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Archive - Oct 2015

October 13th

Gene Therapy with RPGR Gene Preserves Vision in Canine RPGR X-Linked Retinitis Pigmentosa, Even at Later Stages of Blinding Disease After Significant Loss of Photoreceptor Cells

Gene therapy preserved vision in a study involving dogs with naturally occurring, late-stage retinitis pigmentosa, according to research funded by the National Eye Institute (NEI), part of the National Institutes of Health. The findings contribute to the groundwork needed to move gene therapy forward into clinical trials for people with this blinding eye disorder, for which there is currently no cure. Scientists from the University of Pennsylvania and the University of Florida, Gainesville, also determined, for the first time, that gene therapy may be of potential benefit even after there has been significant loss of cells in the eye. Up to this point, animal studies had shown benefits from gene therapy only when it was used in the earliest stages of the disease. "The study shows that a corrective gene can stop the loss of photoreceptors in the retina, and provides good proof of concept for gene therapy at the intermediate stage of the disease, thus widening the therapeutic window," said Neeraj Agarwal, Ph.D., a program director at the NEI. Retinitis pigmentosa is one of the most common inherited diseases that causes degeneration of the retina, the light-sensitive tissue lining the back of the eye. Roughly 1 in 4,000 people are affected and about 10 to 20 percent have a particularly severe form called X-linked retinitis pigmentosa, which predominately affects males, causing night blindness by age 10 and progressive loss of the visual field by age 45. Approximately 70 percent of people with the X-linked form carry mutations that cause loss of function of the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a protein important for maintaining the health of photoreceptors. These are cells in the retina that absorb and convert light into electrical signals, which are then sent to the brain.

October 13th

Male Fruit Fly Pheromone (9-Tricosene) Marks Great Real Estate for Starting a Family; Finding May Extend to Mosquitoes and Be Useful in Malaria Control

In what they say was a lucky and unexpected finding, researchers at the Johns Hopkins University School of Medicine and the Monell Chemical Senses Center say they've discovered that male fruit flies lay down an odorant (pheromone), that not only attracts females to lay eggs nearby, but also guides males and females searching for food. The discovery, they say, offers clues about how flies, and probably other creatures, navigate complex environments and use odors to guide important behavioral decisions. "We didn't know flies could rapidly deposit pheromones in response to odors, but now we have evidence that that's the case with at least three such food odors," says Christopher Potter, Ph.D., Assistant Professor of Neuroscience at the Johns Hopkins University School of Medicine. A summary of the research findings appeared online on September 30, 2015 in an open-access article in the journal. The article is titled “Food Odors Trigger Drosophila Males to Deposit a Pheromone That Guides Aggregation and Female Oviposition Decisions.” Specifically, Dr. Potter says, experiments carried out by himself and his colleagues show that the pheromone known as 9-tricosene "flags a location as an ideal place for flies to mate, settle down, and have kids, so to speak. It's a way to help them associate mating with a food source that will give their offspring a good start in life." According to Potter, the pheromone's role was discovered serendipitously by graduate student Chun-Chieh Lin, who was testing a new experimental setup for use in other fly research. The setup involved placing flies in an enclosure shaped like a square that's been "pinched" on the sides, forming four pointed quadrants, with a glass top and bottom.

Moderate Red Wine Consumption May Help Type 2 Diabetics Manage Cholesterol & Cardiac Health; Red & White Wine Both Improve Sugar Control in Diabetics with Genetic Profiles Indicating They Are “Slow Alcohol Metabolizers”

A glass of red wine every night may help people with type 2 diabetes better manage their cholesterol and cardiac health, according to new findings from a two-year randomized controlled trial (RCT) led by researchers at Ben-Gurion University of the Negev (BGU) in Israel. Additionally, both red and white wine can improve sugar control, depending on genetic profiling indicating an individual’s rate of alcohol metabolism. In this first long-term alcohol study in diabetics, just published online opn October 13, 2015 in the Annals of Internal Medicine, the researchers aimed to assess the effects and safety of initiating moderate alcohol consumption in diabetics, and also sought to determine whether the type of wine matters. The article is titled “Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial." People with diabetes are more susceptible to developing cardiovascular diseases than the general population and have lower levels of "good" cholesterol. Despite the enormous contribution of observational studies, clinical recommendations for moderate alcohol consumption remain controversial, particularly for people with diabetes, due to lack of long-term, randomized controlled trials, which are the "holy grail" of evidence-based medicine. "Red wine was found to be superior in improving overall metabolic profiles, mainly by modestly improving the lipid profile, by increasing good (HDL) cholesterol and apolipoprotein A1 (one of the major constituents of HDL cholesterol), while decreasing the ratio between total cholesterol and HDL cholesterol," the researchers explain.

“Beeting” Altitude Sickness by Drinking Nitrate-Rich Juice to Boost Nitric Oxide Levels in Blood to Improve Compromised Blood Vessel Function

Ever since human beings first began climbing the world's tallest mountains, they have struggled with a basic problem: altitude sickness, caused by lower air pressures which affect the ability of our bodies to take up oxygen. Or, as actor Jason Clarke says in his role as the climbing guide Rob Hall in the recently released movie, Everest, "Human beings simply aren't built to function at the cruising altitude of a 747." How well humans tolerate high altitudes is highly variable, but the best way to minimize the risk of developing acute mountain sickness (AMS) is acclimatization, or simply spending enough time up high to allow the body to make adjustments to lower oxygen levels. But what if you could help your body acclimatize more quickly and thoroughly with the help of a natural substance - like beet juice? A team of Norwegian and Swedish researchers decided to see how nitrate-rich beet juice might affect acclimatization on a 39-day expedition to Kathmandu and at 3700 meters (just over 12,000 feet) in the Rolwaling Valley of Nepal. One aspect of successful acclimatization is that the blood vessels are able to deliver enough oxygen throughout the body. But normal blood vessel function depends on the body's ability to naturally produce a compound called nitric oxide (NO). In healthy people at sea level, production of adequate amounts of NO is not a problem, but with the reduced oxygen availability at high altitude it is a challenge, simply because natural NO production requires oxygen. But the body has a "back-up system" for NO production at altitude, and it is here that beet juice can help. The secret ingredient in beet juice is high levels of nitrate (NO3-), which the body can then convert to NO.

Roles of Stem-Cell-Derived Exosomes in Stromal Remodeling, Tumor Progression, and Cancer Immunotherapy

A recent open-access report, by two scientists from the University of Sao Paulo in Brazil, reviews the potential of stem-cell-derived exosomes in the context of stromal remodeling and the ability of these exosomes to generate cancer-initiating cells in a tumor niche by inducing morphologic and functional differentiation of normal fibroblasts into tumor-initiating fibroblasts. The article also discusses the immunosuppressive potential of stem-cell-derived exosomes in cancer immunotherapy and prospective applications of such exosomes in cell-free therapies in future translational medicine. The first author Farah Fatima, Ph.D., and senior author Muhammad Nalwaz, Ph.D., noted, in their article abstract, that “stem cells are known to maintain stemness at least in part through secreted factors that promote stem-like phenotypes in resident cells. Accumulating evidence has clarified that stem cells release nano-vesicles, known as exosomes, which may serve as mediators of cell-to-cell communication and may potentially transmit stem cell phenotypes to recipient cells, facilitating stem cell maintenance, differentiation, self-renewal, and repair. It has become apparent that stem cell-derived exosomes mediate interactions among stromal elements, promote genetic instability in recipient cells, and induce malignant transformation.” The article was published in the Chinese Journal of Cancer, online on September 13, 2015, and in print in the December 2015 issue of the journal. The article is titled “Stem Cell-Derived Exosomes: Roles in Stromal Remodeling, Tumor Progression, and Cancer Immunotherapy.”

[Chinese Journal of Cancer artice]

Cancer Drug Tamoxifen Boosts Innate Immune System Via Influence on Ceramides in Neutrophils; May Prove Effective Weapon Against Methicillin-Resistant Staph aureus (MRSA) Bacteria

Researchers at University of California, San Diego (UCSD) School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences have found that the breast cancer drug tamoxifen gives white blood cells (specifically, neutrophils) a boost, better enabling them to respond to, ensnare, and kill bacteria in laboratory experiments. Tamoxifen treatment in mice also enhances clearance of the antibiotic-resistant bacterial pathogen MRSA and reduces mortality. (Note: Image shows neutrophil ingesting MRSA bacteria). The study was published online on October 13, 2015 in Nature Communications. The article is titled “Tamoxifen Augments the Innate Immune Function of Neutrophils through Modulation of Intracellular Ceramide.” "The threat of multidrug-resistant bacterial pathogens is growing, yet the pipeline of new antibiotics is drying up. We need to open the medicine cabinet and take a closer look at the potential infection-fighting properties of other drugs that we already know are safe for patients," said senior author Victor Nizet, M.D., Professor of Pediatrics and Pharmacy at the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences. Dr. Nizet is also affiliated with Rady Children’s Hospital in San Diego. "Through this approach, we discovered that tamoxifen has pharmacological properties that could aid the immune system in cases where a patient is immunocompromised or where traditional antibiotics have otherwise failed." Tamoxifen targets the estrogen receptor, making it particularly effective against breast cancers that display the molecule abundantly. But some evidence suggests that tamoxifen has other cellular effects that contribute to its effectiveness, too. For example, tamoxifen influences the way cells produce fatty molecules, known as sphingolipids, independent of the estrogen receptor.

October 12th

“Extraordinary Finding!”--Malaria Plasmodium Protein (VAR2CSA) Binds to Glycosaminoglycan Sugar Molecule in Placenta; Same Molecule Also Found in Most Cancers; Malaria Parasite Protein May Target Attached Anti-Cancer Drugs to 90% of Cancer Types

Scientists at the University of British Columbia (UBC), Vancouver Coastal Health, and the BC Cancer Agency have discovered a protein from malaria that could one day help stop cancer in its tracks. This new approach, which halted the growth of various tumors in mice, was based on a discovery by collaborators at the University of Copenhagen. While exploring why pregnant women are particularly susceptible to malaria and trying to develop a vaccine to protect the more endangered pregnant women, the Copenhagen researchers found that the mosquito-borne parasite produces a protein (VAR2CSA) that binds to a particular type of sugar molecule (a glycosoaminoglycan) in the placenta. That discovery led to another; that same sugar molecule is also found in most cancers, and yet seemingly not on normal, non-placental tissue in the body. This commonality is understandable, because both cancers and placentas grow rapidly, often pushing aside other tissues in the process. The Copenhagen and Vancouver researchers realized that the sugar molecule could be a target for anti-cancer drugs, and that the malarial VAR2SA protein could provide the tool for carrying such drugs to tumors. "Scientists have spent decades trying to find biochemical similarities between placenta tissue and cancer, but we just didn't have the technology to find it," said project leader Mads Daugaard, Ph.D., an Assistant Professor of Urologic Science at UBC and a Senior Research Scientist at the Vancouver Prostate Centre, part of the Vancouver Coastal Health Research Institute. "When my colleagues discovered how malaria uses VAR2CSA to embed itself in the placenta, we immediately saw its potential to deliver cancer drugs in a precise, controlled way to tumors." To test that theory, Dr. Daugaard and colleagues enlisted the expertise of Dr.

Dysregulation of Long Non-Coding RNAs (lncRNAs) Occurs at Multiple Levels in Cancer Genomes; Changes Are “Strikingly Cancer-Type-Specific"-- Researchers ID lncRNAs Associated with 13 Types of Cancer

Growing insights about a significant, yet poorly understood, part of the genome - the so-called "dark matter of DNA" -- have fundamentally changed the way scientists approach the study of diseases. The human genome contains approximately 20,000 protein-coding genes, which represent less than 2 percent of the total total genomic DNA. An estimeated 70 percent of the genome is transcribed into non-coding RNA. [BQ Editor’s Note: There are many categories of non-coding RNAs, including a large, diverse group of RNA segments longer than 200 base pairs called long non-coding RNAs (lncRNAs), and other smaller segments that include miRNAs, snRNAs, snoRNAs, scaRNAs, gRNAs, SL RNAs, piRNAs, siRNAs, tasiRNAs, and rasiRNAs.] Nevertheless, a systematic characterization of these non-coding RNA segments, including the lncRNAs, and their alterations in human cancer, is still lacking. Most studies of genomic alterations in cancer have focused on the miniscule portion of the human genome that encodes protein. An international team, led by researchers at the Perelman School of Medicine at the University of Pennsylvania (Penn), has changed that, with respect to lncRNAs, with new research results published in the October 12, 2015 issue of Cancer Cell. The article is titled “Comprehensive Genomic Characterization of Long Non-Coding RNAs Across Human Cancers.” A team led by Lin Zhang, M.D., the Harry Fields Associate Professor of Obstetrics and Gynecology, and Chi V. Dang, M.D., Ph.D., Director of the Abramson Cancer Center, at Penn, has mined these RNA sequences more fully to identify non-protein-coding segments whose expression is linked to 13 different types of cancer. Dr. Zhang first took this approach in 2014 to identify targets for ovarian cancer. Both of these studies have been supported by the Basser Center for BRCA at Penn.

Dengue Virus Endemic and Diverse in Southern China; First Comprehensive Genomic Analysis Reveals Disturbing New Data; Complex Mix of Virus Sub-Types Suggests Greater Risk of Epidemics in the Future

The first-ever comprehensive genomic analysis of the virus (image) that causes dengue fever suggests that it may survive year-round in southern China. The study, published online on October 12, 2015 in an open-access article in the American Journal of Tropical Medicine and Hygiene, provides evidence that China may be at increased risk for more frequent and severe dengue fever outbreaks similar to the 2014 outbreak in Guangdong Province (China) that sickened more than 40,000 people. The article is titled “Dengue in China: Comprehensive Phylogenetic Evaluation Reveals Evidence of Endemicity and Complex Genetic Diversity.” "We now have compelling evidence that dengue can persist in China--in some case, up to six to eight years," said Rubing Chen, Ph.D., an evolutionary virologist at the University of Texas Medical Branch, Galveston, and lead investigator of the study. "Further, we found a surprisingly complex and diverse mix of viral subtypes represented in China, a factor that can mean greater risk of epidemic dengue in the future." Researchers have disagreed about whether dengue persists in China between disease outbreaks. Several recent studies suggested that dengue remains an imported disease in China, but these studies used small datasets. The current study provides one of the most extensive analyses to date, according to Dr. Chen, and could be a critical tool in adjusting dengue prevention and control efforts to protect millions of people in China. Dengue fever, a viral disease first recognized during outbreaks in the 1950s, is spreading rapidly as the range of the mosquitoes Aedes aegypti and Aedes albopictus that transmit it expands throughout the world.

Children Born in Summer Tend to Be Healthier Adults, Study Suggests; Higher Vitamin D Exposure in Second Trimester May Explain Effect

Children who were born in the summer are more likely to be healthy adults, suggests new research published online on October 12, 2015 in an open-access article in the journal Heliyon, published by Elsevier. The article is titled “Season of Birth Is Associated with Birth Weight, Pubertal Timing, Adult Body Size, and Educational Attainment.” The authors of the study, which involved almost half a million people in the UK, say more sunlight, and therefore higher vitamin D exposure, in the second trimester of pregnancy could explain the effect, but more research is needed. According to the study, birth month affects birth weight and age at menarche, both of which have an impact on overall health in women as adults. The environment in the womb leads to differences in early life, including before birth, that can influence health in later life. The scientists said that their findings provide support for the “fetal programming” hypothesis, refining and extending the impact that season of birth has on childhood growth and development. The researchers behind the new study, from the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, UK, looked at whether birth month had an effect on birth weight, age at menarche, adult height, and body mass index (BMI). They found that children who were born in the summer were slightly heavier at birth and taller as adults. For women, those born in summer months reached menarche slightly later than those born in winter months. No significant association with summer birth with BMI was observed. "When you were conceived and born occurs largely 'at random' - it's not affected by social class, your parents' ages, or their health - so looking for patterns with birth month is a powerful study design to identify influences of the environment before birth," said Dr.