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Archive - 2014

December 29th

Scientific First: Optogenetics Captures Neuronal Transmission in Live Mammalian Brain

Neurons, the cells of the nervous system, communicate by transmitting chemical signals to each other through junctions called synapses. This "synaptic transmission" is critical for the brain and the spinal cord to quickly process the huge amount of incoming stimuli and generate outgoing signals. However, studying synaptic transmission in living animals is very difficult, and researchers have to use artificial conditions that don't capture the real-life environment of neurons. Now, EPFL (Ecole Polytechnique Federale de Lausanne) scientists in Switzerland have observed and measured synaptic transmission in a live animal for the first time, using a new approach that combines genetics with the physics of light. Their breakthrough work was published online on December 24, 2014 in an open-access artic le in Neuron. Drs. Aurélie Pala and Carl Petersen at EPFL's Brain Mind Institute used a novel technique called "optogenetics" that has been making significant inroads in the field of neuroscience in the past ten years. This method uses light to precisely control the activity of specific neurons in living, even moving, animals in real time. Such precision is critical in being able to study the hundreds of different neuron types, and understand higher brain functions such as thought, behavior, language, memory - or even mental disorders. Optogenetics works by inserting the gene of a light-sensitive protein into live neurons, from a single cell to an entire family of cells. The genetically modified neurons then produce the light-sensitive protein, which positions itself on the outside of the cell, on the membrane. There, it acts as an electrical channel - something like a gate. When light is shone on the neuron, the channel opens up and allows electrical ions to flow into the cell, a bit like a battery being charged by a solar cell.

Dominant Ant Genus Evolved Twice—Once in New World, Once in Old World

About one tenth of the world's ants are close relatives; they all belong to just one genus out of 323, called Pheidole. "If you go into any tropical forest and take a stroll, you will step on one of these ants," says Okinawa Institute of Science and Technology Graduate University's Professor Evan Economo. Pheidole fill niches in ecosystems ranging from rainforests to deserts. Yet until now, researchers have never had a global perspective of how the many species of Pheidole evolved and spread across the Earth. Dr. Economo, researchers in the Biodiversity and Biocomplexity Unit, and colleagues at the University of Michigan compared gene sequences from 300 species of Pheidole from around the world. They used these sequences to construct a tree that shows when and where each species evolved into new species. At the same time, in a parallel effort, they scoured the academic literature, museums around the world, and large databases to aggregate data on where all 1,200 or so Pheidole species live on Earth, creating a range map for each species. Their results, published online on November 26, 2014 in an open-access article in the Proceedings of the Royal Society Series B, suggest that Pheidole evolved the same way twice, once to take over the New World, and then again to take over the Old World. Dr. Economo began this project by selecting sample ants to represent each Pheidole species. The team then sequenced the DNA of the sample ants to determine genetic similarities between species, and computationally reconstruct the "family tree" of Pheidole species, providing a history of how they evolved. This may seem like a lot of effort for a group of seemingly inconsequential creatures, but in fact many ecologists use ants to better understand evolution and the terrestrial ecosystems ants inhabit.

December 28th

Scientists Identify Rare Liver Cancer's Genetic Pathway; Asians More Vulnerable and Asian Patients Show Different Mutational Profile

An international research team, including four Simon Fraser University (SFU) scientists, has identified the "mutational landscape" of intrahepatic cholangiocarcinoma (ICC), a rare, highly fatal form of liver cancer that disproportionately affects people in Asian countries. SFU molecular biology and biochemistry professor Dr. Jack (Nansheng) Chen and three of his lab members collaborated with Chinese researchers to identify how these mutations affect genes and signalling pathways that might drive the formation of tumors in ICC. The researchers' findings, which were published online on December 15, 2014 in Nature Communications, could potentially lead to earlier and more accurate diagnosis and increased survival rates for patients with the disease, also known as intrahepatic bile duct cancer. ICC accounts for approximately 10 per cent of primary liver malignancies worldwide, but its incidence and mortality rates have been increasing rapidly in recent years. It currently strikes about one in 100,000 people annually in North America but 96 per 100,000 in Thailand. The prognosis for ICC patients is usually poor, as early tumors are undetectable during routine examinations because the bile ducts are deep inside the body, leading to diagnosis only after symptoms develop and the disease has advanced. There are no effective therapies for ICC and the median survival duration is less than six to nine months after diagnosis, according to a recent study in the Canadian Journal of Gastroenterology. "Our research is by far the most comprehensive sequencing effort to identify mutations associated with ICC and will be an important resource for scientists working to improve understanding and therapy for the disease," says Dr. Chen, who specializes in genomics and bioinformatics.

December 21st

Common TLR5 Polymorphism and Commensal Bacteria Influence Inflammation, Anti-Tumor Immunity, and Outcome for Some Cancer Patients

A common polymorphism - a variation in a person's DNA sequence that is found with regularity in the general population - can lead to a chain of events that dictates how a tumor will progress in certain types of cancer, including a form of breast cancer, as well as ovarian cancer, according to new research from The Wistar Institute in Philadelphia, Pennsylvania, that was published online by the journal Cancer Cell. The research reveals a more explicit role about the symbiotic relationship humans have with the various bacteria that inhabit our body and their role during tumor progression. "Our research indicates that interactions between the helpful bacteria in our bodies and immune cells at places situated away from tumors influence systemic responses in the host that alter how these tumors are able to progress," said José Conejo-Garcia, M.D., Ph.D., Associate Professor and Program Leader in the Tumor Microenvironment and Metastasis Program at The Wistar Institute and lead author of the study. Humans are colonized with trillions of bacteria - known as commensal bacteria because there are benefits to having these bacteria in our bodies - that inhabit the gastrointestinal and respiratory tracts and our skin. These bacteria provide a first line of defense against infection. Recent research has found that interactions between these bacteria and the immune system are critical for providing important defenses against tumors occurring outside of the intestines. In order for the immune system to recognize commensal, as well as microscopic organisms that can cause disease - or pathogens - many of our cells are programmed to recognize pathogen-associated molecular patterns.

New Vaccine Partially Protects Against Prion-Caused Disease in Deer

Researchers at the New York University (NYU) Langone Medical Center and elsewhere say that a vaccination they have developed to fight a brain-based, wasting syndrome among deer and other animals may hold promise on two additional fronts: protecting U.S. livestock from contracting the disease, and preventing similar brain infections in humans. The study, which was published online in Vaccine on December 21, 2014, documents a scientific milestone: the first successful vaccination of deer against chronic wasting disease (CWD), a fatal brain disorder caused by unusual infectious proteins known as prions. Prions propagate by converting otherwise healthy proteins into a disease state. Equally important, the researchers say, this study may hold promise against human diseases suspected to be caused by prion infections, such as Creutzfeldt-Jakob disease, kuru, familial insomnia, and variably protease-sensitive prionopathy. Some studies have also associated prion-like infections with Alzheimer's disease. “Now that we have found that preventing prion infection is possible in animals, it's likely feasible in humans as well," says senior study investigator and neurologist Thomas Wisniewski, M.D., a professor at NYU Langone. CWD afflicts as much as 100 percent of North America's captive deer population, as well as large numbers of other cervids that populate the plains and forests of the Northern Hemisphere, including wild deer, elk, caribou, and moose. There is growing concern among scientists that CWD could possibly spread to livestock in the same regions, especially cattle, a major life stream for the U.S. economy, in much the same manner that bovine spongiform encephalopathy, or Mad Cow Disease, another prion-based infection, spread through the United Kingdom almost two decades ago. According to Dr.

December 20th

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.