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November 24th

Lateral Habenula Key to Decision-Making in Brain

One of the smallest parts of the brain is getting a second look after new research suggests it plays a crucial role in decision-making. A University of British Columbia (UBC) study published online on November 24, 2013 in Nature Neuroscience says the lateral habenula, a region of the brain linked to depression and avoidance behaviors, has been largely misunderstood and may be integral in cost-benefit decisions. "These findings clarify the brain processes involved in the important decisions that we make on a daily basis, from choosing between job offers to deciding which house or car to buy," says Professor Stan Floresco of UBC's Deptartment of Psychology and Brain Research Centre (BRC). "It also suggests that the scientific community has misunderstood the true functioning of this mysterious, but important, region of the brain." In the study, scientists trained lab rats to choose between a consistent small reward (one food pellet) or a potentially larger reward (four food pellets) that appeared sporadically. Like humans, the rats tended to choose larger rewards when costs—in this case, the amount of time they had to wait before receiving food--were low and preferred smaller rewards when such risks were higher. Previous studies suggest that turning off the lateral habenula would cause rats to choose the larger, riskier reward more often, but that was not the case. Instead, the rats selected either option at random, no longer showing the ability to choose the best option for them. The findings have important implications for depression treatment. "Deep brain stimulation – which is thought to inactivate the lateral habenula -- has been reported to improve depressive symptoms in humans," Dr. Floresco says. "But our findings suggest these improvements may not be because patients feel happier.

November 24th

Study ID’s Protein Essential for Immune Recognition and Response to Viral Infection

A Massachusetts General Hospital (MGH)-led research team has identified an immune cell protein that is critical to setting off the body's initial response against viral infection. The report that will be published in an upcoming issue of Nature Immunology and is receiving early online release describes finding that a protein called GEF-H1 is essential to the ability of macrophages – major contributors to the innate immune system – to respond to viral infections like influenza. "The detection of viral genetic material inside an infected cell is critical to initiating the responses that signal the immune system to fight an infection and prevent its spread throughout the body," says Hans-Christian Reinecker, M.D., of the Center for the Study of Inflammatory Bowel Disease in the MGH Gastrointestinal Unit, senior author of the report. "Our findings indicate that GEF-H1 may control immune responses against a wide variety of RNA and DNA viruses that pose a threat to human health." The body's first line of defense against infection, the innate immune system, rapidly responds to invading pathogens by mobilizing white blood cells, chemical factors called cytokines, and antimicrobial peptides. When viruses invade cells, they often move towards the nucleus in order to replicate and sometimes to integrate their own genetic material into that of the host cell, traveling along structures called microtubules (image) that cells use for internal protein transport. But how microtubule-based movement of viral components contributes to induction of the immune response has been unknown. GEF-H1 is known to bind to microtubules, and previous research indicated that it has a role in immune recognition of bacteria. A series of experiments by Dr.

The Secrets of Owls' Nearly Noiseless Wings

Many owl species have developed specialized plumage to effectively eliminate the aerodynamic noise from their wings – allowing them to hunt and capture their prey in silence. A research group working to solve the mystery of exactly how owls achieve this acoustic stealth presented its findings: "Vortex Noise Reductions from a Flexible Fiber Model of Owl Down," at 8:39 a.m. on Sunday, November 24, 2013 at the American Physical Society's (APS) Division of Fluid Dynamics meeting, held November 24 – 26, in Pittsburgh, Pennsylvnia-- work that may one day help bring "silent owl technology" to the design of aircraft, wind turbines, and submarines. "Owls possess no fewer than three distinct physical attributes that are thought to contribute to their silent flight capability: a comb of stiff feathers along the leading edge of the wing; a flexible fringe a the trailing edge of the wing; and a soft, downy material distributed on the top of the wing," explained Dr. Justin Jaworski, assistant professor in Lehigh University's Department of Mechanical Engineering and Mechanics. His group is exploring whether owl stealth is based upon a single attribute or the interaction of a combination of attributes. For conventional wings, the sound from the hard trailing edge typically dominates the acoustic signature. But prior theoretical work carried out by Dr. Jaworski and Dr. Nigel Peake at the University of Cambridge revealed that the porous, compliant character of the owl wing's trailing edge results in significant aerodynamic noise reductions. "We also predicted that the dominant edge-noise source could be effectively eliminated with properly tuned porous or elastic edge properties, which implies that that the noise signature from the wing can then be dictated by otherwise minor noise mechanisms such as the 'roughness' of the wing surface," said Dr. Jaworski.

BioQuick Adds Link to Biotechnology Calendar

Biotechnology Calendar, Inc. (http://www.biotech-calendar.com/) is a full-service event marketing and planning company producing on-campus, life science research tradeshows nationwide for the past 20 years. The company plans and promotes each event to bring the best products and services to the best research campuses across the country. BioQuick believes the Biotechnology Calendar to be a highly useful resource and has arranged to add a direct link to this site in the margin of the BioQuick home page. You can merely click on the link to access the Biotechnology Calendar. The Biotechology Calendar is also available via Facebook (https://www.facebook.com/BiotechCalendar), Twitter (https://twitter.com/biotechcalendar), and Linked-In (http://www.linkedin.com/company/468891?trk=tyah&trkInfo=tas%3ABiotechnol...). Comments by impressed users of the Biotechnology Calendar include the following: "I found the event very impressive, informative, and important for research in Pathology. I am from Japan; there is nothing like this in Japan. I am always looking for new research products. I am going to talk to my research manager about a few of these products when I get back to the lab. I have attended this event for the past eight years,” commented a UCLA researcher attending a Biotechnology Calendar event. “"The seminars were outstanding. I am currently teaching my technician similar procedures so it was very helpful," commented a Harvard University scientist. We hope that our BioQuick readers will appreciate the addition of this useful resource to the home page and would appreciate any and all comments.

November 23rd

World’s Rarest Whale Seen for First Time—DNA Crucial to Identification

A whale that is almost unknown to science has been seen for the first time after two individuals—a mother and her male calf—were stranded and died on a New Zealand beach. A online report on November 6, 2013 in Current Biology, a Cell Press publication, offers the first complete description of the spade-toothed beaked whale (Mesoplodon traversii), a species previously known only from a few bones. The discovery is the first evidence that this whale is still with us and serves as a reminder of just how little we still know about life in the ocean, the researchers say. The findings also highlight the importance of DNA typing and reference collections for the identification of rare species. "This is the first time this species—a whale over five meters in length—has ever been seen as a complete specimen, and we were lucky enough to find two of them," says Dr. Rochelle Constantine of the University of Auckland. "Up until now, all we have known about the spade-toothed beaked whale was from three partial skulls collected from New Zealand and Chile over a 140-year period. It is remarkable that we know almost nothing about such a large mammal." The two whales were discovered in December 2010, when they live-stranded and subsequently died on Opape Beach, New Zealand. The New Zealand Department of Conservation was called to the scene, where they photographed the animals and collected measurements and tissue samples. The whales were initially identified not as spade-toothed beaked whales, but as much more common Gray's beaked whales. Their true identity came to light only following DNA analysis, which is done routinely as part of a 20-year program to collect data on the 13 species of beaked whales found in New Zealand waters.

Relation between Notch Signaling and Immature T-Cells May Have Implications for Fighting T-Cell Leukemias

The lab of Avinash Bhandoola, Ph.D., professor of Pathology and Laboratory Medicine, has studied the origins of T cells for many years. One protein called Notch, which has well-known roles in the development of multiple tissues, plays an essential role in triggering T-cell development. T cells are immune cells that are made in the thymus, a small organ situated under the breastbone near the heart. However, T cells, like all blood-cell types, originate from blood-producing stem cells in the bone marrow. Immature T-cell progenitors leave the bone marrow, settle within the thymus, and eventually give rise to T cells. With graduate student Maria Elena De Obaldia, Dr. Bhandoola describes, in a November 3, 2013 online article in Nature Immunology, how Notch signaling induces expression of genes that promote the maturation of T cells and discourage alternative cell fates. Deficiency of the Notch target gene Hes1 in blood stem cells results in extremely low T-cell numbers, but the underlying mechanism is unknown. Keeping in mind that Notch signaling gone awry induces leukemia, Dr. De Obaldia notes that "understanding the Notch pathway on a molecular level can shed light on how normal cells are transformed in the context of cancer." The current study describes the mechanism of action of Hes1, a repressor protein that acts in the nucleus of immature T cells in the thymus. Dr. De Obaldia and Ms. Bhandoola found that Hes1 turns off genes such as C/EBPalpha, which promote the myeloid-cell fate and antagonize the T-cell fate. Whereas Hes1-deficient mice show severe T-cell defects, deleting the myeloid gene C/EBPalpha could restore normal T-cell development. This provided evidence that Hes1 keeps immature T cells on track by preventing them from defaulting to a myeloid developmental pathway, which controls non-lymphocyte cell maturation.

How Influenza A Viruses Penetrate Protective Mucus Layer

Researchers at the University of California, San Diego (UCSD) School of Medicine have shown, for the first time, how influenza A viruses snip through a protective mucus net to both infect respiratory cells and later cut their way out to infect other cells. The findings, published online in an open-access article in the Virology Journal by principal investigator Pascal Gagneux, Ph.D., associate professor in the Department of Cellular and Molecular Medicine, and colleagues, could point the way to new drugs or therapies that more effectively inhibit viral activity, and perhaps prevent some flu infections altogether. Scientists have long known that common strains of influenza specifically seek out and exploit sialic acids, a class of signaling sugar molecules that cover the surfaces of all animal cells. The ubiquitous H1N1 and H3N2 flu strains, for example, use the protein hemagglutinin (H) to bind to matching sialic acid receptors on the surface of a cell before penetrating it, and then use the enzyme neuraminidase (N) to cleave or split these sialic acids when viral particles are ready to exit and spread the infection. Mucous membrane cells, such as those that line the internal airways of the lungs, nose, and throat, defend themselves against such pathogens by secreting a mucus rich in sialic acids – a gooey trap intended to bog down viral particles before they can infect vulnerable cells. "The sialic acids in the secreted mucus act like a sticky spider's web, drawing viruses in and holding them by their hemagglutinin proteins," said Dr. Gagneux. Using a novel technique that presented viral particles with magnetic beads coated with different forms of mucin (the glycoproteins that comprise mucus) and varying known amounts of sialic acids, Dr.

Epigenetic Changes May Explain Chronic Kidney Disease

The research of physician-scientist Katalin Susztak, M.D., Ph.D., associate professor of Medicine in the Renal Electrolyte and Hypertension Division, at the Perelman School of Medicine, University of Pennsylvania, strives to understand the molecular roots and genetic predisposition of chronic kidney disease. In an open-access online article published October 7, 2013 in Genome Biolog, Dr. Susztak, and her co-corresponding author Dr. John Greally from the Albert Einstein College of Medicine, Bronx, New York, found, in a genome-wide survey, significant differences in the pattern of chemical modifications on DNA that affect gene expression in kidney cells from patients with chronic kidney disease versus healthy controls. This is the first study to show that changes in these modifications – the cornerstone of the field of epigenetics – might explain chronic kidney disease. Epigenetics is the science of how gene activity can be altered without actual changes in the DNA sequence. DNA can be modified by different chemical groups. In the case of this study, these are methyl groups that, like using sticky notes as reminders, open or close up regions of the genome to make these areas more or less available to be "read" as a gene. Chronic kidney disease is a condition in which the kidneys are damaged and cannot adequately filter blood. This damage can cause wastes to build up, which leads to other health problems, including cardiovascular disease, anemia, and bone disease. More than 10% of people, or more than 20 million, aged 20 years or older in the United States have chronic kidney disease, according to the Centers for Disease Control. Past epidemiological studies have shown that adverse intrauterine and postnatal conditions have a long-lasting, over-a-lifetime role in the development of chronic kidney disease.

Widespread Differences Found in Gene Expression and Splicing in Male and Female Brains

University College London (UCL) scientists have shown that there are widespread differences in how genes are expressed and spliced in men’s and women's brains. Based on post-mortem adult human brain and spinal cord samples from over 100 individuals, scientists at the UCL Institute of Neurology were able to study the expression of every gene in 12 brain regions. The results are published online on November 22, 2013 in an open-access article in Nature Communications. They found that the way that the genes are expressed in the brains of men and women were different in all major brain regions and these differences involved 2.5% of all the genes expressed in the brain. Among the many results, the researchers specifically looked at the gene NRXN3, which has been implicated in autism. The gene is transcribed into two major forms and the study results show that although one form is expressed similarly in both men and women, the other is produced at lower levels in women in the area of the brain called the thalamus. This observation could be important in understanding the higher incidence of autism in males. Overall, the study suggests that there is a sex-bias in the way that genes are expressed and regulated, leading to different functionality and differences in susceptibility to brain diseases observed between the sexes by neurologists and psychiatrists. Dr. Mina Ryten, UCL Institute of Neurology and senior author of the paper, said: "There is strong evidence to show that men and women differ in terms of their susceptibility to neurological diseases, but up until now the basis of that difference has been unclear. Our study provides the most complete information so far on how the sexes differ in terms of how their genes are expressed in the brain.

November 22nd

Key Immunity Gene Discovered in Neanderthals

A research group at Bonn University in Germany and international collaborators have discovered a novel receptor, which allows the immune system of modern humans to recognize dangerous invaders, and subsequently elicits an immune response. The blueprint for this advantageous structure was also identified in the genome of Neanderthals, hinting at its origin. The receptor provided these early humans with immunity against local diseases. The presence of this receptor in Europeans but its absence in early men suggests that it was inherited from Neanderthals. The results have been published online on November 8, 2013 in the Journal of Biological Chemistry. When pathogens infect the human body, the immune system identifies and attacks dangerous invaders. During evolution, an efficient defense system developed, which vaguely resembles methods used by secret agents. With the help of certain genes, the human leukocyte antigen (HLA) system produces receptors that assess the risk rate of the pathogens using their profile which has just eight amino acids. "This function can be compared to a text which is identified by a spy as being suspicious, based on just a few letters of a word," says Professor Dr. Norbert Koch from the Institute for Genetics, Department of Immunobiology at the University of Bonn. In order to decipher this message, the immune system breaks down the invader’s proteins into peptides and subsequently scans a proportion of the peptides for their amino acid sequences. Up until now, a total of three different peptide receptors of more than 1000 different manifestations were known, which in humans can read the telltale letter combinations. "This variety is needed so that the immune system can rate the entire spectrum of pathogens relevant for humans," explains Professor Koch.