Researchers at Binghamton University, State University of New York, have identified three key regulators required for the formation and development of biofilms. The discovery could lead to new ways of treating chronic infections. Biofilms -- communities of bacteria in self-produced slime -- may be found almost anywhere that solids and liquids meet, whether in nature, in hospitals or in industrial settings. Biofilms are implicated in more than 80 percent of chronic inflammatory and infectious diseases caused by bacteria, including ear infections, gastrointestinal ulcers, urinary tract infections and pulmonary infections in cystic fibrosis patients, according to the Centers for Disease Control. Biofilms are difficult to eradicate with conventional antimicrobial treatments since they can be nearly 1,500-fold more resistant to antibiotics than planktonic, free-floating cells. Biofilms also pose a persistent problem in many industrial processes, including drinking water distribution networks and manufacturing.

One of the most common reasons for needing a liver transplant is liver failure or liver cancer caused by liver cell infection with hepatitis C virus (HCV). However, in nearly all patients the new liver becomes infected with HCV almost immediately. But now, Hideki Ohdan, Kazuaki Chayama, and colleagues, at Hiroshima University, Japan, have developed an approach that transiently keeps HCV levels down in most treated HCV-infected patients receiving a new liver. The researchers report their findings in the Journal of Clinical Investigation. Specifically, the team took immune cells known as lymphocytes from the donor livers before they were transplanted into the HCV-infected patients, activated them in vitro, and then injected them into the patients three days after they had received their liver transplants. Importantly, these infused cells were able to keep the HCV at bay even though the patients were taking immunosuppressive drugs to prevent their immune systems from rejecting the new livers. Despite showing clear clinical effects, the authors are planning further studies in which they will modify the protocol in an attempt to find a way to keep HCV levels down for longer and in all patients.

An instrument package developed in part by the University of Colorado at Boulder for the $2.2 billion orbiting Herschel Space Observatory launched in May by the European Space Agency has provided one of the most detailed views yet of space up to 12 billion years back in time. The December images have revealed thousands of newly discovered galaxies in their early stages of formation, said CU-Boulder Associate Professor Jason Glenn, a co-investigator on the Spectral and Photometric Imaging Receiver, or SPIRE instrument, riding aboard Herschel. The new images are being analyzed as part of the Herschel Multi-tiered Extragalactic Survey, or HerMES, which involves more than 100 astronomers from six countries. Equipped with three cameras including SPIRE, the Herschel Space Observatory was launched in May 2009 from Europe's Spaceport in French Guiana. The spacecraft -- about one and one-half times the diameter of the Hubble Space Telescope -- is orbiting nearly 1 million miles from Earth. Herschel is the first space observatory to make high-resolution images at submillimeter wavelengths, which are longer than visible and infrared light waves and shorter than radio waves. SPIRE was designed to look for emissions from clouds and dust linked to star-forming regions in the Milky Way and beyond, said Glenn. The most recent observations were made in the constellation Ursa Major, which includes the Big Dipper.

In a mouse model, scientists have discovered that alpha-cells in the pancreas, which do not produce insulin, can convert into insulin-producing beta-cells, advancing the prospect of regenerating beta-cells as a cure for type 1 diabetes. The research team, led by senior author Dr. Pedro L. Herrera of the University of Geneva, demonstrated that beta-cells will spontaneously regenerate after near-total beta-cell destruction in mice and the majority of the regenerated beta-cells are derived from alpha-cells that had been reprogrammed, or converted, into beta-cells. Using a unique model of diabetes in mice, in which nearly all of the beta-cells are rapidly destroyed, the researchers found that if the mice were maintained on insulin therapy, beta-cells were slowly and spontaneously restored, eventually eliminating the need for insulin replacement. Alpha-cells normally reside alongside beta-cells in the pancreas and secrete a hormone called glucagon, which works in opposition to insulin to regulate the levels of sugar in the blood. Alpha-cells are not attacked by the autoimmune processes that destroy beta-cells and cause type 1 diabetes. Dr. Andrew Rakeman, the Juvenile Diabetes Research Foundation (JDRF) Program Manager in Beta-Cell Therapies and who was not involved in the research, said that the breakthrough in Dr. Herrera's work is the demonstration that alpha-to-beta-cell reprogramming can be a natural, spontaneous process. "If we can understand the signals that are triggering this conversion, it will open a whole new potential strategy for regenerating beta-cells in people with type 1 diabetes," he said. "It appears that the body can restore beta-cell function either through reprogramming alpha-cells to become beta-cells or, as previously shown by others, by increasing growth of existing beta cells. This path may be particularly useful in individuals who have had the disease for a long time and have no, or very few, remaining beta cells." Interestingly, the researchers pointed out that the critical factor in sparking the alpha-to-beta-cell reprogramming was removing (or ablating) nearly all the original insulin-producing cells in the mice. In mice where the loss of beta cells was more modest, the researchers either found no evidence of beta cell regeneration (when only half the cells were destroyed) or less alpha cell reprogramming (when less than 95 percent of cells were destroyed). "The amount of beta-cell destruction thus appears to determine whether regeneration occurs. Moreover, it influences the degree of cell plasticity and regenerative resources of the pancreas in adult organisms," said Dr. Herrera. This work was published online on April 4, 2010 in Nature. The image shows three lightly stained islets of Langerhans.

Researchers at the University of Massachusetts Medical School and colleagues have discovered a critical step for blood vessel growth in zebrafish embryos, providing new insight into how vascular systems develop and offering a potential therapeutic target for preventing tumor growth, which depends on vascularization. The researchers have identified a novel microRNA-mediated genetic pathway responsible for new blood vessel growth (angiogenesis) in zebrafish embryos. The work provides new insights into how vascular systems use the forces of existing blood flow to initiate the growth of new vessels. Focusing on the development of the fifth and sixth aortic arches in the zebrafish, senior author Dr. Nathan Lawson described how the forces exerted by blood flow on endothelial cells are a critical component for expressing a microRNA that triggers new vessel development. In the early stages of development, when blood flow is present in the aortic vessels, but the vascular linkages between the two arches have yet to be established, the stimulus provided by active blood flow leads to expression of an endothelial-cell specific microRNA (mir-126). In turn, this microRNA turns on vascular endothelial growth factor (VEGF), a chemical signal produced by surrounding cells that normally stimulates angiogenesis. Thus, blood flow allows the endothelial cells to respond to VEGF by growing into new blood vessels. However, when blood flow in the aortic arches was restricted, mir-126 failed to be expressed. In the absence of this microRNA, new blood vessels were unable to develop due to a block in VEGF signaling. "We have known for over a hundred years that blood flow makes new vessels grow," said Dr. Lawson. "But we never really knew how cells in a growing vessel interpreted this signal. Our results show that miR-126 is the crucial switch that allows flow to turn on VEGF signaling and drive blood vessel growth. Because VEGF is crucial for tumor progression, not to mention a number of other vascular diseases, our findings may provide new ways to modify this pathway in these settings." One possibility, for instance, is that regulation of mir-126 could be a potential therapeutic target in limiting blood vessel development in solid cancers. This work was published online on April 4, 2010 in Nature.

"Personalized Medicine 3.0--Targeting Cancer" is a one-day conference and networking opportunity for health and industry professionals, educators, and scientists. The conference will focus on cancer--using genomic information to characterize tumors precisely and ensure the use of the most effective treatment regimens for individual patients with the fewest side effects. The organizers note that personalized medicine is poised to transform healthcare over the next several decades, and that it offers both the possibility of improved health outcomes and the potential to make healthcare more cost-effective. The conference will be held in San Francisco at San Francisco State University from 9 am to 7 pm on Tuesday, May 25, 2010. The two previous annual conferences on personalized medicine have been enormous successes and similar results are expected for this third conference. The organizers urge you to register early as space is limited and the registration fee is $249 until April 15, 2010. Registration includes a light breakfast, lunch, and a networking reception at the end of the day. Registration details and a preliminary program are available at the conference web site (http://personalizedmedicine.sfsu.edu/), as are additional details on the conference.

New results indicate that targeting a specific microRNA (miR-210) with a drug that could be used topically on the skin might offer new strategies for treating chronic wounds, which are sometimes fatal and cost the U.S. health-care system an estimated $25 billion annually. Ohio State University researchers have discovered, in a new animal study, that the presence of miR-210 in wounds with limited blood flow lowers the production of a protein (E2F3) that is needed to encourage skin cells to grow and close over the wound. In a parallel experiment using human skin cells, the researchers silenced the miR-210 with an experimental drug and saw E2F3 protein levels rise. The skin cells multiplied as a result. The research involved wounds that are ischemic, that is, they heal very slowly or are in danger of never healing because they lack blood flow and oxygen at the wound site. These types of wounds affect approximately 6.5 million patients each year, and are common complications of diabetes, high blood pressure, obesity, and other conditions characterized by poor vascular health. "When blood supply is inadequate, many things are deficient at the wound site, including oxygen. That leads to a condition called hypoxia," said Dr. Chandan Sen, senior author of the study. "We have shown that hypoxia induces miR-210, which actually blocks the ability of the cells to proliferate, a step necessary for the wound-closure process.” This research was published online on March 22, 2010 in PNAS.

Scientists at the University of Hawaii have discovered the first-ever species of insect that are able to survive an entire life stage spent both above and below the water's surface. In mountain streams across the islands of Hawaii, the researchers observed the larvae (caterpillars) of the moth genus Hyposmocoma feeding and breathing both underwater and away from streams on dry rocks. The scientists said that the caterpillars can breathe and feed indefinitely and equally well both above and below the water’s surface, and can mature either submerged or completely dry. The amphibious caterpillars possess no gills or plastron, common structures for underwater respiration in other insects. When submerged, the caterpillars likely rely on the direct diffusion of oxygen through the hydrophilic skin along their abdomens, the researchers said. Perhaps as a result of their need for direct diffusion, the caterpillars occur only in fast-flowing, well-oxygenated streams, the authors wrote, and quickly die in stagnant water. Genetic analysis of DNA from 89 species of Hyposmocoma indicated that the amphibious lifestyle is an example of parallel evolution; the analysis showed evidence of at least three independent invasions of the water by strictly terrestrial clades (evolutionary groups including a single ancestor and all its descendants), beginning more than six million years ago, before the current “high islands” existed (note: high islands are of volcanic origin and are distinguished from “low islands,” which are formed by sedimentation or uplifting of coral reefs). The authors noted that why and how Hyposmocoma, an overwhelmingly terrestrial group, repeatedly evolved unprecedented aquatic species is unclear, although there are many other evolutionary anomalies across the Hawaiian archipelago. How and why certain species of Hyposmocoma have overcome the physiological limitations of breathing directly from both water and air will be the focus of future research, the researchers said. Interestingly, all caterpillars in the genus Hyposmocoma spin silk cases embedded with minute objects from their environment (pebbles, diatoms, algae, and lichens) to protect and camouflage their bodies, serving as essential shelter both in and out of the water. The caterpillars quickly perish when removed from their cases. The article on amphibious caterpillars was published online on March 22, 2010 in PNAS.

When levels of free protein p85 were increased in the livers of severely obese, diabetic mice, researchers at Children's Hospital Boston-Harvard Medical School and the University of Tokyo saw improved glucose tolerance and reduced blood glucose levels. The effect lies in the influence of p85 on the transcription factor XBP-1 (X-box binding protein 1), the scientists said. Under the influence of p85, XBP-1 normally moves to the nucleus and turns on genes for numerous chaperone proteins, which reduce stress on the endoplasmic reticulum (ER) by aiding and stabilizing the folding of proteins that are produced there and then dispatched to do their jobs in the cell. In previous work, the authors had shown that the brain, liver, and fat cells of obese mice have increased stress in the ER. In the presence of obesity, the ER is overwhelmed and its operations break down. This so-called "ER stress" activates a cascade of events that suppress the body's response to insulin, and is a key link between obesity and type 2 diabetes. Until now, however, researchers haven't known precisely why obesity causes ER stress to develop. Senior author Dr. Umut Ozcan and colleagues have now shown that XBP-1 is unable to function properly in obese mice. Instead of traveling to the cell nucleus and turning on chaperone genes, XBP-1 becomes stranded. Probing further, the researchers found the reason: XBP-1 fails to interact with p85, which is part of an important protein (phosphotidyl inositol 3 kinase or PI3K) that mediates insulin's effect of lowering blood glucose levels. Dr. Ozcan's group identified a new complex of p85 proteins in the cell, and showed that normally, when stimulated by insulin, p85 breaks off and binds to XBP-1, helping it get to the nucleus. "What we found is, in conditions of obesity, XBP-1 cannot go to the nucleus and there is a severe defect in the up-regulation of chaperones," says Dr. Ozcan. "But when we increase levels of free p85 in the liver of obese, severely diabetic mice, we see a significant increase in XBP-1 activity and chaperone response and, consequently, improved glucose tolerance and reduced blood glucose levels." The article was published online on March 28, 2010 in Nature Medicine.

A two-drug combination destroys precancerous colon polyps with no effect on normal tissue, opening a new potential avenue for chemoprevention of colon cancer, according to a team of scientists at The University of Texas M.D. Anderson Cancer Center and INCELL Corporation. The drug regimen, tested so far in mouse models and on human colon cancer tissue in the laboratory, appears to address a problem with chemopreventive drugs--they must be taken continuously long term to be effective, exposing patients to possible side effects, said senior author Dr. Xiangwei Wu, associate professor in M.D. Anderson's Department of Head and Neck Surgery. "This combination can be given short term and periodically to provide a long-term effect, which would be a new approach to chemoprevention," Dr. Wu said. The team found that a combination of Vitamin A acetate (RAc) and TRAIL, (tumor necrosis factor-related apoptosis-inducing ligand), kills precancerous polyps and inhibits tumor growth in mice that have deficiencies in a tumor-suppressor gene. That gene, adenomatous polyposis coli (APC) and its downstream signaling molecules, are mutated or deficient in 80 percent of all human colon cancers, Dr. Wu said. Early experiments with APC-deficient mice showed that the two drugs combined or separately did not harm normal colon epithelial cells. Separately, they showed no effect on premalignant polyps. RAc and TRAIL together killed premalignant polyps, causing programmed cell death known as apoptosis. RAc, researchers found, sensitizes polyp cells to TRAIL. The scientists painstakingly tracked the molecular cascade caused by APC deficiencies, and found that insufficient APC sensitizes cells to TRAIL and RAc by suppressing a protein that blocks TRAIL. Before human clinical trials can be considered, Dr. Wu noted, the team will conduct additional research to understand potential side effects and will also try to develop an injectable version of the drug combination, which is administered intravenously now. Today, concerns about cardiovascular side effects limit chemopreventive agents for colon cancer mainly to high-risk patients, Dr. Wu said. "We hope this combination, if it proves to lack toxicities, might be available as a chemopreventive agent to a broader, general population." The article was published online on March 28, 2010 in Nature.