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Archive - Oct 12, 2015

“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.

3D Structure of Biologically Active DNA Revealed in Unprecedented Detail; Myriad Beautiful & Unexpected Shapes Seen in Dynamic Super-Coiled DNA; Hinges May Make Tightly Wound DNA More Open Than Thought

Researchers at the Baylor College of Medicine (USA) and the University of Leeds (UK) have imaged, in unprecedented detail, the three-dimensional structure of supercoiled DNA, revealing that its shape is much more dynamic than the well-known linear double-helix. Various DNA shapes, including figure-8's, were imaged using a powerful microscopy technique by researchers at Baylor, and then examined using supercomputer simulations run at the University of Leeds. As reported online on October 12, 2015 in an open-access article published in Nature Communications, the simulations also show the dynamic nature of DNA, which constantly wiggles and morphs into different shapes - a far cry from the commonly held idea of a rigid and static double-helix structure. Improving the understanding of what DNA looks like when it is in the cell will help us to design better medicines, such as new antibiotics or more effective cancer chemotherapies, the researchers suggest. "This is because the action of drug molecules relies on them recognizing a specific molecular shape - much like a key fits a particular lock," said Dr. Sarah Harris from the School of Physics and Astronomy at the University of Leeds, who led the computer simulation research side of the study. The Nature Communications article is titled “'The Structural Diversity of Supercoiled DNA.” The double-helix shape has a firm place in the public's collective consciousness. It is referenced in popular culture and often features in art and design. But the shape of DNA isn't always that simple. Dr. Harris said: "When Watson and Crick described the DNA double-helix, they were looking at a tiny part of a real genome, only about one turn of the double helix. This is about 12 DNA base pairs, which are the building blocks of DNA that form the rungs of the helical ladder.

Key Virulence Factors of Human Malaria Parasite Much More Ancient Than Thought; Intact Gene Segments Were Exchanged and Evolved in Plasmodium Sub-Genus in Apes Before Emergence of Human Malaria Parasiste (P. falciparum)

The malaria parasite (Plasmodium falciparum) (image) molecules associated with severe disease and death--those that allow the parasite to escape recognition by the immune system--have been shown to share key gene segments with chimp and gorilla malaria parasites, which are separated by several millions of years of evolution, according to a new study led by researchers at the Harvard T.H. Chan School of Public Health. This new information about the origin and genetics of human malaria virulence factors could aid in basic understanding of the causes of malaria and provide targets for drugs and vaccines. The study was published online on October 12, 2015 in an open-access article in Nature Communications. The article is titled “ "Ape Parasite Origins of Human Malaria Virulence Genes.” "The evolution of these key virulence determinants doesn't occur in the same way as in other pathogens. Instead of gradually changing by mutation, as the flu virus, these malaria parasites exchange intact gene segments, like shuffling a deck of cards," said Caroline Buckee, Ph.D., Assistant Professor of Epidemiology at Harvard’s Chan School and senior author of the study. Malaria kills more than 500,000 people a year, mostly children in Sub-Saharan Africa. Severe disease syndromes in human malaria--including severe malarial anemia, pregnancy-associated malaria, and cerebral malaria--have been linked with the malaria parasite's ability to cause infected red blood cells to bind to the inner lining of blood vessels. This ability of the infected cells to adhere in this way--which is key to malaria's virulence--is linked with certain genes called var genes.