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Archive - Mar 2013

March 25th

Cal Tech Scientists Pinpoint Origin of Olfactory Neurons

When our noses pick up a scent, whether the aroma of a sweet rose or the sweat of a stranger at the gym, two types of sensory neurons are at work in sensing that odor or pheromone. These sensory neurons are particularly interesting because they are the only neurons in our bodies that regenerate throughout adult life—as some of our olfactory neurons die, they are soon replaced by newborns. Just where those neurons come from in the first place has long perplexed developmental biologists. Previous hypotheses about the origin of these olfactory nerve cells have given credit to embryonic cells that develop into skin or the central nervous system, where ear and eye sensory neurons, respectively, are thought to originate. But biologists at the California Institute of Technology (Caltech) have now found that neural-crest stem cells—multipotent, migratory cells unique to vertebrates that give rise to many structures in the body such as facial bones and smooth muscle—also play a key role in building olfactory sensory neurons in the nose. "Olfactory neurons have long been thought to be solely derived from a thickened portion of the ectoderm; our results directly refute that concept," says Dr. Marianne Bronner, the Albert Billings Ruddock Professor of Biology at Caltech and corresponding author of a paper published online in the open-access journal eLIFEon March 19, 2013 that outlines the findings. A related article (U. of Sheffield) was published online in eLIFE on March 26, 2013. eLIFE is backed by three of the most prestigious biomedical research funders in the world: the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.

March 25th

Akt Suppression May Prevent Herpes Virus Infections

Researchers at Albert Einstein College of Medicine of Yeshiva University in New York City have discovered a novel strategy for preventing infections due to the highly common herpes simplex viruses, the microbes responsible for causing genital herpes (herpes simplex virus 2) and cold sores (herpes simplex virus 1). The finding, published online on March 18, 2013 in The FASEB Journal, could lead to new drugs for treating or suppressing herpes virus infections. "We've essentially identified the molecular "key" that herpes viruses use to penetrate cell membranes and infect cells of the human body," said Betsy Herold, M.D., professor of pediatrics (infectious diseases), of microbiology & immunology and of obstetrics & gynecology and women's health at Einstein and attending physician of pediatrics, The Children's Hospital at Montefiore. Herpes viruses are known to infect skin cells as well as cells lining the cervix and the genital tract. A 2006 JAMA study estimated that nearly 60 percent of U.S. men and women between the ages of 14 and 49 carry the HSV-1 virus. The Centers for Disease Control (CDC) estimated that about 1 in 6 Americans (16.2 percent) between 14 and 49 are infected with herpes simplex virus type 2 (HSV-2), according to a 2010 national health survey. HSV-2 is a lifelong and incurable infection that can cause recurrent and painful genital sores and can make those infected with the virus two-to-three times more likely to acquire HIV, the virus that causes AIDS. Dr. Herold and her colleagues had previously shown that infection by the herpes viruses depends on calcium released within the cells. In this study, they found that calcium release occurs because the viruses activate a critical cell-signaling molecule called Akt at the cell membrane.

Possible Major Progress on Beta-Thalassemia, Hemochromatosis, and Polycythemia Vera

Two studies led by investigators at Weill Cornell Medical College in New York City shed light on the molecular biology of three blood disorders, leading to novel strategies to treat these diseases. The two new studies -- one published online on March 17, 2013 in Nature Medicine and the other published online on March 25, 2013 in an open-access article in the Journal of Clinical Investigation -- propose two new treatments for beta-thalassemia, a blood disorder which affects thousands of people globally every year. In addition, they suggest a new strategy to treat thousands of Caucasians of Northern European ancestry diagnosed with HFE-related hemochromatosis (i.e., hemochromatosis caused by a defect in the HFE gene) and a novel approach to the treatment of the rare blood disorder called polycythemia vera. These research insights were only possible because two teams that included 24 investigators at six American and European institutions decoded the body's exquisite regulation of iron, as well as its factory-like production of red blood cells. "When you tease apart the mechanisms leading to these serious disorders, you find elegant ways to manipulate the system," says Dr. Stefano Rivella, associate professor of genetic medicine in pediatrics at Weill Cornell Medical College. For example, Dr. Rivella says, two different gene mutations lead to different outcomes. In beta-thalassemia, patients suffer from anemia -- the lack of healthy red blood cells -- and, as a consequence, iron overload. In HFE-related hemochromatosis, patients suffer of iron overload. However, he adds, one treatment strategy that regulates the body's use of iron may work for both disorders.

T-Cell Therapy Eradicates an Aggressive Leukemia in Two Children

Two children with an aggressive form of childhood leukemia had a complete remission of their disease—showing no evidence of cancer cells in their bodies—after treatment with a novel cell therapy that reprogrammed their immune cells to rapidly multiply and destroy leukemia cells. A research team from The Children's Hospital of Philadelphia and the University of Pennsylvania published the case report of two pediatric patients online on March 25, 2013 in an open-access article in The New England Journal of Medicine. One of the patients, 7-year-old Emily Whitehead (photo), was featured in news stories in December 2012 after the experimental therapy led to her dramatic recovery after she relapsed following conventional treatment. Emily remains healthy and cancer-free, 11 months after receiving bioengineered T cells that zeroed in on a target found in this type of leukemia, called acute lymphoblastic leukemia (ALL). The other patient, a 10-year-old girl, who also had a complete response to the same treatment, suffered a relapse two months later when other leukemia cells appeared that did not harbor the specific cell receptor targeted by the therapy. "This study describes how these cells have a potent anticancer effect in children," said co-first author Stephan A. Grupp, M.D., Ph.D., of The Children's Hospital of Philadelphia, where both patients were treated in this clinical trial. "However, we also learned that in some patients with ALL, we will need to further modify the treatment to target other molecules on the surface of leukemia cells." Dr. Grupp is the director of Translational Research for the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia, and a professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.

46-Gene Sequencing Test for Cancer Patients in UK’s National Health Service

The first multi-gene DNA sequencing test that can help predict cancer patients' responses to treatment has been launched in the National Health Service (NHS) in the UK, thanks to a partnership between scientists at the University of Oxford and the Oxford University Hospitals NHS Trust. The test uses the latest DNA sequencing techniques to detect mutations across 46 genes that may be driving cancer growth in patients with solid tumors. The presence of a mutation in a gene can potentially determine which treatment a patient should receive. The researchers say the number of genes tested marks a step change in introducing next-generation DNA sequencing technology into the NHS, and heralds the arrival of genomic medicine with whole genome sequencing of patients just around the corner. The many-gene sequencing test has been launched through the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), a collaboration between the Oxford University Hospitals NHS Trust and Oxford University to accelerate healthcare innovation, and which has partly funded this initiative. The BRC Molecular Diagnostics Centre carries out the test. The lab, based at Oxford University Hospitals, covers all cancer patients in the Thames Valley area. But the scientists are looking to scale this up into a truly national NHS service through the course of this year. The new £300 test could save significantly more in drug costs by getting patients on to the right treatments straightaway, reducing harm from side effects as well as the time lost before arriving at an effective treatment. “We are the first to introduce a multi-gene diagnostic test for tumor profiling on the NHS using the latest DNA sequencing technology,” says Dr.

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.