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Archive - May 17, 2011

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Mass Spec Technology Reveals Dynamics of Crucial Protein Switch

Researchers at the University of Texas Medical Branch at Galveston and the University of California-San Diego School of Medicine have published a study that offers a new understanding of a protein critical to physiological processes involved in major diseases such as diabetes and cancer. This work could help scientists design drugs to battle these disorders. The article was deemed a "Paper of the Week" by the Journal of Biological Chemistry and will be featured on the cover of that journal. The article is scheduled for publication in the May 20, 2011 issue and is now available online. "This study applied a powerful protein structural analysis approach to investigate how a chemical signal called cAMP turns on one of its protein switches, Epac2," said principal investigator Dr. Xiaodong Cheng, professor in the Department of Pharmacology and Toxicology and member of the Sealy Center for Structural Biology and Molecular Biophysics at UTMB. The cAMP molecule controls many physiological processes, ranging from learning and memory in the brain and contractility and relaxation in the heart to insulin secretion in the pancreas. cAMP exerts its action in cells by binding to and switching on specific receptor proteins, which, when activated by cAMP, turn on additional signaling pathways. Errors in cell signaling are responsible for diseases such as diabetes, cancer, and heart failure. Understanding cAMP-mediated cell signaling, in which Epac2 is a major player, likely will facilitate the development of new therapeutic strategies specifically targeting the cAMP-Epac2 signaling components, according to the researchers. The project involved an ongoing collaboration between Dr. Cheng's research group at UTMB, experts in the study of cAMP signaling, and UCSD professor of medicine Virgil Woods Jr.

Sodium Channels Evolved Before Animal Nervous Systems

An essential component of animal nervous systems—sodium channels—evolved prior to the evolution of those systems, researchers from The University of Texas at Austin have discovered. "The first nervous systems appeared in jellyfish-like animals six hundred million years ago or so," says Dr. Harold Zakon, professor of neurobiology, "and it was thought that sodium channels evolved around that time. We have now discovered that sodium channels were around well before nervous systems evolved." Dr. Zakon and his coauthors, Professor David Hillis and graduate student Benjamin Liebeskind, published their findings online in PNAS on May 16, 2011. Nervous systems and their component neuron cells were a key innovation in the evolution of animals, allowing for communication across vast distances between cells in the body and leading to sensory perception, behavior, and the evolution of complex animal brains. Sodium channels are an integral part of a neuron's complex machinery. The channels are like floodgates lodged throughout a neuron's levee-like cellular membrane. When the channels open, sodium floods through the membrane into the neuron, and this generates nerve impulses. Zakon, Hillis and Liebeskind discovered the genes for such sodium channels hiding within an organism that isn't even made of multiple cells, much less any neurons. The single-celled organism is a choanoflagellate, and it is distantly related to multi-cellular animals such as jellyfish and humans. The researchers then constructed evolutionary trees, or phylogenies, showing the relationship of those genes in the single-celled choanoflagellate to those in multi-cellular animals, including jellyfish, sponges, flies, and humans.

Mechanism of Stem Cell to Skeletal Muscle Cell Differentiation

A team led by developmental biologist Professor Christophe Marcelle of Monash University in Australia has determined the mechanism that causes stem cells in the embryo to differentiate into specialized cells that form the skeletal muscles of animals’ bodies. The scientists published their results online in Nature on May 15, 2011. Scientists worldwide are racing to pin down the complex molecular processes that cause stem cells in the early embryo to differentiate into specialist cells such as muscle or nerve cells. The field has the potential to revolutionize medicine by delivering therapies to regenerate tissue damaged by disease or injury. Differentiation happens soon after fertilization, when embryonic cells are dividing rapidly and migrating as the animal’s body takes shape. Professor Marcelle’s team analyzed the differentiation of muscle stem cells in chicken embryos. The mechanisms in birds are identical to those in mammals, so the chick is a good model species for understanding the mechanisms in humans, says team member and the paper’s lead author Anne Rios. The scientists investigated the effect of a known signaling pathway called NOTCH on muscle differentiation. They found that differentiation of stem cells to muscle was initiated when NOTCH signalling proteins touched some of the cells. These proteins were carried by passing cells migrating from a different tissue–the neural crest–the progenitor tissue of sensory nerve cells. Muscle formation in the target stem cells occurred only when the NOTCH pathway was triggered briefly by the migrating neural crest cells. “This kiss-and-run activation of a pathway is a completely novel mechanism of stem cell specification which explains why only some stem cells adopt a muscle cell fate,” Ms. Rios said.

Four New Species of Mysterious Purse-Web Spiders Described

A team of researchers from the University of the Free State in South Africa (Drs. René Fourie and Charles Haddad) and the Royal Museum for Central Africa in Belgium (Dr. Rudy Jocqué) discovered very poorly known purse-web spiders of the genus Calommata in Africa. Four of the species described are new to science. The study was published in the open access journal ZooKeys. What is really unique about purse-web spiders is that, in contrast to trapdoor spiders, they do not construct a structure to close the burrow. Instead, they build a purse-shaped web of dense silk that covers a chamber in which the spider waits for wandering prey to step on the web, before impaling it from beneath with its exceptionally long fangs. Little is known on the biology of these small spiders as they are extremely difficult to locate in nature. The burrows of the African species have never been photographed, and the first ever photograph of a live African Calommata male, captured in a pitfall trap, was taken only last year by Ian Engelbrecht. “While Calommata spiders have been collected elsewhere in Africa throughout the last century, albeit on rare occasions, our study was prompted by the recent rediscovery of these spiders in South Africa, nearly eight decades since the last specimen was collected here in 1923. Currently six African species are recognized, with an additional six species from East Asia and Israel,“ Dr. Haddad said. The new discovery is expected to shed light on the evolutionary history of these spiders, known from two distant geographical regions, and to draw attention to the urgent need for their conservation. These spiders are mostly threatened by habitat loss and urbanization.