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Archive - Jul 2015

July 27th

Much of Polar Bear Y-Chromosome Sequence Is Identified; Study Shows That Two Male Lineages Diverged Over 100,000 Years Ago

For the first time, a team of scientists, led by Professor Axel Janke of the Senckenberg Research Center for Biodiversity and Climate in Franfurt, Germany, has reconstructed part of the male chromosome in polar bears (Ursus maritimus). The scientists were able to assign 1.9 million base pairs specifically to the polar bear Y chromosome. In their study, published online on May 27, 2015 in an open-access article in “Genome Biology and Evolution,” they show that more than 100,000 years ago, the male polar bear lineages split and developed in two separate genetic groups. The article is titled “Genome-Wide Search Identifies 1.9 Megabases from the Polar Bear Y Chromosome for Evolutionary Analyses.” The polar bear is the world’s largest land-dwelling predator and is hard to miss. Nevertheless, it is difficult to study the evolution of this Arctic resident. Polar bears live and die on the frozen sea, and their remains are seldom found. “In order to gain insights into the evolutionary development of Ursus maritimus, we use genetics instead of fossils,” explains Professor Janke. For the first time, the evolutionary geneticist and his Ph.D. student Tobias Bidon, have reconstructed large parts of the polar bear Y chromosome. “In this age of biological revolution, it is possible to sequence the entire genome of an organism rather quickly and cost-effectively,” says Dr. Janke. However, to date, such comprehensive genome projects have mostly been limited to female animals, neglecting the males’ special chromosome – the Y chromosome. Mr. Bidon commented that “this is quite surprising, because the Y chromosome is an important part of the mammalian genome. It is the only genetic material that is passed on from male to male, thereby offering unique insights into the evolutionary history and population dynamics.”

July 26th

DNA Studies Show That Inbreeding Is Likely Not the Cause of Decline in Bighorn Sheep Population in Colorado’s Rocky Mountain National Park

The health of Colorado's bighorn sheep population remains as precarious as the steep alpine terrain the animals inhabit, but a new study led by researchers at the University of Colorado Boulder (CU-Boulder) has found that inbreeding--a common hypothesis for a recent population decline--likely is not to blame. Bighorn herds tend to be small and isolated in their mountain ecosystems, putting the animals at high risk for a genetic "bottleneck," said Catherine Driscoll, a graduate student in the Department of Ecology and Evolutionary Biology at CU-Boulder and lead author of the study. Previous research has shown that inbreeding can weaken a population's immunity to disease across subsequent generations. However, after using mitochondrial DNA data to analyze a diverse set of hereditary markers, researchers found that all five native herds in Colorado’s Rocky Mountain National Park (RMNP) are maintaining healthy levels of genetic variation compared to other bighorn populations across the western United States. "There's been enough gene flow between the herds, primarily due to high ram migration, that the population has been genetically rescued," Ms. Driscoll said. The new findings, which were published in the July 2015 issue of the Journal of Wildlife Management, suggest that other factors, such as nutritional deficiencies, habitat fragmentation, and competition from encroaching mountain goats may play a more significant role in depressing bighorn population growth. The article is titled “A Tale of Two Markers: Population Genetics of Colorado Rocky Mountain Bighorn Sheep Estimated from Microsatellite and Mitochondrial Data.” The researchers used DNA testing to examine genetic diversity across five separate RMNP herds.

Researchers Unravel How TOPLESS Co-Repressor in Plants Interacts with Other Molecules to Turn Genes Off; Work Provides a General Model for Type of Gene Silencing

Scientists at Van Andel Research Institute (VARI), in Grand Rapids, Michigan, have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer. In plants, as in animals and humans, intricate molecular networks regulate key biological functions, such as development and stress responses. The system can be likened to a massive switchboard--when the wrong switches are flipped, genes can be inappropriately turned on or off, leading to the onset of diseases. Now, VARI scientists have unraveled how an important plant protein, known as TOPLESS, interacts with other molecules responsible for turning genes off. The findings in plants provide a general model across species for this type of gene silencing, which is linked to several vital biological functions in humans. The discovery was published in the July 3, 2015 issue of Science Advances. The article is titled "Structural Basis for Recognition of Diverse Transcriptional Repressors by the TOPLESS Family of Corepressors." This is really a fundamental discovery--our structure shows the co-repressor TOPLESS interacting with key repressor motifs, which constitutes a major component of gene silencing in plants," said Van Andel Research Institute's Karsten Melcher, Ph.D., one of the study's corresponding authors. "Understanding this interaction in plants gives us unique insight into similar pathways in humans that involve these proteins, which are notoriously tough to investigate." Using X-ray crystallography, the team determined the three-dimensional structure of TOPLESS, both on its own and when linked with other molecules responsible for turning genes off, thereby regulating gene expression.

July 24th

Scientists ID Protein of Rice Bacterial Blight Pathogen That Activiates XA21 Immune Receptor in Rice; Discovery Has Implications for Worldwide Rice Supply, Future Grass-Type Biofuel Crops, and Perhaps Even Human Disease

A bacterial signal that, when recognized by rice plants, enables the plants to resist a devastating blight disease has been identified by a multi-national team of researchers led by scientists with the U.S. Department of Energy (DOE)'s Joint BioEnergy Institute (JBEI) and the University of California (UC) Davis. The research team discovered that a tyrosine-sulfated bacterial protein called "RaxX," activates the rice immune receptor protein called "XA21." This activation triggers an immune response against Xanthomonas oryzaepv.oryzae (Xoo), a pathogen that causes bacterial blight, a serious disease of rice crops. "Our results show that RaxX, a small, previously undescribed bacterial protein, is required for activation of XA21-mediated immunity to Xoo," says Dr. Pamela Ronald, a plant geneticist for both JBEI and UC Davis, who led this study. "XA21 can detect RaxX and quickly mobilize its defenses to mount a potent immune response against Xoo. Rice plants that do not carry the XA21 immune receptor or other related immune receptors are virtually defenseless against bacterial blight." Dr. Ronald, who directs JBEI's grass genetics program and is a professor in the UC Davis Department of Plant Pathology, is one of two corresponding authors of an open-access paper describing this research that was published in the July 3, 2015 issue of Science Advances. The other corresponding author was Dr. Benjamin Schwessinger, a grass geneticist with JBEI's Feedstocks Division at the time of this study, and now with the Australian National University. The Science Advances paper is titled "The Rice Immune Receptor XA21 Recognizes a Tyrosine-Sulfated Protein from a Gram-Negative Bacterium."

Initiation of Phase 1/2a Clinical Trial of Antisense Drug for Huntington’s Disease Announced by ISIS Pharmaceuticals; ISIS Earns $22 Million Milestone Payment from Collaborator Roche

On July 21, 2015, Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today announced that it has initiated a Phase 1/2a clinical trial of ISIS-HTTRx in patients with Huntington's disease (HD). ISIS-HTTRx is the first therapy to enter clinical development that is designed to directly target the cause of the disease by reducing the production of the protein responsible for HD. HD is a rare genetic neurological disease in which patients experience deterioration of both mental abilities and physical control. Presently, there are no disease-modifying treatments for HD, with current therapies focused only on treating disease symptoms. ISIS-HTTRx has been granted orphan drug designation by the European Medicines Agency for the treatment of patients with HD. Orphan drug designation is granted to products designed to diagnose, prevent, or treat life-threatening or very serious conditions that affect not more than five in 10,000 persons in the European Union. "Although the toxic protein produced from the huntingtin (HTT) gene in HD patients has been a target of interest for many years, no therapies have advanced to clinical trials to treat the underlying cause of the disease. Our antisense technology has enabled us to discover and develop ISIS-HTTRx, the first therapeutic approach designed to treat the genetic cause of HD. Together with Roche, we are committed to investigating this approach to treat patients with HD, a devastating disease that typically affects generations of families," said C. Frank Bennett, Ph.D., Senior Vice President of Research at Isis Pharmaceuticals. "Initiating the clinical study of ISIS-HTTRx in patients with HD is the first step in developing a treatment that could significantly impact a patient's disease. It is also an important milestone in our collaboration with Roche.

Glaucoma Medication May Be Effective in Treatment of Tuberculosis, Even Drug-Resistant Forms; Effectiveness Revealed in Screening of 273,000 Compounds

A new discovery by Michigan State University (MSU) scientists suggests that a common medication used to treat glaucoma could also be used to treat tuberculosis (TB), even the drug-resistant forms. Dr. Robert Abramovitch, an MSU microbiologist, along with graduate student Benjamin Johnson, who helped lead the study, have discovered that ethoxzolamide, a sulfa-based compound found in many prescription glaucoma drugs, actually turns off the TB mycobacterium's ability to invade the immune system. The research paper was published in the August 2015 issue of Antimicrobial Agents and Chemotherapy. The article is titled “The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence.” "Basically, ethoxzolamide stops TB from deploying its weapons...shutting down its ability to grow inside certain white blood cells in the immune system," Dr. Abramovitch said. "We found the compound reduces disease symptoms in mice." According to Dr. Abramovitch, TB mycobacteria may not have eyes and ears, but they have an uncanny ability to sense certain environmental cues in the body and to adapt. One of these abilities is the organism’s ability to detect pH, which is key because particular acid levels indicate to the organism that it is being attacked by a host immune cell and prompt the organism to take effective counter-measures. "The compound we found inhibits TB's ability to detect acidic environments, effectively blindfolding the mycobacterium so it can't resist the immune system's assault," Dr. Abramovitch said. It's estimated that 2 billion people, globally, carry the TB infection, but in most cases it lies dormant and the immune system is able to prevent it from spreading through the body. "It's a standoff, however," Dr.

Mitochondrial DNA Sequencing of Butteflies on Iberian Peninsula Reveals High Level of Potentially New Species; DNA Barcode Reference Library Established; Libray Should Aid Critical Conservation Efforts

Since 2006, a team of researchers has sequenced the mitochondrial DNA of all the known species of butterflies on the Iberian peninsula (228) and its main populations. The result is a report that compiles more than 3500 genetic sequences of all the species, which have been compared to the genetic sequences of other European buttefly populations. The open-access article was published online on July 24, 2015 in Scientific Reports. It is titled “DNA Barcode Reference Library for Iberian Butterflies Enables a Continental-Scale Preview of Potential Cryptic Diversity.” The paper has 277 pages of supplementary material, including pictures and 80 maps of the geographical distribution of the butterfly genetic lineages identified. This is the first time that the butterfly community of two entire countries (Spain and Portugal) has been thoroughly analyzed. Surprisingly, the mtDNA sequences obtained suggest that up to the 28% of the analyzed species could be totally new to science. These species could have been undetected until now because of the difficulties in distinguishing them from others that are morphologically very similar. The results of this research will be very useful to guide future studies of butterfly biodiversity and improving their conservation, establishing priorities, and avoiding the mixing up of divergent lineages. "Knowing the exact number of species and differentiating them is essential for their protection," says the article’s senior author Dr. Roger Vila, Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra, Barcelona, Spain). The CSIC is the Spanish National Research Council. Also, adds Dr.

July 23rd

Exosome Market Dynamics Report (Part III) Published by GEN; “Study of Exosomes in Various Disease Classes—Cancer and Beyond”

“Exosome Market Dynamics, Part III--Study of Exosomes in Various Disease Classes—Cancer and Beyond” produced by Select Biosciences was published on July 21, 2015 by Genetic Engineering & Technology News (GEN). Authored by Gary Oosta, Ph.D., and Enal Razvi, Ph.D., this report represents the third of a series of three reports on the exosome marketplace that GEN has published (note the link to all three full reports are provided at the end of this article. In this last report, Select Biosciences examines studies of the involvement of exosomes in various classes of diseases. According to GEN’s announcement of the report, cancer is the driver of the broader exosome space, driven in large part by the study of exosomes and their cargo as potential biomarkers for cancer. In addition to cancer, other disease classes such as cardiovascular disease as well as CNS diseases are being impacted by exosomes, as evidenced by the publication record. This suggests, GEN states, that the field of exosome research is broadening and potentially can impact various diseases. The large potential opportunity emanating from all the body of research on exosomes is that the potential exists to capture and analyze exosomes from biological fluids in the hope of identifying the cargo contained within the exosomes, with the explicit aim to understand basic cell-cell communication, but also seek to develop diagnostics that leverage the power of exosomes as carriers of circulating biomarkers. Taken together, GEN says, the report’s broad-brush analysis of the entire publications record of exosomes research suggests that the field of exosomes research is now moving from the purely research phased to entering the realm of clinical translation, where studies are being performed to harvest and capture the full potential of exosomes across various disease classes.

Aromatase Inhibitors Significantly Reduce Risk of Death in Postmenopausal Women with Most Common Form of Breast Cancer (ER-Positive); Judged Superior to Tamoxifen in Study of Over 30,000 Women; Positive Biphosphonate Results Reported in Second Study

A class of hormonal drugs called aromatase inhibitors substantially reduce the risk of death in postmenopausal women with the most common type of breast cancer, a major study of more than 30,000 women shows. The research underscores the importance of aromatase inhibitors in the treatment of estrogen receptor (ER)-positive breast cancer - and shows these drugs reduce risk of death by significantly more than the older hormonal treatment tamoxifen. The study, published online on July 23, 2015 in an open-access article in The Lancet, is relevant to postmenopausal women with ER-positive breast cancer, which accounts for over 80 per cent of cases which occur after menopause. Each trial had used both aromatase inhibitors and tamoxifen at various times during the course of treatment. The article is titled “Aromatase Inhibitors Versus Tamoxifen in Early Breast Cancer: Patient-Level Meta-Analysis of the Randomised Trials.” In the study, researchers from the Aromatase Inhibitors Overview Group - chaired by Professor Mitch Dowsett at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust - collaborated with colleagues at the Clinical Trials Service Unit at The University of Oxford, to combine the results from 31,920 women in nine clinical trials. The study was funded by Cancer Research UK and the Medical Research Council (MRC) and conducted under the umbrella of the Early Breast Cancer Trialists Collaborative Group. Aromatase inhibitors suppress the synthesis of estrogens and are taken by postmenopausal women with hormone-sensitive (ER-positive) breast cancer. These inhibitors have previously been reported to reduce the risk of recurrence more effectively than tamoxifen, but improvements in survival had not been demonstrated.

Stink Bugs Can Vary Color of Their Eggs; Darker-Colored Eggs Better-Protected Against UV Radiation; Eggs Are Colored by Previously Unknown Pigment

Stink bug mothers will lay darker or lighter eggs depending on how much light is reflecting off of a surface. The newly discovered adaptation is likely related to how some species of stink bugs are able to deposit their eggs on top of leaves, as the darker-colored eggs are better protected from UV radiation. Surprisingly, the eggs are not darkened by melanin, but by a previously unknown pigment. The findings, published online on July 23, 2015 in Current Biology, were driven by the curiosity of a University of Montreal Ph.D. student (Paul Abram), who uses the stink bugs as hosts for parasitic wasps. The article is titled “An Insect with Selective Control of Egg Coloration.” Egg color variation exists in other species of animals, but how Podisus maculiventris (the spined soldier stink bug, commonly found in fields and backyard gardens across North America) selectively controls egg pigmentation based on light perception is a new take on the trait. Certain birds and insects will lay subtly differently colored eggs, but typically in response to changes in age or diet, not in response to a sensory cue from the environment. "We suspect that these bugs possess some kind of physiological system that receives visual input from the environment and then modulates the application of a pigment in real time," says lead author Abram, who is working toward his doctorate in entomology. "This is the first animal found that can selectively control egg color in response to environmental conditions, but we really doubt that it's the only one." Abram was inspired to pursue this line of research by the crossword puzzle of a newspaper lining the bottom of a stink bug cage. He noticed that darker-colored eggs tended to appear on the black squares of the puzzle and the lighter-colored eggs on the light squares.