2,035 research outputs found

    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

    Synthesis of NH-sulfoximines from sulfides by chemoselective one-pot N- and O-transfers

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    Direct synthesis of NH-sulfoximines from sulfides has been achieved through O and NH transfer in the same reaction, occurring with complete selectivity. The reaction is mediated by bisacetoxyiodobenzene under simple conditions and employs inexpensive N-sources. Preliminary studies indicate that NH-transfer is likely to be first, followed by oxidation, but the reaction proceeds successfully in either order. A wide range of functional groups and biologically relevant compounds are tolerated. The use of AcO15NH4 affords 15N-labeled compounds

    Hypothermic retrograde venous perfusion with adenosine cools the spinal cord and reduces the risk of paraplegia after thoracic aortic clamping

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    AbstractObjective: We evaluated the utility of retrograde venous perfusion to cool the spinal cord and protect neurologic function during aortic clamping. We hypothesized that hypothermic adenosine would preserve the spinal cord during ischemia. Methods: Six swine (group I) underwent thoracic aortic occlusion for 30 minutes at normothermia. Group II animals underwent spinal cooling by retrograde perfusion of the paravertebral veins with hypothermic (4°C) saline solution during aortic occlusion. The spinal cords of group III animals were cooled with a hypothermic adenosine solution in a similar fashion. Intrathecal temperature was monitored and somatosensory evoked potentials assessed the functional status of spinal pathways. Results: Spinal cooling without systemic hypothermia significantly improved neurologic Tarlov scores in group III (4.8 ± 0.2) and group II (3.8 ± 0.4) when compared with group I scores (1.3 ± 0.6) (P < .001). Furthermore, 5 of the 6 animals in group III displayed completely normal neurologic function, whereas only one animal in group II and no animals in group I did (P = .005). Somatosensory evoked potentials were lost 10.6 ± 1.4 minutes after ischemia in group I. In contrast, spinal cooling caused rapid cessation of neural transmission with loss of somatosensory evoked potentials at 6.9 ± 1.2 minutes in group II and 7.0 ± 0.8 minutes in group III (P = .06). Somatosensory evoked potential amplitudes returned to 85% of baseline in group III and 90% of baseline in group II compared with only 10% of baseline in group I (P = .01). Conclusions: We conclude that retrograde cooling of the spinal cord is possible and protects against ischemic injury and that adenosine enhances this effect. The efficacy of this method may be at least partly attributed to a more rapid reduction in metabolic and electrical activity of the spinal cord during ischemia. (J Thorac Cardiovasc Surg 2000;119:588-95

    Generation of three-dimensional multiple spheroid model of olfactory ensheathing cells using floating liquid marbles

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    We describe a novel protocol for three-dimensional culturing of olfactory ensheathing cells (OECs), which can be used to understand how OECs interact with other cells in three dimensions. Transplantation of OECs is being trialled for repair of the paralysed spinal cord, with promising but variable results and thus the therapy needs improving. To date, studies of OEC behaviour in a multicellular environment have been hampered by the lack of suitable three-dimensional cell culture models. Here, we exploit the floating liquid marble, a liquid droplet coated with hydrophobic powder and placed on a liquid bath. The presence of the liquid bath increases the humidity and minimises the effect of evaporation. Floating liquid marbles allow the OECs to freely associate and interact to produce OEC spheroids with uniform shapes and sizes. In contrast, a sessile liquid marble on a solid surface suffers from evaporation and the cells aggregate with irregular shapes. We used floating liquid marbles to co-culture OECs with Schwann cells and astrocytes which formed natural structures without the confines of gels or bounding layers. This protocol can be used to determine how OECs and other cell types associate and interact while forming complex cell structuresJSJ was funded by a grant from the Perry Cross Spinal Research Foundation; NTN was funded from Griffith University through a start-up grant and a grant from the Griffith University Research Infrastructure Program; JAK was funded by an Australian Research Council Discovery Grant DP150104495; JT was funded by an Eskitis Institute scholarship; CO was funded by a Griffith Sciences scholarship; RV was funded by a Griffith University International Postgraduate Research Scholarshi
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