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Archive - Mar 7, 2016

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Songbird Study Offers Insights into Huntington’s Disease

Although Huntington's disease is caused by mutations in a single gene, understanding how it ravages the brain and body has been anything but simple. A new study by Duke University scientists parses the role of the Huntington's disease gene in an area of the brain responsible for complex, sequential movements like those used to talk to a friend, play the violin, or swing a golf club. Described on March 7, 2016 in PNAS, the findings not only give a clearer view of how the genetic mutation that causes Huntington's disease alters brain and behavior, they may also offer a new therapeutic target for treatment. "These new results make a direct link between the genetic mutation, the insults that mutation causes to brain structure and function, and the behavioral pathology," said Richard Mooney, Ph.D., the George Barth Geller Professor of Neurobiology in the Duke School of Medicine. The PNAS article is titled “Focal Expression of Mutant Huntingtin in the Songbird Basal Ganglia Disrupts Corticobasal Ganglia Networks and Vocal Sequences.” Last year, researchers at the Rockefeller University in New York described a genetically altered songbird that shows an array of symptoms reminiscent of Huntington's disease, such as tremor, body stiffness and difficulties vocalizing. The songbird is ideal for studying Huntington's disease, Dr. Mooney said, because of the way evolution has enhanced the regions of its brain that are important in learning and singing songs. A song is produced by a string of precise movements of the vocal and respiratory muscles. Because each bird normally sings the same way every time, researchers can easily measure and detect subtle changes to the birds' movements caused by a faulty gene. The Rockefeller group expressed the mutated gene throughout the entire brain and body of the songbird, affecting many behaviors.

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Liposomes Do Not Cross Skin Barrier

Many cosmetic companies praise liposomes for their alleged ability to transport juvinating and nourishing agents deep into the skin, but also drug researchers have high hopes for liposomes: If they can carry nourishing agents through the skin, then they can also carry medical agents into the body. But now a new study from University of Southern Denmark finds that liposomes cannot penetrate the skin's barrier without breaking. The study is published online on January 11, 2016 in the open-access journal Plos One. The authors include postdoc Jes Dreier and Associate Professor Jonathan Brewer from the Department of Biochemistry and Molecular Biology, University of Southern Denmark. The article is titled “Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier.” The study follows a previous study from 2013, in which the research team showed that liposomes lose their cargo of agents the moment they meet the skin's surface. "This time we use a new method, and once and for all we establish that intact liposomes cannot penetrate the skin's surface. Therefore, we need to revise the way we perceive liposomes - especially in the skin care industry, where liposomes are perceived as protective spheres transporting agents across the skin barrier, says Dr. Brewer. The research group is the first in the world to use a special microscope, called a nanoscope, to study the skin. With this technique it is possible to directly see the individual molecules and liposomes. `One can study their activity and the processes that occur at the molecular level, and this provides a valuable insight into how cells function. The studies have revealed that liposomes cannot carry active agents into the skin. However, the liposomes may in fact in some way help the agents get underway.

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Atomic-Scale View of HIV Capsid and Host Protein Cyclophilin A

A new study offers the first atomic-scale view of an interaction between the HIV capsid - the protein coat that shepherds HIV into the nucleus of human cells - and a host protein known as cyclophilin A. This interaction is key to HIV infection, researchers say. A paper describing the research was published on March 4, 2016 in the journal Nature Communications. The open-acess article is titled “Cyclophilin A Stabilizes the HIV-1 Capsid Through a Novel Non-Canonical Binding Site” Cyclophilin A is found in most tissues of the human body, where it plays a role in the inflammatory response, immunity. and the folding and trafficking of other proteins. When it fails to work properly or is overproduced in cells, cyclophilin A also can contribute to diseases such as rheumatoid arthritis, asthma, cancer, and cardiovascular disease. It also facilitates some viral infections, including HIV. "We have known for some time that cyclophilin A plays a role in HIV infection," said University of Illinois physics professor Klaus Schulten, who led the new study with postdoctoral researcherJuan R. Perilla and University of Pittsburgh professor Peijun Zhang and postdoctoral researcher Chuang Liu. The HIV capsid somehow tricks this cellular protein into providing cover for it as it transits through the cell and makes its way to the nucleus, Dr. Schulten said. Once there, the capsid interacts with a nuclear pore that offers an entrance to the cell's nucleus. The virus uses the pore as a channel to inject its genetic material into the nucleus and commandeer the cell. Studies in cell culture have found that the virus rarely makes it to the nucleus without its cyclophilin disguise. Drugs that interfere with cyclophilin also reduce HIV infections in cell culture. Such drugs cannot be used in human HIV patients because they dampen the immune response.

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Fungus Loses RNA Interfrenece Genes and Becomes More Lethal

For more than a decade, a rare but potentially deadly fungus called Cryptococcus deuterogatti has taken up residence in the Pacific Northwest and Vancouver Island. Unlike its cousin Cryptococcus neoformans, which mostly infects patients with compromised immune systems, this fungus has sickened hundreds of otherwise healthy people. Now, researchers have found that the pathogen tossed aside over a dozen different genes on its way to becoming a new, more virulent species. Surprisingly, most of these discarded genes play a part in RNA interference or RNAi, a defense mechanism employed by fungi and other organisms to protect the integrity of their genomes. The study was published March 4 in PLOS Genetics. The article is titled “Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components in the Cryptococcus Pathogenic Species Complex.” "Genome instability is a bad thing in terms of human health, because it is linked to cancer and other diseases," said Blake Billmyre, lead study author and a graduate student in Dr. Joseph Heitman's lab at Duke University School of Medicine. "But it could be a good thing for single-celled organisms like Cryptococcus, because it enables them to mutate, evolve and adapt to survive under different conditions." Cryptococcus deuterogatti was largely confined to tropical climates until 1999, when it showed up on Vancouver Island and began spreading throughout southwest Canada and into Washington and Oregon. The emerging fungal pathogen causes severe pulmonary and central nervous system infections, and is fatal if left untreated.

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