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Archive - 2013

March 23rd

Specific MicroRNA May Help Initiate Inflammation in Atherosclerosis

Atherosclerosis – otherwise known as hardening of the arteries – is a prevalent cause of death in modern societies. The condition arises from the build-up of localized fatty deposits called plaques in the arteries. Macrophages, the phagocytic cells of the immune system, migrate to these sites, inducing chronic inflammation which exacerbates the accumulation of the atherosclerotic lesions. These can lead to obstruction of major vessels, causing heart attack and stroke. A team of medical researchers led by Ludwig Maxmillians University (LMU) Professor Andreas Schober in Munich, Germany has now identified a particular microRNA (miRNA) that helps initiate the inflammatory process. The work was published online on March 19, 2013 in Circulation. miRNAs are short segments of RNA derived from longer precursors transcribed from defined stretches of the genomic DNA. The miRNAs act as versatile regulators of gene expression in cells, and also control the function of macrophages, in which patterns of gene activity must respond rapidly to changes in the extracellular environment. “However, the miRNAs that control the inflammation process during the various stages of atherosclerosis had not been identified up to now,” says Professor Schober. In an earlier study, Professor Schober and his team had shown that the microRNA miR-155 is a prominent member of the miRNA population in macrophages. The molecule prevents the synthesis of a protein that inhibits the inflammatory reaction, and thus promotes the progression of atherosclerosis. However, miR-155 does not serve as the initiator of inflammation. Professor Schober and his colleagues have now looked at the patterns of microRNA expression in atherosclerotic lesions in the mouse, and noted that levels of a different miRNA, called miR-342-5p, increase in very early plaques.

Genetic Analysis Saves Major Apple-Producing Region of Washington State

In August 2011, researchers from the U.S. Department of Agriculture (USDA) were presented with a serious, and potentially very costly, puzzle in Kennewick, Washington. Because Kennewick lies within a region near the heart of Washington state's $1.5 billion apple-growing region, an annual survey of fruit trees is performed by the Washington State Department of Agriculture (WSDA) to look for any invading insects. This time, the surveyors discovered a crabapple tree that had been infested by a fruit fly that they couldn't identify. It was possible that the fly's larvae, eating away inside the crabapples as they grew toward adulthood, belonged to a relatively harmless species that had simply expanded its traditional diet. In that case, they posed little threat to the surrounding apple orchards in central Washington. But the real fear was that they represented an expansion in the range of the invasive apple maggot fly, known to biologists as Rhagoletis pomonella. If so, then this would trigger a costly quarantine process affecting three counties in the state. "In one of the world's leading apple-growing regions, a great deal of produce and economic livelihood rested on quickly and accurately figuring out which one of the flies was in that tree," says Dr. Jeffrey Feder, professor of biological sciences and a member of the Advanced Diagnostics & Therapeutics initiative (AD&T) at the University of Notre Dame. "And for these flies, it can sometime turn out to be a difficult thing to do." As Dr. Feder and his team, including graduate student Gilbert St. Jean and AD&T research assistant professor Dr. Scott Egan, discuss in a new study in the Journal of Economic Entomology, the WSDA sent larvae samples to Dr.

March 22nd

“Genomic Cruise Missiles” (TALENS) Used to Alter Mosquito Genome

In a study recently published online on March 21, 2013 in the open-access journal PLOS ONE, Virginia Tech scientists used a pair of engineered proteins to cut DNA in a site-specific manner to disrupt a targeted gene in the mosquito genome. The technique could be useful for controlling mosquito-transmitted diseases. Virginia Tech researchers successfully used a gene disruption technique to change the eye color of a mosquito — a critical step toward new genetic strategies aimed at disrupting the transmission of diseases such as dengue fever. Dr. Zach Adelman and Dr. Kevin Myles, both associate professors of entomology in the College of Agriculture and Life Sciences and affiliated researchers with the Fralin Life Science Institute, study the transmission of vector-borne diseases and develop novel methods of control, based on genetics. In the groundbreaking study, the scientists used a pair of engineered proteins to cut DNA in a site-specific manner to disrupt a targeted gene in the mosquito genome. Science magazine heralded these transcription activator-like effector nuclease proteins, known as TALENS, as a major scientific breakthrough in 2012, nicknaming them “genomic cruise missiles” for their ability to allow researchers to target specific locations with great efficiency. While TALENS have been previously used to edit the genomes of animal and human cell cultures, applying them to the mosquito genome is a new approach, according to Dr. Adelman. "Unlike model organisms with large collections of mutant strains to draw upon, the lack of reverse genetic tools in the mosquito has made it is very difficult to assign functions to genes in a definitive manner," Dr. Adelman said.

Novel Method from Johns Hopkins Accurately Predicts Dengue Fever Outbreaks

A team of scientists from The Johns Hopkins University Applied Physics Laboratory (APL) has developed a novel method to accurately predict dengue fever outbreaks several weeks before they occur. The new method, known as PRedicting Infectious Disease Scalable Model (PRISM), extracts relationships between clinical, meteorological, climatic, and socio-political data in Peru and in the Philippines. It can be used in any geographical region and extended to other environmentally influenced infections affecting public health and military forces worldwide. PRISM is aimed at helping decision-makers and planners assess the future risk of a disease occurring in a specific geographic area at a specific time. Developed by APL's Dr. Anna Buczak and a team of researchers for the Department of Defense (DoD), PRISM predicts the severity of a given disease at a specific time and place with quantifiable accuracy, using original analytical and statistical methods. "By predicting disease outbreaks when no disease is present, PRISM has the potential to save lives by allowing early public health intervention and decreasing the impact of an outbreak," says Dr. Sheri Lewis, APL's Global Disease Surveillance Program Manager. DoD is currently evaluating PRISM for use in mitigating the effects of infectious disease in various operational settings. PRISM's distinctive prediction method utilizes Fuzzy Association Rule Mining (FARM) to extract relationships between multiple variables in a data set. These relationships form rules, and when the best set of rules is automatically chosen, a classifier is formed. The classifier is then used to predict future incidence of the disease – in this case dengue fever, the second most common mosquito-borne disease, which puts more than one-third of the world's population at risk.

March 21st

Targeted Cell-Based Immune Therapy at Sloan-Kettering Leads to Complete Remission in Five Patients with Deadly Leukemia

Doctors have traditionally had limited treatment options to offer adults with B cell acute lymphoblastic leukemia (ALL), a rapidly progressing form of blood cancer. The disease often returns, or relapses, after initial treatment with chemotherapy. At that point, patients are often resistant to additional chemotherapy and poor candidates for stem cell transplantation, which is usually effective only if the disease is in complete remission. Now Memorial Sloan-Kettering investigators report that genetically modified immune cells have shown great promise in killing the cancer cells of patients with relapsed B cell ALL. In fact, all five of the patients who have received the new therapy – known as targeted immunotherapy – have gone into complete remission, with no detectable cancer cells. The results of this ongoing clinical trial were reported online on March 20, 2013 in the journal Science Translational Medicine. “This is a very exciting finding for patients with B cell ALL and a major achievement in the field of targeted immunotherapy,” says Dr. Michel Sadelain, Director of Memorial Sloan-Kettering’s Center for Cell Engineering, who led the study along with medical oncologist Dr. Renier J. Brentjens. Targeted immunotherapy is aimed at instructing the immune system to recognize and attack tumor cells. Over the past decade, Drs. Sadelain and Brentjens, and other Memorial Sloan-Kettering researchers – including Dr. Isabelle Rivière, Director of Memorial Sloan-Kettering’s Cell Therapy and Cell Engineering Facility, and physician-scientist Dr. Marco L. Davila – have investigated an approach that involves removing white blood cells called T cells from patients and introducing a new gene into the cells using an engineered viral vector.

Testing Visual Acuity of Archerfish Which Target Prey above the Water

A modified version of an eye test used to assess visual acuity in the military has been given to archerfish by scientists to help explain how these remarkable fish are able to accurately spit down tiny insects high above the water’s surface. Dr. Shelby Temple, now at the University of Bristol in the UK, and his team at the University of Queensland and the University of Western Australia used a modified version of the Landolt C test to discover just how fine a detail the archerfish could resolve. The researchers first trained the fish to spit at one of two letters – an ‘O’ or a ‘C’ – by rewarding them with food. Then they showed them small versions of both letters together and recorded which letter they spat at. Dr. Temple said: "This modified Landolt C test works because the only difference between the two letters is the gap in the ‘C’ so in order to tell the difference and spit at the right target to get their reward the fish must be able to resolve the gap." To test the archerfish's resolving power, the size of the letters were decreased in steps to see just how small they could go. The scientists then compared these behavioural results to the fishes' predicted acuity based on measurements of the photoreceptor density in their retinas. The results, published online ahead of print in the journal Vision Research, show that archerfish are one of the most visually acute freshwater fish, able to resolve approximately 3.5 cycles per degree with the part of their retina that looks up and forwards, which is not surprising given their interesting foraging strategy. Archerfish have a special way of hunting for food that involves spitting jets of water at aerial insects above the water’s surface.

Smelling Different Genome Odors and Mate Choice--Results Point to More Than MHC

It’s a theory much discussed in the media – that animals and humans are able to smell certain genes linked to the immune system – which in turn influences their choice of mate. The genes in question are known as MHC (major histocompatibility complex) genes. Selecting a mate with very different MHC genes from one’s own makes sense, because your offspring will then have a greater variety of immunity genes – and a correspondingly greater resistance to disease. But until now, no scent offering information about MHC genes had been discovered among those scents emitted by humans and animals. Now researchers from the University of Tübingen’s Immunology department and the Proteome Center in Germany, working with their colleagues from the University of Saarland, also in Germany, have managed to do just that. Their results, published online on March 19, 2013 in Nature Communications, will lead scientists to review the “sniff out a mate” theory. It is well known that the MHC genes determine which MHC peptides a cell presents at its surface to the immune system’s killer cells. These peptides are usually composed of the body’s own proteins and therefore do not set off any reaction. But if the MHC peptides come from a virus, the immune system’s killer cells can recognize that and attack it. According to one current theory, the MHC peptides also communicate the smell which offers information about MHC genes – a theory tested in mice. Special sensor cells were found which are able to recognize and distinguish the various MHC peptides from one another. Experiments have shown that synthetic MHC peptides in high concentrations were able to influence the behavior of mice, and that mouse urine carries what is believed to be the smell of MHC genes. Until now, it was not known whether MHC peptides even occurred naturally in urine.

March 20th

New Imaging Agent Enables Better Cancer Detection, More Accurate Staging

Researchers at the University of California (UC), San Diego School of Medicine have shown that a new imaging dye, designed and developed at the UC San Diego Moores Cancer Center, is an effective agent in detecting and mapping cancers that have reached the lymph nodes. The radioactive dye called Technetium Tc-99m tilmanocept, successfully identified cancerous lymph nodes and did a better job of marking cancers than the current standard dye. Results of the Phase III clinical trial were published online on March 20, 2013 in the Annals of Surgical Oncology. "Tilmanocept is a novel engineered radiopharmaceutical specifically designed for sentinel lymph node detection," said David R. Vera, Ph.D., the drug's inventor, who is a professor in the UCSD Department of Radiology. "The molecule, developed at UC San Diego School of Medicine, offers surgeons a new tool to accurately detect and stage melanoma and breast cancers while in the operating room." On March 13, 2013, tilmanocept received U.S. Food and Drug Administration (FDA) approval. After a cancer diagnosis, surgeons want to be sure that the disease has not spread to a patient's lymph nodes, especially the sentinel nodes that may be the first place that a cancer reaches. The lymphatic system is a network of vessels and ducts that carry disease-fighting cells throughout the body, but can also act as a way for cancer cells to access the bloodstream. By surgically removing and examining the sentinel nodes that drain a tumor, doctors can better determine if a cancer has spread. "Tilmanocept advances the molecular targeting in breast cancer.

Baffling Rare Blood Type (Vel-Negative) Finally Explained

In the early 1950’s, a 66-year-old woman, sick with colon cancer, received a blood transfusion. Then, unexpectedly, she suffered a severe rejection of the transfused blood. Reporting on her case, the French medical journal Revue D’Hématologie identified her as, simply, “Patient Vel.” After a previous transfusion, it turns out, Mrs. Vel had developed a potent antibody against some unknown molecule found on the red blood cells of most people in the world—but not found on her own red blood cells. But what was this molecule? Nobody could find it. A blood mystery began, and, from her case, a new blood type, “Vel-negative,” was described in 1952. Soon it was discovered that Mrs. Vel was not alone. Though rare, it is estimated now that over 200,000 people in Europe and a similar number in North America are Vel-negative, about 1 in 2,500. For these people, successive blood transfusions could easily turn to kidney failure and death. So, for sixty years, doctors and researchers have hunted—unsuccessfully—for the underlying cause of this blood type. But now a team of scientists from the University of Vermont (UVM) and France has found the missing molecule—a tiny protein called SMIM1—and the mystery is solved. Reporting in the journal EMBO Molecular Medicine, UVM’s Dr. Bryan Ballif, Dr. Lionel Arnaud of the French National Institute of Blood Transfusion, and their colleagues explain how they uncovered the biochemical and genetic basis of Vel-negative blood. “Our findings promise to provide immediate assistance to health-care professionals should they encounter this rare but vexing blood type,” says Dr. Ballif. The pre-publication results were presented online on March 18, 2013, and the finalized report will be published, as an open-access article, in the next edition of the journal. Last year, Drs.

Plants Recognize and Respond Specifically to Predators

Insect or microbe: plants recognize their attackers and respond by producing specific internal signals that induce the appropriate chemical defenses. That is the main conclusion of a study at the Center for Medical, Agricultural and Veterinary Entomology operated in Gainesville, Florida (USA) by the USDA’s Agricultural Research Service, to which the team around Professor Ted Turlings of the University of Neuchâtel, Switzerland, has contributed. The study was published online on March 18, 2013 in PNAS. When attacked, plants produce cascades of molecular reactions aimed at neutralizing their specific opponents. In response to insect attack plants produce toxins that directly affect the herbivore, but they also emit an odorous cry for help that attracts natural enemies of the pest, thus ensuring indirect protection of the plants. However, the biochemical mechanisms which trigger these defenses have been poorly understood until now. The research to which the biologists of the University of Neuchâtel contributed is directed precisely at this missing link. It has led to the identification of a peptide called ZmPep3, which maize plants produce when their leaves are eaten by herbivorous caterpillars. This peptide triggers the production of insecticidal substances, as well as the emission of a particular odor that specifically attracts natural enemies of the pest, in this case a parasitic wasp that lays its eggs in the caterpillars. To determine the attractiveness of odorous signals, the Gainesville team turned to the Neuchâtel group of experts, known for their discovery of the cry for help in plants.