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July 12th, 2015

Vitamin A Directs Innate Immune Cells to Proper Locations in Intestine

A key set of immune cells that protect the body from infection would be lost without directions provided by vitamin A, according to the results of a recent study. A team of researchers from Purdue University found that retinoic acid, a metabolite that comes from digested vitamin A, is necessary for two of the three types of innate immune cells that reside in the intestine to find their proper place. "It is known that vitamin A deficiencies lead to increased susceptibility to disease and low concentrations of immune cells in the mucosal barrier that lines the intestines," said Dr. Chang Kim, the Professor and Section Head of Microbiology and Immunology in Purdue's College of Veterinary Medicine who led the research. "We wanted to find the specific role the vitamin plays in the immune system and how it influences the cells and biological processes. The more we understand the details of how the immune system works, the better we will be able to design treatments for infection, and autoimmune and inflammatory diseases." Within the immune system there are two categories of cells that work together to rid the body of infection: innate immune cells, the innate lymphoid cells and leukocytes that are fast-acting and immediately present to eliminate infection; and adaptive immune cells, the T-cells and B-cells that arrive later, but are specific to the pathogen and more effective at killing or neutralizing it. All innate immune cells are produced in the bone marrow, but eventually populate other areas of the body. Innate lymphoid cells, which include the group studied by Dr. Kim, are present in barrier tissues. While it is known that innate lymphoid cells are concentrated in the intestines, it has been unknown how these cells find their way there, Dr. Kim said.

UCLA Scientists Show Rare Coding Variants Affecting Protein Function Are More Common in Schizophrenics; Results Support Origin of Schizophrenia During Early Stages of Brain Development

A new study by UCLA scientists adds to the understanding of the genetic architecture of schizophrenia. Past research has shown the impact of commonly occurring genetic variants on a person’s risk of developing schizophrenia. This new study focused instead on rare coding mutations that affect protein function. It found that people with schizophrenia have a higher-than-normal share of these mutations. “While we cannot point to specific mutations that play a causal role in schizophrenia, we show that schizophrenia patients, collectively, have more of these mutations than unaffected individuals,” said Dr. Loes Olde Loohuis, the study’s first author and a postdoctoral fellow at UCLA’s Center for Neurobehavioral Genetics. The Center is part of the UCLA’s Jane and Terry Semel Institute for Neuroscience and Human Behavior. The findings were published online on July 9, 2015 in an open-access article in Nature Communications. The article is titled “Genome-Wide Burden of Deleterious Coding Variants Increased in Schizophrenia.” “Genes that are affected by these mutations play a key role in fetal brain development,” said Dr. Roel Ophoff, the study’s senior author and a principal investigator at the Center for Neurobehavioral Genetics. “Our finding further supports the hypothesis that schizophrenia is a disorder that may originate during the early stages of brain development.” A professor of psychiatry and human genetics, Dr. Ophoff has conducted research on the genetic basis of schizophrenia for the past decade. He is also one of the founding members of the Psychiatric Genomics Consortium’s schizophrenia study group. The consortium is an international collaboration of researchers investigating the genetics of schizophrenia and related disorders.

Research Identifies Genetic Signatures in Sorghum Wheat Associated with Abilities to Adapt to Different Environmental Stressors; Findings May Aid Farmers in World’s Toughest Crop-Growing Regions

A new study led by a Kansas State University geneticist has shown that genomic signatures of adaptation in crop plants can help predict how crop varieties respond to stress from their environments. It is the first study to document that these genomic signatures of adaptation can help identify plants that will do well under certain stresses, such as drought or toxic soils, said Dr. Geoff Morris, Assistant Professor of Agronomy at Kansas State University and a researcher affiliated with the University's Feed the Future Innovation Lab for Collaborative Research on Sorghum and Millet. Researchers conducted the study with sorghum, one of the oldest and most widely grown cereal grain crops in the world. Sorghum is grown in Africa and Asia, as well as in some of the world's harshest crop-growing regions. More than 43,000 sorghum varieties around the world have been collected and stored in crop gene banks, which are centers that serve as repositories for crop diversity. "While sorghum is grown in some of the toughest climates in the world, we need to continue to increase the amount of grain it produces and its resilience to harsh environments because nearly half a billion people depend on sorghum as a staple food source," Dr. Morris said. "We want this important crop plant to produce more food and have less loss." Sampling from the crop gene banks, Dr. Morris and colleagues at Cornell University and the International Crops Research Institute for Semi-Arid Tropics, or ICRISAT, took "snapshots" of genetic information in the genomes of about 2,000 sorghum varieties. Because each sorghum variety was from a particular known location in an African or Indian village, the researchers were able to tie the genetic differences of each variety to its survival in a particular environment. With this data, Dr. Morris and colleague Dr.

Retrosplenial Cortex Is “Junction” in Brain Where Different Forms of Location Information Are Combined and Organized, Enabling Successful Navigation; Defects Seen in Early Alzheimer’s

Ever wake at night needing a drink of water and then find your way to the kitchen in the dark without stubbing your toe? Researchers at the University of California, San Diego (UCSD) say they have identified a region of the brain that enables you to do that - and generally helps you navigate the world. Dr. Douglas Nitz, Associate Professor of Cognitive Science in the UCSD Division of Social Sciences, and graduate student Andrew Alexander worked with rats, also known as "navigational geniuses," recording the firing activity of neurons while the animals ran on a zigzag track in different locations, to show that the retrosplenial cortex appears to be critical in putting together all the information necessary for successfully getting from point A to point B. They describe their findings in a paper published online on July 6, 2015 in the journal Nature Neuroscience. The article is titled “Retrosplenial Cortex Maps the Conjunction of Internal and External Spaces.” The world we and other animals navigate is complex and non-linear, quite unlike the way a proverbial crow flies. The authors say our ability to get around its numerous indirect points depends, at minimum, on mapping our position within the environment, knowing routes that take us between locations, and an awareness of the correct actions to initiate at any given time: turn right, turn left, go straight. Currently, we know that cells encoding these different forms of spatial knowledge are stored in different neural structures. Place cells and grid cells are neurons in the hippocampal circuit that are responsible for mapping the position of an animal with respect to the broader environment.

July 11th

Exosome Market Dynamics Report (Part II) Published by GEN; Deep Analysis of Molecular Entities Associated with Exosomes

“Exosome Market Dynamics, Part 2” produced by Select Biosciences was published on July 9, 2015 by Genetic Engineering & Technology News (GEN). Authored by Gary Oosta, Ph.D., and Enal Razvi, Ph.D., this report represents the second of a series of three reports on the exosome marketplace that GEN plans on publishing. This second report is the Select Biosciences in-depth analysis of the association of various molecular entities — genetic elements, small RNA species (microRNAs), as well as traditional cancer protein biomarkers — with exosomes. These emerging associations are important because they provide an opportunity to explore the biomarker potential of exosomes and the potential deployment in the future of exosomes as circulating biomarkers class for biofluid/liquid biopsy development. According to GEN’s announcement of this second report, the key takeaways from the data and analysis presented are that there are very specific associations of molecular species with exosomes — indeed these are merely research associations and do not represent bona fide biomarkers because these research associations need to be validated across clinical samples in many studies for their potential utility as biomarkers to be harvested. With regard to the authors, Gary M. Oosta holds a Ph.D. in Biophysics from Massachusetts Institute of Technology and a B.A. in Chemistry from Eastern Michigan University He has 25 years of industrial research experience in various technology areas including medical diagnostics, thin-layer coating, bio-effects of electromagnetic radiation, and blood coagulation. Dr. Oosta has authored 20 technical publications and is an inventor on 77 patents worldwide. In addition, he has managed research groups that were responsible for many other patented innovations. Dr.

Aethlon Common Stock to Begin Trading on NASDAQ on Monday; Key Product is Hemopurifier to Eliminate Infectious Viruses and Cancer-Promoting Exosomes from Circulation; Exosome Sciences Is Wholly-Owned Subsidiary of Aethlon

On July 8, 2015, Aethlon Medical, Inc. (OTCQB:AEMD), the pioneer in creating affinity biofiltration devices to treat life-threatening diseases, announced that the Company's application to list its common stock on the Nasdaq Capital Market has been approved by The NASDAQ Stock Market LLC. Aethlon's common stock is expected to begin trading on the Nasdaq Capital Market at the opening of market hours on Monday, July 13, 2015 under its existing trading symbol, AEMD. "Trading on Nasdaq is a pivotal corporate milestone that will help raise the visibility of our therapeutic endeavors and increase the appeal of our shares to mutual funds, pension funds, and other institutional investors that may have previously been restricted from trading our shares," stated Jim Joyce, Chairman and CEO of Aethlon Medical. Aethlon Medical creates affinity biofiltration devices to treat life-threatening diseases. The company’s lead therapeutic candidate is the Aethlon Hemopurifier® (image), a first-in-class device that targets the rapid elimination of infectious viruses and cancer-promoting exosomes from the circulatory system of treated individuals. U.S. clinical progression of Hemopurifier therapy is being advanced under an FDA approved clinical study. The company also provides government contracting services to the Defense Advanced Research Projects Agency related to the development of a biofiltration device to treat sepsis. Also of note is that the start-up company Exosome Science, Inc. (ESI), is a wholly-owned subsidiary of Aethlon Medical, Inc. ESI creates diagnostic tools to detect and quantify the presence of exosomes in blood and other fluids.

Legumes Distinguish Friendly from Pathogenic Bacteria & Fungi Using First Known Exopolysaccharide Receptor; Research Alters Understanding of Carbohydrates As Signaling Molecules

An international team of researchers has discovered how legumes are able to tell helpful and harmful invading bacteria (and fungi) apart. The research has implications for improving the understanding of how other plants, animals, and humans interact with bacteria in their environment and defend themselves against hostile infections. These findings can have profound implications for both agricultural research and medical science. The study, which changes the understanding of carbohydrates as signal molecules, was published online on June 27, 2015 in the leading international journal Nature. The article is titled “A Plant Receptor-Like Kinase Required for Both Bacterial and Fungal Symbiosis.” Legumes form a unique symbiotic relationship with bacteria known as rhizobia, which the the legumes allow to infect their roots. This leads to root nodules being formed in which the bacteria convert nitrogen from the air into ammonia that the plant can use for growth. Exactly how these plants are able to distinguish and welcome compatible rhizobia for this self-fertilizing activity - while halting infection by incompatible bacteria - has been a mystery. Now the researchers at the Centre for Carbohydrate Recognition and Signalling (CARB) from Denmark and New Zealand and their collaborators from the Centre for Complex Carbohydrate Research in Georgia, USA, have determined how legumes perceive and distinguish compatible bacteria based on the exopolysaccharides featured on the invading cells' surfaces. Using an interdisciplinary approach involving plant and microbial genetics, biochemistry, and carbohydrate chemistry, the researchers have identified the first known exopolysaccharide receptor gene, called Epr3.

University of Chicago Innovation Fund Awards $150,000 to Therapeutic Human Exosome Project for Multiple Sclerosis & Migraine; Two Other Projects Also Receive Significant Funding

On July 7, 2015, it was announced that three teams from the University of Chicago and Argonne National Laboratory are one step closer on the journey to commercializing their innovative discoveries and technology. They have each been selected to receive funding from the University of Chicago Innovation Fund. The Innovation Fund awards grants and invests in promising technologies and start-ups created by University of Chicago faculty, students, and staff. Since its inception, the Fund has invested over $3.1 million in 35 projects with high potential for societal and commercial impact. For the Spring 2015 cycle, the Innovation Fund awarded funding to 3F4AP, a PET tracer created to reveal lesions associated with multiple sclerosis during a PET scan; to Therapeutic Human Exosomes, a biologic designed to repair de-myelinated neurons in multiple sclerosis; and to the Array of Things, an urban sensing network of interactive, modular sensor boxes built by Urban Center for Computation and Data (UrbanCCD. The Array of Things collects real-time data on the city’s environment, infrastructure, and activity, bringing the Internet of Things to the “built environment,” and essentially creating a “fitness tracker” for the city. Details of the three funded projects are provided here. 3F4AP: The 3F4AP team has developed a PET tracer that could help reveal important targeted hallmarks of multiple sclerosis. PET tracers are radioactive molecules that, when injected into a subject, can reveal disease-relevant features such as tumors or lesions in the brain during a PET scan. The team took a drug that is typically used to treat MS (4-aminopyridine) and converted it into a PET tracer, which they believe will help doctors visualize demyelinated lesions in the brain and provide a way to monitor response to new remyelinating therapies.

Huge Concern: Bumblebees Being Pushed from Heating South of Europe and North America Due to Climate Change, But Failing to Extend Their Northern Range; Vital Pollinators Being Lost

Researchers from the University of Calgary and the University of Ottawa have made an astonishing find when it comes to the habitat range of bumble bees, and the results are troubling. Findings published in the July 10 issue of Science, demonstrate that climate change is having a significant impact on bumblebee species in North America and Europe. The article is titled “Climate Change Impacts on Bumblebees Converge Across Continents.” Bumblebees are losing vital habitat in the southern regions of North America and Europe, which is cause for concern, but another pressing issue is that bumblebee species generally haven't expanded north," explains Dr. Paul Galpern, Assistant Professor of Landscape Ecology in the Faculty of Environmental Design, University of Calgary, co-author of study. "Climate change may be making things too hot for them in the south, but is not pulling them north as expected," says Dr. Galpern. For many wildlife species, when climate warms, they expand into areas that used to be too cold for them, pushing into areas that are closer to the North Pole in response. Bumblebee species are experiencing a different fate and being held at their northern-most range, while losing ground rapidly in the south. "Picture a vice, now picture the bumble bee habitat in the middle of the vice," says Dr. Jeremy Kerr, Professor and University Research Chair in Macroecology and Conservation, University of Ottawa, and lead researcher of the study. "As the climate warms, bumblebee species are being crushed as the 'climate vice' compresses their geographical ranges. The result is widespread, rapid declines of pollinators across continents, effects that are not due to pesticide use or habitat loss.

Primary Cilia, Dysfunctional Autophagy, and Perhaps Even Exosomes May Be Key to Pathology in Huntington’s Disease

In a new review article, scientists suggest that there may be an important link between primary cilia and dysfunctional autophagy and the pathology of Hungtington’s disease (HD). The authors also hint at a possible role for exosomes that may be secreted by primary cilia. The review was published online July 10, 2015 in Cell Death & Differentiation. The article is titled “Primary Cilia and Autophagic Dysfunction in Hungtington’s Disease.” The scientists noted that “because protein misfolding and aggregation are central features of HD, it has long been suspected that cellular housekeeping processes such as autophagy might be important to disease pathology. Indeed, multiple lines of research have identified abnormal autophagy in HD, characterized generally by increased autophagic induction and inefficient clearance of substrates. To date, the origin of autophagic dysfunction in HD remains unclear and the search for actors involved continues. To that end, recent studies have suggested a bidirectional relationship between autophagy and primary cilia, which are oft-overlooked signaling organelles of most mammalian cells and novel regulators of autophagy. Interestingly, primary cilia structure is defective in HD, suggesting a potential link between autophagic dysfunction, primary cilia and HD pathogenesis. In addition, because polyQ-HTT also accumulates in primary cilia, the possibility exists that primary cilia might play additional roles in HD: perhaps by disrupting signaling pathways or acting as a reservoir for secretion and propagation of toxic, misfolded polyQ-HTT fragments.” According to the authors, primary cilia are single, non-motile organelles found on the surface of most mammalian cells.