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Archive - Sep 2015

September 19th

Cell Death Enzyme RIPK3 Found to Trigger Signals from Mitochondria to Natural Killer T Cells, Activating Inflammatory Cytokines; Newly Identified Pathway Influences Both Autoimmunity and Immune Response to Tumors

Scientists at The Scripps Research Institute (TSRI) have discovered a new role for an enzyme involved in cell death. Their study shows how the enzyme, called RIPK3 (image), relays signals between the cell's mitochondria "powerhouses" and the immune system. The new study shows that this crosstalk is important, not only for launching immune responses against tumors, but also for regulating the inflammatory responses that may result in autoimmune diseases. "This finding could be helpful for developing strategies to target cancer and inflammatory diseases," said TSRI Assistant Professor of Immunology Young Jun Kang, who collaborated on the study with the laboratory of TSRI Institute Professor Richard A. Lerner, who is also the Lita Annenberg Hazen Professor of Immunochemistry at TSRI. The study was published online on September 18, 2015 in an open-access article in Nature Communications. The article is titled “Regulation of NKT Cell-Mediated Immune Responses to Tumors and Liver Inflammation by Mitochondrial PGAM5-Drp1 Signaling." Previous studies have shown RIPK3 controls the induction of a type of programmed cell death, called necroptosis, which protects the body from harmful mutations and infections. However, scientists had not fully understood RIPK3's role in the immune system. In this new study, the scientists investigated the role of RIPK3 by studying RIPK3-deficient mice. The research results suggest that RIPK3 regulates the activation of natural killer T cells (NKTs), the immune cells that play dual roles in the development of autoimmune diseases and the destruction of cancers. RIPK3 does not directly cause necroptosis; rather, it regulates the activity of a mitochondrial enzyme (PGAM5) to trigger the expression of inflammatory cytokines in NKTs.

September 18th

Nanopore DNA Sequencing Offers Four Times More Rapid Characterization of Bacteria Causing Urinary Tract Infections (UTIs) Than Conventional Culturing When Testing Heavily Infected Urine; Approach Can Also Detect Antibiotic Resistance

Urinary tract infections (UTIs) could be treated more quickly and efficiently by analyzing urine with a DNA sequencing device the size of a USB stick (see image), according to research from the University of East Anglia (UEA). Researchers used a new device called MinION to perform nanopore sequencing to characterize bacteria from urine samples four times more quickly than can be done using traditional culture methods. The new method can also detect antibiotic resistance, allowing patients to be treated more effectively and improving stewardship of diminishing antibiotic reserves. The findings will be unveiled today, Saturday, September 19, 2015, at an international four-day medical conference in San Diego, California, run jointly by the American Society for Microbiology's Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) and the International Society of Chemotherapy (ICC). The pertinent presentation is titled “MinION Nanopore Sequencing to Identify Pathogens and Resistance Genes Directly from Urine Specimens” and will be presented by Katarzyna Schmidt and Dr. Justin O'Grady, both of the UEA. Professor David Livermore, from UEA's Norwich Medical School, said: "Urinary tract infections are among the most common reasons for prescribing antibiotics. Most are mild and only affect the lower urinary tract, but a few are more troublesome. These 'ascending' UTIs cause a growing burden of hospitalizations, mostly of elderly patients.” "At worst, infection spills into the bloodstream, leading to a condition called urosepsis, which can be fatal. There were more than 30,000 cases of Escherichia coli bloodstream infection recorded in England in 2014, mostly with a urinary origin. "Antibiotics are vital, especially if bacteria have entered the bloodstream, and must be given urgently.

Genome of Darwin’s “Living Fossil” Is Sequenced in Japan; Surprisingly, This Ancient Brachiopod Genome Is Found to Be Evolving Rapidly

A group of scientists from Okinawa Institute of Science and Technology Graduate University (OIST), Nagoya University, and the University of Tokyo have sequenced the first lingulid brachiopod genome, from Lingula anatina collected at Amami Island, Japan. (Note that this press release is also available in Japanese at (http://www.eurekalert.org/pub_releases_ml/2015-09/aaft-_1091715.php). Their paper was published online on September 18, 2015 in an open-access article in Nature Communications and presents the results of their analysis of over 34,000 genes comprising the L. anatina genome and shows that, despite Lingula's reputation as a "living fossil," its genome is actively evolving. The article is titled “The Lingula Genome Provides Insights into Brachiopod Evolution and the Origin of Phosphate Biomineralization.” Brachiopods are marine invertebrates with external shells and a stalk. They are often confused with molluscs; however, the resemblance is superficial. Unlike bivalves (clams and mussels) that have shells on the sides of their bodies, brachiopod shells are on the top and bottom. As a result, the plane of symmetry in a bivalve runs along the hinge; hence the two valves are mirror images of one another. In brachiopods the plane of symmetry is perpendicular to the hinge, so that the halves of the valves mirror each other. Brachiopods are one of the first known examples of animal biomineralization, a process whereby living organisms stiffen or harden tissues with minerals. The earliest discovered brachiopod fossils date back to the early Cambrian period, approximately 520 million years ago. Brachiopods quickly spread all over the world and dominated the seas during the Paleozoic era (542-251 million years ago) and, by virtue of their mineralized shells, left an abundance of fossils.

Three Genetic Variants That Modify Huntington’s Disease Age of Onset Are Located; Two on Chromosome 15 and One on Chromosome 8; GWAS of Over 4,000 HD Patients Provides New Clues to Possible Disease Intervention

A study that took a novel approach to investigating factors affecting the emergence of symptoms of Huntington’s disease (HD) has identified at least two genome sites that house variants that can hasten or delay symptom onset. In its report in the July 30, 2015 issue of Cell, the multi-institutional research team describes how genome-wide association analysis of samples from more than 4,000 HD patients found that particular variants on two chromosomes were more common in individuals who first exhibited HD-associated movement disorders either earlier or later than would otherwise have been expected. The article is titled “Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease.” “Most previous research into ways of delaying the onset of HD symptoms have focused on studying the mutant protein in cells or in animal models, but the relevance of abnormalities in those systems to what actually happens in patients remains a huge assumption,” says James Gusella, Ph.D., Director of the Center for Human Genetic Research (CHGR) at Massachusetts General Hospital (MGH), and corresponding author of the Cell paper. “Our approach does not rely on model systems, but on DNA samples and clinical data from human patients. In essence, we are analyzing the results of a ‘clinical trial’ conducted by nature, a trial in which naturally occurring variations in genes other than the HD gene intervened to influence the course of the disease. Now it is up to scientists to figure out how those genetic interventions work and to build on them to develop effective therapies based on understanding how these processes operate in humans.” Dr.

58,000 Fruit Flies Help Answer 100-Year-Old Question on Limits of Evolution

Why do certain body shape and size relationships remain consistent over long periods? One such example is found in flies, where small wings are normally rounder than large wings. Researchers from Norway and the United States bred fruit flies to change that relationship as a way to explore the limits of evolution and shed light on a question that biologists have puzzled over for the last 100 years. Throughout the natural world, shape, physiology and behavior are strongly related to the size of the organisms. These relationships are found both within species and between species, and often remain unchanged in species separated for millions of years. For example, the hearts of small species beat much faster than those of large species, and the antlers of small deer species are smaller, relative to body size, compared to antlers of large species. Sometimes these relationships are so strong that they are considered to be laws of nature, so much so that generations of biologists over the last 100 years have wondered whether or not these relationships can be changed by natural selection. In a paper published online on September 14, 2015 in PNAS, researchers from the Norwegian University of Science and Technology's Center for Biodiversity Dynamics (CBD), the Centre for Evolutionary and Ecological Synthesis at the University of Oslo, and Florida State University now say that the answer to this question is both yes (in principle), but no (in practice). The article is titled “Complex Constraints on Allometry Revealed by Artificial Selection on the Wing of Drosophila melanogaster.” "Our results suggest that these traits can evolve, but changing these relationships creates deleterious side effects for the organism.

September 17th

Link Established Between Bovine Leukemia Virus Infection and Human Breast Cancer; If Infected with BLV, Woman Is at 3.1 Higher Risk of Having Breast Cancer; BLV-Associated Odds Ratio for Breast Cancer Exceeded Only by Genetics, Ionizing Radiation, and Age

A new study by University of California (UC) Berkeley researchers establishes for the first time a link between infection with the bovine leukemia virus and human breast cancer. In the study, published on September 2, 2015 in the open-access journal PLOS ONE, researchers analyzed breast tissue from 239 women for the presence of BLV, comparing samples from women who had breast cancer with women who had no history of the disease. They found that 59 percent of breast cancer samples had evidence of exposure to BLV, as determined by the presence of viral DNA. By contrast, 29 percent of the tissue samples from women who never had breast cancer showed exposure to BLV. “The association between BLV infection and breast cancer was surprising to many previous reviewers of the study, but it’s important to note that our results do not prove that the virus causes cancer,” said study lead author Dr. Gertrude Buehring, a Professor of Virology in the Division of Infectious Diseases and Vaccinology at UC Berkeley’s School of Public Health. “However, this is the most important first step. We still need to confirm that the infection with the virus happened before, not after, breast cancer developed, and if so, how.” BLV infects dairy and beef cattle’s blood cells and mammary tissue. The retrovirus is easily transmitted among cattle, primarily through infected blood and milk, but it only causes disease in fewer than 5 percent of infected animals. A 2007 U.S. Department of Agriculture survey of bulk milk tanks found that 100 percent of dairy operations with large herds of 500 or more cows tested positive for BLV antibodies. This may not be surprising because milk from one infected cow is mixed in with others. Even dairy operations with small herds of fewer than 100 cows tested positive for BLV 83 percent of the time.

September 16th

Small Burrowing Owls Colonize Urban Region of Buenos Aires Over Few Decades; Differing Fear of Humans Appears to Influence Non-Random Choice of Urban Versus Rural Life by the Owls

Think of the city and images of traffic, pollution, noise, and crowds spring to mind. The metropolis doesn't seem to be the most ideal habitat for any animals other than humans. However, Spanish and Argentinean scientists have demonstrated that some species, such as the burrowing owl, have spent decades closing in on the city from the country without suffering from stress. The accelerated rate of human population growth and the consequent expansion of urban areas is one of the greatest threats to the conservation of biodiversity in the world. This is due to the presence of new competitors, noise, changes to food sources, light pollution, and human disturbances. In this way, different studies suggest that, amongst other things, urban habitats can be a significant source of stress for animals living there. Yet, while the immense majority of species are not able to survive in these modified environments, others live there successfully and their populations even grow to greater numbers than in their natural environments. "This suggests that maybe urban areas are not always a source of stress," says Dr. Martina Carrete, a researcher at the Pablo de Olavide University (UPO). The new study, published online on September 8, 2015 in an open-access article in Scientific Reports, has analyzed the situation of burrowing owls (Athene cunicularia) which have colonized the city of Bahía Blanca, in the province of Buenos Aires (Argentina) in just a few decades. The results reveal that both the rural and urban individuals present the same levels of stress.

September 16th

Exosomes from Differentiating Nerve Cells Used to Cause Human Mesenchymal Stem Cells (hMSCs) to Differentiate into Neuron-Like Cells

Regenerative medicine using stem cells is an increasingly promising approach to treat many types of injury. Transplanted stem cells can differentiate into just about any other kind of cell, including neurons to potentially reconnect a severed spinal cord and repair paralysis. A variety of agents have been shown to induce transplanted stem cells to differentiate into neurons. Tufts University biomedical engineers recently published the first report of a promising new way to induce human mesenchymal stem cells (hMSCs) (see image), which are derived from bone marrow, to differentiate into neuron-like cells. That new way is treating the hMSCs with exosomes. Exosomes are very small, essentially hollow (although often filled with all sorts of biomolecules) vesicles that are secreted from virtually every, if not every, type of cell. Exosomes can contain functional proteins and genetic materials and can serve as vehicles for communication between cells. In the nervous system, exosomes are known to guide the direction of nerve growth, control nerve connection, and help regenerate peripheral nerves. In a series of experiments reported online on August 6, 2015 in an open-access article in PLOS ONE, the Tufts researchers showed that exosomes from PC12 cells (neuron-like progenitor cells derived from rats) at various stages of their own differentiation could, in turn, cause hMSCs to become neuron-like cells. Exosomes had not previously been studied as a way to induce human stem cell differentiation.

Stanford Issues Urgent Call for Revised WHO Guidelines to Address Parasitic Worm Infections Worldwide; 1.5 Billion People Now Affected in Developing World; New Study Shows Large-Scale Treatment Programs Highly Cost-Effective

Stanford University School of Medicine researchers and their colleagues are calling for an urgent re-evaluation of global guidelines for the treatment of parasitic-worm diseases in light of a new study showing that large-scale treatment programs are highly cost-effective. Parasitic-worm diseases afflict some 1.5 billion people in the developing world, causing gastrointestinal problems, anemia, wasting, and cognitive and growth deficits in children, and in some cases, liver, bladder and intestinal problems that can be fatal. About 150,000 people die of complications from these parasitic infections every year. World Health Organization (WHO) guidelines on treatment of the diseases focus only on school-aged children, as they are heavily affected by these diseases and can be easily treated in a school setting. The current guidelines call for annual or biennial treatment of children in high-prevalence areas. But the latest study, a modeling analysis of four different communities in the Ivory Coast, suggests that more frequent, community-wide treatment programs are far more beneficial, both for children and adults, and are cost-effective. "Most of the money spent on treating these diseases is focused on helping kids. But there are a lot of symptoms of disability in adults as well, and our results support the expansion of treatment to this adult population," said Nathan Lo, a third-year Stanford medical student and research associate. Moreover, treating adults benefits children by reducing the chances they will become re-infected, he said. "If you only treat children, it might help them, but they often come home to neighbors, parents, and teachers who may be infected, and the children can once again become infected," Lo said.

IRB Barcelona ID's Overexpressed MAF Oncogene As Key to Metastasis of Breast Cancer to Bone

Physicians currently have no tools to help them detect which breast cancer patients will suffer metastasis to the bone, a process that occurs in 15-20% of cases. A study led by ICREA (Catalan Institution for Research and Advanced Studies) researcher Dr. Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona), and published online on September 16, 2015 in an open-access article in the Journal of the National Cancer Institute (JNCI), has uncovered a gene that allows breast cancer cells to invade bones and create new tumors, or to metastasize. This discovery has been patented and transferred to Inbiomotion, a spin off from the IRB Barcelona and ICREA, founded at the end of 2010. Inbiomotion, led by the venture investor Ysios Capital, has developed the technology necessary to validate the marker in clinical trials, which are already underway. The JNCI article is titled “Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis.” Bone metastasis is the only type of metastasis that can be controlled, but not cured, by drugs. Treatment is only given once the metastasis has been identified, which is normally too late. Preliminary studies indicate that the same drugs used to treat metastasis could also be used to prevent it, and identifying those patients at risk of developing bone metastasis is therefore very important. “This is where the discovery made at IRB Barcelona could be of great use to clinicians and would avoid unnecessary treatment of patients who are not at risk," suggests Dr. Gomis. About one million new cases of breast cancer are diagnosed each year.