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Archive - 2013

March 8th

Hypocretin Peptide May Play Role in Human Happiness

The neurochemical changes underlying human emotions and social behavior are largely unknown. Now though, for the first time in humans, scientists at UCLA have measured the release of a specific peptide, a neurotransmitter called hypocretin, which greatly increased when subjects were happy, but decreased when they were sad. The finding suggests that boosting hypocretin could elevate both mood and alertness in humans, thus laying the foundation for possible future treatments of psychiatric disorders like depression by targeting measureable abnormalities in brain chemistry. In addition, the study measured for the first time the release of another peptide, this one called melanin concentrating hormone, or MCH. Researchers found that its release was minimal during waking periods, but greatly increased during sleep, suggesting a key role for this peptide in making humans sleepy. The study was published online on March 5, 2013 in Nature Communications. "The current findings explain the sleepiness of narcolepsy, as well as the depression that frequently accompanies this disorder," said senior author Dr. Jerome Siegel, a professor of psychiatry and director of the Center for Sleep Research at UCLA's Semel Institute for Neuroscience and Human Behavior. "The findings also suggest that hypocretin deficiency may underlie depression from other causes." In 2000, Dr. Siegel's team published findings showing that people suffering from narcolepsy, a neurological disorder characterized by uncontrollable periods of deep sleep, had 95 percent fewer hypocretin nerve cells in their brains than those without the illness. That study was the first to show a possible biological cause of the disorder. Because depression is strongly associated with narcolepsy, Dr.

Signaling Molecule May Help Stem Cells Make Bone Despite Age, Disease

A signaling molecule that helps stem cells survive in the naturally low-oxygen environment inside the bone marrow may hold clues to helping the cells survive when the going gets tougher with age and disease, researchers report. They hope their findings, reported online on March 5, 2013 in the open-access journal PLOS ONE, will result in better therapies to prevent bone loss in aging and enhance success of stem cell transplants for a wide variety of conditions from heart disease to cerebral palsy and cancer. The scientists found that inside the usual, oxygen-poor niche of mesenchymal stem cells, stromal cell-derived factor-1, or SDF-1, turns on a survival pathway called autophagy that helps the cells stay in place and focused on making bone, said Dr. William D. Hill, stem cell researcher at the Medical College of Georgia (MCG) at Georgia Regents University (GRU) and the study's corresponding author. Unfortunately, with age or disease, SDF-1 appears to change its tune, instead reducing stem cells' ability to survive and stay in the bone marrow, said Samuel Herberg, GRU graduate student and the study's first author. Additionally, cells that do stay put may be less likely to make bone and more likely to turn into fat cells in the marrow. The researchers believe it's the changes in the normal environment that come with age or illness, including diminished nutrition, that prompt SDF-1's shifting role. "You put new cells in there and, all of the sudden, you put them in a neighborhood where they are being attacked," Dr. Hill said.

Algae Tolerant of Extreme Environments Offer Wal-Mart of Genomic Material

Most organisms would die in the volcanic sulfur pools of Yellowstone and Mount Etna. Robust simple algae call these extreme environments home, and their secrets to survival could advance human medicine and bioremediation. Dr. Mike Garavito, Michigan State University (MSU) professor of biochemistry and molecular biology was part of a research team that revealed how primitive red algae use horizontal gene transfer, in essence stealing useful genes from other organisms to evolve and thrive in harsh environments. Their study, published in the March 8, 2013 issue of Science, shows that the algae’s ability to adapt to a hot and extremely acidic environment ¬lies in part in their membrane proteins. “The algae’s membrane proteins are biologically quite interesting because they’re receptors and transporters, the same classes of proteins that play key roles in energy metabolism and human immune response,” said Dr. Garavito. “This has applications in human medicine because virtually all of the important pathways that contribute to disease treatment involve membrane proteins.” What makes the algae’s membrane proteins attractive as a model for humans is their robustness. Other traditional candidates, such as yeast, insect cell cultures, and slime mold, are fragile. The hardy algae give researchers extra time to manipulate and examine their membrane proteins. Dr. Garavito was part of a team of researchers led by Dr. Andreas Weber, former MSU researcher now at Heinrich-Heine-Universitat Dusseldorf (Germany). While at MSU, Dr. Weber led a team in first sequencing the algae, one of the first major genome sequencing projects at MSU. “Dr. Weber knew that this would be a good organism from which to harvest a wide variety of genes that could be potential models for those involved in human health and disease,” said Dr.

Sequencing Study of Dust Mites Demonstrates Reversible Evolution

In evolutionary biology, there is a deeply rooted supposition that you can't go home again: Once an organism has evolved specialized traits, it can't return to the lifestyle of its ancestors. There's even a name for this pervasive idea. Dollo's law states that evolution is unidirectional and irreversible. But this "law" is not universally accepted and is the topic of heated debate among biologists. Now a research team led by two University of Michigan (U-M) biologists has used a large-scale genetic study of the lowly house dust mite to uncover an example of reversible evolution that appears to violate Dollo's law. The study shows that tiny free-living house dust mites, which thrive in the mattresses, sofas, and carpets of even the cleanest homes, evolved from parasites, which in turn evolved from free-living organisms millions of years ago. "All our analyses conclusively demonstrated that house dust mites have abandoned a parasitic lifestyle, secondarily becoming free-living, and then speciated in several habitats, including human habitations," according to Dr. Pavel Klimov and Dr. Barry O’Connor of the U-M Department of Ecology and Evolutionary Biology. Their paper is scheduled to be published online on March 8, 2013 in the journal Systematic Biology. Mites are arachnids related to spiders (both have eight legs) and are among the most diverse animals on Earth. House dust mites, members of the family Pyroglyphidae, are the most common cause of allergic symptoms in humans, affecting up to 1.2 billion people worldwide. Despite their huge impact on human health, the evolutionary relationships between these speck-sized creatures are poorly understood. According to Drs.

March 7th

Toward Unlimited Cloning: Japanese Scientists Make 25 Generations of Mouse Clones

Using the same technique that was used to create Dolly the sheep, researchers from the RIKEN Center for Developmental Biology in Kobe, Japan, have identified a way to produce healthy mouse clones that live a normal lifespan and can be sequentially cloned indefinitely. Their study was published as the cover story of the March 7, 2013 issue of Cell Stem Cell. In an experiment that started in 2005, the team led by Dr. Teruhiko Wakayama has used a technique called somatic cell nuclear transfer (SCNT) to produce 581 clones of one original “donor” mouse, through 25 consecutive rounds of cloning. SCNT is a widely used cloning technique whereby a cell nucleus containing the genetic information of the individual to be cloned is inserted into a living egg that has had its own nucleus removed. It has been used successfully in laboratory animals, as well as farm animals. However, until now, scientists had not been able to overcome the limitations of SCNT that resulted in a low success rates and restricted the number of times mammals could be recloned. Attempts at recloning cats, pigs, and mice more than two to six times had failed. “One possible explanation for this limit on the number of recloning attempts is an accumulation of genetic or epigenetic abnormalities over successive generations,” explains Dr. Wakayama. To prevent possible epigenetic changes, or modifications to DNA function that do not involve a change in the DNA itself, Dr. Wakayama and his team added trichostatin, a histone deacetylase inhibitor, to the cell culture medium. Using this technique, they increased cloning efficiency by up to 6-fold. By improving each step of the SCNT procedure, the scientists were able to clone the mice repeatedly 25 times without seeing a reduction in the success rate.

March 6th

Excess Dietary Salt May Drive the Development of Autoimmune Diseases

Increased dietary salt intake can induce a group of aggressive immune cells that are involved in triggering and sustaining autoimmune diseases. This is the result of a study conducted by an international group of scientists, including ones from Yale University, the Broad Institute, MIT, Harvard University, Vanderbilt University, the Max-Delbrück Center for Molecular Medicine in Berlin, and the University of Erlangen-Nuremberg, among others. The authors of the report, which was published online in Nature on March 6, 2013, included Dr. Markus Kleinewietfeld, Professor David Hafler, Dr. Ralf Linker, Professor Jens Titze, and Professor Dominik N. Müller. A second study, published on the same day in Nature, describes how a salt-sensing enzyme might be involved in the induction of autoimmune disease. A third study, also published on the same day in Nature, describes the molecular pathways involving T helper cells that can lead to autoimmune disease. Together, this suite of three Nature articles may significantly advance our understanding of the origins of autoimmune disease. The focus here is on the first article on the effects of excess dietary salt. In recent decades, scientists have observed a steady rise in the incidence of autoimmune diseases in the Western world. Because this increase cannot be explained solely by genetic factors, researchers hypothesize that the sharp increase in these diseases is linked to environmental factors. Among the suspected culprits are changes in lifestyle and dietary habits in developed countries, where highly processed food and fast food are often on the daily menu. These foods tend to have substantially higher salt content than home-cooked meals.

High Level of Epigenomic Diversity May Aid Plant Adaptation

Scientists at the Salk Institute for Biological Studies in La Jolla, California, have identified patterns of epigenomic diversity that not only allow plants to adapt to various environments, but could also benefit crop production and the study of human diseases. Published online on March 6, 2013 in Nature, the findings show that in addition to genetic diversity found in plants throughout the world, their epigenomic makeup is as varied as the environments in which they are found. Epigenomics is the study of the pattern of chemical markers that serve as a regulatory layer on top of the DNA sequence. Depending on where they grow, the plants' epigenomic differences may allow them to rapidly adapt to their environments. Epigenomic modifications alter gene expression without changing the letters of the DNA alphabet (A-T-C-G), providing cells with an additional tool to fine-tune how genes control the cellular machinery. These changes occur not only in plants, but in humans as well. "We looked at plants collected from around the world and found that their epigenomes are surprisingly different," says senior author Dr. Joseph R. Ecker, a professor in Salk's Plant Biology Laboratory and holder of the Salk International Council Chair in Genetics. "This additional diversity may create a way for plants to rapidly adapt to diverse environments without any genetic change in their DNA, which takes a very long time." By understanding epigenomic alterations in plants, scientists may be able to manipulate them for various purposes, including biofuels and creating crops that can withstand stressful events such as drought.

Stem Cell Origin of Aggressive Ovarian Cancer in Humans Suggested by Results of Mouse Study

Cornell University researchers have discovered a likely origin of epithelial ovarian cancer (ovarian carcinoma), the fifth leading cause of cancer death among women in the United States. Pinpointing where this cancer originates has been difficult because 70 percent of patients are in advanced stages of disease by the time it is detected. Because the origin of ovarian carcinoma development is unknown, early diagnostic tests have so far been unsuccessful. Some epithelial cancers are known to occur in transitional zones between two types of epithelium (layers of tissue that line the body and organs and form glands), while others originate in epithelial tissue stem cells. Many organs have the capacity for regeneration, which is done by adult stem cells located in areas of each organ called stem cell niches. With this knowledge, the researchers discovered a novel stem cell niche for the ovarian surface epithelium in mice and showed that ovarian carcinoma preferentially originates from stem cells found in that niche, according to the study published online on March 6, 2013 in Nature. This stem cell niche lies in a transitional area known as the hilum region, a layer of cells that links the ovary to the rest of the body. "We now know where these cells are located in mice, so we can look in humans in those areas," said Dr. Alexander Nikitin, professor of pathology, leader of the Cornell Stem Cell Program and the Nature paper's senior author. Dr. Andrea Flesken-Nikitin, a postdoctoral researcher in Dr. Nikitin's lab, is the paper's lead author. The findings also provide a guide for scientists to look for stem cell niches and sources of cancer in other transitional zones in other organs, Dr. Nikitin added.

MicroRNAs May Predict Cancer Progression of Barrett's Esophagus

A series of microRNA expression signatures that may help to define progression of the precancerous condition Barrett's esophagus into esophageal adenocarcinoma was reported in the March 2013 issue of Cancer Prevention Research, a journal of the American Association for Cancer Research. "Once a rare cancer representing only 5 percent of all esophageal cancers in the United States, esophageal adenocarcinoma is the cancer with the fastest-rising incidence — six-fold increase in the past three decades — and currently comprises more than 80 percent of all new esophageal cancer cases in this country," said Xifeng Wu, M.D., chair of the Department of Epidemiology, Division of Cancer Prevention and Population Sciences at The University of Texas MD Anderson Cancer Center, in Houston. "To reduce the mortality of esophageal adenocarcinoma, the best hope in the near term is to detect it at its early stage, or even better, to prevent the progression of esophageal adenocarcinoma from its premalignant lesion, which is called Barrett's esophagus." Dr. Wu and colleagues evaluated microRNAs, which are a class of small ribonucleic acids in cells capable of regulating a large number of genes. Research has shown that aberrant expression of microRNAs can be involved in cancer development. The researchers compared hundreds of microRNAs in normal esophageal epithelia and in Barrett's esophagus and esophageal adenocarcinoma tissues of different histological grades with distinct progression risks. They identified a number of differentially expressed microRNAs at each histological stage. "The expression of microRNAs in Barrett's esophagus and esophageal adenocarcinoma tissues was remarkably similar, indicating that the microRNA aberrations were very early events in the development of Barrett's esophagus," Dr. Wu said.

Visceral Fat Causally Linked to Intestinal Cancer in Mouse Study

Visceral fat, or fat stored deep in the abdominal cavity, is directly linked to an increased risk for colon cancer, according to data from a mouse study published in the March 2013 issue of Cancer Prevention Research, a journal of the American Association for Cancer Research. "There has been some skepticism as to whether obesity per se is a bona fide cancer risk factor, rather than the habits that fuel it, including a poor diet and a sedentary lifestyle," said Derek M. Huffman, Ph.D., postdoctoral fellow at the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx, New York. "Although those other lifestyle choices play a role, this study unequivocally demonstrates that visceral adiposity is causally linked to intestinal cancer." Prior research has shown that obesity markedly increases the likelihood of being diagnosed with and dying from many cancers. Dr. Huffman and colleagues sought to determine if removing visceral fat in mice genetically prone to developing colon cancer might prevent or lessen the development of these tumors. They randomly assigned the mice to one of three groups. Mice in the first group underwent a sham surgery and were allowed to eat an unrestricted "buffet style" diet for the entirety of the study, which resulted in these mice becoming obese. Those in the second group were also provided an unrestricted diet and became obese, but they had their visceral fat surgically removed at the outset of the study. Mice in the third group also underwent a sham surgery, but were provided only 60 percent of the calories consumed by the other mice in order to reduce their visceral fat by dieting. "Our sham-operated obese mice had the most visceral fat, developed the greatest number of intestinal tumors, and had the worst overall survival," Dr. Huffman said.