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.

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.

Contrary to conventional wisdom that the symptoms of Down syndrome are likely caused by an overabundance of certain proteins due to the additional copy of chromosome 21, scientists at Ohio State University and collaborators have found evidence that at least some of the symptoms may actually be associated with underexpression of a certain protein or proteins due to the presence of five microRNA genes on chromosome 21. MicroRNAs bind to messenger RNA and cause the inhibition of protein synthesis for that messenger RNA. Computer analysis revealed over 1,600 proteins that were potential targets of the five microRNAs on chromosome 21, all of which could cause problems in Down syndrome because they would be underexpressed. Based on other evidence, the researchers selected one of the protein genes (for methyl-CpG-binding protein 2, known as MeCP2) for further study. Among the reasons for selecting this gene was that it is known to be mutated in Rett syndrome, an inherited cognitive disorder. The researchers used just two of the five microRNAs on chromosome 21 for the experiments in this study, miR-155 and miR-802, to match the only microRNAs available in the genetically engineered mouse model of Down syndrome. First, the researchers made copies of the relevant microRNAs. In human brain cell lines, they manipulated levels of those two molecules to show the inverse relationship with MeCP2. If the microRNAs were overexpressed, the level of the MeCP2 protein went down. When the microRNAs were underexpressed, the protein levels went up.

Next, the researchers examined adult and fetal human brain tissue from healthy and Down syndrome samples obtained from a national tissue bank. “In both adult and fetal Down syndrome brain samples, it didn’t matter which area of the brain we were looking at, the MeCP2 proteins were down. These are just observations with no manipulation on our part, and the MeCP2 is almost non-existent in the Down syndrome brain,” senior author Dr. Terry Elton said. “We marked the protein with a fluorescent molecule, and by comparison, we could visualize and appreciate how much MeCP2 was being made by neurons in the control samples.”

MeCP2 is a transcription factor, meaning that it turns genes on and off. If its levels are too low in the brain, this suggests that genes influenced by its presence should be malfunctioning too. Based on previous research by another group, Dr. Elton and colleagues focused on two genes affected by the MeCP2 protein for their next set of experiments. Looking again at the human brain tissue samples, they found that the genes were indeed affected by the lowered protein level in Down syndrome brains--one gene that MeCP2 normally silences was in abundance, and the gene that should have been activated was underexpressed. Because the two genes examined have known roles in neural development, Dr. Elton said the results suggested even more strongly that the lowered protein’s effects on the genes likely contribute to cognitive problems associated with Down syndrome.

Finally, the researchers tested an experimental drug called an antagomir on mice that serve as models for Down syndrome research. Antagomirs are relatively new agents that render microRNAs inactive. The scientists injected an antagomir into the brains of these mice to silence the miR-155 with the intent to increase levels of the MeCP2 protein. Seven days after the injection, the level of the protein in the treated mouse brains resembled levels in normal mouse brains. “We showed that we can fix the protein abnormality in mice that model Down syndrome. But we can’t undo the pathology that has already occurred,” Elton said. “It’s a starting point, but it appears that we have new therapeutic targets to consider.”

This work was published in the January 8, 2010 issue of the Journal of Biological Chemistry.

University at Buffalo biophysicists have found a protein in tarantula venom that shows promise as a potential therapy for muscular dystrophy (MD). They have formed a start-up biotech company in Buffalo -- Rose Pharmaceuticals -- to advance the drug to clinical trials.

Fredrick Sachs, PhD, professor of physiology and biophysics at the University at Buffalo, and colleagues in his laboratory, discovered the peptide, called GsMTx4.

Therapies for muscular dystrophy are classed as "orphan drugs" by the FDA, allowing a shorter testing period than normal drugs. Sachs said he anticipates Rose Pharmaceuticals may be able to obtain FDA approval of the peptide for human use within two years. The new company is named for "Rose," the pet tarantula that has been in residence in Sachs' lab for nearly 20 years (see photo links).

The first target of the peptide is MD, a condition Sachs has been investigating for several years, but the peptide also has potential as a therapy for several other conditions, such as neuropathic pain and atrial fibrillation. Formation of the company was motivated by the goal of finding an MD therapy for the grandson of Sachs' friend Jeffrey Harvey.

The start-up is a collaboration between Sachs, Harvey, Thomas Suchyna, PhD, and Philip Gottlieb, PhD. Suchyna and Gottlieb, UB research scientist and UB research associate professor, respectively, have been working with Sachs at the university for several years to develop the peptide. Their work was supported by a grant from UB's Interdisciplinary Research and Creative Activities Fund. In collaboration with Eric Hoffman, PhD, director of the Wellstone Muscular Dystrophy Center at Children's National Medical Center in Washington, D.C., the team tested the effect of GsMTx4 on MD mice extensively. Results showed that the drug increased muscle strength and caused no mortality, morbidity or toxicity.

Rose Pharmaceuticals now is concentrating on developing methods to administer the drug. The peptide and its mirror image are covered by U.S. patents obtained by UB's Office of Science, Technology Transfer and Economic Outreach (STOR), and licensed to Rose Pharmaceuticals. Sachs noted that there are no other drugs known to act specifically on mechanosensitive ion channels, the target of GsMTx4. "Unlike most drugs, GsMTx4 seems to generate only positive side effects," said Sachs. "In addition to its effectiveness in MD, it inhibits atrial fibrillation, a cardiac arrhythmia that affects 2 million Americans, and for which there currently is no reliable drug therapy.

"In a second application, research groups in Korea and UC San Francisco have shown that GsMTx4 can inhibit mechanically induced pain (pain originating in nerve fibers)," he said. "This therapy is at least half as effective as morphine, but does not act on the brain, only at the site of increased sensitivity." Mark Kristal, Ph.D., UB professor of psychology, has been collaborating on the pain testing.

Vitamin-fortified foods and dietary health supplements can ease health worries. But what kinds of vitamins are right for you? And how much of them should you take, and how often?

A research group from Tel Aviv University has done the most comprehensive and accurate study of clinical data on Vitamin E use and heart disease to date, and it warns that indiscriminate use of high-dose Vitamin E supplementation does more harm than good. Their results were recently reported in ATVB, a leading journal of cardiology, and discussed in the journal BioFactors.

"There were so many conflicting reports about Vitamin E and its effect on various diseases, particularly heart disease, that we wanted to set the record straight, says Prof. Dov Lichtenberg of TAU's Sackler School of Medicine.

Our new study shows that some people may be harmed by the treatment, whereas others may benefit from it. Now we're trying to identify groups of people that are most likely to benefit from the effects of Vitamin E," adds study co-researcher Dr. Ilya Pinchuk. The TAU research team also included decision analyst Dr. Moshe Leshno of the Sackler Faculty of Medicine and the Leon Recanati Faculty of Management and Dr. Yedidya (Didi) Dotan, whose PhD thesis is the basis for this analysis.

Rising threats and attacks on humanitarian operations, as well as the imposition of a string of unacceptable demands from armed groups, have made it virtually impossible for the World Food Programme (WFP) to continue reaching up to one million people in need in southern Somalia.

WFP's humanitarian operations in southern Somalia have been under escalating attacks from armed groups, leading to this partial suspension of humanitarian food distributions in much of southern Somalia.

WFP is deeply concerned about rising hunger and suffering among the most vulnerable due to these unprecedented and inhumane attacks on purely humanitarian operations.

Forty-one percent of college students with weight problems opened and read spam e-mail advertising weight loss products and 18.5 percent bought these weight loss products, according to a new study published in the January issue of the Southern Medical Journal. The research was conducted by Joshua Fogel, Ph.D., an Associate Professor of the Business Program at the Department of Economics at Brooklyn College , and Sam Shlivko, B.S., a former Brooklyn College student and currently a student at New York Law School.

In additional analyses considering the impact of a number of relevant variables, those with weight problems as compared to those without weight problems, were three times more likely to open/read and also three times more likely to purchase weight loss products from this spam e-mail. Also, increased psychological stress was associated with an increase in purchases of these weight loss products advertised in spam e-mail.

As lead investigator, Dr. Fogel analyzed data from a survey of 200 college students, who were asked if they had weight problems and if in the past year they received, opened/read, or purchased products from spam e-mail about weight loss topics. Psychological stress was measured by the Perceived Stress Scale

The master regulator of muscle differentiation, MyoD, functions early in myogenesis to help stem cells proliferate in response to muscle injury, according to researchers at Case Western Reserve University. The study appears online Jan. 4 in the Journal of Cell Biology.

MyoD is a transcription factor that activates muscle-specific genes as myoblast precursors differentiate and fuse to form mature muscle fibers. But MyoD is also expressed at an earlier stage of myogenesis when quiescent stem cells rapidly expand in number to generate the myoblasts needed to repair tissue damage. The transcription factor's function in this proliferative phase is unknown.

The team found that MyoD bound to the promoter of CDC6, a gene that initiates DNA replication, suggesting that MyoD might activate Cdc6 expression in muscle stem cells to promote their reentry into the cell cycle and rapid proliferation. Indeed, Cdc6 was expressed shortly after MyoD in stimulated muscle progenitors, and knocking down MyoD reduced Cdc6 production and slowed cells' entry into S phase. MyoD works in conjunction with transcription factors from the E2F family. E2F3a activated the CDC6 promoter with MyoD, but was replaced by the repressive family member E2F4 as myoblasts began to differentiate.

Researchers at UC Davis have identified 10 locations in California where the incidence of autism is higher than surrounding areas in the same region. Most of the areas, or clusters, are in locations where parents have higher-than-average levels of educational attainment. Because children with more educated parents are more likely to be diagnosed with an autism spectrum disorder, one need look no further for a cause, the authors say. The other clusters are located close to major autism treatment centers.

The clusters are located primarily in the high-population areas of Southern California and, to a lesser extent, in the San Francisco Bay Area. The researchers said that, while children born within the clusters during the study period were more likely to be diagnosed with autism, the majority of the state's children with autism were born in adjacent areas outside the clusters.

For the rigorous study, published online today in the journal Autism Research, scientists examined nearly all of the approximately 2-1/2 million births recorded in the state of California from 1996 through 2000. About 10,000 children born during that five-year period were later diagnosed with an autism spectrum disorder, according to the California Department of Developmental Services (DDS).

Arizona marked a historic milestone with the number of rabid animals in 2009. One case in particular, of a rabid bobcat walking into a bar, sounded more like the beginning of a joke, but highlighted the importance of rabies awareness.

So far 261 animals tested positive for rabies, 85 more than 2008. During the record breaking year, two counties established quarantines, another first for the state. "There is no sign of rabies letting up in many parts of the state," said Craig Levy, Vector-Borne Disease Program Manager. "As we head into 2010, we need to be prepared for more rabid animals and the exposures to people and pets that they bring."

ADHS works closely with Arizona Department of Game and Fish to educate the public about wild animals and rabies, as well as county health departments and local animal control programs.

In December, Santa Cruz County instituted a 60-day quarantine for the entire county, similar to Coconino County's quarantine earlier in the year. Both counties ordered people to keep their dogs in their yards or on a short leash, bring dishes of pet food indoors at night and vaccinate all pets.

Rabies is transmitted through bites or saliva contact with a rabid animal. It is almost always fatal once symptoms appear; for this reason people must be treated promptly to prevent infection. In 2009, 47 people in Arizona were exposed to confirmed rabid animals. They received the correct treatment quickly and the infection was stopped.