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Archive - Mar 2016


March 7th

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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March 4th

Scientists Obtain Deeper Insight into Function of BRCA1 Gene (Angelie Jolie Gene)

Scientists from the Cancer Therapy & Research Center (CTRC) in San Antonio today (March 4, 2016) published work that provides deeper insight into how the so-called “Angelina Jolie” gene, BRCA1, functions in normal breast tissue and how its loss results in breast cancer. The CTRC -- a National Cancer Institute-designated Cancer Center -- is part of the University of Texas (UT) Medicine San Antonio, the clinical practice of the School of Medicine at The University of Texas Health Science Center at San Antonio. BRCA1 is known to suppress cancer by repairing breaks in DNA, the molecule that contains the genetic blueprint of each cell. This DNA damage occurs with aging and environmental insults. In the new study, published online Nature Communications, CTRC researchers found that BRCA1 also serves as a limiter or governor on a gene called COBRA1 that regulates breast cell growth. The new open-access article is titled “Genetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development.” "We now have solid and compelling evidence that BRCA1 in breast tissue is doing something independent of DNA repair," said study lead author Rong Li, Ph.D., Professor of Molecular Medicine at the Health Science Center. "We still think DNA repair is important for BRCA1 to suppress tumor development, but we just don't think it's the whole story." Because DNA repair is needed in every cell of the body, scientists, including Dr. Li, have puzzled over why loss of BRCA1 function predisposes women to only breast and ovarian cancers. Also, diminished BRCA1 activity doesn't affect men significantly, as it does women.

Lifespan in Nematode Hermaphrodites

Pristionchus nematodes come in two varieties: Most species consist of typical males and females, but in several species the females have evolved the ability to produce and use their own sperm for reproduction. Scientists from the Max Planck Institute of Developmental Biology in Tübingen, Germany, discovered that these so called “hermaphrodites” have shorter lifespans, with normal females frequently living over twice as long as closely related hermaphrodites. The article was published online on February 18, 2016 in The American Naturalist and is titled “Mating System Transitions Drive Life Span Evolution in Pristionchus Nematodes.” The ways that males and females interact affects many biological processes, including the evolution of important traits like lifespan and the rate of aging. While the male-female mating system is found in most vertebrates, and all mammals--many animal species employ alternative arrangements. Ralf Sommer, Ph.D, and Cameron Weadick, Ph,D., from the Max Planck Institute of Developmental Biology are doing research on the evolutionary consequences of such differences. They wanted to find out if self-fertilizing hermaphrodite nematodes would evolve to live longer, healthier lives; or if they would evolve shorter life cycles, characterized by quick bursts of reproduction followed by senescent decay. By comparing species that utilize different mating systems, it's possible to see how much of a role sexual interactions play in shaping life-history evolution. The researchers measured adult lifespan in females and hermaphrodites from eleven different Pristionchus nematode (roundworm) species. They discovered that hermaphrodites, which fertilize their own eggs with their own sperm, live significantly shorter than their female relatives.

March 3rd

Achilles Heel of Aggressive Form of Leukemia

Researchers at The Ottawa Hospital and the University of Ottawa have found the Achilles' heel of one of the most aggressive forms of leukemia that affects both children and adults. They have also identified a possible new treatment that exploits this fatal weakness. Their study, published in Genes & Development on March 1, 2016, focuses on a type of acute lymphoblastic leukemia (ALL) that involves a gene called TAL-1. The article is titled “UTX Inhibition As Selective Epigenetic Therapy Against TAL1-Driven T Cell Acute Lymphoblastic Leukemia.” Senior author Dr. Marjorie Brand and her team discovered that a compound called GSK-J4 can kill this form of cancer. By transplanting cancer cells from human patients into normal mice, the authors showed that the compound can kill the leukemia quickly, efficiently, and with no short-term side effects. GSK-J4 was created by the pharmaceutical industry for research purposes, and has never been used as a cancer therapy. "It's very exciting because this is the first time anyone has found a potential personalized treatment for this aggressive disease," said Dr. Brand, a senior scientist at The Ottawa Hospital and professor at the University of Ottawa. "Unlike current therapies, ours targets the offending gene without harming the rest of the body." Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. It develops in the white blood cells that usually help the body fight infection. The type of cancer Dr. Brand studies is called T-ALL, because it affects a particular kind of white blood cells called T-cells. T-ALL represents 15 percent of childhood ALL cases. This study in particular dealt with a common form of T-ALL called TAL-1.

Gene for Graying Hair Identified

The first gene identified for graying hair has been discovered by an international University College London (UCL)-led study, confirming that graying hair has a genetic component and is not just environmental. Published omn March xx, 2016 in Nature Communications, the study analyzed a population of over 6,000 people with varied ancestry across Latin America to identify new genes associated with hair color, graying, density, and shape, i.e. straight or curly. The article is titled “A Genome-Wide Association Scan in Admixed Latin Americans Identifies Loci Influencing Facial and Scalp Hair Features.” "We already know several genes involved in balding and hair color, but this is the first time a gene for graying has been identified in humans, as well as other genes influencing hair shape and density," said lead author, Dr. Kaustubh Adhikari, UCL Cell & Developmental Biology. "It was only possible because we analyzed a diverse melting pot of people, which hasn't been done before on this scale. These findings have potential forensic and cosmetic applications as we increase our knowledge on how genes influence the way we look." The findings could help develop forensic DNA technologies that build visual profiles based on an individual's genetic makeup. Research in this field has previously used samples from people of European descent, but these new results could help forensic reconstructions in Latin America and East Asia. The gene identified for gray hair -- IRF4 -- is known to play a role in hair color but this is the first time it has been associated with the graying of hair. This gene is involved in regulating production and storage of melanin, the pigment that determines hair, skin and eye color.

Cancer Treatment on a Cellular Level

The most common treatments for cancer are radiation and chemotherapy. However these treatments have side effects and also damage healthy tissues. Moreover, their effectiveness is limited when the cancer has spread throughout the body. Researchers at the Niels Bohr Institute in Copenhagen are therefore working to develop a gentler treatment that “tricks” the cancer cells, which would absorb a cytotoxin and therefore be destroyed, while healthy cells would remain unaffected. The results were published on March 2, 2016 in the scientific journal, Scientific Reports. The open-access article is titled “Restricted Mobility of Specific Functional Groups Reduces Anti-Cancer Drug Activity in Healthy Cells.” Physicist Murillo Martins, Ph.D., at the Niels Bohr Institute at the University of Copenhagen had an idea. He wanted to construct a kind of nanoscale “lorry” that could transport the cytotoxin directly to the cancer cells via the bloodstream and would prompt the cells to let the “load” in so that the cancer cells were destroyed. It is something you could imagine in a science fiction film, but could it be `done in the real world? The first task was the “vehicle” itself. For that he decided to use tiny magnetic beads, an approach well known in medical research. You can inject the beads into the bloodstream and by placing a magnet at the site where the tumor is located you can get the beads to move there. The next step was the cytotoxic load.

March 2nd

Finnish and Singaporean Researchers Publish First Empirical Study on Evolution of Musical Aptitude

Geneticists at the University of Helsinki and the National University of Singapore have teamed up to explore the evolution of musical aptitude in the first-ever empirical study of the evolution of music. The Finnish scientists in the project were supported by funding from the Academy of Finland. The study was published online on February 16, 2016 in Scientific Reports, a peer-reviewed scientific journal of the Nature Publishing Group. The open-access article is titled “Detecting Signatures of Positive Selection Associated with Musical Aptitude in the Human Genome.” In the study, the researchers applied genomic methods to identify candidate regions in the human genome showing positive selection regions with musical aptitude. They found that the associated regions contained numerous candidate genes, among them genes known to affect ear function, language development, memory, bird song, and the brain’s reward mechanism. “We started out from the hypothesis that genetic variants associated with musical aptitude have a pivotal role in musical practices. This assumption is based on the idea that the evolution of the human genome progresses much more slowly than cultural evolution. The structure and function of the auditory system is very similar in modern humans and the first primates, suggesting high evolutionary conservation of auditory perception among species,” says Docent Irma Järvelä, the principal investigator of the study. FOXP1, one of the candidate genes discovered, has been previously found to affect both human language development and songbirds’ singing. The researchers also identified RGS9 as another gene that is implicated in song learning and singing in songbirds. RGS9 is expressed in the corpus striatum together with dopamine receptors. The striatum is activated by expectations in music.