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Archive - Oct 2015

October 10th

Fungus-Farming Leaf-Cutter Ants May Be Controlled by Escovopsis Parasitic Fungus That Destroys the Ants’ Larval Food Source: Their Farmed Mutualistic Fungus

A 15-year study of leaf-cutter ants and their relatives across North and South America has found that their nests are susceptible to infection by a diverse group of specialized fungal parasites. The discovery, by biologists from Rice University, São Paulo State University in Rio Claro, Brazil, and the University of Texas at Austin (UT-Austin), could provide new clues for controlling the agricultural and garden pests. The study, which was published online on September 30, 2015 in the open –access journal Royal Society Open Science, is one of the largest ever undertaken of parasites associated with leaf-cutter ants. The study began in 2000 and involved collecting, cataloging, and analyzing samples of parasitic fungi called Escovopsis from dozens of colonies of leaf-cutter ants and their relatives in Brazil, Argentina, Panama, Mexico, and the Caribbean islands of Guadeloupe and Trinidad and Tobago. Researchers identified 61 new strains of the fungi, which attack the ants' food source. The article is titled “Shared Escovopsis Parasites Between Leaf-Cutting and Non-Leaf-Cutting Ants in the Higher Attine Fungus-Growing Ant Symbiosis.” According to Wikipedia, different species of leaf-cutter ants farm different species of fungus as mutualistic partners, but all of the fungi the ants use are members of the Lepiotaceae family. The ants actively cultivate their fungus, feeding it with freshly cut plant material and keeping it free from pests and molds. This mutualistic relationship is further augmented by another symbiotic partner, a bacterium that grows on the ants and secretes chemicals; essentially, the ants use portable antimicrobials. Leaf-cutter ants are sensitive enough to adapt to the fungi's reaction to different plant material, apparently detecting chemical signals from the fungus.

Type 2 Diabetes Risk and Body Shape in Women Are Influenced by Genetic Variant Near KLF14 Gene; KLF14 Gene Expression Regulates Hundreds of Genes Governing How and Where Fat Is Stored in Women’s Bodies; Findings Reported at ASHG 2015 Annual Meeting

A genetic variant near the KLF14 gene regulates hundreds of genes that govern how and where women’s bodies store fat, which affects their risk of developing Type 2 diabetes, according to research presented on Saturday, October 10, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore, Maryland. Specifically, different alleles, or versions, of the variant cause fat-storing cells to function differently. “At the whole-body level, these differences between alleles are not associated with changes to overall weight or body mass index, but they do affect women’s hip circumference,” explained Kerrin Small, Ph.D., Head of the Genomics of Regulatory Variation Research Group at King’s College London and lead author on the study. “Previous studies have shown that, on average, women who carry fat in their hips – those with a ‘pear-shaped’ body type – are significantly less likely to develop diabetes than those with smaller hips. Looking at the variant we studied, large-scale genome-wide association studies show that women with one allele tend to have larger hips than women with the other one, which would have a protective effect against diabetes,” she said. The variant is located near the KLF14 gene, which encodes a protein that Dr. Small and her colleagues discovered directly regulates the expression of hundreds of other genes in fat tissue. KLF14 is maternally imprinted, which means that a person’s expression of KLF14 and the resulting effects on fat tissue are determined by the version of the gene inherited from his or her mother; the father’s allele does not affect levels of this regulatory protein. Researchers first identified the relationship between the variant near KLF14 and Type 2 diabetes risk in a large, genome-wide association study of a broad population.

Key Target of Aspirin’s Active Metabolite Salicylic Acid Identified; SA Blocks Activity of HMGB1 Protein, a Very General Inflammation Trigger; Much More Potent SA Derivatives Synthesized & Also Isolated from Licorice Plant

Researchers have found that salicylic acid (main breakdown product of aspirin) targets the activities of HMGB1 (high mobility group box 1) (image), an inflammatory protein associated with a wide variety of diseases, offering hope that more powerful aspirin-like drugs may be developed. Aspirin is one of the oldest and most commonly used medicines, but many of its beneficial health effects have been hard for scientists and physicians to explain. A recent study conducted by researchers at the Boyce Thompson Institute (BTI) in Ithac, New York, in collaboration with colleagues at Rutgers University in New Jersey and at San Raffaele University and Research Institute in Italy, shows that aspirin's main breakdown product, salicylic acid, blocks HMGB1, which may explain many of the drug's therapeutic properties. The findings were published on September 23, 2015 in an open-access article in the journal Molecular Medicine. The article is titled “Aspirin′s Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses.” "We've identified what we believe is a key target of aspirin's active form in the body, salicylic acid, which is responsible for some of the many therapeutic effects that aspirin has. This protein, HMGB1, is associated with many prevalent, devastating diseases in humans, including rheumatoid arthritis, heart disease, sepsis, and inflammation-associated cancers, such as colorectal cancer and mesothelioma," said senior author Daniel Klessig, Ph.D., a Professor at BTI and Cornell University. Aspirin's pain relieving effects have long been attributed to its ability to block the enzymes cyclooxygenase 1 and 2, which produce prostaglandins--hormone-like compounds that cause inflammation and pain--a discovery that netted its discoverer, Dr. John Vane, a Nobel prize.

Antioxidants Can Double Rate of Melanoma Metastasis; New Results Reinforce Earlier Findings That Antioxidants Hasten Progression of Lung Cancer; Researchers Advise Cancer Patients to Avoid Antioxidant Supplements

Fresh research at Sahlgrenska Academy, University of Gothenburg, Sweden, has found that antioxidants can double the rate of melanoma metastasis in mice. The results reinforce previous findings that antioxidants hasten the progression of lung cancer. According to Professor Martin Bergö of the Academy, people with cancer or an elevated risk of developing the disease should avoid nutritional supplements that contain antioxidants. Researchers at Sahlgrenska Academy demonstrated in January 2014 that antioxidants hastened and aggravated the progression of lung cancer. Mice that were given antioxidants developed additional and more aggressive tumors. Experiments on human lung cancer cells confirmed the results. Given well-established evidence that free radicals can cause cancer, the research community had simply assumed that antioxidants, which destroy them, provide protection against the disease. Found in many nutritional supplements, antioxidants are widely marketed as a means of preventing cancer. Because the lung cancer studies called the collective wisdom into question, they attracted a great deal of attention. The follow-up studies at Sahlgrenska Academy have now found that antioxidants double the rate of metastasis in malignant melanoma, the most perilous type of skin cancer. The new results were published online on October 7, 2015 in Science Translational Medicine. The article is titled “Antioxidants Can Increase Melanoma Metastasis in Mice.” "As opposed to the lung cancer studies, the primary melanoma tumor was not affected," Professor Bergö says. "But the antioxidant boosted the ability of the tumor cells to metastasize, an even more serious problem because metastasis is the cause of death in the case of melanoma.

Hard-to-Detect Balanced Chromosomal Abnormalities (BCAs) May Cause Large Percentage of Neurodevelopmental Birth Defects; Findings from New MGH/Broad Institute Study Reported at ASHG 2015 Annual Meeting

Balanced chromosomal abnormalities (BCAs), a category of structural changes to the human genome, may account for a large portion of birth defects related to brain development and function, according to research presented on Saturday, October 10, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore, Maryland. BCAs are changes to the structure of an individual’s chromosomes, in which one or more fragments of DNA breaks apart from the regions around it and is reattached elsewhere in the genome, either on the same chromosome or on a different one. In their simplest form, a single fragment is moved to another region of the genome, but more complex BCAs may involve more than one fragment from more than one chromosome. Unlike chromosomal deletions or duplications, BCAs do not result in the gain or loss of any genetic material. However, they do disrupt the function of DNA at the breakpoints of the fragments involved, in both their original locations and their new ones, and BCAs have been implicated in neurodevelopmental birth defects. “We studied BCAs in 111 patients with congenital neurodevelopmental conditions and 36 with other conditions and mapped where the breakpoints were,” explained Claire Redin (photo), Ph.D., a postdoctoral researcher at Massachusetts General Hospital (MGH) and the Broad Institute, and first author on the new study. “By mapping the breakpoints, we were able to identify genes that were disrupted in patients with birth defects, which suggests that these genes play a key role in normal brain development,” she said. Because no genetic material is gained or lost, conventional tools for genome analysis cannot generally detect BCAs. Thus, they have not received much attention as a significant cause of disease. To overcome this challenge, Dr.

Agilent Technologies Shares Its Vision for Precision Medicine at ASHG 2015 Conference; Single-Cell Analysis, Liquid-Biopsies, and Enhanced Bioinformatics Are Emphasized

Agilent Technologies Inc. (NYSE:A) is sharing its vision for precision medicine this week at the annual meeting of the American Society of Human Genomics (ASHG) in Baltimore, Maryland (October 6-10). The conference is a forum for discussing recent advances in all areas of human genetics. “As new technologies and greater understanding of the causes and pathways of diseases are moving through the research-clinical continuum, they are driving a revolution in precision medicine—a revolution that is enabling physicians to identify and treat maladies earlier, more effectively, and at a lower cost,” said Herman Verrelst, Agilent Vice President and General Manager, Genomics Solutions Division and Clinical Applications Division. “Precision medicine requires precision genomics,” he said. “Agilent is focusing its efforts on developing solutions for human and reproductive genetics and cancer genetics. Our latest products, which we are showcasing at ASHG, demonstrate how Agilent is enabling clinical researchers to detect disease-associated genetic changes faster, more cost-effectively, and with confidence.” A speaker at the conference, Verrelst noted that Agilent has initiatives in place to develop products for single-cell and liquid-biopsy analyses and is currently collaborating with key laboratories. These initiatives, he said, will be important in screening for and tracking genetic changes in reproductive and cancer samples. In addition, he said, Agilent’s recent acquisition of Cartagenia enhances its bioinformatics portfolio and provides customers with access to clinical-grade data-interpretation support software to visualize, assess, and report clinical genetics data in the context of patient information.

October 9th

Geneticists Reconstruct Population History of New York City; Findings Reported at ASHG 2015 Annual Meeting

By combining genetic data, ancestry information, and electronic health records, scientists have been able to identify neighborhood-level patterns of migration in the New York City area, according to research presented on Friday, October 9, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore, Maryland. In addition to supplementing historical and census data, these sorts of findings can inform biomedical and public health efforts in New York and other locations, the study authors said. “New York City is an important point of entry and immigration, and has long been one of the major ‘melting pots’ of the world. The population structure there is complex and interesting from a variety of perspectives, including the genetic one,” said Gillian Belbin, M.S., a graduate student at the Icahn School of Medicine at Mount Sinai (ISMMS) in New York City and first author on the study. “These days, other cities such as London and Shanghai are reaching the same levels of diversity as New York, and many of our methods and findings can be applied to those cities’ populations as well,” added Eimear Kenny, Ph.D., Assistant Professor at ISMMS and senior author on the study. Ms. Belbin and her colleagues are investigating a variety of questions related to migration into New York City, population transitions among its ethnic enclaves, and effects of historical events and trends on recent generation,s as well as during the last few centuries. They are using the ISMMS BioMed Biobank (http://icahn.mssm.edu/departments-and-institutes/genomics/about/resource...), an anonymized database of electronic health record and genetic information from more than 32,000 ISMMS patients who have volunteered to share their medical data with researchers.

Researchers Study Costs of Integrating Whole Genome Sequencing into Clinical Care; Initial Findings from MedSeq Project Reported at ASHG 2015 Annual Meeting

Integrating whole genome sequencing into primary care and heart disease care is unlikely to substantially increase the costs of health care utilization and follow-up tests, according to research presented on Friday, October 9, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore, Maryland. “This finding helps to allay the worry that patients whose genomes are sequenced will run out and spend thousands of dollars on follow-up tests and care, which may or may not improve their eventual health outcomes,” said Jason L. Vassy, M.D., M.P.H., a primary care physician and co-investigator on the study at Brigham and Women’s Hospital. The cost analysis was conducted as part of the MedSeq Project (http://www.genomes2people.org/the-medseq-project/), a broader study of the best ways to integrate genome sequencing into clinical medicine and how these might impact health systems and individuals. The project has enrolled a total of 200 patients: 100 healthy adults in primary care settings and 100 adults receiving care for complex cardiomyopathy, a type of heart disease. Half of the patients in each group were randomly assigned to receive the standard of care, which included a discussion of family history of disease, and the other half received the standard of care plus whole genome sequencing, a personalized Genome Report, and a discussion of the results. Results from 108 of the 200 patients, 70 in the primary care group and 38 in the cardiology group, were included in the preliminary cost analysis presented at the ASHG annual meeting. On average, patients whose genomes were sequenced incurred a cost of $719 in follow-up tests and care over the following year, including out-of-pocket expenses, while standard treatment and follow-up averaged $430 per patient.

Tumor Microbiome Analysis Allows Genetic Classification of Colorectal Tumors; First Study to Integrate Tumor Microbiome Characteristics & Colorectal Cancer Mutations; Results Reported at ASHG 2015 Annual Meeting

By analyzing the types of gut bacteria present around colorectal tumors, researchers have found a way to predict key genetic mutations in the tumors themselves, a method that could eventually inform the development of colorectal cancer diagnostics and therapeutics. Their findings were presented on Friday, October 9, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore, Maryland. Led by Ran Blekhman, Ph.D., Assistant Professor of Genetics, Cell Biology, and Development at the University of Minnesota and senior author on the study, the researchers examined the genetic differences between colorectal tumor cells and healthy colon cells from 44 adults with colorectal cancer. They looked for correlations between specific mutations in the tumor cells and the composition of the tumor microbiome – the types of bacteria present in the tumor’s immediate environment and their relative abundance – and found relationships between the two. “Ours was the first study to analyze both of these factors together,” said Michael B. Burns, Ph.D., a postdoctoral researcher in Dr. Blekhman’s laboratory. “Previous studies have found associations between certain mutations and colorectal cancer, and between certain microbiome characteristics and cancer, but had not integrated the two,” he explained. The researchers found that in general, the more cancer-associated mutations a person’s tumor cells had, the more varied his or her tumor microbiome was. In fact, specific mutations in tumor cells were associated with the presence of specific types of bacteria in the microbiome. Together with Dan Knights, Ph.D., Assistant Professor of Computer Science and Biotechnology at the University of Minnesota, Dr.

Majority of Teens Value Results of Genetic Tests to Inform Future Life Decisions; Survey Conducted by Cincinnati Children’s Hospital; Findings Reported at ASHG 2015 Annual Meeting

The majority of adolescents in grades 7-12 would prefer to know the results of unanticipated findings found in whole exome sequencing genetic testing, even if the findings are not medically actionable until adulthood, according to survey data presented on October 9, 2015 at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore. The survey addressed secondary findings – genetic findings unrelated to the initial indication that prompted the test – gleaned from sequencing the protein-coding regions of a person’s genome. “Whole exome sequencing in minors can potentially reveal an elevated risk for a condition unrelated to the initial reason they underwent genetic testing, and there may be no medical intervention to mitigate that risk until adulthood,” said Sophia Bous Hufnagel, M.D., a pediatric geneticist at Cincinnati Children’s Hospital Medical Center and first author on the study. “Some people prefer to know about these secondary findings anyway, while others would rather not know,” she said. Clinical guidelines urge physicians to counsel adult patients through choosing which types of secondary findings, if any, are disclosed to them. For minors, however, the consensus has been to discourage disclosure, except in rare cases. “Some argue that disclosing such findings to teens would take away their right to decide later, as an adult, what they want to know. Many people also felt that disclosing results to children may cause psychological harm, especially when there are no prevention or treatment options available until adulthood – that you should just let a kid be a kid,” Dr. Hufnagel explained. “Others argue that a truly non-actionable finding does not exist and that knowledge of such results, despite available treatment options, has value and benefit in itself.