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Archive - 2014

October 25th

Mosaic Loss of Y-Chromosome Associated with Shorter Life Span, Increased Risk of Cancer

Age-related mosaic loss of the Y chromosome (LOY) from blood cells, a frequent occurrence among elderly men, is associated with elevated risk of various cancers and earlier death, according to research presented on Tuesday, October 21, at the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San Diego. This finding could help explain why men tend to have a shorter life span and higher rates of sex-unspecific cancers than women, who do not have a Y chromosome, said Lars Forsberg, Ph.D., lead author of the study and a geneticist at Uppsala University in Sweden. LOY, which occurs occasionally as a given man’s blood cells replicate – and thus takes place inconsistently throughout the body – was first reported nearly 50 years ago and remains largely unexplained in both its causes and effects. Recent advances in genetic technology have allowed researchers to use a blood test to detect when only a small fraction of a man’s blood cells have undergone LOY. Dr. Forsberg and colleagues studied blood samples from 1,153 elderly men aged 70 to 84 years, who were followed clinically for up to 40 years. They found that men whose samples showed LOY in a significant fraction of their blood cells lived an average of 5.5 years less than men whose blood was not affected by LOY. In addition, having undergone LOY significantly increased the men’s risk of dying from cancer during the course of the study. These associations remained statistically significant when results were adjusted for men’s age and other health conditions. “Many people think the Y chromosome only contains genes involved in sex determination and sperm production,” said Jan Dumanski, M.D., Ph.D., co-author on the study and a professor at Uppsala University.

Mutation Associated with Cleft Lip and Palate in Dog and Humans Identified

Scientists studying birth defects in humans and purebred dogs have identified an association between cleft lip and cleft palate – conditions that occur when the lip and mouth fail to form properly during pregnancy – and a mutation in the ADAMTS20 gene. Their findings were presented on Sunday, October 19, at the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San Diego, California. ADAMTS stands for “A Disintegrin And Metalloproteinase with Thrombospondin Motifs” and represents a family of peptidases. 19 members of this family, including ADAMTS20, have been identified in humans. Known functions of the ADAMTS proteases include processing of procollagens and von Willebrand factor as well as cleavage of aggrecan, versican, brevican, and neurocan. These proteins have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis, and cell migration. A homologous subfamily of ADAMTSL (ADAMTS-like) proteins, which lack enzymatic activity, has also been described. “These results have potential implications for both human and animal health, by improving our understanding of what causes these birth defects in both species,” said Zena Wolf, B.S., a graduate student at the University of California, Davis, School of Veterinary Medicine. In both humans and dogs, cleft lip and cleft palate occur naturally with varying degrees of severity, and can be caused by various genetic and environmental factors. Because purebred dogs breed only with each other, there is less genetic variation to consider, making cleft lip and cleft palate easier to understand in these populations, Ms. Wolf explained. From previous studies, the researchers knew that a mutation in the dog genes DLX5 and DLX6, which are involved in face and skull development, explained 12 of 22 cases of cleft palate.

Children’s Genes Can Affect Mother’s Risk of Rheumatoid Arthritis

A child’s genetic makeup may contribute to his or her mother's risk of rheumatoid arthritis, possibly explaining why women are at higher risk of developing the disease than men. This research was presented Tuesday, October 21, at the American Society of Human Genetics (ASHG) 2014 Annual Meeting in San Diego, Californai. Rheumatoid arthritis, a painful inflammatory condition that primarily affects the joints, has been tied to a variety of genetic and environmental factors, including lifestyle factors and previous infections. Women are three times more likely to develop rheumatoid arthritis than men, with peak rates among women in their 40s and 50s. Certain versions of the immune system gene HLA-DRB1, known collectively as the shared epitope alleles, are associated with the condition. HLA genes are best known for their involvement in the immune system’s response to infection and in transplant medicine for differentiating between one’s own cells and those that are foreign. The female predilection of rheumatoid arthritis strongly suggests that factors involved in pregnancy are involved, said Giovanna Cruz, MS, graduate student at the University of California, Berkeley, and first author on the new study. “During pregnancy, you’ll find a small number of fetal cells circulating around the mother’s body, and it seems that in some women, they persist as long as several decades. Women with rheumatoid arthritis are more likely to have this persistence of fetal cells, known as fetal microchimerism, than women without the condition, suggesting that it is a potential risk factor for the development of rheumatoid arthritis,” Ms. Cruz said. “Why it happens, we don’t know, but we suspect HLA genes and their activity may be involved,” she explained.

October 8th

2014 Chemistry Nobel Awarded to Two Americans, One German for Development of Fluorescence-Based Nano-Microscopy

On October 8, 2014, The Royal Swedish Academy of Sciences announced that it had decided to award the Nobel Prize in Chemistry for 2014 to Eric Betzig (photo), Ph.D., Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA, Stefan W. Hell, Ph.D., Max Planck Institute for Biophysical Chemistry, Göttingen, and German Cancer Research Center, Heidelberg, Germany, and William E. Moerner, Ph.D., Stanford University, Stanford, CA, USA “for the development of super-resolved fluorescence microscopy.” For a long time optical microscopy was held back by a presumed limitation: that it would never obtain a better resolution than half the wavelength of light. Helped by fluorescent molecules, the Nobel Laureates in Chemistry 2014 ingeniously circumvented this limitation. Their ground-breaking work has brought optical microscopy into the nanodimension. In what has become known as nanoscopy, scientists visualize the pathways of individual molecules inside living cells. They can see how molecules create synapses between nerve cells in the brain; they can track proteins involved in Parkinson’s, Alzheimer’s, and Huntington’s diseases as they aggregate; they follow individual proteins in fertilized eggs as these divide into embryos. It was all but obvious that scientists should ever be able to study living cells in the tiniest molecular detail. In 1873, the microscopist Ernst Abbe stipulated a physical limit for the maximum resolution of traditional optical microscopy: it could never become better than 0.2 micrometers. Eric Betzig, Stefan W. Hell, and William E. Moerner are awarded the Nobel Prize in Chemistry 2014 for having bypassed this limit. Due to their achievements the optical microscope can now peer into the nanoworld. Two separate principles are rewarded.

October 7th

High-Sugar Diet No Problem for Worms with Mutant SKN-1 Gene

Imagine being able to take a pill that lets you eat all of the ice cream, cookies, and cakes that you wanted – without gaining any weight. New research from the University of Southern California (USC) suggests that dream may not be impossible. A team of scientists led by Dr. Sean Curran of the USC Davis School of Gerontology and the Keck School of Medicine of USC has found a new way to suppress the obesity that typically accompanies a high-sugar diet, pinning it down to a key gene that pharmaceutical companies have already developed drugs to target. So far, Dr. Curran's work has been carried out solely on the worm Caenorhabditis elegans (C. elegans) (image) and human cells in a petri dish – but the genetic pathway he studied is found in almost all animals from yeast to humans. Next, he plans to test his findings in mice. Dr. Curran's research is outlined in a study that was published online on October 6, 2014 in an open-access article in Nature Communications. Building on previous work with C. elegans, Dr. Curran and his colleagues found that certain genetic mutants – specifically, those with a hyperactive SKN-1 gene – could be fed incredibly high-sugar diets without gaining any weight, while regular C. elegans worms ballooned on the same diet. "The high-sugar diet that the bacteria (sic—worms) ate was the equivalent of a human eating the Western diet," Dr. Curran said, referring to the diet favored by the Western world, characterized by high-fat and high-sugar foods, such as burgers, fries, and soda. The SKN-1 gene also exists in humans, where it is called Nrf2, suggesting that the findings might translate, he said.

Natural Gene Selection Can Produce Orange Corn Rich in Provitamin A

Purdue researchers and collaborators have identified a set of genes that can be used to naturally boost the provitamin A content of corn kernels, a finding that could help combat vitamin A deficiency in developing countries and macular degeneration in the elderly. Professor of Agronomy Torbert Rocheford and fellow researchers found gene variations that can be selected to change nutritionally poor white corn into biofortified orange corn with high levels of provitamin A carotenoids - substances that the human body can convert into vitamin A. Vitamin A plays key roles in eye health and the immune system, as well as in the synthesis of certain hormones. "This study gives us the genetic blueprint to quickly and cost-effectively convert white or yellow corn to orange corn that is rich in carotenoids - and we can do so using natural plant breeding methods, not transgenics," said Dr. Rocheford, the Patterson Endowed Chair of Translational Genomics for Crop Improvement at Purdue. The research was published online on September 25, 2014 in Genetics. Vitamin A deficiency causes blindness in 250,000 to 500,000 children every year, half of whom die within a year of losing their eyesight, according to the World Health Organization. The problem most severely affects children in Sub-Saharan Africa, an area in which white corn, which has minimal amounts of provitamin A carotenoids, is a dietary mainstay. Insufficient carotenoids may also contribute to macular degeneration in the elderly, a leading cause of blindness in older populations in Europe and the U.S. Identifying the genes that determine carotenoid levels in corn kernels will help plant breeders develop novel biofortifed corn varieties for Africa and the U.S.

EpiCypher Announces Five Epigenetics Grant Winners

On October 7, 2014, EpiCypher™, Inc., announced the award of five grants for Histone Peptide Array Screening Services to researchers at Indiana University, Memorial Sloan-Kettering Cancer Center, The University of Florida, The University of Montreal, and The Structural Genomics Consortium, as part of their first annual grant program in support of chromatin biology and epigenetics research. The scientific founders of EpiCypher reviewed each grant application and selected the winners, each of whom will receive histone modification screening services employing EpiCypher’s world-class EpiTitan™ Histone Peptide Arrays, along with a statistical analysis of their protein’s or antibody’s histone modification binding profile. The grantees are: Levi Blazer, Ph.D., Structural Genomics Consortium; El Bachir Affar, Ph.D., University of Montreal; Omar Abdel-Wahab, M.D., Memorial Sloan-Kettering Cancer Center; Feng-Chun Yang, Ph.D., Indiana University School of Medicine; and Daiqing Liao, Ph.D, University of Florida. The grant recipients and their respective organizations will work individually but collaboratively with EpiCypher’s scientific team to help answer each project’s fundamental biological question. EpiCypher is dedicated to giving researchers access to the highest-quality, most productive approaches for more meaningful investigations into chromatin biology and epigenetics research. “We look forward to introducing these winners to the many benefits of our transformative products and incorporating them into their research so they can experience their advantages to chromatin research first hand,” says EpiCypher CEO Sam Tetlow.

October 6th

Nobel Prize Awarded for Discovery of GPS in Brain

The Nobel Assembly at Karolinska Institutet has today (October 6, 2014) decided to award The 2014 Nobel Prize in Physiology or Medicine with one half to John O´Keefe, Ph.D. (photo), in the UK, and the other half jointly to the wife-husband team of May-Britt Moser, Ph.D., and Edvard I. Moser, Ph.D., in Norway, for their discoveries of cells that constitute a positioning system in the brain. How do we know where we are? How can we find the way from one place to another? And how can we store this information in such a way that we can immediately find the way the next time we trace the same path? This year´s Nobel Laureates have discovered a positioning system, an “inner GPS” in the brain that makes it possible to orient ourselves in space, demonstrating a cellular basis for higher cognitive function. In 1971, Dr. O´Keefe discovered the first component of this positioning system. He found that a type of nerve cell in an area of the brain called the hippocampus was always activated when a rat was at a certain place in a room. Other nerve cells were activated when the rat was at other places. Dr. O´Keefe concluded that these “place cells” formed a map of the room. More than three decades later, in 2005, Drs. May-Britt and Edvard Moser discovered another key component of the brain’s positioning system. They identified another type of nerve cell, which they called “grid cells,” that generate a coordinate system and allow for precise positioning and pathfinding. Their subsequent research showed how place and grid cells make it possible to determine position and to navigate. The discoveries of Drs.

Glia-Secreted Exosomes Play Key Role in Functioning of Nerve Cells

Tiny vesicles containing protective substances which they transmit to nerve cells apparently play an important role in the functioning of neurons. As cell biologists at Johannes Gutenberg University Mainz (JGU) have discovered, nerve cells can enlist the aid of mini-vesicles of neighboring glial cells to defend themselves against stress and other potentially detrimental factors. These vesicles, called exosomes, appear to stimulate the neurons on various levels: they influence electrical stimulus conduction, biochemical signal transfer, and gene regulation. Exosomes are thus multifunctional signal emitters that can have a significant effect in the brain. The scientists reported these results in the September 2014 issue of The Philosophical Transactions of the Royal Society B (Biological Sciences). The researchers in Mainz already observed in a previous study that oligodendrocytes release exosomes on exposure to neuronal stimuli. These exosomes are absorbed by the neurons and improve neuronal stress tolerance. Oligodendrocytes are a type of glial cell and they form an insulating myelin sheath around the axons of neurons. The exosomes transport protective proteins such as heat shock proteins, glycolytic enzymes, and enzymes that reduce oxidative stress from one cell type to another, but also transmit genetic information in the form of ribonucleic acids. "As we have now discovered in cell cultures, exosomes seem to have a whole range of functions," explained Dr. Eva-Maria Krämer-Albers. By means of their transmission activity, the small bubbles that are the vesicles not only promote electrical activity in the nerve cells, but also influence them on the biochemical and gene regulatory level. "The extent of activities of the exosomes is impressive," added Dr. Krämer-Albers.

October 5th

Pain Receptor Found on T-Cells; Regulates Calcium Influx and Cell Activation

Researchers at the University of California, San Diego, School of Medicine have discovered that T-cells – a type of white blood cell that learns to recognize and attack microbial pathogens – are activated by a pain receptor. The study, reported online on October 5, 2014 in Nature Immunology, shows that the receptor helps regulate intestinal inflammation in mice and that its activity can be manipulated, offering a potential new target for treating certain autoimmune disorders, such as Crohn's disease and possibly multiple sclerosis. "We have a new way to regulate T-cell activation and potentially better control immune-mediated diseases," said senior author Eyal Raz, M.D., Professor of Medicine. The receptor, called a TRPV1 channel (image), has a well-recognized role on nerve cells that help regulate body temperature and alert the brain to heat and pain. It is also sometimes called the capsaicin receptor because of its role in producing the sensation of heat from chili peppers. The study is the first to show that these channels are also present on T-cells, where they are involved in gating the influx of calcium ions into cells – a process that is required for T-cell activation. "Our study breaks current dogma in which certain ion channels called CRAC are the only players involved in calcium entry required for T-cell function," said lead author Dr. Samuel Bertin, a postdoctoral researcher in the Raz laboratory. "Understanding the physical structures that enable calcium influx is critical to understanding the body's immune response." T-cells are targeted by the HIV virus and their destruction is why people with AIDS have compromised immune function. Certain vaccines also exploit T-cells by harnessing their ability to recognize antigens and trigger the production of antibodies, conferring disease resistance.