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Archive - Mar 14, 2015

Worm Neuron Study Suggests How Single Stimulus Can Trigger Different Responses

If offered a delicious smell, a roundworm will usually stop its wandering to investigate the source, but sometimes it won't. Just as with humans, the same stimulus does not always provoke the same response, even from the same individual. New research at Rockefeller University, published online on March 12, 2015 in Cell, offers a new neurological explanation for this variability, derived by studying a simple three-cell network within the roundworm brain. "We found that the collective state of the three neurons at the exact moment an odor arrives determines the likelihood that the worm will move toward the smell. So, in essence, what the worm is thinking about at the time determines how it responds," says study author Dr. Cori Bargmann, Torsten N. Wiesel Professor, Head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior at Rockefeller University. "It goes to show that nervous systems aren't passively waiting for signals from outside, they have their own internal patterns of activity that are as important as any external signal when it comes to generating a behavior." The researchers went a step deeper to tease out the dynamics within the network. By changing the activity of the neurons individually and in combination, first author Andrew Gordus, a research associate in the lab, and his colleagues could pinpoint each neuron's role in generating variability in both brain activity and the behavior associated with it. The human brain has 86 billion neurons and 100 trillion synapses, or connections, among them. The brain of the microscopic roundworm Caenorhabditis elegans, by comparison, has 302 neurons and 7,000 synapses. So while the worm's brain cannot replicate the complexity of the human brain, scientists can use it to address tricky neurological questions that would be nearly impossible to broach in our own brains.

Chitin Production Demonstrated for First Time in Vertebrates

Scientists at Benaroya Research Institute (BRI) at Virginia Mason have made an unexpected discovery that overturns a long-standing belief in the biological sciences. Research, led by Chris Amemiya, Ph.D., a member at BRI, and primarily conducted by Joyce Tang, was published online on March 12, 2015 in Current Biology. The research demonstrates that chitin, a molecule that was previously thought to be absent in vertebrates and that has been shown to trigger an allergy/immune reaction in mammals, is endogenously produced in fishes and amphibians. "Based on our observations, it is clear that vertebrates probably use chitin in very different ways than invertebrates or fungi," noted Dr. Amemiya. "Our hope is that by studying the biological roles of chitin in vertebrates, we will uncover broad generalizable principles, thereby allowing us to extend its use in biomedical and practical applications." Chitin is primarily known as a molecule that forms hard structures like fungal cell walls and the exoskeletons of invertebrates such as insects (image) and crustaceans. It is a polymer made up of many repeating units of a sugar called N-acetylglucosamine, is naturally produced in many organisms, and forms a strong and pliable material that is made even stronger when complexed with other materials (such as proteins and minerals) to form the protective outer shells of insects and crustaceans. The general belief that vertebrates lack chitin was largely based on the presumed absence within vertebrate genomes of a gene called chitin synthase, whose activity is necessary to produce chitin. However, upon closer examination of many vertebrate genomes, the Amemiya laboratory identified fish and amphibian genes that strongly resembled chitin synthase genes found in insects.

Hair Keratin Mutations Associated with Risk for Dental Caries

On March 14, 2015, at the 93rd General Session and Exhibition of the International Association for Dental Research (IADR) in Boston, researcher Dr. Olivier Duverger, National Institutes of Health-National Institute of Neurological Disorders and Stroke, Bethesda, Md., USA, presented a study titled "Hair Keratins As Structural Organic Components of Mature Enamel: The Link Between Hair Disorders and Susceptibility to Dental Caries." The IADR General Session is being held in conjunction with the 44th Annual Meeting of the American Association for Dental Research and the 39th Annual Meeting of the Canadian Association for Dental Research. Hair and teeth are ectodermal appendages that share common developmental mechanisms. However, the major structural components making up hair and teeth are very distinct. The hair shaft is essentially made of keratin filaments that are highly cross-linked. Tooth enamel matrix is primarily composed of enamel proteins (amelogenin, ameloblastin) that are degraded and replaced by minerals during enamel maturation. Fully mineralized enamel contains a small fraction of cross-linked organic material that has not been fully characterized. In this study, researchers assessed the presence and functionality of a specific set of hair keratins in this organic fraction of enamel. Transcriptomic analysis was performed on the enamel organ from conditional knockout mice lacking the transcription factor distal-less homeobox 3 (DLX3), previously shown to regulate hair keratin expression in the hair follicle. Immunolocalization of hair keratins was performed on mouse enamel organ and mature human enamel. Utilizing data from genetic and intra-oral examination, the researchers tested the association of polymorphisms in hair keratins with dental caries susceptibility.

Rockefeller Scientists Illuminate Role of miR-122 in Hepatitis C Infections

In the battle between a cell and a virus, either side may resort to subterfuge. Molecular messages, which control the cellular machinery both sides need, are vulnerable to interception or forgery. New research at Rockefeller University has revealed the unique twist on just such a strategy deployed by the liver-infecting hepatitis C virus - one that may help explain the progression of liver disease and that the researchers suspect may be found more widely in the world of disease-causing viruses. Led jointly by Dr. Charles Rice, the Maurice R. and Corinne P. Greenberg Professor in Virology and Head of the Laboratory of Virology and Infectious Disease and Dr. Robert Darnell, Senior Attending Physician, Robert and Harriet Heilbrunn Professor, and Head of the Laboratory of Molecular Neuro-Oncology, the research was published online on March 12, 2015 in Cell. It employed a powerful combination of techniques to map the interactions between the hepatitis C virus and a small piece of genetic material - known as miRNA-122 - that is produced almost exclusively by liver cells, which normally use it to regulate expression of their own genes. "It is well known that once inside a liver cell, the hepatitis C virus must bind to miRNA-122 in order to establish a persistent infection. We found an unanticipated consequence of this interaction: By binding to miRNA-122, the virus acts like a sponge, soaking up these gene-regulating molecules," says first author Joseph Luna, a graduate student with a joint appointment in the labs. "Our experiments showed this has the effect of skewing gene activity in infected liver cells." The fight between an infecting virus and its host is often viewed as proteins fighting like soldiers.

Anti-IL-23 Produces Dramatic, Single-Dose Psoriasis Improvement in Clinical Trial

Many patients suffering from psoriasis showed significant recovery after just a single dose of an experimental treatment with a human antibody that blocks an immune signaling protein crucial to the disease, researchers report. By the end of the trial, conducted at Rockefeller University and seven other centers, nearly all of the 31 patients to receive treatment saw dramatic, if not complete, improvement in their symptoms. "The striking result we achieved using a human antibody that targets the signal interleukin-23 suggests we are on the threshold of doing something very different from our current model of treating psoriasis with immunosuppressive drugs throughout an adult lifetime," says study author Dr. James Krueger, Director of the Milstein Medical Research Program, D. Martin Carter Professor in Clinical Investigation and head of the Laboratory of Investigative Dermatology at Rockefeller University. "It raises the possibility of working toward long-term remission -- in other words, a cure." The results were published online on March 12, 2015 in the Journal of Allergy and Clinical Immunology. Psoriasis is a debilitating disease in which the body's immune system mistakenly turns on the skin, producing red, itchy, scaly patches. In 2004, Dr. Krueger and colleagues suggested a dominant role for interleukin-23 in the disease, and research since then has supported this hypothesis. It appears that interleukin-23, a type of immune signaling molecule known as a cytokine, kicks off a cascade of interactions that leads to inflammation in the skin and excessive growth of skin cells and dilation of blood vessels.

Listening to Classical Music Modulates Expression of Genes Involved in Brain Function

Although listening to music is common in all societies, the biological determinants of listening to music are largely unknown. According to the most recent study, listening to classical music enhanced the activity of genes involved in dopamine secretion and transport, synaptic neurotransmission, learning, and memory, and down-regulated the genes mediating neurodegeneration. Several of the up-regulated genes were known to be responsible for song-learning and singing in songbirds, suggesting a common evolutionary background of sound perception across species. Listening to music represents a complex cognitive function of the human brain, which is known to induce several neuronal and physiological changes. However, the molecular background underlying the effects of listening to music is largely unknown. A Finnish study group has investigated how listening to classical music affected the gene expression profiles of both musically experienced and inexperienced participants. All the participants listened to W.A. Mozart’s violin concert Nr 3, G-major, K.216 that lasts 20 minutes. As noted, listening to music enhanced the activity of genes involved in dopamine secretion and transport, synaptic function, learning, and memory. One of the most up-regulated genes, synuclein-alpha (SNCA) is a known risk gene for Parkinson’s disease that is located in the strongest linkage region of musical aptitude. SNCA is also known to contribute to song-learning in songbirds. The results were published on March 12, 2015 in an open-access article in PeerJ. “The up-regulation of several genes that are known to be responsible for song-learning and singing in songbirds suggest a shared evolutionary background of sound perception between vocalizing birds and humans”, says Dr. Irma Järvelä, the leader of the study.