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.