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July 14th, 2018

Antioxidant Benefits of Sleep Suggested in Fly Study

Understanding sleep has become increasingly important in modern society, where chronic loss of sleep has become rampant and pervasive. As evidence mounts for a correlation between lack of sleep and negative health effects, the core function of sleep remains a mystery. But in a new study published on July 12, 2018 in the open-access journal PLOS Biology, Dr. Vanessa Hill, Dr. Mimi Shirasu-Hiza, and colleagues at Columbia University, New York, found that short-sleeping fruit fly mutants shared the common defect of sensitivity to acute oxidative stress, and that sleep supports antioxidant processes. Understanding this ancient bi-directional relationship between sleep and oxidative stress in the humble fruit fly could provide much-needed insight into modern human diseases such as sleep disorders and neurodegenerative diseases. The article is titled “A Bidirectional Relationship Between Sleep and Oxidative Stress in Drosophila.” Why do we sleep? During sleep, animals are vulnerable, immobile, and less responsive to their environments; they are unable to forage for food, to mate, or to run from predators. Despite the cost of sleep behavior, almost all animals sleep, suggesting that sleep fulfills an essential and evolutionarily conserved function from humans to fruit flies. The researchers reasoned that if sleep is required for a core function of health, animals that sleep significantly less than usual should all share a defect in that core function. For this study, they used a diverse group of short-sleeping Drosophila (fruit fly) mutants. They found that these short-sleeping mutants do indeed share a common defect: they are all sensitive to acute oxidative stress. Oxidative stress results from excess free radicals that can damage cells and lead to organ dysfunction.

Massive Genome Havoc in Breast Cancer Is Revealed Using Long-Read Sequencing Technology from Pacific Biosciences

In cancer cells, genetic errors wreak havoc. Misspelled genes, as well as structural variations -- larger-scale rearrangements of DNA that can encompass large chunks of chromosomes -- disturb carefully balanced mechanisms that have evolved to regulate cell growth. Genes that are normally silent are massively activated and mutant proteins are formed. These and other disruptions cause a plethora of problems that cause cells to grow without restraint, cancer's most infamous hallmark. On June 28, 2018, scientists at Cold Spring Harbor Laboratory (CSHL) published online in Genome Research one of the most detailed maps ever made of structural variations in a cancer cell's genome. The map reveals about 20,000 structural variations, few of which have ever been noted due to technological limitations in a long-popular method of genome sequencing. The article is titled “Complex Rearrangements and Oncogene Amplifications Revealed by Long-Read DNA and RNA Sequencing of a Breast Cancer Cell Line.” The team, led by sequencing experts Dr. Michael C. Schatz and Dr. W. Richard McCombie, read genomes of the cancer cells with so-called long-read sequencing technology from Pacific Biosciences. This technology reads much lengthier segments of DNA than older short-read technology. When the results are interpreted with two sophisticated software packages recently published by the team, two advantages are evident: long-read sequencing is richer in terms of both information and context. It can, for instance, make better sense of repetitive stretches of DNA letters - which pervade the genome - in part by seeing them within a physically larger context.

July 14th

First-Line Treatment with Checkpoint Inhibitors Associated with Improved Overall Survival for Patients with Melanoma Brain Metastases

Among patients with cutaneous melanoma who had melanoma brain metastases (MBM), first-line treatment with a checkpoint inhibitor was associated with a 1.4-fold increase in median overall survival, according to results from a national cohort. These results were published online on July 12, 2018 in Cancer Immunology Research. The article is titled “Improved Risk-Adjusted Survival for Melanoma Brain Metastases in the Era of Checkpoint Blockade Immunotherapies: Results from a National Cohort.” The first author of the study is J. Bryan Iorgulescu, MD, postdoctoral fellow in the Department of Pathology at Brigham and Women's Hospital/Harvard Medical School and Department of Medical Oncology at the Dana-Farber Cancer Institute. Senior authors are Timothy Smith, MD, PhD, MPH, Director of the Computational Neuroscience Outcomes Center at the Department of Neurosurgery at Brigham and Women's Hospital/Harvard Medical School; and mentor to Dr. Iorgulescu, and David A. Reardon, MD, Clinical Director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. "Checkpoint blockade immunotherapies have revolutionized how we care for patients with advanced melanoma, leading to long-lasting treatment responses in many patients," said Dr. Iorgulescu. "However, many of the early clinical trials of checkpoint blockade immunotherapies included few melanoma patients with brain metastases - despite their high incidence - and so the survival benefits of these exciting therapies remained unclear for this substantial subset of patients." Dr. Iorgulescu and colleagues evaluated data collected from the National Cancer Database (NCDB), which includes information for approximately 70 percent of newly diagnosed patients with cancer in the United States.

Yale Researchers Identify Target for Novel Malaria Vaccine

A Yale-led team of researchers has created a vaccine that protects against malaria infection in mouse models, paving the way for the development of a human vaccine that works by targeting the specific protein that parasites use to evade the immune system. The study was published online on July 13, 2018 in Nature Communications. The open-access article is titled “Neutralization of the Plasmodium-Encoded MIF Ortholog Confers Protective Immunity Against Malaria Infection.” Malaria is the second leading cause of infectious disease worldwide, and took more than a half million lives in 2013. To date, no completely effective vaccine exists, and infected individuals only develop partial immunity against disease symptoms. In a prior study, senior author Richard Bucala, MD, described a unique protein produced by malaria parasites, Plasmodium macrophage migration inhibitory factor (PMIF) (image), which suppresses memory T cells, the infection-fighting cells that respond to threats and protect the body against reinfection. In the new study, Dr. Bucala and his co-authors collaborated with Novartis Vaccines, Inc. to test an RNA-based vaccine designed to target PMIF. First, using a strain of the malaria parasite with PMIF genetically deleted, they observed that mice infected with that strain developed memory T cells and showed stronger anti-parasite immunity. Next, the research team used two mouse models of malaria to test the effectiveness of a vaccine using PMIF. One model had early-stage liver infection from parasites carried by mosquitos, and the other, a severe, late-stage blood infection. In both models, the vaccine protected against reinfection. As a final test, the researchers transferred memory T cells from the immunized mice to "naïve" mice never exposed to malaria. Those mice were also protected.

July 12th

BioQuick News Wins 2018 Publishing Excellence Award

BioQuick Online News (R) (http://www.bioquicknews.com) has recently been awarded an APEX 2018 Award for Publishing Excellence in the category of Electronic Media: Electronic Publications. BioQuick has won nine consecutive previous APEX Publishing Excellence Awards in the years 2010-2018, i.e., one in every year of its existence. BioQuick presently features over 4,700 online articles on major life science advances in the last nine years and articles on topics of interest are readily accessible by means of the publication’s powerful search engine. New articles are published on a daily basis. BioQuick has readers in over 160 countries and includes a Japanese language edition (http://www.biomarket.jp/bioquicknews/) directed by Yoshimitsu Obata, MS, in Tokyo (https://biomarket.jp/). BioQuick currently offers free and open access to all of its content. To subscribe for free biweekly emailed updates of highlights from BioQuick News, please go to (http://www.bioquicknews.com/node/3817). To learn more about the highly competitive international APEX Publishing Awards, please visit the awards web site at (http://www.apexawards.com). One indicator of the overall quality of the APEX publications competition is the high caliber of organizations numbering among the winners. This year, these winners include the University of Michigan Comprehensive Cancer Center, Fox Chase Cancer Center, Hospital for Special Surgery, National Science Foundation, American Society of Clinical Oncology (ASCO), Sandia National Laboratories, NASA, Purdue University, American Society of Hematology, American Academy of Dermatology, College of American Pathologists, Thermo Fisher Scientific, Multiple Sclerosis Association of America, National Library of Medicine, and Children’s Hospital Los Angeles.

July 12th

Nitroprusside Treatment Prevents Symptoms of Schizophrenia in Tests with Rats

Researchers at the Federal University of São Paulo (UNIFESP) in Brazil have tested a treatment with sodium nitroprusside in a strain of rats that spontaneously develop some of the symptoms associated with schizophrenia. The results obtained with a group of adolescent animals suggest that preventive treatment of the disease may be possible in the future for young people considered at risk owing to cases of schizophrenia in their family history - 15% to 30% of risk cases develop the disease later in life. The research was supported by the São Paulo Research Foundation - FAPESP. The principal investigator was Dr. Vanessa Costhek Abílio, a professor in the Pharmacology Department of UNIFESP's Medical School (Escola Paulista de Medicina). The findings were published online on April 14, 2018 in CNS Neuroscience & Therapeutics. The article is titled “Sodium Nitroprusside Is Effective in Preventing and/or Reversing the Development of Schizophrenia‐Related Behaviors in an Animal Model: The SHR Strain.” "What if we could develop a safe preventive treatment for these children so as to avert development of schizophrenia in adulthood?" Dr. Abílio wondered. Schizophrenia is an incurable neuropsychiatric disorder that typically develops in late adolescence or early adulthood. Sodium nitroprusside is a salt that acts as a significant donor of nitric oxide, a powerful vasodilator. For this reason, it has been prescribed since the 1920s for severe hypertension. More recently, evidence has been found that it might also benefit patients with schizophrenia. (read about it further in this article). The experiment used rats that spontaneously become hypertensive and also display behavioral alterations. These rats belong to a strain selected in Japan in the 1960s and used since then in animal models of hypertension and cardiovascular problems.

July 11th

The Highly Complex Sugarcane Genome Has Finally Been Sequenced

CIRAD and its partners* had to use cunning to establish the first sugarcane reference sequence. The plant's genome is so complex that conventional sequencing techniques had proved useless. This meant that sugarcane was the last major cultivated plant to have its genome sequenced. (CIRAD is Centre de Coopération Internationale en Recherche Agronomique pour le Développement.) The team took up the gauntlet using a novel approach based on a discovery made at CIRAD some 20 years previously: the genome structures of sugarcane and sorghum are very similar. The term used for this is "collinearity,” which means that there is a degree of parallelism, with numerous genes occurring in the same order. Dr. Olivier Garsmeur, a CIRAD researcher and lead author of the study, was thus able to use the sorghum genome as a template to assemble and select the sugarcane chromosome fragments to sequence. "Thanks to this novel method, the reference sequence obtained for a cultivar from Réunion, R570, is very good quality", says Dr. Angélique D'Hont, a CIRAD geneticist who coordinated the study. That reference sequence is a vital step towards fully sequencing the sugarcane genome and analysing the variations between the various sugarcane varieties more effectively. Dr. D'Hont had the same experience with the banana genome in 2012. As she says, "having a reference sequence for a species radically changes all the genomic and more broadly genetic approaches for that species.” The sugarcane genome sequencing was described online on July 6, 2018 in Nature Genetics. The open-access article is titled “A Mosaic Monoploid Reference Sequence for the Highly Complex Genome of Sugarcane." As with all other cultivated plants before it, sugarcane breeding will now be able to enter the age of molecular biology.

July 10th

Risk of Tick-Borne Diseases in Oak-Dominated Forests in US Is Strongly Tied to Fluctuating Acorn Supply and Structure of Predator Community

In the eastern US, risk of contracting Lyme disease is higher in fragmented forests with high rodent densities and low numbers of resident fox, opossum, and raccoons. These are among the findings from an analysis of 19 years of data on the ecology of tick-borne disease in a forested landscape, published online on May 8, 2018 in Ecology. The article is titled “Tick‐Borne Disease Risk in a Forest Food Web.” Lyme disease is the most frequently reported vector-borne disease in the US. "Using nearly two decades of data on the forest food web, we were interested in untangling the ecological conditions that regulate the number of infected ticks in the landscape," explains Dr. Richard S. Ostfeld, a disease ecologist at the Cary Institute of Ecosystem Studies in Millbrook, New York, and one of the paper's lead authors. Long-term data were collected in Dutchess County, NY, an epicenter for Lyme disease. Variables monitored at six forested field plots (2.2 hectares each) on the grounds of the Cary Institute included: small mammals, blacklegged ticks, tick-borne pathogens, deer, acorns, and climate. Predator communities and tick infection rates were also recorded at 126 sites throughout Dutchess County over two years. Dr. Taal Levi of Oregon State University, also a lead author, notes, "Our goal was to identify ecological indicators that could be used to protect public health. By analyzing these long-term data holistically, we can tease out how changes in things like predator populations and food resources shift the community structure of the forest ecosystem, and ultimately the abundance of infected blacklegged ticks searching for a meal." Blacklegged ticks take a single blood meal at each of their three life stages: larva, nymph, and adult.

July 8th

New Targets Found for Potential Reduction of Blood Vessel Damage in Diabetes; Exosomes May Play Role in Possible Delivery Systems

In diabetes, both the tightly woven endothelial cells that line our blood vessels and the powerhouses that drive those cells start to come apart as early steps in the destruction of our vasculature. Now scientists have evidence that these breakups occur as another relationship falls apart. Levels of the enzyme PDIA1, which enables a healthy homeostasis of endothelial cells, as well as production of new blood vessels, decrease in diabetes, while activity of Drp1, a key regulator of fission regulated by PDIA1, goes way up, Medical College of Georgia scientists reported in the June 19, 2018 issue of Cell Reports. Their open-access article is titled “Redox Regulation of Mitochondrial Fission Protein Drp1 by Protein Disulfide Isomerase Limits Endothelial Senescence.” The imbalance drives endothelial cells and their powerhouses apart, setting up a vicious cycle where too much reactive oxygen species (ROS), gets made by the mitochondria, says Dr. Masuko Ushio-Fukai (photo), vascular biologist in the Vascular Biology Center and Department of Medicine at MCG at Augusta University. Powerhouses further fragment, more Drp1 gets oxidized and activated, and even more ROS gets produced, says the study's corresponding author. "Fission induces fragmentation which induces more ROS which contributes to Drp1 oxidation," says Dr. Ushio-Fukai of the mounting feedback loop. The biological glue that helps hold endothelial cells together begins to come apart and so do the previously tightly connected cells. "It's very leaky and promotes inflammatory cells, like macrophages, to the endothelial cells which causes even more disruption," Dr. Ushio-Fukai says.

July 8th

mTORC1 Protein Complex Serves As Bridge Between Environmental Signals and Metabolic Programs to Influence Fate of Developing T Cells

Like a mentor helping medical students choose between specialties, a protein complex helps shape the destiny of developing T cells, St. Jude Children's Research Hospital scientists have reported. The research was published in the July 6, 2018 issue of Science Immunology and adds to growing evidence of the critical role cell metabolism plays in the immune system. The article is titled “Metabolic Signaling Directs the Reciprocal Lineage Decisions of αβ and γδ T Cells.” The protein complex is mTORC1, which regulates cell growth and metabolism. St. Jude immunologists found that mTORC1 acts in response to cues from in and around developing T cells, and intersects with metabolic activity, to influence whether the cells become conventional or unconventional T cells. To their surprise, researchers found that disrupting mTORC1 led to metabolic changes that favored development of unconventional T cells at the expense of conventional T cells. The research comes amid excitement about harnessing the immune system to fight cancer, tame autoimmune diseases, and combat infectious diseases. "We know that conventional and unconventional T cells are fundamentally different," said corresponding author Hongbo Chi (photo), PhD, a member of the St. Jude Department of Immunology faculty. "They express different cell surface receptors. The cells have different functions. But until now, the mechanism that helps decide their fates has remained largely unknown." T cells play a central role in the adaptive immune system, functioning like elite commando units trained to find and eliminate specific viruses and other threats. T cell development occurs in the thymus after immature (precursor) cells in the bone marrow travel there to mature and specialize.