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Archive - Jun 1, 2015

94-Protein Network Regulates Fat Storage in Yeast; Graph Theory Predictions Are Confirmed in Yeast Network Experiments; Removal of Proteins with Highest “Centrality Scores” Has Largest Effect on Yeast Fat Production, Caltech/Princeton Study Shows

A team of biologists and a mathematician has identified and characterized a network composed of 94 proteins that work together to regulate fat storage in yeast. "Removal of any one of the proteins results in an increase in cellular fat content, which is analogous to obesity," says study co-author Dr. Bader Al-Anzi, a research scientist at Caltech. The findings, published on May 28, 2015 in the open-access journal PLOS Computational Biology, suggest that yeast could serve as a valuable test organism for studying human obesity. The article is titled “"Experimental and Computational Analysis of a Large Protein Network That Controls Fat Storage Reveals the Design Principles of a Signaling Network." "Many of the proteins we identified have mammalian counterparts, but detailed examinations of their role in humans has been challenging," says Dr. Al-Anzi. "The obesity research field would benefit greatly if a single-cell model organism such as yeast could be used--one that can be analyzed using easy, fast, and affordable methods." Using genetic tools, Dr. Al-Anzi and his research assistant Patrick Arpp screened a collection of approximately 5,000 different mutant yeast strains and identified 94 genes that, when removed, produced yeast with increases in fat content, as measured by quantitating fat bands on thin-layer chromatography plates. Other studies have shown that such "obese" yeast cells grow more slowly than normal, an indication that in yeast, as in humans, too much fat accumulation is not a good thing. "A yeast cell that uses most of its energy to synthesize fat that is not needed does so at the expense of other critical functions, and that ultimately slows down its growth and reproduction," Dr. Al-Anzi says.

Study Suggests Surprising Possible Role for Staph aureus in Causing Type 2 Diabetes

Bacteria and viruses have an obvious role in causing infectious diseases, but microbes have also been identified as the surprising cause of other illnesses, including cervical cancer (human papilloma virus) and stomach ulcers (H. pylori bacteria). A new study by University of Iowa microbiologists now suggests that bacteria may even be a cause of one of the most prevalent diseases of our time, i.e., type 2 diabetes. The research team led by Patrick Schlievert, Ph.D., Professor and DEO of Microbiology at the University of Iowa (UI) Carver College of Medicine, found that prolonged exposure to a toxin produced by Staphylococcus aureus (Staph) bacteria causes rabbits to develop the hallmark symptoms of type 2 diabetes, including insulin resistance, glucose intolerance, and systemic inflammation. "We basically reproduced type 2 diabetes in rabbits simply through chronic exposure to the Staph superantigen," Dr. Schlievert says. The UI findings suggest that therapies aimed at eliminating Staph bacteria or neutralizing the superantigens might have potential for preventing or treating type 2 diabetes. Obesity is a known risk factor for developing type 2 diabetes, but obesity also alters a person's microbiome, i.e., the ecosystem of bacteria that colonize our bodies and affect our health. "What we are finding is that as people gain weight, they are increasingly likely to be colonized by Staph bacteria - to have large numbers of these bacteria living on the surface of their skin," Dr. Schlievert says. "People who are colonized by Staph bacteria are being chronically exposed to the superantigens the bacteria are producing." Dr.

Sixth Gene Mutation Causing Achromatopsia Identified; Inherited Disease Reduces or Eliminates Color Vision and Causes Extreme Sensitivity to Light; Newly Discovered Mutated Gene (ATF6) Normally Regulates Unfolded Protein Response

People with achromatopsia, an inherited eye disorder, see the world literally in black and white. Worse yet, their extreme sensitivity to light makes them nearly blind in bright sunlight. Now, researchers at University of California (UC), San Diego School of Medicine and the Shiley Eye Institute at UC San Diego Health System have identified a previously unknown gene mutation that underlies this disorder, as do five other previously known gene mutations. The study was published online on June 1, 2015 in Nature Genetics. The article is titled “Mutations in the Unfolded Protein Response Regulator ATF6 Cause the Cone Dysfunction Disorder Achromatopsia.” "There are whole families with this sort of vision problem all over the world," said Jonathan Lin, M.D., Ph.D., senior study author and an Associate Professor in the UC San Diego School of Medicine Department of Pathology. "We're very excited to have discovered a mutation in the ATF6 (activating transcription factor 6) gene which plays a major role in this disorder." As noted, five other genetic mutations have previously been identified by research groups as pivotal in achromatopsia, which causes markedly reduced visual acuity and very poor or no color vision. "But we still had families that didn't have any of those gene mutations," said Dr. Lin, also a researcher at the UC San Diego Shiley Eye Institute. "We knew this meant there must be other genes and proteins involved." The current study, which involved an international collaboration of inherited retinal disease specialists, found that a mutation in the ATF6 gene damaged proteins necessary for proper function of the eye's cone photoreceptors. The eye has millions of these receptors, which control color recognition and daytime vision.

Cannabis Use in Male African Pygmies Linked to Decreased Risk of Parasitic Worm Infection

In a population of Congo Basin foragers called the Aka, better known as “pygmies,” 67% of men—but only 6% of women—use cannabis, and the practice seems to protect against infection with parasitic worms. The large sex difference, which is also seen in tobacco use, might be a consequence, in part, of women's avoidance of potentially toxic substances during childbearing years. The results provide evidence of a link between parasite infection and drug use, two of the developing world's great health problems, and they highlight the need for more research on the high rate of substance use in Aka men. “Recreational drug use is rarely studied in hunter gatherers. We’re intrigued by the possible link between cannabis use and parasitic worms, which resembles the self-medication behavior seen in numerous species,” said Dr. Edward Hagen, Department of Anthropology, Washington State University, and senior author of the American Journal of Human Biology open-access study, which was published online on May 29, 2015. “We need to be cautious, though, in generalizing from one study in a unique population to other populations.” The AJHB article is titled “High Prevalence of Cannabis Use among Aka Foragers of the Congo Basin and Its Possible Relationship to Helminthiasis.” The researchers noted that cannabis might not be the only recreational drug that protects against parasites. “Our previous research showed that tobacco use also seems to protect against parasitic infection, and many other recreational drugs contain antiparasitic compounds,” said first author Dr. Casey Roulette, also from Washington State University. The two additional authors, Dr. Mirdad Kazanji and Dr. Sébastien Breurec, are from the Institute Pasteur, Bangui, Central African Republic.

ASCO News: MD Anderson’s James Allison Honored by ASCO for His Achievements in Cancer Immunotherapy

The world's leading organization of oncologists has honored Jim Allison, Ph.D., for his pioneering research that led to a new way to treat cancer by unleashing an immune system attack rather than targeting tumors directly. Dr. Allison, Chair of Immunology at The University of Texas MD Anderson Cancer Center, received the Science of Oncology Award during the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting in Chicago on Sunday, May 31. In its announcement of the award, ASCO noted Allison's "research on T-cell response mechanisms and cancer's evasion of attack by the immune system led to the clinical development of ipilimumab to block CTLA-4 and its approval as a melanoma treatment." Ipilimumab, known commercially as Yervoy, thwarts CTLA-4, a protein receptor on T cells that acts as a brake on immune response. Long-term follow-up of patients with late-stage melanoma showed that 22 percent of those treated with Yervoy survived at least four years, unprecedented results for the disease. Importantly, those who survived three years have gone on to live up to 10 years and beyond. Other immune checkpoints have been identified and targeted, and checkpoint blockade has become one of the most promising areas of cancer treatment. Because the approach treats the immune system rather than tumors directly, it is spreading through clinical trials to treat other cancer types. "I'm grateful for this recognition from ASCO and optimistic that immune checkpoint blockade, in rational combination with other therapies, may prove to be curative for many patients across different types of cancer," Dr. Allison said. His award lecture was titled “Immune Checkpoint Blockade in Cancer Therapy: New Insights, Opportunities, and Prospects for a Cure.” Dr.

Compendium of Cardiovascular Drugs and Genetic Variants Affecting Different Responses Authored by Stanford and U. Chicago Physicians; Published in Mayo Clinic Proceedings; Impact of This Now-Readily-Accessible Information Could Be “Prodigious”

There is a wealth of published information describing interactions between drugs used to treat cardiovascular disease and the genetic variations that can affect how patients respond to them. But few heart specialists make routine use of this potentially life-saving data. To help physicians make better-informed clinical decisions, researchers from the University of Chicago and Stanford University combed through scientific literature on the pharmacogenomics of 71 leading cardiovascular drugs and compiled summaries, published in an article in the June 2015 issue of the Mayo Clinic Proceedings, where it was named the “Editor’s Choice” article. This article is titled “Evidence for Clinical Implementation of Pharmacogenomics in Cardiac Drugs.” The article is accompanied by an open-access editorial in the Mayo Clinic Proceedings. The editorial is titled “Clinical Implementation of Cardiovascular Pharmacogenomics.” "Tens of thousands of patients have been studied and the connections between common medications and the genetic variants that can lead to adverse drug reactions or treatment non-response have been described, but few physicians track this information or even know where to find it," said study author Peter H. O'Donnell, M.D., Assistant Professor of Medicine at the University of Chicago. "One dose does not fit all," he said. "So we set out to boost awareness and simplify access. We assessed the quantity and quality of the literature, ranked the most relevant studies for clinicians and condensed the data into a series of prescribing decision aids." Cardiovascular drugs are a common cause of the estimated two million adverse drug reactions that occur each year in the United States. More than 50,000 patients are treated in emergency rooms annually for bad reactions to cardiovascular drugs.

Ancient Diatoms Found in Glacial Ice in Peru: First Such Discovery in Tropical Glaciers; “Irreplaceable Snapshots in Archeological Time and Space,” Author States

The remains of tiny creatures found deep inside a mountaintop glacier in Peru are clues to the local landscape more than a millennium ago, according to a new study by scientists at Rice University, the University of Nebraska-Lincoln, and Ohio State University. The unexpected discovery of diatoms, a type of algae, in ice cores pulled from the Quelccaya Summit Dome Glacier demonstrate that freshwater lakes or wetlands that currently exist at high elevations on or near the mountain were also there in earlier times. The abundant organisms would likely have been transported in air currents to the glacier, where they were deposited on its surface, dead or alive, and ultimately became frozen within the glacial ice and persisted there for hundreds of years. The study is the first to show the presence of diatoms in glacial ice from tropical regions. The diatoms offer useful information about conditions in and around the Andes when they were deposited on the ice. The paper is the result of a unique collaboration among Rice chemists Dr. Ed Billups and Dr. Bruce Brinson, Ohio State climatologist Dr. Lonnie Thompson and lead author Dr. Sherilyn Fritz, a geoscientist at the University of Nebraska. The article was published in the May 2015 issue of Arctic, Antarctic, and Alpine Research, a journal published by the University of Colorado-Boulder. Of the four scientists, Dr. Billups, Dr. Brinson and even Dr. Thompson had something in common with the focus of their study: They were all, figuratively, fish out of water. "I was the lucky latecomer to the group," said Dr. Fritz, who studies diatoms from cores she and her students drill from South American lakebeds. "It's only because Bruce was so observant and curious and did such a nice job on documenting the diatoms that it happened at all." Over a long and storied career, Dr.

ASCO News: Low Dose of Modified Polio Virus Works Best in Promising Duke Glioblastoma Trial

A modified polio virus therapy that is showing promising results for patients with glioblastoma brain tumors works best at a low dosage, according to the research team at Duke's Preston Robert Tisch Brain Tumor Center where the investigational therapy is being pioneered. This trial was recently described on television’s 60 Minutes on March 29, 2015 and a report was written up the same day in BioQuick News (see link below). Details of the Duke therapeutic protocol can be found in the BioQuick article and attached references. According to more recent news, the dosage findings for the first 20 patients in the phase 1 trial will be presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago that runs from May through June 2 (abstract #2068). "The purpose of a phase 1 trial is to identify the optimal dose to minimize toxicity," said Annick Desjardins, M.D., lead author of the ASCO presentation and Director of Clinical Research at the Brain Tumor Center in the Duke Cancer Institute. "Our trial design included escalating to higher doses, which is what is done with chemotherapy. "For chemotherapy, we are trained to give the largest dose possible with acceptable toxicity, because that is how the drugs work to attack tumors," Dr. Desjardins said. "But that does not appear to be necessary with our therapy, and, in fact, a lower dose attacks the tumor as well and results in fewer side effects." At the higher doses, Dr. Desjardins and colleagues report, inflammation at the tumor site increased the severity of side effects, including weakness and seizures. Patients required prolonged steroid use to reduce the inflammation, but this also dampened the immune response that the modified polio virus is designed to initiate.