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September 29th, 2014

Researchers Explain 38-Year Mystery of Heart Failure: Disordered Structure of Troponin I

In a new study published online on September 22, 2014 in PNAS, researchers at the University of Alberta's Faculty of Medicine & Dentistry in Canada have explained how the function of a key protein in the heart changes in heart failure. Heart disease is the number-one killer in the developed world. The end stage of heart disease is heart failure, in which the heart cannot pump enough blood to satisfy the body's needs. Patients become progressively short of breath as the condition worsens, and they also begin to accumulate fluid in the legs and lungs, making it even more difficult to breathe. The molecular structure of the heart muscle changes as heart failure progresses, though scientists cannot always agree on what changes are good or bad. One change that occurs is an increase in "calcium sensitivity." Calcium ions are pumped in and out of the muscle cell with each heartbeat, turning contractions on and off. When the calcium sensitivity increases, contractility increases, but at a price: the relaxation of the heart becomes slower. Both phases of cardiac function are important: impaired contraction leads to systolic heart failure, while impaired relaxation leads to diastolic heart failure. Both types of heart failure are similar in terms of overall prevalence, symptoms, and mortality. Since 1976, medical researchers have known that the heart regulates its calcium sensitivity by phosphorylating a key cardiac protein called troponin I. The troponin complex is made up of three proteins, C, I, and T, which trigger muscle contraction in response to calcium. In heart failure, the phosphate groups are removed from troponin I, but it wasn't known how this caused an increase in calcium sensitivity. Dr.

Oilseed Boosts Liver Detoxification Enzymes

University of Illinois (U of I) scientists have found compounds that boost liver detoxification enzymes nearly fivefold, and they've found them in a pretty unlikely place—the crushed seeds left after oil extraction from an oilseed crop used in jet fuel. "The bioactive compounds in Camelina sativa (image) seed, also known as “Gold of Pleasure,” are a mixture of phytochemicals that work together synergistically far better than they do alone. The seed meal is a promising nutritional supplement because its bioactive ingredients increase the liver's ability to clear foreign chemicals and oxidative products. And that gives it potential anti-cancer benefit," said Dr. Elizabeth Jeffery, a U of I professor of nutritional toxicology. Oilseed crops, including rapeseed, canola, and camelina, contain some of the same bioactive ingredients—namely, glucosinolates and flavonoids—found in broccoli and other cruciferous vegetables and in nearly the same quantities, she noted. Because the oil from oilseed crops makes an environmentally friendly biofuel, scientists have been hoping to find a green use for the protein-rich seed meal left after oil extraction. Animal feed was the obvious choice, but there were a couple of problems. Some rapeseed glucosinolates are toxic, and producers have balked at paying Canada for canola seed, the low-glucosinolate rapeseed that country had developed. Dr. Jeffery thought Camelina sativa was worth a look so she began to work with USDA scientist Dr. Mark Berhow. In the first study of camelina's bioactive properties, Dr. Berhow isolated four major components—three glucosinolates and the flavonoid quercetin—from its defatted seed meal. Back at Dr. Jeffery's U of I lab, researchers began to test these components on mouse liver cells both individually and together.

September 29th

Mountain Pine Beetles Getting Bad Rap for Fires, Study Says

Mountain pine beetles (image) get a bad rap, and understandably so. The grain-of-rice-sized insects are responsible for killing pine trees over tens of millions of acres in the Western U.S. and Canada over the last decade. But contrary to popular belief, these pests may not be to blame for more severe wildfires like those that have recently swept through the region. Instead, weather and topography play a greater role in the ecological severity of fires than these bark-boring beetles. New research led by the University of Wisconsin-Madison and the Washington State Department of Natural Resources provides some of the first rigorous field data to test whether fires that burn in areas impacted by mountain pine beetles are more ecologically severe than in those not attacked by the native bug. In a study published online on September 29, 2014 in PNAS, UW-Madison zoology professor Dr. Monica Turner and her graduate student, Brian Harvey, show that pine beetle outbreaks contributed little to the severity of six wildfires that affected more than 75,000 acres in the Northern Rocky Mountains in 2011. They also show that the beetle outbreaks, which occurred from 2000 through 2010, have not directly impacted post-fire recovery of the forests. The study does not, however, address fire behavior, such as how quickly fires spread or how dangerous they are to fight. While the findings may exonerate the insect scapegoats, they should also help ecosystem managers better respond to changes in the face of climate-driven disturbances, like drought and warmer temperatures. Large, severe fires are typical in the lodgepole pine forests found throughout the region, even without mountain pine beetle outbreaks. However, as the climate has warmed, outbreaks and big fires have both become more common.

Erectile Dysfunction Drugs Could Affect Vision of Genetically Susceptible Users

Sildenafil, the active ingredient in the erectile dysfunction drug Viagra®, could cause unusual visual responses in people who carry a common mutation for eye disease and may have long-term detrimental effects on their vision, University of New South Wales (UNSW) Australia researchers warn. Sildenafil can inhibit an enzyme which is important for transmitting light signals from the retina to the brain, and it is already known from clinical trials of Viagra® that its use in high doses can cause transient disturbances in the vision of some healthy people. "Side effects can include sensitivity to bright light, blurred vision, and altered color vision," says Dr. Lisa Nivison-Smith, of the UNSW School of Optometry and Vision Science. "We are concerned that people who have normal vision, but who carry a single copy of the mutant gene for the blinding disease, retinitis pigmentosa, could be more susceptible to these changes." A team led by Dr. Nivison-Smith and UNSW's Professor Michael Kalloniatis studied the effects of a single dose of sildenafil on normal mice and mice with a single copy of the mutant gene. The results were published online on September 17, 2014 in the journal Experimental Eye Research. They found the normal mice had a transient loss of visual function after sildenafil treatment, but this effect was heightened in the mice with the mutation, and the response lasted longer. They also found early signs of cell death in the eyes of carrier mice, but not in the normal mice, suggesting sildenafil may cause degeneration in carriers of retinal disease. "These finding are highly significant because about one in 50 people are likely to be carriers of recessive genes which cause retinal disease but are unlikely to know this, because their vision is normal," says first author of the study, Dr. Nivison-Smith.

Dolphins Are Attracted to Magnets

Dolphins are indeed sensitive to magnetic stimuli, as they behave differently when swimming near magnetized objects. So say Dr. Dorothee Kremers and her colleagues at the Ethos unit of the Université de Rennes in France, in a study published online on September 30, 2014 in the journal Naturwissenschaften – The Science of Nature. The research, conducted in the delphinarium of Planète Sauvage in France, provides experimental behavioral proof that these marine animals are magnetoreceptive. Magnetoreception implies the ability to perceive a magnetic field. It is supposed to play an important role in how some land and aquatic species orientate and navigate themselves. Some observations of the migration routes of free-ranging cetaceans, such as whales, dolphins, and porpoises, and their stranding sites have suggested that they may also be sensitive to geomagnetic fields. Because experimental evidence in this regard has been lacking, Dr. Kremers and her colleagues set out to study the behavior of six bottlenose dolphins in the delphinarium of Planète Sauvage in Port-Saint-Père. This outdoor facility consists of four pools, covering 2,000 square meters of water surface. The scientists watched the animals’ spontaneous reaction to a barrel containing a strongly magnetized block or a demagnetized one. Except from this characteristic, the blocks were identical in form and density. The barrels were therefore indistinguishable as far as echolocation was concerned, the method by which dolphins locate objects by bouncing sound waves off them. During the experimental sessions, the animals were free to swim in and out of the pool where the barrel was installed. All six dolphins were studied simultaneously, while all group members were free to interact at any time with the barrel during a given session.

Zone in with Zon--Oligonucleotide Therapeutics & Nanomedicine--Feel the Heat!

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, dated September 29, 2014, focuses on nanomedicine and was triggered by consideration of the upcoming Oligonucleotide Therapeutics Society (OTS) annual meeting on October 12-15, 2014 in San Diego, Californiaq and an intriguing scheduled presentation by Professor Weihong Tan—an extraordinarily prolific researcher at the University of Florida—entitled “DNA-based molecular medicine and nanomedicine.” First, Dr. Zon attempts to define nanomedicine, but runs into the problem that multiple different definitions exist in the literature. After considerable research, he comes up with a relevant list of key nanomedicine comments provided in an editorial in the International Journal of Nanomedicine (IJM): (a) “Although defining a term such as nanomedicine may sound simple, by comparing several main funding agencies from around the world, one quickly realizes that a uniform international definition of nanomedicine does not currently exist. This is typical of a new field, but can be problematic to those trying to understand the field, make significant contributions to it, and especially in how the public views nanomedicine.” (b) “[In NIH’s 2006] Roadmap for Medical Research in Nanomedicine, [it] is defined as ‘an offshoot of nanotechnology [that] refers to highly specific medical interventions at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve.’” (c) “[N]anomedicine emerged from nanotechnology which is generally defined by the creation and use of materials at the level of molecules and atoms (sometimes specifically less than 100 nm, other times this dimension is more diffuse and confusing).” Dr. Zon seizes upon this last point, a size-based definition, as being particularly pertinent. Dr.

September 28th

Primate Genome Study Reveals Ongoing Battle to Control “Jumping Genes” with Specific Repressor Proteins, Driving Evolution of Ever-Greater Genomic Complexity

New findings by scientists at the University of California, Santa Cruz (UC Santa Cruz), suggest that an evolutionary arms race between rival elements within the genomes of primates drove the evolution of complex regulatory networks that orchestrate the activity of genes in every cell of our bodies. The arms race is between mobile DNA sequences known as "retrotransposons" (also known as "jumping genes") and the genes that have evolved to control them. The UC Santa Cruz researchers have, for the first time, identified genes in humans that make repressor proteins to shut down specific jumping genes. The researchers also traced the rapid evolution of the repressor genes in the primate lineage. Their findings, published online on September 28, 2014 in Nature, show that, over evolutionary time, primate genomes have undergone repeated episodes in which mutations in jumping genes allowed them to escape repression, which drove the evolution of new repressor genes, and so on. Furthermore, their findings suggest that repressor genes that originally evolved to shut down jumping genes have since come to play other regulatory roles in the genome. "We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about," said Dr. Sofie Salama, a research associate at the UC Santa Cruz Genomics Institute who led the study. Retrotransposons are thought to be remnants of ancient viruses that infected early animals and inserted their genes into the genome long before humans evolved. Now they can only replicate themselves within the genome. Depending on where a new copy gets inserted into the genome, a jumping event can disrupt normal genes and cause disease.

Researchers ID Early Sign of Pancreatic Cancer

Collaborating scientists at Dana-Farber Cancer Institute, the Massachusetts Institute of Technology (MIT), and other institutions have discovered a sign of the early development of pancreatic cancer – an upsurge in certain amino acids that occurs before the disease is diagnosed and symptoms appear. The research is being published online on September 28, 2014 in Nature Medicine. Although the increase isn't large enough to be the basis of a new test for early detection of the disease, the findings will help researchers better understand how pancreatic cancer affects the rest of the body, particularly how it can trigger the sometimes deadly muscle-wasting disease known as cachexia. "Most people with pancreatic ductal adenocarcinoma (PDAC) (by far the most common form of cancreatic cancer) are diagnosed after the disease has reached an advanced stage, and many die within a year of diagnosis," said Brian Wolpin, M.D., M.P.H., of Dana-Farber, co-senior author of the new study with Matthew Vander Heiden, M.D., Ph.D., of MIT and Dana-Farber. "Detecting the disease earlier in its development may improve our ability to treat it successfully. In this study, we asked whether PDAC produces metabolic changes – changes in the way the body uses energy and nutrients – that can be detected before the disease is diagnosed." The researchers utilized blood samples collected years earlier from 1,500 people participating in large health-tracking studies. The scientists analyzed the samples for more than 100 different metabolites – substances produced by the metabolic process – and compared the results from participants who had gone on to develop pancreatic cancer and those who had not.

Camels Are Primary Source of MERS-CoV Transmission, NIH Study Suggests

National Institutes of Health (NIH) and Colorado State University (CSU) scientists have provided experimental evidence supporting dromedary camels as the primary reservoir, or carrier, of Middle East respiratory syndrome coronavirus (MERS-CoV). The study, designed by scientists from CSU and NIH's National Institute of Allergy and Infectious Diseases (NIAID), involved three healthy camels exposed through the eyes, nose, and throat to MERS-CoV isolated from a patient. Each camel developed a mild upper respiratory tract infection consistent with what scientists have observed throughout the Middle East. Samples taken from the camels showed high levels of infectious virus in secretions, primarily from the nose, for up to a week after infection; the scientists detected components of the virus for up to 35 days. Although the camels quickly recovered from infection without apparent complications, the researchers say the nasal secretions provide a likely source of transmission to people who handle the animals. The researchers theorize that vaccinating camels could reduce the risk of MERS-CoV transmission to people and other camels; NIAID and others are supporting research to develop candidate vaccines for potential use in people and camels. The MERS outbreak, which began in 2012, continues throughout the Middle East. Since the outbreak began, NIAID researchers have focused on understanding how the virus causes disease and how it can be treated effectively. As of July 23, 2014, the World Health Organization has reported a total of 837 human cases of MERS-CoV infection, including at least 291 deaths. The open-access article describing the current study was published online, ahead of print, in Emerging Infectious Diseases, produced by the CDC, and is scheduled for print publication in December 2014.

September 27th

Discovery of Branched Carbon Molecule in Space Supports Interstellar Origin of Life

Hunting from a distance of 27,000 light years, astronomers have discovered an unusual carbon-based molecule – one with a branched structure – contained within a giant gas cloud in interstellar space. Like finding a molecular needle in a cosmic haystack, astronomers have detected radio waves emitted by isopropyl cyanide. The discovery suggests that the complex molecules needed for life may have their origins in interstellar space. Using the Atacama Large Millimeter/submillimeter Array, known as the ALMA Observatory, a group of radio telescopes funded partially through the National Science Foundation, researchers studied the gaseous star-forming region Sagittarius B2. Astronomers from Cornell, the Max Planck Institute for Radio Astronomy, and the University of Cologne describe their discovery in the September 26, 2014 issue of Science. Organic molecules usually found in these star-forming regions consist of a single “backbone” of carbon atoms arranged in a straight chain. But the carbon structure of isopropyl cyanide branches off, making it the first interstellar detection of such a molecule, says Dr. Rob Garrod, Cornell senior research associate at the Center for Radiophysics and Space Research. This detection opens a new frontier in the complexity of molecules that can be formed in interstellar space and that might ultimately find their way to the surfaces of planets, says Dr. Garrod. The branched carbon structure of isopropyl cyanide is a common feature in molecules that are needed for life – such as amino acids, which are the building blocks of proteins. This new discovery lends weight to the idea that biologically crucial molecules, like amino acids that are commonly found in meteorites, are produced early in the process of star formation – even before planets such as Earth are formed. Dr.