topoisomerase inhibitors can turn on the father’s inactive copy of the gene in brain cells of mice with a version of Angelman syndrome. The team reports the achievement online December 21 in Nature.
The prospect that a drug could correct the underlying defect responsible for Angelman syndrome is exciting, says Stormy Chamberlain, a geneticist at the University of Connecticut Health Center in Farmington. “There’s every reason to have hope that it will help our Angelman syndrome kids,” she says.
Angelman syndrome is linked to severe developmental delays that keep people from attaining vocabularies of more than a few words. People with the disorder are apparently always cheerful and may laugh and smile inappropriately and have uncoordinated movements, as well as other physical and behavioral characteristics.
Charles Williams, a University of Florida pediatrician and geneticist who chairs the Angelman Syndrome Foundation’s scientific advisory committee, is also enthusiastic about the finding. “It’s a seismic shift. It is a really important breakthrough,” he says. “Having said that, a lot of us in the Angelman syndrome community are really worried that our expectations will not be met.”
Researchers don’t yet know whether the drugs can restore UBE3A production in human brain cells, or if turning the gene back on will reverse abnormalities in Angelman syndrome mice. More work with mice will be needed to determine whether the gene must be activated at some particular time during development, or if restoring gene activity can reverse the disorder at any time. Also, the drugs might inactivate other genes that should remain on in order to maintain health, producing unwanted side effects.
Clinical trials should not be attempted in people with Angelman syndrome, Williams says. Speaking on behalf of the foundation, he says, “We are very keen at this point that clinical trials not be prematurely started.”
For the new study, University of North Carolina neuroscientist Benjamin Philpot and his colleagues used brain cells from mice genetically engineered so their cells make a fluorescent protein whenever the father’s copy of UBE3A is active. The researchers tested more than 2,000 chemicals to see whether any could turn on the dad’s copy of the gene.
Most imprinted genes are tagged with chemicals either on the DNA or on associated proteins, so the researchers were surprised to find that drugs that affect those chemical tags didn’t restore the gene’s activity. Instead, drugs that inhibit the activity of DNA-unwinding proteins called topoisomerases did the trick.
DNA-unwinding proteins have never been implicated in imprinting before, so the discovery is likely to generate lots of new research on how the proteins are involved in the process, says Yong-hui Jiang, a clinical geneticist and neurobiologist at the Duke University School of Medicine. “Whether it’s working on resetting imprinting is an open question,” he says.

Deep-sea glow serves as bait Marine bacteria light up to get a ride elsewhere

Bioluminescent bacteria glow in the ocean for the same reason roadside eateries display neon signs: They want to attract hungry diners.
New laboratory experiments bolster the longstanding theory that marine bacteria light up to get themselves a free ride to other parts of the ocean in the digestive tracts of larger beasts, scientists from Israel and Germany report online December 27 in the Proceedings of the National Academy of Sciences.
“It’s terrific to see this experiment,” says J. Woodland Hastings, a bioluminescence expert at Harvard University who was not involved in the research. “It’s nice to see these ideas confirmed.”
Many deep-sea creatures, from bacteria to fish to squid, are bioluminescent — meaning they generate light inside their bodies through chemical reactions. Different organisms glow for different reasons; the anglerfish, for instance, can light up a lure to attract prey, while some plankton glow when disturbed to attract predators of whatever is stirring them up.
Bioluminescent bacteria live throughout the ocean, and may have several reasons to explain their built-in glow. More than three decades ago, researchers suggested that one such reason could be to mark the presence of a floating food particle, so that a passing fish would see it and eat it. But no one had tracked this idea all the way to its logical conclusion — until now.
Margarita Zarubin, a graduate student at the Interuniversity Institute for Marine Sciences in Eilat, Israel, started with a type of luminescent bacterium, Photobacterium leiognathi, found 600 meters deep in the Red Sea. She put one bag of glowing bacteria at one end of a seawater tank, and at the other end she put another bag of bacteria that had a genetic change that kept the microbes dark. Shrimp and other small animals clustered around only the glowing bacteria.
Next she let brine shrimp swim in water with the luminescent bacteria. After two and a half hours, the shrimp themselves began to glow from their microbial dinner. “We could see the luminescence from inside their guts,” says Zarubin, who did the work while at the University of Oldenburg in Germany and is now with the Hebrew University of Jerusalem.
Then she dropped both glowing and dark shrimp into a flume so they were swept past a hungry cardinalfish; the fish ate only the luminescent shrimp. Finally, the scientists tested the fish feces, and found that the bacteria had passed unscathed through the fish guts and came out intact. The whole process spreads the bacteria through the water faster than they could move otherwise, Zarubin says. 
For their part, the shrimp must balance the benefit of eating a food particle that happens to glow against the drawback of becoming luminescent themselves, thus making themselves more vulnerable to predators. But in deep dark waters where food is scarce, the advantage of getting a snack probably outweighs the disadvantage of potentially being eaten, Zarubin says.
Some animals have pigment in their guts that can block light emission as they digest glowing particles, says Michael Latz, a marine biologist at the Scripps Institution of Oceanography in La Jolla, Calif. Only when the animal pops out a glowing fecal pellet do the bacteria become visible again, signaling another creature to eat them and keep the microbes on the move.
Such deep-sea bacterial recycling could be important for more than just understanding bioluminescence, Latz says. The guts of shrimp and other small marine creatures may serve as a highway for spreading bacterial pathogens throughout the sea, like the one that causes cholera.

Molecule ties itself in a complex knot

Chemists have tangled themselves a complicated knot: a molecule whose 160 atoms loop over one another like a five-pointed star.
The molecule’s design, called a pentafoil, is the most complex knot synthesized from building blocks other than DNA. Knowing how to make a pentafoil, its discoverers say, could lead to ways to make materials lighter, stronger or more flexible than before.
“By knowing how to design types of knots, hopefully we can optimize these properties,” says David Leigh, a chemist at the University of Edinburgh. He and his colleagues report the new knot in the January issue of Nature Chemistry.
The simplest knot is the “unknot,” a loop that doesn’t cross over itself. The next simplest — a “trefoil,” with three crossing points — was first made out of a molecule in 1989. Leigh’s team decided to take things a step further and aim for the five-crossing pentafoil. 
The scientists took negatively charged chloride ions and added ingredients such as positively charged iron ions and long chains of carbon and other atoms, then chemically programmed the whole thing to assemble itself. Five of the chains looped over one another and hooked up, along with five irons, with each chloride to create the pentafoil.
This molecule turns out to be interesting for more than just its shape, Leigh says. “The pocket where the chloride ion sits turns out to be a perfect fit, and if you remove it, the molecule is desperate to bind chloride back in there,” he says. So the molecule could be used as a sensor to help detect chlorine in its surroundings, he says.
Building bigger knots could also help scientists uncover general rules of knotted molecules. Rubber, for instance, gets much of its stretchiness from knots within its polymer chains.
But given that mathematicians know of more than 6 billion kinds of knots, chemists still have a long way to go.

Face deficit holds object lesson Recognizing mugs may not be special in the brain

A brain-damaged man who can’t remember faces has nosed into a scientific debate about how people learn to recognize other complex objects. Deaf users of sign language also have a hand in this dispute.
The brain-damaged man’s facial failures are one symptom of a general inability to perceive configurations of object parts, suggests a new investigation led by psychologist Cindy Bukach of the University of Richmond in Virginia. The man thus stumbles at identifying not only people’s faces but also computer-generated, three-part objects called Greebles, even after extensive training, Bukach’s team reports online December 8 in Neuropsychologia.
Bukach and her colleagues studied LR, a man who fails to recognize his daughter when shown a picture of her but remembers distinctive facial features, such as Elvis’ sideburns. Damage in a car accident to a brain area just under the right temple caused this condition, called prosopagnosia.
“There are many ways in which face recognition can be disrupted, but our evidence shows that LR’s type of prosopagnosia impairs recognition of objects with multiple parts, with faces as the most obvious example,” Bukach says. Relative positions of the eyes, nose and mouth, as well their shapes, contribute to perceiving a face as a single entity.
In a 2006 report, her team designed a collection of eight faces using different combinations of two sets of eyes, noses and mouths. After briefly viewing a face, LR correctly selected it from all eight faces 25 percent of the time — about what would be expected if he based choices on a single facial feature, Bukach says. Further testing showed that LR homed in on the mouth.
In the new study, the researchers designed eight Greebles, using different combinations of two versions of three distinctive appendages. LR recognized Greebles he had just seen 31 percent of the time, improving little after several one-hour, weekly training sessions. Four healthy volunteers struggled at discerning Greebles at first but recognized most of them after training.
Bukach opposes an influential view that the brain evolved systems for dealing with key types of knowledge, including face recognition (SN: 7/7/01, p. 10). A proponent of that view, psychologist Bradley Duchaine of Dartmouth College, previously reported that a prosopagnosia patient named Edward — who cited lifelong problems recognizing faces — learned to discriminate Greebles but not human faces.
If face recognition depends on a general capacity for learning to recognize multi-part objects, Duchaine holds, healthy volunteers should recognize novel Greebles as poorly as prosopagnosia patients do at first but perform better than patients after seeing lots of Greebles. LR’s Greeble difficulties exceeded those of healthy volunteers from the start, a sign of fundamental object-recognition problems that make the results hard to interpret, Duchaine contends. “These new results don’t help us understand mechanisms used for face processing,” he says.
LR’s poor Greeble-detection accuracy before and after training indicates that he focused on only one Greeble appendage when trying to tell the funny-looking objects apart, Bukach responds.
Support for the idea that brains use a general mechanism to recognize complex objects comes from deaf people who communicate with American Sign Language. Just as upside-down faces look weird and often unrecognizable to healthy volunteers, so do upside-down signs shown to fluent ASL users, say psychologists David Corina of the University of California, Davis, and Michael Grosvald of the University of California, Irvine.
Because healthy individuals perceive faces as whole entities, topsy-turvy faces look bizarre, Corina says. Likewise, ASL users learn to see signs as integrated sets of movements that look peculiar when inverted, the researchers propose in a paper published online December 6 in Cognition.
Many researchers assume that people understand sign language by breaking each sign down into hand shapes, arm movements and other elements.
Corina and Grosvald also find that deaf ASL users are faster than hearing nonsigners at recognizing videos of head scratching and other common grooming actions. Sign languages exploit brain areas devoted to detecting human actions in general, they propose.
Psycholinguist Karen Emmorey of San Diego State University calls new evidence that fluent signers perceive signs as whole entities “a key insight.” Further work needs to confirm that learning a sign language modifies action-related brain areas, she adds.

Tuberous sclerosis complex

<a href="http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Tuberous_sclerosis_complex_(TSC)?open">Tuberous sclerosis complex (TSC) - Better Health Channel</a><br/>
Tuberous sclerosis complex is a genetic disorder that affects various parts of the body to varying degrees of severity. Its common characteristic is the formation of tuber-like growths in the brain. The growths can cause seizures, delayed development and autism, however, approximately half of people with TSC are of normal intelligence. There is no cure.

Gene therapy helps counter hemophilia B

A gene therapy based on a cargo-toting virus that gravitates to liver cells might provide hemophilia B patients with long-lasting protection against bleeding, an international team of scientists reports online December 10 in the New England Journal of Medicine.
Hemophilia B is the second-most common form of hemophilia, a hereditary disorder in which blood fails to clot properly. Patients must receive preventive injections of a clotting compound called factor IX to prevent bleeding from cuts, scratches or bruises. In the new study, four of six hemophilia B patients given the gene therapy no longer need the clotting compound.
The work “is truly a landmark study, since it is the first to achieve long-term expression of a blood protein at therapeutically relevant levels,” physician Katherine Ponder of Washington University in St. Louis, who wasn’t part of the study team, wrote in the same issue of the journal. The findings were also presented December 11 in San Diego at a meeting of the American Society of Hematology.
British researchers treated six men ages 27 to 64 with the gene therapy, an innocuous virus coupled with components that induce liver cells to make factor IX. Before the study, the men had been getting intravenous infusions of factor IX two to three times a week, says study coauthor Andrew Davidoff, a surgeon at St. Jude Children’s Research Hospital in Memphis, Tenn., where the gene therapy was designed.
Each patient received a single infusion of the therapy, called serotype-8-pseudotyped, self-complementary adenovirus-associated virus vector. Scientists have now monitored the men for nine to 20 months.
Four patients who received medium or high doses of the therapy have made enough factor IX themselves to cease getting the preventive infusions of it. Two patients who were given low doses of the gene therapy are making less. While they still need factor IX infusions, they have cut back to one every 10 to 14 days, Davidoff says.
The virus used as the delivery vehicle, known as AAV-8, was chosen in part because it is unlikely that many people receiving it would have been exposed to it and already made antibodies against it, Davidoff says. The virus also targets liver cells, which naturally make factor IX. And although AAV-8 enters a cell it doesn’t integrate with material in the nucleus, greatly reducing the risk that the therapy would interfere with normal cell function.
Because of these attributes, “there’s a modest level of excitement” about this approach, says hematologist W. Keith Hoots of the National Heart, Lung, and Blood Institute in Bethesda, Md., which funded the study in part. The treatment cannot be repeated in a patient, however, because the immune system would recognize AAV-8 the second time around. Even so, the approach has promise because there are dozens of other AAVs that are still untapped, Hoots says.
Two of the patients were given a brief course of steroid drugs when they showed signs of liver inflammation, but no other side effects emerged. Earlier tests in large animals had shown that this therapy could last 10 years or longer. Further testing in people is planned, Davidoff says.

Eggs have own biological clock Aging mechanisms in worms’ reproductive cells differ compared with rest of body

DENVER — Egg cells age differently than cells in the rest of the body, a new study shows.

The finding, from experiments with roundworms presented December 5 at the annual meeting of the American Society for Cell Biology, might one day lead to ways to predict how long women will stay fertile or even to extend a woman’s fertile years.

Princeton University biologist Coleen Murphy and her colleagues study aging in the roundworm, Caenorhabditis elegans. The worms typically live for about 21 days, but fertility drops off sharply after about a week and the worms can no longer reproduce after they are about 9 days old. Even though 9-day-old worms still have plenty of eggs left, the egg cells, also called oocytes, are of such poor quality they can’t produce embryos.

Women experience a similar sharp decline in fertility starting in their late 30s. This drop-off in reproductive capability is one of the earliest signs of aging.

In earlier work, Murphy and colleagues discovered that certain mutations in biological processes regulated by insulin prolonged worms’ lives and gave them about three extra fertile days. Mutations in a different biological process, controlled by a protein called TGF-beta, extended fertility but not life span.

In the new study, the researchers examined which genes are turned on or off to prolong life and fertility in the oocytes and other body cells of the long-lived worms.

“We were really surprised to find this was a completely different mechanism” controlling aging in eggs compared with other body cells, Murphy said at the cell biology meeting. “In fact, there was almost no overlap between the genes involved in the long life of worms and those that extend fertility in the oocytes.”

Body, or somatic, cells are known to turn on stress-management genes to protect proteins and change metabolism as they age. But oocytes don’t bother with guarding proteins, Murphy and her colleagues found. Instead, eggs ramp up production of factors that protect them from or repair DNA damage and make more of proteins that help egg cells divvy up their chromosomes correctly, the researchers reported.

Because the entire job of an egg is to provide genetic information used to build a new generation, it is perhaps not so surprising that eggs devote resources to making sure the DNA stays healthy and chromosomes and are allocated properly, said Craig Blackstone, a physician and researcher at the National Institute of Neurological Disorders and Stroke in Bethesda, Md. “It makes sense that this would happen, but it hadn’t been shown before,” he said. “It’s clever of her to study this.”

Cilia control eating signal Little hairlike appendages in brain cells control weight by sequestering an appetite hormone

A primary cilium (red) protrudes from a neuron (green). Most normal cells in healthy people have primary cilia. New research shows that the hairlike cilia help suppress appetite.

DENVER — The action of tiny hair-like appendages on cells can mean the difference between fat and thin. Now scientists have a better idea of how the little hairs, called primary cilia, control appetite.

Primary cilia — single, hairlike projections that all cells in vertebrates usually have — seem to sequester a protein that senses and responds to an appetite-stimulating hormone, Nicolas Berbari of the University of Alabama at Birmingham reported December 6 at the annual meeting of the American Society for Cell Biology. In people and mice that lack primary cilia, the appetite stimulant works overtime, leading to overeating and obesity, Berbari said.

These findings may lead to new ways to control appetite and prevent or reverse obesity.

And the study may help scientists better understand the process of eating, said Kirk Mykytyn, a cell biologist at Ohio State University in Columbus. “This work is important because it’s more thoroughly clarifying the molecular mechanism involved in obesity associated with the loss of cilia,” he said.

A mouse that lacks primary cilia in its cells becomes obese (right) compared with a normal mouse (left).

People with Bardet-Biedl syndrome have defects in genes responsible for building primary cilia. A prominent consequence of the disease is obesity. Working with mice that also lack primary cilia due to defects in the same genes, Berbari and his colleagues tried to figure out exactly how the cellular appendages are involved in appetite.

Previous research had suggested that primary cilia work like tiny antennae, helping nerve cells in an eating-control center of the brain to sense an appetite-dampening hormone called leptin. The theory was that taking away the cilia also removed leptin’s ability to put the brakes on eating.

But Berbari and colleagues found that mice lacking cilia still respond to leptin as an appetite suppressant, suggesting that sensing the hormone is not the problem.

“The original work was barking up what was the most obvious tree, but turned out to be the wrong tree,” Berbari said.

Instead, the researchers discovered that a protein called MCHR1, which senses an appetite stimulant called melanin-concentrating hormone, is normally found in primary cilia. Concentrating the sensor protein in the cilia may keep the protein from inappropriately triggering eating.

Berbari has preliminary evidence that his hypothesis may be correct. He fed peanut butter pellets containing a drug that inactivates MCHR1 to mice with intact cilia and to mice that have no cilia. The mice with intact cilia maintained their regular weight despite having unlimited access to food. Mice lacking cilia lost weight when given the drug, suggesting that turning off MCHR1’s ability to stimulate appetite corrects the appetite-control problems caused by missing cilia.

The researchers still don’t know exactly how MCHR1 activity stimulates appetite or how the cilia keep the sensor in check.

Biology’s big bang had a long fuse

A new effort to date the early history of modern animals finds a lot of evolutionary dawdling.

The last common ancestor of all living animals probably arose nearly 800 million years ago, a multidisciplinary research team reports in the Nov. 25 Science. From that common ancestry, various animal lineages diverged and evolved on their own paths. Yet the major animal groups living today didn’t arise until roughly 200 million years later, in an exuberant burst of forms preserved in fossils during what’s called the Cambrian explosion.

“There’s a deeper history that’s been missing from the fossil record,” says study coauthor Kevin Peterson of Dartmouth College. He and his colleagues have been pushing back that date for a last common ancestor, and now, he reports, the analysis has the broadest reach yet. “We show that animals evolved quite a bit before they show up in the fossil record.”

This work updates the notion of a long evolutionary lag, when much of the basic biological toolkit was already in place for a later surge of new body forms, says paleontologist and study coauthor Douglas Erwin of the National Museum of Natural History in Washington, D.C., and the Santa Fe Institute.

“The Cambrian explosion is like the industrial revolution,” Erwin says. Inventions that would later be important for a major shift in technology — or, in this case, genetic novelties important for evolution — appeared long before they played a role in widespread changes that had a major impact on life.

For understanding animal origins, the new paper “is really worthwhile as it stands back and tries to make sense of the whole picture,” says James Valentine of the University of California, Berkeley, who studies animal evolution.

Just what happened with animals during that Cambrian explosion remains one of the more celebrated puzzles in the history of life. Charles Darwin mused over how diverse animal forms appear suddenly (geologically speaking) without much in the way of precursors. Darwin’s answer, as Erwin puts it, was that paleontologists just needed to look harder.

More than a century of hard looking has turned up some signs, fossils as well as traces of biological chemistry, of enigmatic animal life before the Cambrian period began about 541 million years ago. Yet the relationship to modern animals often is not clear. Theories themselves have exuberantly exploded in number and form.

For the new study, Erwin and the rock side of the team updated the scorecard on the earliest fossil occurrences with recent fossil finds and the current thinking on dates of rock layers. On the molecular side, Peterson and his colleagues expanded the family tree to cover seven genes from 118 different kinds of living animals. Fossils provided dates for a scattering of branch points in the tree, allowing researchers to estimate time from rates of change.

Combining fossil dates and the DNA analysis, Peterson, Erwin and their colleagues conclude that the basic genetic tools for fancy animal bodies arose long before a surge of evolutionary innovation around the Cambrian period gave rise to modern animal forms.

During that 200 million-year-plus run-up to the Cambrian explosion, animals did evolve more diverse cell chemistry to regulate basic genes, and the environment changed. But Peterson attributes much of the Cambrian rise of modern animal forms to changes in the interactions among organisms themselves. “You see an evolutionary explosion, if you will, because animals are eating other animals for the first time,” he says.

The paper’s discussion of toolkit genes and the diverse cell chemistry that arose to orchestrate them overlooks some possibly important complexity, objects molecular biologist Mark Q. Martindale of the University of Hawaii’s Kewalo Marine Laboratory. At least 30 percent of the genes of animals analyzed so far have no recognizable similar gene in another species. “These so-called orphan genes could have a tremendous amount to do with diversification of animal lineages, but people just pooh-pooh these differences and focus on the things that are shared,” he says.

Some of the relationships in the evolutionary tree “have been and will continue to be controversial,” says evolutionary biologist Casey Dunn of Brown University in Providence, R.I., who wasn’t involved in the research. “But the point of the tree isn’t the relationships themselves — it is some key dates.”

Neuron transplant in damaged brain fixes obesity

A neuron transplant has rewired damaged brain areas in mice, raising hopes that similar transplants might one day help to treat spinal-cord injuries, Parkinson's disease and other brain conditions.

Jeffrey Macklis at Harvard University and his colleagues took healthy neurons from mouse embryos that had been labelled with a green fluorescent protein. They used them to repair a brain circuit involved in the regulation of food intake and body weight in response to a hormone called leptin in mutant mice born with damage to that area, which become dangerously overweight as a result.

The fluorescent neurons survived the transplant, integrated into the brain circuit, and differentiated into mature neurons that could communicate with existing neurons and respond to leptin, insulin and glucose – suggesting that they had repaired the damaged circuit. The treated obese mice went on to weigh 30 per cent less than their untreated counterparts.

"These embryonic neurons were wired in with less precision than one might think, but that didn't seem to matter," says Jeffrey Flier, dean of Harvard Medical School, who was part of the team. "They are like antennas that were immediately able to pick up the leptin signal."

The next question is whether transplanted neurons could rewire other complex brain circuits involved in diseases or brain injury, which might be more dependent on signals coming from other neurons, rather than signals coming from the blood. "In these cases, can we rebuild circuitry in the mammalian brain? I suspect that we can," says Macklis.

Journal reference: Science, DOI: 10.1126/science.1209870

Exceptional memory linked to bulked-up parts of brain.....People who can recall life’s events in detail have enlarged region linked to obsessive-compulsive disorder

WASHINGTON — Like the fictional detective Carrie Wells on the TV show Unforgettable, some real-life people can remember every day of their lives in detail. Those superrememberers have more bulk in certain parts of their brains, possibly explaining the remarkable ability to recall minutiae from decades ago, researchers said November 13 at the annual meeting of the Society for Neuroscience.

One brain region involved in such incredible recall has been implicated in obsessive-compulsive disorder, hinting that OCD and superior memory might have a common architecture in the brain.

Scientists have long studied people with memory deficits, but there haven’t been many studies on people with exceptional memories. “Looking at memory from a deficit gave us a lot of insight into memory,” said study coauthor Aurora LePort of the University of California, Irvine. “Looking at memory from a superior perspective gives us a new tool. It may just broaden our knowledge and ability to know what’s going on.”

In 2006, UC Irvine neuroscientist Larry Cahill and collaborators published a report on a woman who could remember detailed accounts of her life. Cahill and colleagues then began hearing from many people who claimed to have extraordinary memories. After sifting through and eliminating the impostors, the team was left with 11 people who scored off the charts for autobiographical memory. These people could effortlessly remember, for instance, what they were doing on November 2, 1989, and could also tell you that it was a Thursday. “They’re not going home and saying ‘OK, let me write down what I did today and memorize it,’ ” LePort said.

Using brain scans, researchers found that people with supermemories had larger brain regions associated with memory, including the left temporoparietal junction and the left posterior insula. What’s more, a brain structure called the lentiform nucleus, a cone-shaped mass in the core of the brain, was bigger in people with exceptional memories. This brain area has been linked to obsessive-compulsive disorder.

The subjects haven’t been clinically evaluated for OCD, but LePort says that there are some similarities. “The ability to organize their memories by dates seems to relieve anxiety,” she says.

Researchers don’t know how the brain accomplishes this feat. These people could encode information more effectively, or have a better system of retrieving it, or both. “Right now, we can see the brain areas that are coming out and speculate about what’s going on,” LePort says.

The team hopes to do further studies examining what’s happening in the brain as these people remember.

One tantalizing lead suggests that genetics might be involved. Though no genetic tests have been performed, some of the volunteers have reported that family members share extraordinary powers of recall, LePort says.

The result “certainly pushes us beyond the boundaries of what we might normally think,” said memory expert Howard Eichenbaum of Boston University. “It violates a standard principle that most of us have, which is that normal memory is pretty damn optimized.”

The volunteers are now keeping detailed diaries, so that the scientists can test whether particular kinds of memories are better suited to recollection. People might be better at remembering emotional memories, for instance.

Radiation sickness treatment shows promise

A drug composed of an ordinary antibiotic combined with a microbe-fighting compound may be enough to protect thousands of people from the ravages of radiation sickness in the aftermath of a major nuclear accident or attack, experiments with mice suggest.

Researchers exposed mice to a heavy dose of radiation and 24 hours later gave some of them injections of an antibiotic and a protein that’s made naturally by the immune system. Thirty days later, most mice that received no treatment were dead, whereas nearly 80 percent of mice that received the treatment still appeared healthy, a team reports in the Nov. 23 Science Translational Medicine.

Follow-up studies are still needed before the combo can be used to treat people, but versions of the antibiotic and the protein have already been used in humans, so the new approach looks promising. It might even be used as a preemptive measure for first responders.

“This could potentially be very useful,” says radiobiologist Gayle Woloschak of Northwestern University in Chicago, who was not involved with the study.

Radiation exposure of levels up to 10 gray (the mice received 7 gray, about 45,000 times the dose of a chest X-ray) would usually require a bone marrow transplant and probably treatment with a compound that stimulates bone marrow growth. “During a mass casualty event you’re not going to be able to do bone marrow transplants,” says Woloschak. And while questions remain about long-term survival of mice given the new treatment, “it’s quite exciting,” she says.

When the body is exposed to intense levels of radiation, bone marrow is one of the first things to shut down. Bone marrow is where most white blood cells arise, so the body’s immune system can’t fight infection properly when compromised. And a working, fighting immune system is just what’s needed after exposure to radiation. Radiation can cause bacteria that are usually confined to the gut to leak into the blood, causing blood pressure to spike, fever, abnormal blood clotting and even organ failure.

The new treatment goes after these marauding bacteria. The fluoroquinolone antibiotic, a mouse version of Cipro, aims to kill any bacteria it comes across. And the protein, called BPI, mops up and latches onto bacterial endotoxin, a nasty molecule on the coats of many bacteria.

“We think we have a combination here that is multifunctional,” says stem cell transplant doctor Eva Guinan of the Dana-Farber Cancer Institute and Harvard Medical School, who led the work with Ofer Levy, also of Harvard and Children’s Hospital Boston. “We still have a lot more to explore in detail, but the results are really encouraging.”

Immune cells function beyond battle

The immune system isn’t just about defense; it works in partnership with other cells to regulate body functions.

A new study shows that immune cells called B cells carry on a three-way conversation with gut microbes and cells lining the intestines to control fat uptake. The finding, reported online November 20 in Nature Medicine, challenges conventional wisdom that the immune system’s only job is to fight bad guys. The new knowledge also may shed some light on why people with HIV and other chronic infections become malnourished, and it might suggest ways to treat malnutrition.

The study grew out of a comment that systems biologist Andrey Morgun, now a researcher at Oregon State University in Corvallis, once heard at an immunology conference. “A speaker mentioned that the immune system isn’t just a war machine,” Morgun says.

For Morgun and his wife and research partner, Natalia Shulzhenko, also now at Oregon State, the idea was intriguing. Both had training in clinical immunology, where the immune system is thought of as a protective mechanism, not something involved in daily life outside the disease process, Morgun says. While working at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., the couple convinced their research adviser there, immunologist Polly Matzinger, that the idea was worth testing.

Other researchers have noted that mice lacking antibody-producing B cells have abnormal digestive systems. In particular, the mice have difficulty absorbing fat from the diet and become malnourished. In the new study, Morgun and Shulzhenko discovered that B cells’ ability to make a type of antibody called immunoglobulin A, or IgA, is important for fat uptake. IgA is secreted in tears, saliva, milk and mucus, and helps cells lining the intestine maintain a healthy relationship with friendly bacteria.

The researchers reared mice without B cells in a sterile environment so the mice also lacked gut bacteria. The mice didn’t have a problem absorbing fat, despite their lack of immune cells. That told the researchers that intestinal microbes are involved in the process, but exactly what the microbes do to change fat uptake is still unknown.

A closer look at cells lining the intestine, called epithelial cells, showed that those cells have two jobs — self-defense and metabolism, including absorbing fat. Somehow, IgA antibodies produced by B cells trigger gut microbes to send a signal to the epithelial cells. Those cells then determine whether to devote more resources to protecting themselves, by making antimicrobial compounds, or to carry on absorbing fat and other nutrients from food.

Andrew Gewirtz, an immunologist at Georgia State University in Atlanta, draws a comparison between this newly identified role for the immune system and community services such as crowd control performed by the police: “The police don’t just show up when there’s a crime.”

Intestinal epithelial cells taken from people who have immune defects, such as those caused by HIV or a genetic condition called common variable immunodeficiency, behave similarly to those from mice lacking B cells, the researchers found. That raises the possibility that those people might be treated for malnutrition by giving them IgA antibodies.