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Archive - Oct 2015

October 31st

Optogenetics Used to Show That Axon Initial Segments (AIS’s) Can Change Length and Influence Repetitive Spike Firing Much More Rapidly Than Previously Thought

Neurons communicate by passing electrical messages, known as action potentials, between each other. Each neuron has a highly specialized structural region, the so-called “axon initial segment” (AIS), whose primary role is in the generation and sending of these messages. The AIS can undergo changes in size, length, and location in response to alterations of a neuron's ongoing electrical activity. However, until now, all such “AIS plasticity” has been believed to be exceptionally slow, occurring over a timescale of days. Work by researchers from the MRC Centre for Developmental Neurobiology (MRC CDN), part of the Institute of Psychiatry, Psychology & Neuroscience at King's College London at King’s College London, has now shown that AIS changes can occur much more quickly, influencing the way cells fire action potentials. These results were published online on October 29, 2015 in an open-access article in the journal Cell Reports. The article is titled “Rapid Modulation of Axon Initial Segment Length Influences Repetitive Spike Firing.” Located near the beginning of the axon, which is the neuron's major output structure, the AIS has a crucial role in kick-starting communication between brain cells. However, for AIS plasticity to play a more prominent role in the brain's responses to altered activity, the structure needs to be able to change far more quickly than has previously been shown. For this reason, Dr. Mark Evans (now at the Gladstone Institute of Neurological Disease in San Francisco), Dr. Adna Dumitrescu, Dr. Dennis Kruijssen, Dr. Samuel Taylor, and Dr. Matthew Grubb decided to investigate how rapidly an AIS can be altered.

Semi-Automated Method Developed to ID European Corn Borer; Destructive Pest Causes $2 Billion in Damage Annually in U.S. Alone; Wing Venation Pattern in Corn Borer Moths Is Key; Improved ID May Allow Better Control of This Pest

Farmers who need to control the destructive European corn borer (Ostrinia nubilalis) may soon be able to distinguish it from look-alike species by simply scanning an image of its wing into a computer and tapping a few keys. A technique developed by Polish scientists marks the first time that measurements of key structural features in the wing have been used to identify the borer, a potentially major advance in controlling the pest. The new identification method was developed by Dr. Lukasz Przybylowicsz, Dr. Michal Pniak, and Dr. Adam Tofilski, and it is described in an open-access article published online on October 20, 2015 in the Journal of Economic Entomology. The article is titled “Semiautomated Identification of European Corn Borer (Lepidoptera: Crambidae.” The European corn borer is a prime pest on corn, but also impacts more than 200 other crops, and, by some estimates, causes up to $2 billion in damage annually in the United States alone. Most farmers are not able to identify adult corn borers or distinguish these destructive pests from other species. The identification method developed by the scientists focuses on the arrangement of veins in the wings of the moths, applying a technique known as geometric morphometry. Essentially, it examines and compares the geometry of an organism's structures -- in other words, where its parts are positioned in relation to one another. Computerized statistical analysis is key to attaining results. The researchers selected nine points -- called "landmarks" -- at junctions of veins in the central part of the wing. Landmarks, such as where veins join, are a common feature among species.

UK Study Shows Climate Change Affecting Different Butterfly & Moth Species Differently; Some Increasing in Number, Some Decreasing; Varied Responses Viewed As "Surprising" for Cool, Rainy Britain

New research led by ecologists at the University of York shows that certain species of moths and butterflies are becoming more common, and others rarer, as species differ in how they respond to climate change. Collaborating with the Natural Environment Research Council's Centre for Ecology and Hydrology, the charity Butterfly Conservation, the University of Reading, and Rothamsted Research, scientists analyzed how the abundance and distribution of 155 species of British butterflies and moths have changed since the 1970s. Using data collected by thousands of volunteers through “citizen science” schemes, responses to recent climate change were seen to vary greatly from species to species. Published in an open-access article in the October 2, 2015 issue of Science Advances, this research shows that variation among species can be attributed to differing sensitivity to climate change, and also because species vary in how much the climate has changed for them (their “exposure”). The article is titled “Individualistic Sensitivities and Exposure to Climate Change Explain Variation in Species’ Distribution and Abundance Changes.” Sensitivity is a measure of how much species' numbers change as a result of year-to-year changes in the weather - each species is sensitive to different aspects of the climate, such as winter temperature or summer rainfall. Variation in how much the climate they are sensitive to has changed for them - their “exposure” - is also a contributing factor in their varied responses. Results show that species such as the treble brown spot moth (Idaea trigeminata) and the speckled wood butterfly (Pararge aegeria)(image) which are sensitive to climate, and for which the climate has improved the most, have experienced the greatest increases in their distribution size and abundance.

October 29th

Loss of 1,300 Chimney-Trapped Migrating Swifts in BC Sparks Study That May Spur New Conservation Efforts

Resembling swallows,, but more closely related to hummingbirds, swifts have unique migratory behavior, roosting for days at a time in chimneys or hollow trees along their migratory route in groups of hundreds or thousands of individuals. Little is known about whether groups that travel and roost together during migration are all from the same wintering site or are made up of individuals from across their winter range. A 2012 mortality event in British Columbia that killed more than 1,300 migrating swifts provided researcher Matthew Reudink, Ph.D., of Thompson Rivers University in Kamloops, British Columbia, and his colleagues with the opportunity to determine where the birds had spent the winter. Their results, published online on October 28, 2015 in an open-access article in The Condor: Ornithological Applications, suggest that the birds in the roost all came from the same two or three wintering sites. Bird breeding populations strongly connected to specific wintering areas may be more vulnerable to population declines, so this has important implications for swift conservation. The new article is titled “"Patterns of Migratory Connectivity in Vaux's Swifts at a Northern Migratory Roost: A Multi-Isotope Approach.” Like many birds that catch insects on the wing, Vaux's swifts (Chaetura vauxi) have experienced significant population declines, and the May 2012 mortality event in Cumberland, British Columbia, may have killed nearly 3% of the province's population. "The circumstances surrounding the event are a bit unclear, but our understanding is that the birds became trapped in a chimney that was in a residence and were unable to escape out of the top," explains Dr. Reudink.

October 29th

Electric Eels Use Sophisticated Electrical System As Both Weapon and Sensory Tool

The electric eel may be one of the most remarkable predators in the entire animal kingdom. That is the conclusion of Kenneth Catania, Ph.D., Stevenson Professor of Biological Sciences at Vanderbilt University, who has spent the last three years studying the way this reclusive South American fish uses electric fields to navigate through the muddy waters of the Amazon and Orinoco basins where it lives, to locate hidden prey, and to stun them into submission. Electric eels can grow to lengths exceeding eight feet and weights of more than 44 pounds. Over two thirds of the eel's body is filled with specialized cells called electrocytes that store electricity like small biological batteries. When the eel is threatened or attacking prey, these cells discharge simultaneously, emitting electrical discharges of at least 600 volts, five times the voltage of a standard U.S. wall socket. "Historically, electric eels have been viewed as unsophisticated, primitive creatures that have a single play in their playbook: shocking their prey to death," said Dr. Catania. "But it turns out that they can manipulate their electric fields in an intricate fashion that gives them a number of remarkable abilities." One of the biologist's latest discoveries, reported online on October 28, 2015 in the journal Current Biology, is that the eels have a special maneuver that allows them to double the electrical shock that they can deliver to particularly large or difficult prey. This article is titled “Electric Eels Concentrate Their Electric Field to Induce Involuntary Fatigue in Struggling Prey.” The eel's electrical system essentially provides it with a wireless Taser that it uses to stun its prey. In a study published last year, Dr.

HHMI Develops First Light Microscope (IsoView) Capable of Imaging Large, Non-Transparent Specimens at Sub-Second Temporal Resolution and Sub-Cellular Spatial Resolution in All Dimensions

A new microscope developed at the Howard Hughes Medical Institute's (HHMI’s) Janelia Research Campus in Virginia is giving scientists a clearer, more comprehensive view of biological processes as they unfold in living animals. The microscope produces images of entire organisms, such as a zebrafish or fruit fly embryo, with enough resolution in all three dimensions so that each cell appears as a distinct structure. What's more, the new microscope does so at speeds fast enough to watch cells move as a developing embryo takes shape and to monitor brain activity as it flashes through neuronal circuits. Nearly two years in development, Janelia group leader Dr. Philipp Keller says his team has built the first light microscope capable of imaging large, non-transparent specimens at sub-second temporal resolution and sub-cellular spatial resolution in all dimensions. Dr. Keller and his team at Janelia aim to understand how a functioning nervous system emerges in an embryo. Over the last five years, they have devised several imaging technologies that make it possible to image large biological samples at high speed. His lab's newest microscope, called the IsoView light sheet microscope, overcomes a final challenge--improving spatial resolution--without sacrificing the performance features of his team's previous microscopes. The IsoView microscope is described in an article published online on October 26, 2015, in the journal Nature Methods. The article is titled “Whole-Animal Functional and Developmental Imaging with Isotropic Spatial Resolution.” The publication includes complete building plans for the microscope and the associated image processing software developed by Dr. Keller's team. In 2012, Dr. Keller's team developed the SiMView microscope, which provides fast three-dimensional imaging of large specimens.

Gladstone iPSC Nobel Laureate Elected to National Academy of Medicine

Nobel Laureate (2012) Shinya Yamanaka (photo), M.D., Ph.D., a Senior Investigator at the Gladstone Institutes in San Francisco and inventor of induced pluripotent stem cells (iPSCs), has been elected to the National Academy of Medicine. “This latest accomplishment further acknowledges Shinya’s tremendous contributions to the fields of science and medicine. His discovery of induced pluripotent stem cells has revolutionized biomedical research and has the potential to improve the lives of millions. This distinction is well deserved,” says Gladstone President R. Sanders “Sandy” Williams, M.D. “It is a great honor to be named to this distinguished institution and join such an esteemed group of scientists. It is especially meaningful that the decision is made by a panel of my peers,” says Dr. Yamanaka, who is also the L.K. Whittier Foundation Investigator in Stem Cell Biology at Gladstone, a Professor of Anatomy at the University of California, San Francisco (UCSF), and Director and Professor at the Center for iPS Cell Research and Application (CiRA), Kyoto University in Japan. Election to the National Academy of Medicine, formerly the Institute of Medicine, is considered one of the highest accomplishments in the fields of health and medicine and recognizes individuals around the world who have demonstrated outstanding professional achievement and commitment to service. “Our newly elected members represent the brightest, most influential, and passionate people in health, science, and medicine in our nation and internationally,” said Academy President Victor J. Dzau in a press release (http://nam.edu/nam-elects-80-new-members/) announcing this year’s election of new members. “They are at the top of their fields and are committed to service.

CTL-Associated Antigen-4 Immunoglobulin (CTLA4Ig) Suppresses Liver Damage in New Mouse Model of Acute Hepatitis B Infection

A promising new avenue for treating hepatitis B has been reported by researchers at Hiroshima University in Japan who have developed a new animal model of the disease. Approximately two million people worldwide have been exposed to hepatitis B virus. Liver transplantation is often necessary to save the lives of patients who have severe liver damage that results from acute overreaction of the immune system. To develop therapies against acute hepatitis, an appropriate animal model is necessary. “The number of patients who can receive liver transplantation is limited, so there is an urgent need to develop new treatment options,” said Professor Kazuaki Chayama of Hirioshima University. Professor Chayama and his research group used mice with so-called “humanized” livers, and injected them with human blood. They found that hepatitis in these “human hepatocyte chimeric mice” was caused by white blood cells known as cytotoxic T lymphocytes (CTLs) that were specifically targeted to hepatitis B virus. This was very similar to human acute hepatitis B. The researchers also found that treating the mice with a molecule called CTL-associated antigen-4 immunoglobulin (CTLA4Ig) suppressed damage to liver cells infected with hepatitis B virus, suggesting that this might be a potential approach to treatment in humans. The mouse model should also be useful for studying the immunological reactions and viral clearance in hepatitis B virus infection, the authors note in their article posted online on August 5, 2015 in the Journal of Virology.

Rockefeller-Led Research Reveals Key Cancer-Promoting Activity of Histone Demethylase Enzyme (JMJD1C) in Acute Myeloid Leukemia (AML), and Perhaps Other Myeloid Leukemias; Possible New Drug Target

New treatment options are badly needed for acute myeloid leukemia (AML), a relatively rare form of cancer. The malignancy begins in the bone marrow, and from there, can spread rapidly to the bloodstream, depriving the body of the essential blood cells that carry oxygen and fight infections. Now, new work from a team led by Rockefeller University researchers in New York City has revealed a potential genetic weakness of this leukemia, offering insights into the molecular mechanisms behind AML, and suggesting a new target for drug development. Previously, researchers had identified a variety of mutations associated with this disease, including a DNA rearrangement found in approximately 15 percent of patients. The abnormal DNA-binding protein produced as a result of this rearrangement takes on entirely new functions, dramatically altering a set of genes that are turned on in a cell to promote the cancer. But how this mutation effects these changes has remained a mystery. In their new work published in the October 15, 2015 issue of Genes and Development, the researchers describe how they identified the molecular mechanism responsible for this gene activation. Their article is titled “JMJD1C Is Required for the Survival of Acute Myeloid Leukemia by Functioning As a Coactivator for Key Transcription Factors.” The research team, led by Dr. Robert G. Roeder, Arnold and Mabel Beckman Professor and Head of Rockefeller's Laboratory of Biochemistry and Molecular Biology, began by searching for proteins that interact with the mutant protein, known as AE (AML/ETO) fusion protein, which is produced by the DNA rearrangement. Their screen identified JMJD1C, an enzyme that removes chemical tags, known as methyl groups, from histones, which are proteins contained in chromosomes.

October 28th

[TECHNOLOGY USED; UPDATE 10-31] Cancer-Derived Exosomes with Specific Integrin “Zip-Code” Signatures Target & Prime Specific Organs for Later Metastastis; New Work Supports Century-Old “Soil & Seed” Hypothesis for Metastatic Organotropism

[SEE LAST PARAGRAPH TO VIEW UPDATE ON THE TECHNOLOGY USED IN THIS LANDMARK STUDY] It's been a longstanding mystery — why certain types of cancers spread to particular organs in the body. Now, investigators from Weill Cornell Medicine, together with an international team of collaborators, have discovered precisely how this happens, supporting a century-old hypothesis known as the “seed and soil” theory of metastasis. The culprit? Protein signatures on the membranes of small, sub-cellular, tumor-secreted vesicles (exosomes) containing the blueprint that drives cancers to distant organs. These signatures could offer doctors a powerful new way to detect whether a patient's tumor will metastasize and to where, providing critical insights into the estimated 1.6 million new cancer cases diagnosed every year. Ninety percent of all cancer-related deaths are related to metastasis. In the new study, published online on October 28, 2015 in Nature, scientists investigated the role of cancer-derived exosomes, comprised of tumor-derived proteins, in preparing a microenvironment fertile for cancer metastasis. Working with exosomes derived from multiple cancers, the scientists discovered that the proteins exosomes carry act as "ZIP codes" that direct exosomes to distinct organs, where they lay the molecular groundwork for metastases to form. The Nature article is titled “Tumor Exosome Integrins Determine Determine Organotroppic Metastasis.” "Our research offers a new approach to identifying patients who are likely to develop metastatic disease," says senior author Dr. David Lyden, the Stavros S. Niarchos Professor in Pediatric Cardiology and a Professor of Pediatrics and of Cell and Developmental Biology at Weill Cornell Medicine in New York City.