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Archive - Apr 12, 2015

Selenide Can Reduce Heart Muscle Damage After Cardiac Arrest by Nearly 90% If Administered Before Blood Flow Restored; Action Apparently Supplements Body’s Naturally Protective Mechanism of Providing Selenide to Injured Tissue

Damage to heart muscle from insufficient blood supply during cardiac arrest and reperfusion injury after blood flow is restored can be reduced by nearly 90 percent if selenide, a form of the essential nutrient selenium, is administered intravenously in the wake of the attack, according to a new preclinical study by researchers at Fred Hutchinson Cancer Research Center in Seattle, Washington. Mark Roth, Ph.D., and colleagues in the Fred Hutch Basic Sciences Division have published their findings online on April 6, 2015 in Critical Care Medicine. The article is titled “"Selenide Targets to Reperfusing Tissue and Protects it From Injury.” "We found that administration of selenide after the heart has been deprived of blood flow and before blood flow is restored significantly protects the heart tissue in a mouse model of acute myocardial infarction and reperfusion injury," Dr. Roth said. Ischemia, or insufficient blood supply, as occurs during a heart attack or stroke, causes tissues to become starved of oxygen. In the highly oxygenated tissues of the heart and brain, ischemia can cause irreversible damage in as little as three to four minutes at normal body temperature. Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function. Using two different mouse models of ischemia reperfusion injury, Dr. Roth and colleagues found that selenium is specifically taken up by injured tissues following temporary loss of blood flow while blood selenium levels simultaneously decrease.

First Small Molecule Inhibitors of mRNA-Binding HuR Oncoprotein Identified; Results Hold Promise for Possible Treatments of Wide Variety of Cancers; Molecules May Be Active in Inhibiting Cancer Stem Cells

A team of scientists at the University of Kansas (KU) has pinpointed six chemical compounds that thwart HuR, an "oncoprotein" that binds to RNA and promotes tumor growth. The findings, which could lead to a new class of cancer drugs, were published online on March 9, 2015 in the journal ACS Chemical Biology. The article is titled “Identification and Validation of Novel Small Molecule Disruptors of HuR-mRNA Interaction.” "These are the first reported small-molecule HuR inhibitors that competitively disrupt HuR-RNA binding and release the RNA, thus blocking HuR function as a tumor-promoting protein," said Liang Xu, M.D., Ph.D., Associate Professor of Molecular Biosciences and corresponding author of the paper. The results hold promise for treating a broad array of cancers in people. The researcher said HuR has been detected at high levels in almost every type of cancer tested, including cancers of the colon, prostate, breast, brain, ovaries, pancreas, and lung. "HuR inhibitors may be useful for many types of cancer," Dr. Xu said. "Because HuR is involved in many stem cell pathways, we expect HuR inhibitors will be active in inhibiting 'cancer stem cells,' or the seeds of cancer, which have been a current focus in the cancer drug discovery field." HuR has been studied for many years, but, until now, no direct HuR inhibitors have been discovered, according to Dr. Xu. "The initial compounds reported in this paper can be further optimized and developed as a whole new class of cancer therapy, especially for cancer stem cells," he said. "The success of our study provides a first proof-of-principle that HuR is druggable, which opens a new door for cancer drug discovery. Many other RNA-binding proteins like HuR, which are so far undruggable, can also be tested for drug discovery using our strategy."

NMR Study of Xylan in Wood Reveals Unexpected Shape of This Polymer in Cell Walls; Discovery Could Accelerate Use of Plants for Renewable Materials, Energy, and Building Construction

Major steps forward in the use of plants for renewable materials, energy and for building construction could soon arise, thanks to a key advance in understanding the structure of wood. The step forward follows research by the Universities of Warwick and Cambridge and the unexpected discovery of a previously unknown arrangement of molecules in plant cell walls. The paper describing this work was Editors' Choice for the American Chemical Society (ACS) for March 25, 2015. The article, titled “Probing the Molecular Architecture of Arabidopsis thaliana Secondary Cell Walls Using Two- and Three-Dimensional 13C Solid State Nuclear Magnetic Resonance Spectroscopy,” was published online on March 4, 2015 in the ACS journal Biochemistry. As an Editor’s Choice article, the paper is fully and freely available as an open-access publication. The researchers investigated the polymer xylan, which comprises a third of wood matter. Professor Ray Dupree from the University of Warwick, one of the research's authors, says: "Using advanced NMR techniques we found that the xylan polymer, which comprises about a third of wood, has an unexpected shape inside the plant cell walls." The structure of the xylan was ascertained by creating 2D maps of the molecular structure of the woody stalks of thale cress in the UK's most advanced solid-state Nuclear Magnetic Resonance (NMR) Facility, based at the University of Warwick. Professor Paul Dupree of the University of Cambridge (son of Professor Ray Dupree) says, "For the first time, we have been able to study the arrangement of molecules in woody plant materials. Plant cell walls provide the mechanical strength to plants. This major step forward in understanding the molecular architecture of plant cell walls will impact the use of plants for renewable materials, energy, and for building construction."

Kyoto University Scientists Discover How Nerve Cells Adjust to Low Energy Environments During Brain’s Growth Process

Scientists from Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) in Japan have have discovered how nerve cells adjust to low energy environments during the brain's growth process. The new study, published in the April 8, 2015 issue of the Journal of Neuroscience, may one day help find treatments for nerve cell damage and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The article is titled "Synergistic Action of Dendritic Mitochondria and Creatine Kinase Maintains ATP Homeostasis and Actin Dynamics in Growing Neuronal Dendrites." Neurons in the brain have extraordinarily high energy demands due to its complex dendrites that expand to high volume and surface areas. It is also known that neurons are the first to die from restriction of blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism. Little was known, however, about how cells adjust to low energy level environments in the developing brain, when mitochondria--the so-called "power plants" of the cell--do not get delivered on time, and a lag in the energy distribution occurs, which may lead to a variety of neurodegenerative disorders. To unlock the mystery, the research team studied mitochondria and energy consumption in a live, growing nerve cell over the course of a week. "If neurons try to grow in low ATP energy levels, they could end up deformed, and even worse, put the life of the cell itself at stake," said Dr. Kansai Fukumitsu, who was involved in the study.

TGen Uses Personalized Whole-Exome Sequencing to Successfully Determine Genetic Causes of Six Rare, Difficult-to-Diagnose, and Difficult-to-Treat Neuromuscular Disease (NMD) Cases

Scientists at the Translational Genomics Research Institute (TGen) in Arizona, using state-of-the-art genetic technology, have discovered the likely cause of a child's rare type of severe muscle weakness. The child was one of six cases in which TGen sequenced -- or decoded -- the genes of patients with neuromuscular disease (NMD) and was then able to identify the genetic source, or likely genetic source, of each child's symptoms, according to a study published online on April 8, 2015 in the journal Molecular Genetics & Genomic Medicine. The article is titled “Novel Pathogenic Variants and Genes for Myopathies Identified by Whole Exome Sequencing.” According to the researchers, “neuromuscular diseases (NMDs) account for a significant proportion of infant and childhood mortality and devastating chronic disease. Determining the specific diagnosis of NMD is challenging due to thousands of unique or rare genetic variants that result in overlapping phenotypes.” "In all six cases of myopathy, or muscle weakness, these children had undergone extensive, expensive and invasive testing -- often over many years -- without a successful diagnosis, until they enrolled in our study," said Dr. Lisa Baumbach-Reardon, an Associate Professor of TGen's Integrated Cancer Genomics Division and the study's senior author. This is a prime example of the type of "personalized medicine" TGen uses to zero in on diagnoses for patients, and to help their physicians find the best possible treatments. "Our results demonstrate the diagnostic value of a comprehensive approach to genetic sequencing," said Dr. Baumbach-Reardon. "This type of next-generation sequencing can greatly improve the ability to identify pathogenic, or disease-causing, genetic variants with a single, timely, affordable test."