2,702 research outputs found

    The glia response after peripheral nerve injury: A comparison between Schwann cells and olfactory ensheathing cells and their uses for neural regenerative therapies

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    The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory nerve, and Schwann cells (SCs), which are present in the rest of the PNS. These two glial types share many similar morphological and functional characteristics but also exhibit key differences. The olfactory nerve is constantly turning over throughout life, which means OECs are continuously stimulating neural regeneration, whilst SCs only promote regeneration after direct injury to the PNS. This review presents a comparison between these two PNS systems in respect to normal physiology, developmental anatomy, glial functions and their responses to injury. A thorough understanding of the mechanisms and differences between the two systems is crucial for the development of future therapies using transplantation of peripheral glia to treat neural injuries and/or disease.Griffith Health, School of Nursing and MidwiferyFull Tex

    Algorithms for detecting dependencies and rigid subsystems for CAD

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    Geometric constraint systems underly popular Computer Aided Design soft- ware. Automated approaches for detecting dependencies in a design are critical for developing robust solvers and providing informative user feedback, and we provide algorithms for two types of dependencies. First, we give a pebble game algorithm for detecting generic dependencies. Then, we focus on identifying the "special positions" of a design in which generically independent constraints become dependent. We present combinatorial algorithms for identifying subgraphs associated to factors of a particular polynomial, whose vanishing indicates a special position and resulting dependency. Further factoring in the Grassmann- Cayley algebra may allow a geometric interpretation giving conditions (e.g., "these two lines being parallel cause a dependency") determining the special position.Comment: 37 pages, 14 figures (v2 is an expanded version of an AGD'14 abstract based on v1

    Human visceral nociception: findings from translational studies in human tissue.

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    Peripheral sensitization of nociceptors during disease has long been recognized as a leading cause of inflammatory pain. However, a growing body of data generated over the last decade has led to the increased understanding that peripheral sensitization is also an important mechanism driving abdominal pain in highly prevalent functional bowel disorders, in particular, irritable bowel syndrome (IBS). As such, the development of drugs that target pain-sensing nerves innervating the bowel has the potential to be a successful analgesic strategy for the treatment of abdominal pain in both organic and functional gastrointestinal diseases. Despite the success of recent peripherally restricted approaches for the treatment of IBS, not all drugs that have shown efficacy in animal models of visceral pain have reduced pain end points in clinical trials of IBS patients, suggesting innate differences in the mechanisms of pain processing between rodents and humans and, in particular, how we model disease states. To address this gap in our understanding of peripheral nociception from the viscera and the body in general, several groups have developed experimental systems to study nociception in isolated human tissue and neurons, the findings of which we discuss in this review. Studies of human tissue identify a repertoire of human primary afferent subtypes comparable to rodent models including a nociceptor population, the targeting of which will shape future analgesic development efforts. Detailed mechanistic studies in human sensory neurons combined with unbiased RNA-sequencing approaches have revealed fundamental differences in not only receptor/channel expression but also peripheral pain pathways.Non

    Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons.

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    Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin-releasing hormone (GnRH) neurons to enter the embryonic forebrain, resulting in anosmia and sterility. Sox10 mutations have been associated with Kallmann's syndrome phenotypes, but their effect on olfactory system development is unknown. We recently showed that Sox10 is expressed by neural crest-derived olfactory ensheathing cells (OECs). Here, we demonstrate that in homozygous Sox10(lacZ/lacZ) mouse embryos, OEC differentiation is disrupted; olfactory axons accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor neurons express the maturation marker OMP (most likely owing to the failure of axonal targeting). Furthermore, GnRH neurons clump together in the periphery and a smaller proportion enters the forebrain. Our data suggest that human Sox10 mutations cause Kallmann's syndrome by disrupting the differentiation of OECs, which promote embryonic olfactory axon targeting and hence olfactory receptor neuron maturation, and GnRH neuron migration to the forebrain.This work was supported by the Wellcome Trust [grant 091555 to C.V.H.B. and P.B.], a Griffith University Encouragement Research grant to J.A.S., and Deutsche Forschungsgemeinschaft [grant We1326/9 to M.W.].This is the final version of the article. It was first available from The Company of Biologists via http://dx.doi.org/10.1242/bio.2013524
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