Overexpression of splicing protein in skin repair causes early changes seen in skin cancer
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Normally, tissue injury triggers a mechanism in cells that tries to repair damaged tissue and restore the skin to a normal, or homeostatic state. Errors in this process can give rise to various problems, such as chronic inflammation, which is a known cause of certain cancers.
“It has been noted that cancer resembles a state of chronic wound healing, in which the wound-healing program is erroneously activated and perpetuated,” says Professor Adrian Krainer of Cold Spring Harbor Laboratory (CSHL). In a paper published today in Nature Structural & Molecular Biology, a team led by Dr. Krainer reports that a protein they show is normally involved in healing wounds and maintaining homeostasis in skin tissue is also, under certain conditions, a promoter of invasive and metastatic skin cancers.
The protein, called SRSF6, is what biologists call a splicing factor: it is one of many proteins involved in an essential cellular process called splicing. In splicing, an RNA “message” copied from a gene is edited so that it includes only the portions needed to instruct the cell how to produce a specific protein. The messages of most genes can be edited in multiple ways, using different splicing factors; thus, a single gene can give rise to multiple proteins, with distinct functions.
The SRSF6 protein, while normally contributing to wound healing in skin tissue, when overproduced can promote abnormal growth of skin cells and cancer, Krainer’s team demonstrated in experiments in mice. Indeed, they determined the spot on a particular RNA message - one that encodes the protein tenascin C - where SRSF6 binds abnormally, giving rise to alternate versions of the tenascin C protein that are seen in invasive and metastatic cancers.
In the blink of an eye
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Imagine seeing a dozen pictures flash by in a fraction of a second. You might think it would be impossible to identify any images you see for such a short time. However, a team of neuroscientists from MIT has found that the human brain can process entire images that the eye sees for as little as 13 milliseconds - the first evidence of such rapid processing speed.
That speed is far faster than the 100 milliseconds suggested by previous studies. In the new study, which appears in the journal Attention, Perception, and Psychophysics, researchers asked subjects to look for a particular type of image, such as “picnic” or “smiling couple,” as they viewed a series of six or 12 images, each presented for between 13 and 80 milliseconds.
“The fact that you can do that at these high speeds indicates to us that what vision does is find concepts. That’s what the brain is doing all day long - trying to understand what we’re looking at,” says Mary Potter, an MIT professor of brain and cognitive sciences and senior author of the study.
This rapid-fire processing may help direct the eyes, which shift their gaze three times per second, to their next target, Potter says. “The job of the eyes is not only to get the information into the brain, but to allow the brain to think about it rapidly enough to know what you should look at next. So in general we’re calibrating our eyes so they move around just as often as possible consistent with understanding what we’re seeing,” she says.
Low national funding for LGBT health research contributes to inequities, analysis finds
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Only one-half of 1 percent of studies funded by the National Institutes of Health (NIH) between 1989 and 2011 concerned the health of lesbian, gay, bisexual and transgender (LGBT) people, contributing to the perpetuation of health inequities, according to a University of Pittsburgh Graduate School of Public Health-led analysis.
The findings, which grew from the Fenway Institute’s Summer Institute in LGBT Population Health in Boston and continued at Pitt Public Health’s Center for LGBT Health Research, are in the February issue of the American Journal of Public Health, published today. The researchers make several recommendations for how to stimulate LGBT-related research.
“The NIH is the world’s largest source of health research funding and has placed a low priority on LGBT health research,” said Robert W.S. Coulter, M.P.H., a doctoral student in Pitt Public Health’s Department of Behavioral and Community Health Sciences. “In general, LGBT people experience stigma associated with their sexual and gender minority status, disproportionate behavioral risks and psychosocial health problems, and higher chronic disease risk factors than their non-LGBT counterparts. Increased NIH funding for research on these topics, particularly focusing on evidence-based interventions to reduce health inequities, could help alleviate these negative health outcomes.”
About 3.5 percent of the U.S. adult population is estimated to be gay, lesbian or bisexual, according to recent research based on national- and state-level population surveys.
New strategy emerges for fighting drug-resistant malaria
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Malaria is one of the most deadly infectious diseases in the world today, claiming the lives of over half a million people every year, and the recent emergence of parasites resistant to current treatments threatens to undermine efforts to control the disease. Researchers are now onto a new strategy to defeat drug-resistant strains of the parasite. Their report appears in the journal ACS Chemical Biology.
Christine Hrycyna, Rowena Martin, Jean Chmielewski and colleagues point out that the parasite Plasmodium falciparum, which causes the most severe form of malaria, is found in nearly 100 countries that, all totaled, are home to about half of the world’s population. Every day, P. falciparum and its relatives hitch rides via mosquitoes to find a human home. An effective vaccine remains elusive and the continuing emergence of drug-resistant parasites is cause for alarm. The good news is that these scientists have designed compounds that work against P. falciparum strains that are resistant to drugs such as chloroquine. The team wanted to understand how these compounds worked and to develop new candidate antimalarials.
In the lab, the scientists designed and tested a set of molecules called quinine dimers, which were effective against sensitive parasites, and, surprisingly, even more effective against resistant ones. The compounds have an additional killing effect on the drug-resistant parasites because the compounds bind to and block the resistance-conferring protein. This resensitizes the parasites to chloroquine, and appears to block the normal function of the resistance protein, killing the parasite. “This highlights the potential for devising new antimalarial therapies that exploit inherent weaknesses in a key resistance mechanism of P. falciparum,” they state.
Tweaking MRI to track creatine may spot heart problems earlier, Penn Medicine study suggests
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A new MRI method to map creatine at higher resolutions in the heart may help clinicians and scientists find abnormalities and disorders earlier than traditional diagnostic methods, researchers at the Perelman School of Medicine at the University of Pennsylvania suggest in a new study published online today in Nature Medicine. The preclinical findings show an advantage over less sensitive tests and point to a safer and more cost-effective approach than those with radioactive or contrasting agents.
Creatine is a naturally occurring metabolite that helps supply energy to all cells through creatine kinase reaction, including those involved in contraction of the heart. When heart tissue becomes damaged from a loss of blood supply, even in the very early stages, creatine levels drop. Researchers exploited this process in a large animal model with a method known as CEST, or chemical exchange saturation transfer, which measures specific molecules in the body, to track the creatine on a regional basis.
The team, led by Ravinder Reddy, PhD, professor of Radiology and director of the Center for Magnetic Resonance and Optical Imaging at Penn Medicine, found that imaging creatine through CEST MRI provides higher resolution compared to standard magnetic resonance spectroscopy (MRS), a commonly used technique for measuring creatine. However, its poor resolution makes it difficult to determine exactly which areas of the heart have been compromised.
“Measuring creatine with CEST is a promising technique that has the potential to improve clinical decision making while treating patients with heart disorders and even other diseases, as well as spotting problems sooner,” said Reddy. “Beyond the sensitivity benefits and its advantage over MRS, CEST doesn’t require radioactive or contrast agents used in MRI, which can have adverse effects on patients, particularly those with kidney disease, and add to costs.”
Cancer drug protects against diabetes
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New research shows that low doses of a cancer drug protect against the development of type 1 diabetes in mice. At the same time, the medicine protects the insulin-producing cells from being destroyed. The study is headed by researchers from the Faculty of Health and Medical Sciences at the University of Copenhagen, and has just been published in the distinguished scientific journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Very low doses of a drug used to treat certain types of cancer protect the insulin-producing cells in the pancreas and prevent the development of diabetes mellitus type 1 in mice. The medicine works by lowering the level of so-called sterile inflammation. The findings have been made by researchers from the University of Copenhagen, the Technical University of Denmark and the University of Southern Denmark working with researchers in Belgium, Italy, Canada, Netherlands and the USA.
“Diabetes is a growing problem worldwide. Our research shows that very low doses of anticancer drugs used to treat lymphoma - so-called lysine deacetylase inhibitors - can reset the immune response to not attack the insulin-producing cells. We find fewer immune cells in the pancreas, and more insulin is produced when we give the medicine in the drinking water to mice that would otherwise develop type 1 diabetes,” says postdoc Dan Ploug Christensen, who is the first author on the article and responsible for the part of the experimental work carried out in Professor Thomas Mandrup-Poulsen’s laboratory at the Department of Biomedical Sciences, University of Copenhagen.
Fresh faced: Looking younger for longer
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Newcastle University researchers have identified an antioxidant Tiron, which offers total protection against some types of sun damage and may ultimately help our skin stay looking younger for longer.
Publishing in The FASEB Journal, the authors describe how in laboratory tests, they compared the protection offered against either UVA radiation or free radical stress by several antioxidants, some of which are found in foods or cosmetics. While UVB radiation easily causes sunburn, UVA radiation penetrates deeper, damaging our DNA by generating free radicals which degrades the collagen that gives skin its elastic quality.
The Newcastle team found that the most potent anti-oxidants were those that targeted the batteries of the skin cells, known as the mitochondria. They compared these mitochondrial-targeted anti-oxidants to other non-specific antioxidants such as resveratrol, found in red wine, and curcumin found in curries, that target the entire cell. They found that the most potent mitochondrial targeted anti-oxidant was Tiron which provided 100%, protection of the skin cell against UVA sun damage and the release of damaging enzymes causing stress-induced damage.
Older Firefighters May Be More Resilient to Working in Heat
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Older firefighters who are chronically exposed to heat stress on the job could be more heat resilient over time. A recent study published in the December issue of the Journal of Occupational and Environmental Hygiene (JOEH) found that older firefighters may be able to tolerate more challenging or arduous work environments before they feel affected by the heat, compared to non-heat-exposed workers who would need to stop work prematurely.
“We found that the firefighters experienced reduced subjective feelings of thermal and cardiovascular strain during exercise compared to the non-firefighters, potentially indicative of greater heat resilience in firefighters due to the nature of their occupation,” said study investigator Glen P. Kenny, PhD, a professor at the School of Human Kinetics at the University of Ottawa in Ontario, Canada.
The researchers examined a group of older, physically active non-firefighters and firefighters, approximately 51 years old, during intermittent exercise in two heat stress conditions, to investigate the potential thermal, cardiovascular and hydration effects of repeated occupational heat stress.
Does ObamaCare cause psychological distress among US adults?
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The Affordable Care Act, dubbed ‘ObamaCare’, has proven to be one of the most controversial legislative acts of the Obama presidency. New research, published in Stress & Health explores the psychological relationship between patients and health insurance coverage, finding that adults with private or no health insurance coverage experience lower levels of psychological distress than those with public coverage. In contrast, average absolute levels of distress were high among those with no coverage, compared to those with private coverage.
To examine the relationship between psychological distress and health insurance status, data was taken from the 2001–2010 National Health Interview Survey, from which the team used date representing U.S. adults aged between 18 and 64.
Adults with private or no health insurance coverage had lower levels of psychological distress than those with public or other forms of coverage.
