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  • 1
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Mutations in copper/zinc superoxide dismutase (SOD1) account for 10–20% of a familial form of amyotrophic lateral sclerosis (ALS). A common feature of SOD1 mutants is abnormal aggregation of the aberrant SOD1 in neurons and glia. We now report that in ALS transgenic mouse models the constitutively expressed heat shock protein 70 (Hsp70) is mislocalized into aggregates together with mutant SOD1 and ubiquitin. Forcing increased synthesis of Hsp70 ameliorates both aggregate formation and toxicity in primary motor neurons in culture. However, chronic increase in an inducible form of Hsp70 to about 10-fold its normal level is shown here not to affect disease course or pathology developed in mice from accumulation of any of three familial ALS causing SOD1 mutants with different underlying biochemical characteristics. Therefore, increasing Hsp70 to a level that is protective in mouse models of acute ischemic insult and selected neurodegenerative disorders is not sufficient to ameliorate mutant SOD1-mediated toxicity.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: The premotor cortex of macaque monkeys is currently subdivided into at least six different subareas on the basis of structural, hodological and physiological criteria. To determine the degree of divergence/convergence of thalamocortical projections to mesial [supplementary motor area (SMA)-proper and pre-SMA] and lateral (PMd-c, PMd-r, PMv-c and PMv-r) premotor (PM) subareas, quantitative analyses were performed on the distribution of retrograde labelling after multiple tracer injections in the same animal. The results demonstrate that all PM and SMA subareas receive common inputs from several thalamic nuclei, but the relative contribution of these nuclei to thalamocortical projections differs. The largest difference occurs between subareas of SMA, with much greater contribution from the mediodorsal (MD) and area X, and a smaller contribution from the ventral lateral anterior (VLa) and ventral part of the ventral lateral posterior (VLpv) to pre-SMA than to SMA-proper. In PM, differences between subareas are less pronounced; in particular, all receive a significant contribution from MD, the ventral anterior (VApc) and area X. However, there are clear gradients, such as increasing projections from MD to rostral, from VLa and VLpv to caudal, and from dorsal VLp (VLpd) to dorsal premotor subareas. Intralaminar nuclei provide widespread projections to all premotor subareas. The degree of overlap between thalamocortical projections varies among different PM and SMA subareas and different sectors of the thalamus. These variations, which correspond to different origin and topography of thalamocortical projections, are discussed in relation to functional organizations at thalamic and cortical levels.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 25 (1997), S. 0 
    ISSN: 1365-2958
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie , Medizin
    Notizen: Endospore formation in Bacillus subtilis is primarily dependent on the phosphorylation of the key transcription factor Spo0A by two major kinases, KinA and KinB, thought to be activated by distinct signals. Using a strategy designed to detect mutations that specifically affect the signalling pathway to KinB, we have isolated a Tn10 insertion mutant in one of two adjacent lrp-like genes coding for homologues of the Escherichia coli leucine-responsive regulatory protein (Lrp) and another mutant in the glyA gene encoding the serine hydroxymethyl transferase (SHMT). SHMT catalyses interconversion of serine and glycine while transferring the resulting one-carbon unit into the C1 pool through methylene tetrahydrofolate. Sporulation experiments performed in a series of supplemented media indicated that the role of SHMT in the KinB pathway is to feed the pool of C1 units recruited for the biosynthesis of key metabolites, which include the methyl donor S-adenosyl-methionine (SAM). The results of experiments using l-ethionine suggest that SAM is involved in post-synthetic methylation reactions or biosynthesis of metabolites that serve to activate KinB. Truncated LrpA and LrpB peptides that have retained the DNA-binding domain but have lost the C-terminal half of the protein appear to act as repressors of glyA transcription and KinB-dependent sporulation. However, deletions of lrpA, lrpB or lrpAB have little effect on glyA transcription or sporulation through KinB, suggesting that other effectors, such as additional Lrp homologues, may act in conjunction with LrpA and LrpB. Our results indicate that lrpA–lrpB together with the biosynthetic glyA gene lie on a common signalling pathway meant to activate the KinB sensor kinase.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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