Syndicate content

Archive - 2014

November 24th

How Environment and Oxidized Nucleotides Contribute to Several Human Diseases

Using a new imaging technique, NIH researchers have found that the biological machinery that builds DNA can insert molecules into the DNA strand that are damaged as a result of environmental exposures. These damaged molecules trigger cell death that produces some human diseases, according to the researchers. The work, published online on November 17, 2014 in Nature, provides a possible explanation for how one type of DNA damage may lead to cancer, diabetes, hypertension, cardiovascular and lung disease, and Alzheimer’s disease. Time-lapse crystallography was used by National Institute of Environmental Health Sciences (NIEHS) researchers to determine that DNA polymerase, the enzyme responsible for assembling the nucleotides or building blocks of DNA, incorporates nucleotides with a specific kind of damage into the DNA strand. Time-lapse crystallography is a technique that takes snapshots of biochemical reactions occurring in cells. Samuel Wilson, M.D., senior NIEHS researcher on the team, explained that the damage is caused by oxidative stress, or the generation of free oxygen molecules, in response to environmental factors, such as ultraviolet exposure, diet, and chemical compounds in paints, plastics, and other consumer products. He said scientists suspected that the DNA polymerase was inserting nucleotides that were damaged by carrying an additional oxygen atom. After the DNA polymerase inserts a damaged nucleotide into DNA, the damaged nucleotide is unable to bond with its undamaged partner. As a result, the damaged nucleotide swings freely within the DNA, interfering with the repair function or causing double-strand breaks. These steps may ultimately lead to several human diseases.

November 24th

Babies Remember Good Feeling-Associated Images, Study Shows

Parents who spend their time playing with and talking to their five-month-old baby may wonder whether their child remembers any of it a day later. Thanks to a new Brigham Young University (BYU) study, we now know that they at least remember the good times. The study, published in the November 2014 issue of Infant Behavior and Development, shows that babies are more likely to remember something if there is a positive emotion, or affect, that accompanies it. “People study memory in infants, they study discrimination in emotional affect, but we are the first ones to study how these emotions influence memory,” said BYU psychology professor Dr. Ross Flom, lead author of the study. Although the five-month-olds can’t talk, there are a number of different ways that researchers can analyze how the babies respond to testing treatments. In this particular study, the scientists monitored the infants’ eye movements and how long they looked at a test image. The babies were set in front of a flat paneled monitor in a closed-off partition and then exposed to a person on screen speaking to them with either a happy, neutral, or angry voice. Immediately following the emotional exposure, they were shown a geometric shape. To test their memory, the researchers did follow-up tests five minutes later and again one day later. In the follow-up tests, babies were shown two side-by-side geometric shapes: a brand new one, and the original one from the study. The researchers then were able to record how many times the baby looked from one image to the next and how long they spent looking at each image. Babies’ memories didn’t improve if the shape had been paired with a negative voice, but they performed significantly better at remembering shapes attached to positive voices.

Long-Term Survivors of Retinoblastoma Fare Well Cognitively and Socially; Diagnosis in First Year of Life Leads to Better Scores in Many Tests

Most long-term survivors of retinoblastoma, particularly those who had been diagnosed with tumors by their first birthdays, have normal cognitive function as adults, according to a St. Jude Children’s Research Hospital study. The research, which was published online on November 24, 2014 in the journal Cancer, found that the vast majority of survivors work full time, live independently, and fulfill other milestones of adult life. The study is the first to examine how adult survivors of retinoblastoma fare cognitively and socially decades after their diagnosis. The findings contrast with research involving survivors of other childhood cancers that suggest a younger age at cancer diagnosis may put survivors at risk for reduced cognitive functioning later in life. “As a group, adult survivors of retinoblastoma are doing quite well based on their cognitive functioning and attainment of adult social milestones,” said the study’s first and corresponding author Tara Brinkman, Ph.D., an assistant member of the St. Jude Department of Epidemiology and Cancer Control and the Department of Psychology. “This suggests that for children whose visual system is damaged very early in life, the brain may compensate by reorganizing areas responsible for processing visual information to enhance processing of verbal and auditory information,” Dr. Brinkman said. “This highlights the importance of early intervention and rehabilitation for these patients.” Retinoblastoma is diagnosed in about 350 children annually in the U.S., and 95 percent of patients are younger than 5 years old when their tumor is identified. Today, more than 95 percent of retinoblastoma patients become long-term survivors. Previous research with retinoblastoma survivors focused on cognitive functioning in childhood. The results of those studies were mixed.

Landmark Evolution Research Groups Turtles Closest to Birds, Crocodiles, & Dinosaurs; Not Lizards & Snakes

A team of scientists, including researchers from the California Academy of Sciences, has reconstructed a detailed "tree of life" for turtles. The specifics of how turtles are related--to one another, to other reptiles, and even to dinosaurs--have been hotly debated for decades. Next-generation sequencing technologies in Academy labs have generated unprecedented amounts of genetic information for a thrilling new look at turtles' evolutionary history. These high-tech lab methods have revolutionized the way scientists explore species origins and evolutionary relationships, and provide a strong foundation for future looks into Earth's fossil record. Research results, which were published online on November 4, 2014 in an open-access article in Molecular Phylogenetics and Evolution, describe how a new genetic sequencing technique called Ultra Conserved Elements (UCE) reveals turtles' closest relatives across the animal kingdom. The new genetic tree uses an enormous amount of data to refute the notion that turtles are most closely related to lizards and snakes. Instead, authors place turtles in the newly named group "Archelosauria" with their closest relatives being birds, crocodiles, and dinosaurs. Scientists suspect the new group will be the largest group of vertebrates to ever receive a new scientific name. The UCE technique used in high-tech labs allowed scientists to move beyond years of speculation and place the Archelosauria group in its rightful place on the reptile tree of life. UCE has been available since 2012, yet scientists are just beginning to tap its potential for generating enormous amounts of genetic data across vertebrates.

ASU & IBM Make Progress Toward Ultra Low-Cost DNA Sequencing with Fixed-Gap Tunnel Junction Device

A team of scientists from Arizona State University's Biodesign Institute and IBM's T.J. Watson Research Center has developed a prototype DNA reader that could make whole-genome profiling an everyday practice in medicine. "Our goal is to put cheap, simple, and powerful DNA and protein diagnostic devices into every single doctor's office," said Dr. Stuart Lindsay (photo), an ASU physics professor and director of Biodesign's Center for Single Molecule Biophysics. Such technology could help usher in the age of personalized medicine, where information from an individual's complete DNA and protein profiles could be used to design treatments specific to their individual makeup. The report was published online on November 7, 2014 in ACS Nano. Such game-changing technology is needed to make genome sequencing a reality. The current hurdle is to do so for less than $1,000, an amount for which insurance companies are more likely to provide reimbursement. In their latest research breakthrough, the team fashioned a tiny, DNA reading device a thousands of times smaller than the width of a single human hair. The device is sensitive enough to distinguish the individual chemical bases of DNA when they are pumped past the reading head. Proof-of-concept was demonstrated, by using solutions of the individual DNA bases, which gave clear signals sensitive enough to detect tiny amounts of DNA (nanomolar concentrations), even better than today's state-of-the-art, so-called next-generation DNA sequencing technology. Making the solid-state device is similar to making a sandwich, just with ultra-high-tech semiconductor tools used to slice and stack the atomic-sized layers of meats and cheeses like the butcher shop's block.

November 23rd

Four Gene Loci Newly Identified for Severe Food Allergy

Scientists have identified four gene loci newly associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the findings may point toward potential new treatments for EoE. "This research adds to the evidence that genetic factors play key roles in EoE, and broadens our knowledge of biological networks that may offer attractive targets for therapy," said study leader Hakon Hakonarson (image), M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia (CHOP). Dr. Hakonarson and colleagues from other hospitals and academic centers published the study online on November 19, 2014 in Nature Communications. The research builds on a 2010 study by Dr. Hakonarson and colleagues that identified TSLP (thymic stromal lymphopoietin ) as the first major gene associated with EoE. Only recently recognized as a distinct condition, EoE has been rapidly increasing in prevalence over the past 20 years. Its hallmark is inflammation and painful swelling in the esophagus, along with high levels of immune cells called eosinophils. It can affect people of any age, but is more common among young men who have a history of other allergic diseases such as asthma and eczema. EoE is often first discovered in children with feeding difficulties and failure to thrive. Because children with EoE are often allergic to many foods, they may be placed on a highly-restricted diet containing no large food proteins, to allow time for their symptoms to resolve. Physicians then perform tests to determine which foods a child can or cannot eat.

Winners of the 2014 Life Science Industry Awards Announced

On Tuesday, November 18, winners of the 2014 Life Science Industry Awards® were formally announced at the Grand Hyatt Washington in Washington, D.C. The Life Science Industry Awards recognize those life science suppliers that are best-in-class in 28 product and service categories. The awards were presented by BioInformatics LLC, considered by many to be the premier market research and advisory firm serving the life science industry. The event was attended by industry executives and product and marketing professionals from 41 life science companies Using industry best-practices market research methodologies, almost 6,000 scientists were surveyed to reveal preferred suppliers in 28 product, communications, and support categories. These scientists were drawn from BioInformatics LLC’s online panel of scientists, The Science Advisory Board®. From the data collected, BioInformatics LLC analysts calculated an overall score for each nominated company based on the number of nominations received, as well as key measurements of customer satisfaction and loyalty. “The vision and foresight of the companies we honored last night have made possible many of the scientific advances of the past decade,” said Jennifer Cotteleer, CEO of BioInformatics LLC.

Histone Variant H3.3 and Its Clipped Version (H3.3cs1) May Promote Senescence and Limit Abnormal Cell Growth in Tumors

Changes to the structure of the histone variant H3.3 may play a key role in silencing genes that regulate cancer cell growth, according to a study led by researchers from the Icahn School of Medicine, Mount Sinai Hospital, in New York City. The results were published online on November 14, 2014 in Nature Communications. According to the authors, this is the first study to identify H3.3 as a key regulator in cellular senescence, a process in which cells stop multiplying. Cellular senescence has garnered significant scientific interest lately because it may be one key to prevent the initiation of cancer. However, little is known about this process and how genes that enable cells to divide and multiply (the cell cycle) are turned off. A growing body of evidence suggests that the process of cellular senescence is driven by changes in the protein complexes called chromatin in the nuclei of cells. Using models of senescence, researchers found that histone variant H3.3, a protein that works closely with chromatin to package and regulate genetic material within cells, and, in particular, the clipped form of this protein, H3.3cs1, help to silence target genes that regulate the cell cycle. Could the presence of this protein stop cells from dividing? Indeed, using genome-wide transcriptional profiling, the researchers discovered that expression of clipped H3.3 (i.e., 3.3cs1) silences genes that regulate the division and duplication of a cell. "Cellular senescence creates a chromatin environment that represses cell multiplication, and thus cell or tumor growth, but how this happens molecularly is what we sought to discover," said lead investigator Emily Bernstein, Ph.D., Department of Oncological Sciences, Icahn School of Medicine, Mount Sinai Hospital.

November 21st

Two New Drugs Significantly Reduce High Potassium Levels

Research published today found that the investigational drug patiromer decreased high potassium levels and maintained normal potassium levels in patients with chronic kidney disease in a Phase 3 study. The results of the multicenter trial appear today (November 21, 2014) in an open-access article in the New England Journal of Medicine. This article is accompanied by a second open-access article on Phase 3 results for another anti-hyperkalemia drug (ZS-9), as well as by an open-access editorial entitled, “A New Era for the Treatment of Hyperkalemia?” Elevated potassium, a condition called hyperkalemia, increases the risk of death in high-risk patients and limits the use of several types of drugs, called RAAS (renin-angiotensin-aldosterone system) inhibitors, commonly used to control hypertension and cardiovascular disease and to prevent kidney disorders. "Patients with advanced kidney disease are at highest risk for hyperkalemia thanks to a double whammy," says the study's principal investigator, Matthew R. Weir, M.D., Professor of Medicine and Director of the Division of Nephrology at the University of Maryland School of Medicine. "Their kidneys are unable to remove potassium from the body effectively, and the patient may also be taking certain blood pressure control drugs that have been linked to high potassium levels. Current medications for hyperkalemia have gastrointestinal side effects that limit their extended use. We hoped the drug in this study would do the job with minimal side effects." In this Phase 3 study of 237 patients with chronic kidney disease who were receiving RAAS inhibitors, 76 percent of the patients reached the target potassium level after four weeks on patiromer.

Key Factor in Liver Cancer Progression Is Discovered

One of the most aggressive and common forms of liver cancer is hepatocellular carcinoma. A team of researchers from the Institute of Cancer Research at the Medical University of Vienna (MedUni Vienna) has now identified the crucial factor involved in the development and progression of this malignant type of tumor: namely, the AXL receptor, which supports cancer-promoting processes and slows down cancer-inhibiting factors. This key finding could make a targeted therapeutic approach possible in future. In the Western world, metabolic diseases and infections with hepatitis C are the most common causes of hepatocellular carcinoma (HCC). The team led by Dr. Wolfgang Mikulits, Head of the Tumor Progression and Metastasis Research Group at the MedUni Vienna Institute of Cancer Research (ICR) and member of the Comprehensive Cancer Center (CCC) Vienna, investigated the role of the AXL receptor tyrosine kinase in the context of liver cancer as part of a study. Says Dr. Mikulits: "Until now, the function of AXL had been barely investigated at all, which is astonishing since this receptor is shown to have been activated in more than 50 per cent of all HCC patients." The researchers were able to demonstrate that the expression and activation of AXL lead to a diversion of signaling pathways, enabling the migration and metastasis of liver cancer cells. As a result, AXL, after binding a 14-3-3 adapter protein, is able to influence the extremely important transforming growth factor beta (TGF-beta) signaling pathway in such a way that it only causes the invasion and metastasis of HCC cells. In contrast to this, AXL inhibits the anti-oncogenic function of TGF-beta. AXL is therefore the crucial factor in the aggressive development of hepatocellular carcinoma.