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Biomedical subjects

S L Osborne

Publications and source records attributed to S L Osborne.

8 recordsLinked to original sources
PubMed2004

Nogo A expression in the adult enteric nervous system.

Neuronal plasticity plays an important role in physiological and pathological processes within the gastrointestinal (GI) tract. Nogo A is a major contributor to the negative effect central nervous system (CNS) myelin has on neurite outgrowth after injury and may also play a role in maintaining synaptic connections in the healthy CNS. Nogo A is highly expressed during neuronal development but in the CNS declines postnatally concomitantly with a loss of regenerative potential while ganglia of the Peripheral Nervous System (PNS) retain Nogo A. The enteric nervous system shares a number of features in common with the CNS, thus the peripheral distribution of factors affecting plasticity is of interest. We have investigated the distribution of Nogo in the adult mammalian gastrointestinal tract. Nogo A mRNA and protein are detectable in the adult rat GI tract. Nogo A is expressed heterogeneously in enteric neurons throughout the GI tract though expression levels appear not to be correlated with neuronal sub-type. The pattern of expression is maintained in cultured myenteric plexus from the guinea-pig small intestine. As is seen in developing neurons of the CNS, enteric Nogo A is present in both neuronal cell bodies and axons. Our results point to a hitherto unsuspected role for Nogo A in enteric neuronal physiology.

Animals↗
PubMed2001

Phosphoinositides as key regulators of synaptic function.

Phosphoinositides have recently emerged as key regulators of a variety of synaptic processes, including neurosecretory vesicle targeting, exo-endocytosis, and ion channel modulation. These pleiotropic activities derive from their ability to serve either as membrane targeting sites for cytosolic factors, as allosteric ligands, or as nucleation points for coat proteins and cytoskeletal elements. This versatility depends upon the existence of highly diversified enzymatic machinery for their synthesis and degradation, which governs, both temporally and spatially, their appearance in the microenvironment of the synapse.

Endocytosis↗
PubMed2001

Nuclear PtdIns(4,5)P2 assembles in a mitotically regulated particle involved in pre-mRNA splicing.

Phosphoinositide turnover regulates multiple cellular processes. Compared with their well-known cytosolic roles, limited information is available on the functions of nuclear phosphoinositides. Here, we show that phosphatidylinositol(4,5)-bisphosphate (PtdIns(4,5)P2) stably associates with electron-dense particles within the nucleus that resemble interchromatin granule clusters. These PtdIns(4,5)P2-containing structures have a distribution which is cell-cycle dependent and contain components of both the transcriptional and pre-mRNA processing machinery, including RNA polymerase II and the splicing factor SC-35. Immunodepletion and add-back experiments demonstrate that PtdIns(4,5)P2 and associated factors are necessary but not sufficient for pre-mRNA splicing in vitro, indicating a crucial role for PtdIns(4,5)P2-containing complexes in nuclear pre-mRNA processing.

Antibodies, Monoclonal↗
PubMed1999

Calcium-dependent oligomerization of synaptotagmins I and II. Synaptotagmins I and II are localized on the same synaptic vesicle and heterodimerize in the presence of calcium.

Synaptotagmins constitute a large family of membrane proteins characterized by their distinct distributions and different biochemical features. Genetic evidence suggests that members of this protein family are likely to function as calcium sensors in calcium-regulated events in neurons, although the precise molecular mechanism remains ill defined. Here we demonstrate that different synaptotagmin isoforms (Syt I, II, and IV) are present in the same synaptic vesicle population from rat brain cortex. In addition, Syt I and II co-localize on the same small synaptic vesicle (SSV), and they heterodimerize in the presence of calcium with a concentration dependence resembling that of the starting phase of SSV exocytosis (EC50 = 6 +/- 4 microM). The association between Syt I and Syt II was demonstrated by immunoprecipitation of the native proteins and the recombinant cytoplasmic domains and by using fluorescence resonance energy transfer (FRET). Although a subpopulation of SSV containing Syt I and IV can be isolated, these two isoforms do not show a calcium-dependent interaction. These results suggest that the self-association of synaptotagmins with different calcium binding features may create a variety of calcium sensors characterized by distinct calcium sensitivities. This combinatorial hypothesis predicts that the probability of a single SSV exocytic event is determined, in addition to the gating properties of the presynaptic calcium channels, by the repertoire and relative abundance of distinct synaptotagmin isoforms present on the SSV surface.

Amino Acid Sequence↗
PubMed1999

Functional characterisation of tetanus and botulinum neurotoxins binding domains.

Tetanus and botulinum neurotoxins constitute a family of bacterial protein toxins responsible for two deadly syndromes in humans (tetanus and botulism, respectively). They bind with high affinity to neurons wherein they cause a complete inhibition of evoked neurotransmitter release. Here we report on the cloning, expression and use of the recombinant fragments of the heavy chains of tetanus neurotoxin and botulinum neurotoxin serotypes A, B and E as tools to study the neurospecific binding of the holotoxins. We found that the recombinant 50 kDa carboxy-terminal domains of tetanus and botulinum neurotoxins alone are responsible for the specific binding and internalisation into spinal cord cells in culture. Moreover, we provide evidence that the recombinant fragments block the internalization of the parental holotoxins in a dose-dependent manner, as determined by following the neurotoxin-dependent cleavage of their targets VAMP/synaptobrevin and SNAP-25. In addition, the recombinant binding fragments cause a significant delay in the paralysis induced by the corresponding holotoxin on the mouse phrenic nerve-hemidiaphragm preparation. Taken together, these results show that the carboxy-terminal domain of tetanus and botulinum neurotoxins is necessary and sufficient for the binding and internalisation of these proteins in neurons and open the possibility to use them as tools for the functional characterisation of the intracellular transport of clostridial neurotoxins.

Animals↗
PubMed1996

Sex-role attitudes and clinical appraisal in psychiatry residents.

OBJECTIVE: To measure sex-role beliefs of psychiatry residents and to examine bias in clinical appraisal. METHOD: Residents (45 female, 51 male) evaluated 1 of 4 possible clinical case histories-a female or male patient with histrionic personality disorder (HPD) or antisocial personality disorder (APD)-and completed the Sex-Role Egalitarianism Scale (SRES). RESULTS: As predicted, female residents were more egalitarian than male residents (P < 0.03) according to the SRES. As expected, significantly more male than female patients received the diagnosis of APD (P < 0.00002). Although it was predicted that female patients would more often be given the HPD diagnosis than males, no significant gender differences were found. Sex of resident was not found to influence clinical behaviour significantly. CONCLUSIONS: These results highlight differential sex-role attitudes, as measured by the SRES, between female and male residents and suggest that residents' sex-role biases affect the diagnosis of APD. These results have implications for psychiatric assessment and treatment. Further understanding of these issues is critical to the development of educational tools to address sex biases in psychiatry.

Adult↗