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.

CSI: Fleming reveals true identity of penicillin

The discovery of penicillin kick-started the antibiotic revolution. But a forensic-style investigation of the lab in which Alexander Fleming discovered the world-famous fungus suggests the Nobel prizewinner's find has been misunderstood for 80 years.

Fleming returned from a family vacation in August 1928 to find that a fungus had contaminated the samples of bacteria he had left in his lab, and that it was evidently a bacteria killer. Figuring that the fungus was secreting something that could be useful in treating human bacterial infections, Fleming sent his samples off to researchers in the US. They identified the fungus as Penicillium chrysogenum and looked for similar strains to find the one that would yield the largest antibiotic secretions. The hero strain came from a mouldy cantaloupe melon, and was tweaked to produce the penicillin used today.

Daniel Henk, Matthew Fisher and their colleagues at Imperial College London took a closer look at the fungal samples still preserved in Fleming's lab in London, now a museum. They even swabbed his old notebook. They then compared them with fungal samples collected by 300 volunteers around the world.

Henk and Fisher's team investigated the genetics of all the samples by studying certain easily recognised chunks of the genome: these don't tend to code for specific proteins, but are characterised by particular repeating patterns of short DNA sequences.
Not one, not two, not three

In the samples that would originally have been classed as P. chrysogenum, the team identified four distinct species – the original species and three brand new ones. "There is so much diversity within what we thought was a single species," says Henk.

Fleming's fungus – one of the previously unknown species – appears to be the most common of the four. "It's likely amongst the most common multicellular organisms on the planet," says Fisher.

The investigation also revealed that the fungus has two sexes and that its genome carries hallmarks of recombination, suggesting that the organism has been having sex even though it has not be seen doing so. "They're having what's known as cryptic sex – sneaky sex," says Fisher. "We can't make it happen in the lab – we can only see evidence that it has happened."

The team hope their work will help others find new antibiotics. "When the US Department of Agriculture was looking for fungi with antimicrobial properties, it was sampling randomly," says Henk. He says the new analysis suggests that doing so will simply throw up Fleming's species most of the time. In future it will be possible to use the DNA sequences to confirm that wild samples carry something truly new and worth investigating.

Henk and Fisher hope Fleming's species will be named Penicillium flemingii, but before it is, they'll have to convince the rest of the community that the fungus truly is new. Jens Frisvad at the Technical University of Denmark in Kongens Lyngby has some doubts. Based on his research, he suspects that the species might in fact have already been named P. rubens – five years before Fleming's auspicious holiday.

Journal reference: Molecular Ecology, DOI: 10.1111/j.1365-294X.2011.05244.x

Babies may benefit from moms’ lasting melancholy

A double dose of mom’s depression may do a baby good.

Infants generally thrive physically and mentally if their mothers’ emotional condition, whether healthy or depressed, remains stable before and after birth, say psychologist Curt Sandman of the University of California, Irvine, and his colleagues. Kids whose mothers stayed depressed from the fourth month of pregnancy on displayed first-year mental and physical development comparable to that of youngsters whose mothers stayed emotionally healthy for the same stretch, Sandman’s team will report in Psychological Science.

In contrast, babies’ first-year physical and mental development lagged if their mothers’ emotional state during pregnancy changed after giving birth. That pattern held whether depression during pregnancy resolved after giving birth or depression first appeared after delivering a child.

“A human fetus that prepares for inadequate care after birth based on biological messages from a depressed mother will have a survival advantage,” Sandman says. A fetus that gets thrown a caretaking curve upon leaving the womb — whether biologically primed to expect sufficient or deficient treatment — tends to struggle developmentally, at least for the first year, he suggests.

Related investigations have found that people whose mothers nearly starved during pregnancy eventually developed higher rates of diabetes and other metabolic disorders if they received enough food after birth, but not if they too got inadequate nutrition. Until now, no one has reported a health advantage for babies exposed to maternal depression before and after birth.

University of California, Davis, psychologist Jay Belsky calls the new findings “surprising, if not astonishing.” He awaits confirmation of Sandman’s results by other researchers before concluding that babies benefit from a womb with a view of upcoming hardships.

Babies may respond to maternal depression differently based on their genetic makeup, Belsky suggests (SN Online: 4/6/11). In the March 15 Biological Psychiatry, he and his colleagues reported that infants carrying two copies of a particular serotonin transporter gene variant frequently became scared and agitated if their mothers experienced intense anxiety during pregnancy.

For the new study, Sandman’s team studied 221 women at five points during their pregnancies. The women and their babies were then assessed at three-month intervals for one year. Experimenters used play tasks to measure infants’ physical and mental development.

Kids whose mothers displayed consistent emotional health or depression scored higher than those exposed to inconsistent maternal moods on physical tasks at age three months, on both physical and mental tasks at age six months, and on mental tasks at age 1. The researchers plan to see if that mental advantage lasts longer or if maternal depression eventually undermines mental development.

Results so far underscore the need to rapidly treat pregnant women’s depression so that their children experience positive maternal health before and after birth, Sandman suggests. But antidepressant medication presents health risks for fetuses, and the new findings indicate that women who attain emotional health shortly after giving birth create conditions that slow their babies’ development.

“What is best for the mother may not be best for the fetus or infant,” Sandman says.

Plastic isn’t over yet Tough new form could extend applications of the 20th century material

A tough new plastic that’s easily healed if scratched or damaged could find use in products prone to getting beat up, such as paints or parts for cars and sailboats. What’s more, it can be ground up and recycled into completely new products like plastic molding for electronic devices or optical lenses.

By adding some extra ingredients to traditional epoxy resins and a dash of a zinc compound to help move the chemistry along, researchers made a material whose chemical bonds continually break and reform. At really high temperatures, the bonding switcheroo makes the material malleable, but the reactions are so sluggish at ordinary temperatures that the material’s shape is essentially fixed, resisting deformation, the researchers report in the Nov. 18 Science.

“They developed a unique and very powerful approach that will have a great deal of applications,” says polymer chemist Christopher Bowman of the University of Colorado at Boulder. “It’s quite exciting.”

Most plastics that are super durable — such as those used for kitchenware and some car parts — are molded into shape and then “cured,” turning them into one giant cross-linked molecule. The molecules of softer plastics, like those used in soda bottles, typically aren’t held together with these strong bonds and can be melted and reshaped. To get an in-between material, scientists led by Ludwik Leibler of France’s National Center for Scientific Research in Paris made a regular epoxy resin, the sort available at your local hardware store. Then the researchers added acids to the mix and used a zinc-based compound to help them interact. .

The resulting material consists of a network of molecules, each holding hands with four others. These molecules are constantly switching up who they are holding hands with, but the number of bonded hands in the material always stays the same. When heated, this molecular hand swap speeds up; the number of switches that would take 100 years to complete at room temperature happen in a few seconds at 200 degrees Celsius, says Leibler.

The molecular flexibility means that at high temperatures the material can easily be remolded. Full-scale injection molding works, but so does shaping or repairing it with a hand-held hot air blower. And depending on the amount of hardeners and other ingredients, the chemistry can yield very hard plastics or ones with a more rubbery feel.

“You can do anything you want,” Leibler says. “You can work it like wood, you can make big parts if you want, and the beauty of it is all of the ingredients are things that are already used in composites.”

Busting blood clots with a nanoparticle

Nanosized gobs containing a blood clot–dissolving drug can seek out trouble spots in the body and break down blockages responsible for heart attacks, Japanese researchers reported November 14 at a meeting of the American Heart Association. The microscopic packaging seems to improve the drug’s potency and might limit its main drawback — a risk of internal bleeding — by focusing its effect at the clot.

Although the technology has been tested only in pigs, some doctors find the early results intriguing. “This could be a tremendous step forward,” said Roger Blumenthal, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore. If it tests well in people, he said, this controllable form of the clot-busting drug, called tPA, might be a boon for heart attack patients in remote areas that lack hospitals equipped to deliver the highest standard of care for heart attacks.

About half of people for whom heart attacks are fatal die before reaching a hospital and getting angioplasty, in which doctors thread a balloon-tipped catheter up to the heart to prop open blocked coronary arteries with mesh cylinders called stents. With every minute that passes after a heart attack begins, part of the heart muscle is damaged by lack of blood. “It’s one thing to have a heart attack in a metropolitan area,” Blumenthal said. “But sometimes a catheterization lab may be four hours away.” A safer form of tPA, a drug that has largely gone out of use for heart attacks in the United States because of its internal bleeding risk, could play a role In such rural areas, he said.

The Japanese team, led by cardiologist Yoshihiko Saito of Nara Medical University in Kashihara, tested a form of tPA made safer by packaging it in a coating of gelatin-based nanoparticles that prevent tPA from releasing in the blood stream.

Tests in mice showed that the nanoparticles were three times more likely than regular tPA to attach to clots, because the tiny blobs stick to a common clotting compound in the body that standard tPA doesn’t bind.

The researchers then injected either the nanoparticle drug or standard tPA into 30 pigs in which the scientists had induced blood clots. Once the nanoparticles had arrived at the clot, the researchers burst the tiny blobs with ultrasound waves and released the tPA cargo at the clot.

After 30 minutes, blood flow through obstructed vessels improved by 90 percent in pigs getting the nanoparticle drug but by only 10 percent in pigs getting standard tPA. There was also less stray tPA in the bloodstream afterward with the nanoparticles.

The new technology might expand the range of people who could administer tPA, said Robert Bonow, a cardiologist at Northwestern University School of Medicine in Chicago. Paramedics typically don’t give tPA in the United States, even to heart attack patients, because of the bleeding risk. “In theory, this would be safer,” he said.

People with pulmonary embolisms might also benefit from the nanotechnology if it succeeds in further tests, said cardiologist Vincent Bufalino of Midwest Heart Specialists in Naperville, Ill., a cardiology practice. In those patients a clot obstructs blood flow to the lungs.

Doctors use tPA for some strokes that arise when a clot jams an artery supplying the brain with blood. But that medical scenario wasn’t tested in this study.

Magic trick reveals unconscious knowledge

Magic tricks prey on people’s subpar powers of perception, but new work finds that the brain has tricks of its own up its sleeve: People notice more than they think.

In the research, presented November 12 at the annual meeting of the Society for Neuroscience, Luis Martinez of CSIC- Miguel Hernandez University in Spain and colleagues amazingly “read minds” with the Princess Card Trick, invented by magician Henry Hardin in 1905. Volunteers mentally chose a playing card from a panel of six cards, which then disappeared. When a second group of cards appeared, the researchers had miraculously figured out which card a person had in mind and removed it. Few people caught the trick: All the cards in the second set were different, not just the card people had chosen.

A few seconds after viewing the two panels of cards, participants were asked which of two new cards was present in the first panel. None of the volunteers could consciously recall which card was present. Despite these avowals of ignorance, when forced to choose, people got the right answer about 80 percent of the time. “People say they don’t know, but they do,” Martinez said. “The information is still there, and we can use it unconsciously if we are forced to.”

To see whether this unconscious knowledge works for objects other than cards, Martinez and his colleagues performed a similar experiment with pictures of men’s faces. A similar kind of visual short-term memory helped people choose which face they had seen before, even when volunteers didn’t perceive that they knew the correct answer.

These unconscious, short-term memories are finicky, Martinez and his colleagues found. If the researchers talked to the volunteers while performing the trick, the ability to identify the card that had been present worsened. (Magicians may deploy a steady stream of patter for this very reason.) And if the researchers revealed the secret of the trick, participants performed no better than chance at identifying the card.

Exceptional memory linked to bulked-up parts of brain

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.