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.

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.

The momentum in support of the introduction of new members to the dental team continued to build with the release of a report on dental therapists by the W.K. Kellogg Foundation. Kellogg released a wide-ranging assessment of international and U.S. experiences in training and deploying dental therapists who help fill gaps in care for underserved populations who struggle to obtain dental services. The report addresses the potential impact of both a two-year educated dental therapist model as well as a three-year educated provider model that would incorporate dental hygiene and dental therapy.

Dental therapists focus their practice on the administration of restorative dental services and also provide a limited range of preventive services and offer patient nutrition and oral hygiene education. Dental therapists work in collaboration with dentists and other health care providers in the administration of care and have delivered safe, quality oral health care for decades. The Kellogg report explored the training of dental therapists, a type of provider currently in practice in more than 50 countries internationally and in remote Alaskan villages.

ADHA has long acknowledged the need for new dental providers to deliver needed oral health care services, particularly for the more than 108 million Americans who do not currently have dental insurance. In addition, ADHA advocates for additional entry points into the oral health care delivery system for population groups that cannot access services through the traditional private practice dental office. The association supports efforts toward the creation of new dental team members who have graduated from accredited educational programs, are licensed, and are able to provide care directly to the public.

The National Alliance on Mental Illness (NAMI) praises a new report, Caregiving in the U.S. 2009, which offers a revealing portrait of the nearly one-in-three American adults who serve as a family caregiver.

The study is based on interviews with 1,480 caregivers chosen at random and offers a national profile of people caring for adults, the elderly and children with special needs. It follows similar studies conducted in 2004 and 1997, but for the first time, caregivers for children, as well as those caring for adults over the age of 18, were surveyed.

The report echoes the findings of NAMI's own depression survey and schizophrenia survey, which include the perspective of caregivers for people living with these serious mental illnesses. All these reports suggest that caregivers face daily stresses that can impact their own health and other relationships. For example, NAMI's depression survey, released in November, found that while almost one-half (48 percent) of caregivers for people with depression have been diagnosed with depression themselves, only about 25 percent were engaged in treatment at the time of the survey.

Postmenopausal women with hormone receptor-positive (HR+) breast cancer who develop arthralgia and/or myalgia (A/M) while being treated with anastrozole may want to consider a switch to letrozole therapy, researchers said at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS).

In fact, their study - known as the Rheumatologic Evaluation of Adjuvant Letrozole in Postmenopausal Women with Breast Cancer (REAL) study - found that women who experienced ≥ grade 2 A/M while receiving anastrozole and switched to letrozole developed significantly less A/M and had an improved quality of life compared with baseline.

Denise A. Yardley, MD, Director of Breast Cancer Research at the Sarah Cannon Research Institute in Nashville, Tennessee, and colleagues conducted a study to determine whether switching to letrozole reduced the rate of grade 2 to 3 A/M symptoms and the rate of discontinuation in 261 women who had previously discontinued anastrozole therapy due to A/M.

An international team of scientists has found that cells that protect nerves are likely to be the origins of a fatal cancer known as Devil Facial Tumour Disease (DFTD) that is spreading rapidly through populations of Tasmanian devils in Australia: if unchecked, scientists estimate the cancer, which is spread through biting, could wipe out the wild devil population within the next 30 years or so. The findings are the subject of a collaborative study led by Australian scientists that was published in the international journal Science on 1 January.

Devil Facial Tumour Disease (DFTD) is a transmissible cancer that affects only the Tasmanian devil, a carnivorous marsupial about the size of a small dog that is found in Australia and Tasmania. The disease causes large tumours that occur mostly on the face and mouth but also spreads to internal organs.

First reported in 1996, DFTD spreads by biting and quickly kills infected animals; so much so, they are now considered an endangered species facing extinction.

A group led by Dr. Gregory A. Elder of the James J. Peters Veteran's Affairs Medical Center, Bronx, NY has demonstrated that presenilin-1 plays a role in the vascular pathology found in Alzheimer disease. Their report can be found in the January 2010 issue of the American Journal of Pathology.

Alzheimer disease accounts for half of all dementias diagnosed each year. Mutations in presenilin-1 (PS-1), which cleaves amyloid precursor protein, are one of the most common causes of early onset cases of familial Alzheimer disease (FAD), which accounts for 5-10% of all Alzheimer disease sufferers.

Alzheimer disease is accompanied by vascular pathology, where blood vessels and microvessels are damaged. To determine if mutated PS-1 contributes to the vascular pathology observed in FAD, Gama Sosa et al generated a mouse model that over expressed either wild-type or mutated human PS-1. They found age-related vascular pathology in these FAD model mice that was especially prominent in the microvasculature. However, the basis for this pathology appears to lie in the neurons, as neurons but not vascular endothelial or glial cells express PS-1 in these mice. Taken together, these results implicate a role for neuronal to vascular signaling in the pathogenesis of vascular pathology in FAD.

Dr. Johannes M. Weiss and colleagues at the University of Ulm, Ulm, Germany have discovered that osteopontin (OPN) contributes to allergic contact dermatitis. They present these findings in the January 2010 issue of the American Journal of Pathology.

Allergic contact dermatitis is a hyperreaction of the immune system to either allergens or irritants on the skin, such as poison ivy, nickel, or latex. Contact dermatitis results in large, burning, and itchy rashes, which can take anywhere from several days to weeks to heal. Once allergic contact dermatitis occurs, only strict avoidance can prevent a recurrence, and there is no method to resist persistent sensitization.

Seier et al hypothesized that OPN, an immune mediator that has been shown to worsen the effects of autoimmune disease, played a role in eliciting and facilitating chronic allergic contact dermatitis. They found that both skin cells and immune cells secreted OPN in allergic contact dermatitis lesions. OPN was strongly induced in antigen-specific immune cells in a murine model of chronic contact hypersensitivity, and OPN-deficient mice had a less severe chronic contact hypersensitivity response. As anti-OPN antibody treatment partially suppressed the symptoms of chronic contact hypersensitivity, OPN may serve as a new therapeutic target for allergic contact dermatitis.

Dr. Weiss's group suggests that "[their] data support a model in which OPN has an important function for [immune]-mediated skin inflammation, which may open the perspective to use anti-OPN antibody preparations for the treatment of therapy refractory [immune] cell-mediated skin disease."

Seier AM, Renkl AC, Schulz G, Uebele T, Sindrilaru A, Iben S, Liaw L, Kon S, Uede T Weiss JM: Antigen-Specific Induction of Osteopontin Contributes to the Chronification of Allergic Contact Dermatitis. Am J Pathol 2010, 176: 246-258