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April 12th, 2011

Loss of Cell Adhesion Protein Drives Oral/Esophageal Cancers in Mice

Squamous cell cancers of the oral cavity and esophagus are common throughout the world, with over 650,000 cases of oral cancer each year and esophageal cancer representing the sixth most common cause of cancer death in men. Research by University of Pennsylvania School of Medicine investigators has shown that a protein that helps cells stick together is frequently absent or out of place in these cancers, but it's unclear if its loss causes the tumors. The investigators report that mice engineered to lack this protein, called p120-catenin (p120ctn), in the oral-upper digestive tract develop squamous cell cancers. The data, reported in the April 12, 2011 issue of Cancer Cell, settles a 20-year debate and proves that p120ctn is a tumor-suppressor protein. What's more, the tumors that form in this mouse model closely resemble human disease and may point the way to novel therapies and early detection strategies. "As the mice aged, what we saw was a dramatic evolution of precancer to cancer," says senior author Dr. Anil K. Rustgi, the T. Grier Miller Professor of Medicine and Genetics and chief of Gastroenterology. "Both the precancerous growth, called dysplasia, and the cancer look exactly like what we see in humans. This is really exciting because it supports efforts for prevention and early detection, especially in people who drink alcohol and smoke cigarettes excessively and are at high risk for the disease in many regions of the world." In healthy tissues, p120ctn is part of a protein complex that holds epithelial cells in tightly packed sheets. When p120ctn (or another of these cell adhesion proteins) is lost, a wide variety of cancers, including those in prostate, breast, pancreas, colon, skin, bladder, and the endometrium, can result.

Discovery of Two Genes May Aid Battle Against Staph Aureus

The discovery of two genes that encode copper- and sulfur-binding repressors in the hospital terror Staphylococcus aureus means two new potential avenues for controlling the increasingly drug-resistant bacterium, scientists say in the April 15, 2011 issue of the Journal of Biological Chemistry. "We need to come up with new targets for antibacterial agents," said Indiana University Bloomington biochemist Dr. David Giedroc, who led the project. "Staph is becoming more and more multi-drug resistant, and both of the systems we discovered are promising." The work was a collaboration of members of Giedroc's laboratory, and those of Vanderbilt University School of Medicine infectious disease specialist Dr. Eric Skaar, and University of Georgia chemist Dr. Robert Scott. MRSA, or multidrug-resistant Staphylococcus aureus, is the primary cause of nosocomial infections in the United States. About 350,000 infections were reported last year, about 20 percent of which resulted in fatalities, according to the Centers for Disease Control. One to two percent of the U.S. population has MRSA in their noses, a preferred colonization spot. One of the repressors the scientists discovered, CsoR (copper-sensitive operon repressor), regulates the expression of copper resistance genes, and is related to a CsoR previously discovered by the Giedroc group in Mycobacterium tuberculosis, the bacterium that causes tuberculosis in humans. When the bacterium is exposed to excess copper, the repressor binds copper (I) and falls away from the bacterial genome to which it is bound, making it possible for the copper resistance genes to be turned on.

Pigeons Can Recognize Human Faces and Emotions

A study published by two University of Iowa researchers in the March 31, 2011 issue of the Journal of Vision found that pigeons recognize a human face's identity and emotional expression in much the same way as people do. Pigeons were shown photographs of human faces that varied in the identity of the face, as well as in their emotional expression -- such as a frown or a smile. In one experiment, pigeons, like humans, were found to perceive the similarity among faces sharing identity and emotion. In a second, key experiment, the pigeons' task was to categorize the photographs according to only one of these dimensions and to ignore the other. The pigeons found it easier to ignore emotion when they recognized face identity than to ignore identity when they recognized face emotion, according to Dr. Ed Wasserman, Stuit Professor of Experimental Psychology, and graduate student Fabian Soto, both of the UI College of Liberal Arts and Sciences Department of Psychology. "This asymmetry has been found many times in experiments with people and it has always been interpreted as the result of the unique organization of the human face processing system." Soto said. "We have provided the first evidence suggesting that this effect can arise from perceptual processes present in other vertebrates. The point of the project is not that pigeons perceive faces just as we do or that people do not have specialized processes for face perception. Rather, the point is that both specialized and general processes are likely to be involved in peoples' recognition of faces and that the contributions of each should be carefully determined empirically," he added. In fact, the findings could make scientists reconsider their assumptions about how uniquely human cognitive processes might interact with more general processes in complex tasks such as face recognition.

How Anti-Depressants Make New Brain Cells

For the first time in a human model, scientists have discovered how anti-depressants make new brain cells. This implies that researchers can now develop better and more efficient drugs to combat depression. Previous studies have shown that anti-depressants make new brain cells, however, until now it was not known how they did it. In a study published online on April 12, 2011, in the journal Molecular Psychiatry, researchers from the Institute of Psychiatry, King's College London, show that anti-depressants regulate the glucocorticoid receptor (GR) - a key protein involved in the stress response. Moreover, the study shows that all types of anti-depressant are dependent on the GR to create new cells. Depression is expected to be the second leading burden of disease worldwide by the year 2020. Recent studies have demonstrated that depressed patients show a reduction in a process called ‘neurogenesis,’ that is, a reduction in the development of new brain cells. This reduced neurogenesis may contribute to the debilitating psychological symptoms of depression, such as low mood or impaired memory. With as much as half of all depressed patients failing to improve with currently available treatments, developing new effective anti-depressant treatment still remains a great challenge, which makes it crucial to identify new potential mechanisms to target. The Laboratory of Stress, Psychiatry and Immunology (SPI-lab) at King's has been looking into the role of the GR in depression for a number of years. In this study, scientists used human hippocampal stem cells, the source of new cells in the human brain, as a new model to investigate, 'in a dish,' the effects of anti-depressants on brain cells.

April 11th

New Mechanism of Tumor Invasiveness Discovered

Researchers at the Hebrew University of Jerusalem have discovered a previously unknown mechanism whereby tumor cells invade normal tissues, spreading cancer through various organs. The ability of tumor cells to invade adjacent structures is a prerequisite for metastasis and distinguishes malignant tumors from benign ones. Thus, understanding the mechanisms that drive malignant cells to invade and a possible avenue for halting that mechanism could have tremendous potential for enhancing early detection of malignant cells and for therapeutic treatment.It has previously been assumed that tumor cells turn invasive upon accumulation of multiple mutations, each giving the cancer cell some invasive properties. Now, Professor Yinon Ben-Neriah and Dr. Eli Pikarsky of the Institute for Medical Research Israel-Canada at the Hebrew University Faculty of Medicine and their colleagues are reporting an alternative mechanism through which tumor cells become invasive. They found a program that is operated by a concerted group of genes that, when activated together, confer invasive properties upon epithelial cells. (Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands.) An article reporting their work appeared in the February 17, 2011 issue of the journal Nature. Interestingly, the expression of this entire gene group is normally suppressed by a single gene – p53 – that is considered as the most important tumor suppressor but unfortunately is inactivated in the majority of human cancers. Some key properties of the protein produced by the p53 gene -- arresting cell growth and induction of cell death – were previously discovered by Dr. Moshe Oren of the Weizmann Institute of Science, another member of the current research team.

Saturated Fatty Acids and Type 2 Diabetes

A diet high in saturated fat is a key contributor to type 2 diabetes, a major health threat worldwide. Several decades ago scientists noticed that people with type 2 diabetes have overly active immune responses, leaving their bodies rife with inflammatory chemicals. In addition, people who acquire the disease are typically obese and are resistant to insulin, the hormone that removes sugar from the blood and stores it as energy. For years no one has known exactly how the three characteristics are related. But a handful of studies suggest that they are inextricably linked. New research from the University of North Carolina at Chapel Hill School of Medicine adds clarity to the connection. The study published online April 10, 2011, in the journal Nature Immunology finds that saturated fatty acids, but not the unsaturated type can activate immune cells to produce an inflammatory protein, called interleukin-1beta.“The cellular path that mediates fatty acid metabolism is also the one that causes interleukin-1beta production,” says senior study co-author Dr. Jenny Y. Ting, William Kenan Rand Professor in the Department of Microbiology and Immunology. “Interleukin-1beta then acts on tissues and organs such as the liver, muscle and fat (adipose) to turn off their response to insulin, making them insulin-resistant. As a result, activation of this pathway by fatty acid can lead to insulin resistance and type 2 diabetes symptoms.” Dr. Ting is also a member of the UNC Lineberger Comprehensive Cancer Center, and the UNC Inflammatory Diseases Institute. [Press release] [Nature Immunology abstract]

Cold and Asthma Virus Grown in Tissue Culture

Using sinus tissue removed during surgery at University of Wisconsin Hospital and Clinics, researchers at the University of Wisconsin-Madison have managed to grow a recently discovered species of human rhinovirus (HRV), the most frequent cause of the common cold, in culture. The researchers found that the virus, which is associated with up to half of all HRV infections in children, has reproductive properties that differ from those of other members of the HRV family. The accomplishments, reported in Nature Medicine on April 10, 2011, should allow antiviral compounds to be screened to see if they stop the virus from growing. The report sheds light on HRV-C, a new member of the HRV family that also includes the well-known HRV-A and HRV-B. Discovered five years ago, HRV-C has been notoriously difficult to grow in standard cell cultures and, therefore, impossible to study. "We now have evidence that there may be new approaches to treating or preventing HRV-C infections," says senior author Dr. James Gern, professor of medicine at the UW-Madison School of Medicine and Public Health and an asthma expert at American Family Children's Hospital. Future drugs could be especially useful for children and adults who have asthma and other lung problems, Dr. Gern says. Recent studies have shown that in addition to its major role in the common cold, HRV-C is responsible for between 50 percent and 80 percent of asthma attacks. HRV-C is a frequent cause of wheezing illnesses in infants and may be especially likely to cause asthma attacks in children. HRV infections of all kinds also can greatly worsen chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Like other scientists, Dr. Yury Bochkov, a virologist in Gern's lab, was unable to grow HRV-C in standard cell lines.

April 10th

Scope of Interferon Activity Investigated

When viruses attack, one molecule (interferon) more than any other fights back. Interferon triggers the activation of more than 350 genes, and despite the obvious connection, the vast majority have never been tested for antiviral properties. A team of researchers, led by scientists from Rockefeller University, for the first time has carried out a comprehensive, systematic evaluation of the antiviral activity of interferon-induced factors. The findings, published online on April 10, 2011, in the journal Nature, are a first step toward unraveling how these naturally occurring molecules work to inhibit viruses. "We hope this study will open the door to future work on the mechanisms of antiviral molecules," says first author Dr. John Schoggins, a postdoctoral associate in Dr. Charles M. Rice's Laboratory of Virology and Infectious Disease at Rockefeller. "Such mechanistic studies may set the stage for the development of new and much-needed drugs to combat a diverse array of viruses that pose significant health threats to people worldwide." The researchers were interested in type I interferon, a cellular molecule that is made when a person becomes infected with certain viruses. Type I interferon is used clinically in the treatment of some viral diseases, such as hepatitis C, and its presence has been shown to significantly limit the severity of certain viral infections. Dr. Schoggins and his colleagues, including researchers from the Aaron Diamond AIDS Research Center and the Howard Hughes Medical Institute, systematically evaluated the majority of common interferon-induced genes, one by one, to determine which of them had antiviral activity against a panel of disease-causing viruses, including the hepatitis C virus, HIV, West Nile virus, the yellow fever virus, and chikungunya virus.

April 8th

Researchers Develop New Method to Screen and Analyze Mutations

A single change to even one of the thousands of DNA codes that make up each gene in the human genome can result in severe diseases such as cancer, cystic fibrosis, or muscular dystrophy. A similarly minor change in the DNA of a virus or bacteria can give rise to drug-resistant strains that are difficult for physicians to treat with standard drug therapies. For these reasons, scientists have long sought ways to study the effects genetic mutations can have on an organism but have been hampered in these efforts by an inability to easily and efficiently produce and analyze the thousands of potential changes possible in even one small gene. A new study by scientists at the University of Massachusetts Medical School, published in PNAS online on April 4, 2011, describes a novel technique to produce all potential individual mutations and using deep sequencing technology simultaneously analyze each change's impact on the cell. "In nature, genetic mutations actually occur infrequently and at random," said Dr. Daniel N. A. Bolon, assistant professor of biochemistry & molecular pharmacology and lead author of the PNAS study. "But these small changes have profound consequences on an organism's ability to survive. We've developed an approach that allows us to generate all the possible individual changes and, at the same time in the same test tube, study the impact of each change." Using sequencing technology inspired by the human genome project, Bolon and colleagues have developed a method called EMPIRIC to analyze hundreds of different mutations in a single test tube. Ordinarily used to read a DNA sequence over an entire genome, Dr. Bolon utilizes the ability of a band-aid-sized sequencing chip to accurately count and record the abundance of hundreds of distinct cells in a test tube that differ by individual mutations.

Caffeine and Diabetes

A growing body of research suggests that caffeine disrupts glucose metabolism and may contribute to the development and poor control of type 2 diabetes, a major public health problem. A review article in the March 2011 inaugural issue of Journal of Caffeine Research: The International Multidisciplinary Journal of Caffeine Science, a quarterly peer-reviewed journal from Mary Ann Liebert, Inc. publishers, examines the latest evidence, contradicting earlier studies suggesting a protective effect of caffeine. The entire issue is available free online. Dr. James Lane, of Duke University, describes numerous studies that have demonstrated caffeine's potential for increasing insulin resistance (impaired glucose tolerance) in adults that do not have diabetes, an effect that could make susceptible individuals more likely to develop the disease. In adults with type 2 diabetes, studies have shown that the increase in blood glucose levels that occurs after they eat carbohydrates is exaggerated if they also consume a caffeinated beverage such as coffee. This effect could contribute to higher glucose levels in people with diabetes and could compromise treatment aimed at controlling their blood glucose. "More than 220 million people worldwide have diabetes, says Editor-in-Chief Dr. Jack E. James, School of Psychology, National University of Ireland, Galway, Ireland. "The links that have been revealed between diabetes and the consumption of caffeine beverages (especially coffee) are of monumental importance when it is acknowledged that more than 80% of the world's population consumes caffeine daily. Dr.