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Archive - Dec 20, 2014


New Technique Further Probes Integrin-Independent Movement of Neutrophils

Neutrophils (image), a type of white blood cell, are the immune system's all-terrain vehicles. The cells are recruited to fight infections or injury in any tissue or organ in the body despite differences in the cellular and biochemical composition. Researchers from Brown University's School of Engineering and the Department of Surgery in Brown’s Warren Alpert Medical School collaborated to devise a new technique for understanding how neutrophils move in these confined spaces. The technique involves two hydrogel sacks sandwiched together with a miniscule space in between. Neutrophils can be placed in that space, mimicking the confinement they experience within tissue. Time-lapse cameras can then measure how fast the cells move, and traction force microscopes can determine the forces the cells exert on the surrounding gel. In a paper published online on December 18, 2014 in the Journal of Biological Chemistry, the researchers used the device to reveal new details about the motion of neutrophils. Bodily tissues are highly confined, densely packed, three-dimensional spaces that can vary widely in physical shape and elasticity. The researchers showed that neutrophils are sensitive to the physical aspects of their environment: They behave differently on flat surfaces than in confined three-dimensional space. Ultimately, the team hopes the system can be useful in screening drugs aimed at optimizing neutrophils to fight infection in specific tissue types. Traditionally, research on neutrophil motion in the lab is often done on two-dimensional, inflexible surfaces composed of plastic or glass. Those studies showed that neutrophils move using arm-like appendages called integrins. The cell extends the integrins, which grab onto to flat surfaces like tiny grappling hooks. By reeling those integrins back in, the cell is able to crawl along.

Study Suggests Mother’s Use of Certain SSRI Antidepressants During Third Trimester May Have Positive Effects in Adulthood for Developing Fetus

About 15 percent of women in the United States suffer from anxiety disorders and depression during their pregnancies, and many are prescribed antidepressants. However, little is known about how early exposure to these medications might affect their offspring as they mature into adults. The answer to that question is vital, as 5 percent of all babies born in the U.S. - more than 200,000 a year - are exposed to antidepressants during gestation via transmission from their mothers. Now, a UCLA team has studied early developmental exposure to two different antidepressants, Prozac and Lexapro, in a mouse model that mimics human third trimester medication exposure. They found that, although these serotonin-selective reuptake inhibiting antidepressants (SSRIs) were thought to work the same way, they did not produce the same long-term changes in anxiety behavior in the adult mice. The mice exposed to Lexapro had permanent changes in serotonin neurotransmission and were less anxious as adults than the mice exposed to Prozac, said study senior author Dr. Anne M. Andrews, professor of psychiatry and chemistry and biochemistry and the Richard Metzner Endowed Chair in Clinical Neuropharmacology at the Semel Institute for Neuroscience & Human Behavior and California NanoSystems Institute. "This was quite surprising, since these medications belong to the same drug class and are believed to work by the same mechanism. The implications of these findings are that with additional investigation, it may be possible to identify specific antidepressants that are safer for pregnant women," Dr. Andrews said.

Cell Division and Flow Dynamics in Blood Vessel with a Clot

A layer of cells called endothelial cells lines the interior of blood vessels. When blood flows through the vessels, such the endothelial cells only divide to replace dead cells. However, if there is a blood clot preventing blood from flowing across the endothelial cells, they begin to divide more actively. New research from the Niels Bohr Institute in Denmark demonstrates that cell division is a very orderly process. The new cells move away from each other and create a dynamic movement with eddies in a large area. This presumably helps to widen the vessel around the blockage. The results were published online on December 8, 2014 in Nature Communications. Living tissue is unlike other materials in that it is comprised of cells with a metabolism and the ability to divide and renew themselves. Normally, in an adult body, cells only divide to form new cells to replace old, dead cells. But if there are abnormal conditions, the body can begin to form extraordinary new cells. "If, for example, there is a blood clot blocking the flow of blood across the innermost layer of the endothelial cells, they begin to actively divide. But what happens in the tissue? How do the newly formed cells move in relation to each other - and which mechanisms control their movements? This is what we wanted to investigate," explains biophysicist Dr. Lene Oddershede, head of the research group Optical Tweezers at the Niels Bohr Institute at the University of Copenhagen. The researchers investigated the dynamics of new cell formation in a layer of endothelial cells where there was no liquid flowing over them. The investigations took place in a laboratory system that mimicked the conditions in an endothelial cell layer where a blood clot blocks the blood flow.

Ibuprofen May Extend Heathy Lifespan

Ibuprofen, a common over-the-counter drug used to relieve pain and fever, could hold the keys to a longer healthier life, according to a study by researchers at the Buck Institute for Research on Aging. Publishing online on December 18, 2014 in the open-access journal PLOS Genetics, collaborating scientists showed that regular doses of ibuprofen extended the lifespan of yeast, worms, and fruit flies. "There is a lot to be excited about," said Brian Kennedy, Ph.D., CEO of the Buck Institute, who said treatments, given at doses comparable to those used in humans, extended lifespan an average of 15 percent in the model organisms. "Not only did all the species live longer, but the treated flies and worms appeared healthier," he said. "The research shows that ibuprofen impacts a process not yet implicated in aging, giving us a new way to study and understand the aging process." But most importantly, Dr. Kennedy said the study opens the door for a new exploration of so-called "anti-aging medicines." "Ibuprofen is a relatively safe drug, found in most people's medicine cabinets," he said. "There is every reason to believe there are other existing treatments that can impact healthspan and we need to be studying them." The work was the result of a collaboration between the Buck Institute and Texas A & M's Agrilife program. Michael Polymenis, Ph.D., an AgriLife Research biochemist started the work in baker's yeast and then moved it into worms and flies. Dr. Polymenis, who is also a professor in the biochemistry and biophysics department at Texas A&M University, said the three-year project showed that ibuprofen interferes with the ability of yeast cells to pick up tryptophan, an amino acid found in every cell of every organism.

Breeding Songbirds Sense Coming Tornadic Storm and Take Flight

Golden-winged warblers apparently knew in advance that a storm that would spawn 84 confirmed tornadoes and kill at least 35 people last spring was coming, according to a report published online on December 18, 2014 in Current Biology. The birds left the scene well before devastating supercell storms blew in. The discovery was made quite by accident while researchers were testing whether the warblers, which weigh "less than two nickels," could carry geolocators on their backs. It turns out they can, and much more. With a big storm brewing, the birds took off from their breeding ground in the Cumberland Mountains of eastern Tennessee, where they had only just arrived, for an unplanned migratory event. All told, the warblers travelled 1,500 kilometers in 5 days to avoid the historic tornado-producing storms. "The most curious finding is that the birds left long before the storm arrived," says Dr. Henry Streby of the University of California, Berkeley. "At the same time that meteorologists on The Weather Channel were telling us this storm was headed in our direction, the birds were apparently already packing their bags and evacuating the area. The birds fled from their breeding territories more than 24 hours before the arrival of the storm, Dr. Streby and his colleagues report. The researchers suspect that the birds did it by listening to infrasound associated with the severe weather, at a level well below the range of human hearing. "Meteorologists and physicists have known for decades that tornadic storms make very strong infrasound that can travel thousands of kilometers from the storm," Dr. Streby explains. While the birds might pick up on some other cue, he adds, the infrasound from severe storms travels at exactly the same frequency the birds are most sensitive to hearing.

Nobelist Leads Effort Revealing Beneficial Function of Endogenous Retroviruses in Immune Response

Retroviruses are best known for causing contagious scourges such as AIDS, or more sporadically, cancer. But researchers at the University of Texas (UT) Southwestern Medical Center and Karolinska Institutet in Stockholm, Sweden, have found that endogenous retroviruses (ERV) also play a critical role in the body’s immune defense against common bacterial and viral pathogens. “Most scientists have become used to the view that retroviruses are generally harmful,” said Nobel Laureate Dr. Bruce Beutler, Professor and Director of UT Southwestern’s Center for the Genetics of Host Defense. “We have found that ERV fulfill at least one beneficial function critical to producing protective antibodies.” Retroviruses are able to insert into the genomic DNA of cells they infect, including germ cells. In this way, and by a process called retrotransposition, they have become a major part of the genome of each person. About 45 percent of a person’s DNA is of retroviral origin, and some of the better preserved copies are termed “endogenous retroviruses” (ERV). Writing in the journal Science in an article published online on December 19, 2014, the researchers found that when B cells are activated by large polymeric antigens such as polysaccharides of bacteria, they rapidly produce protective antibodies in what is termed the Type II T-independent antibody response. This response, central to the body’s defense against common bacterial and viral pathogens, is dependent on ERV. Within activated B cells, the ERV are driven to express RNA copies of themselves, which in turn are copied into DNA by an enzyme called reverse transcriptase. The RNA copies of ERV are detected by a protein called RIG-I, and the DNA copies are detected by another protein called cGAS.