Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropeptide FMRFamide modulates synaptic transmission between identified neurons of the pond snail Helisoma trivolvis. FMRFamide causes a presynaptic inhibition of transmitter release by actions on ion channels and secretory machinery (Man-Son-Hing et al., 1989). The actions of FMRFamide on secretory machinery were studied using giant synapses that form between somata in culture. Using the calcium cage DM-nitrophen, synchronized, calcium-clamped release of neurotransmitter was promoted by UV photolysis. A series of UV flashes (15 msec duration) repeatedly promoted the transient synchronized release of neurotransmitter. Addition of FMRFamide reduced the magnitude of these flash-evoked inhibitory postsynaptic currents. Under conditions of synchronized transmitter release, FMRFamide modulates the secretory responsiveness to internal calcium. The release of neurotransmitter at somasoma synapses was determined to be quantal in nature. To test for the involvement of G-proteins in mediating the effects of FMRFamide on secretory machinery, the modulation of the frequency of miniature inhibitory postsynaptic currents (MIPSCs) was examined. Addition of FMRFamide reduced the frequency of MIPSCs without affecting intracellular free calcium measured with fura-2. Injection of a nonhydrolyzable analog of GTP, GTP gamma S, mimicked the effect of FMRFamide and reduced MIPSC frequency. Preinjection of the presynaptic soma with the A-protomer of pertussis toxin (PTX) prevented FMRFamide from reducing MIPSC frequency. Thus, a PTX-sensitive G-protein mediates the action of FMRFamide on secretory machinery. Similarly, preinjection of the presynaptic soma with PTX prevented FMRFamide from reducing the magnitude of action potential-evoked IPSC. Dose-response curves for the actions of FMRFamide on secretory machinery and calcium current were constructed and demonstrated that secretory machinery can be modulated at concentrations of FMRFamide (less than or equal to 10(-7) M) that do not affect calcium current magnitude. At a concentration of 10(-7) M FMRFamide, action potential-evoked synaptic transmission was reduced. Thus, synaptic transmission can be regulated by the modulation of secretory machinery, without a requirement for the modulation of ion channels.
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PMID:FMRFamide modulation of secretory machinery underlying presynaptic inhibition of synaptic transmission requires a pertussis toxin-sensitive G-protein. 168

White mice used for protection tests with pertussis vaccines when marked with fuchsin before challenge showed reduced survival rates compared with their equally treated but unmarked cage mates. The fuchsin used had been dissolved in denaturated alcohol. On account of the small amounts of marking material applied, there was probably no direct toxic effect. Further methods of marking have then been studied in this delicate test system. Contrary to expectations the marking with picric acid solution showed no adverse effect at all. The shearing of an area of the fur, however, resulted in an even more detrimental effect than the use of fuchsin. The clipping of the top of one ear rested below the level of significance. Most probably the marked mice were neither affected adversely by the handling when marked nor by an actual chemical or mechanical impairment, but by the initiation of stress induced by the majority of their unmarked cage mates. At any rate, a possible influence of the marking of animals on the result of test procedures should be carefully considered.
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PMID:[Effect of marking laboratory animals on the results of pertussis vaccine potency tests]. 685 46

This paper describes the results of a study of the effects of modified housing conditions, conditioning and habituation on humans using a rabbit model for monitoring whole-cell pertussis vaccine (pWCV)-induced adverse effects. The study has been performed with reference to previous vaccine safety studies of pWCV in rabbits in which results were difficult to interpret due to the large variation in experimental outcome, especially in the key parameter deep-body temperature (T(b)). Certain stressful laboratory conditions, as well as procedures involving humans, e.g. blood sampling, inoculation and cage-cleaning, were hypothesized to cause this large variation. The results of this study show that under modified housing conditions rabbits have normal circadian body temperatures. This allowed discrimination of pWCV-induced adverse effects in which handled rabbits tended to show a dose-related increase in temperature after inoculation with little variance, whereas non-handled rabbits did not. Effects of experimental and routine procedures on body temperature were significantly reduced under modified conditions and were within the normal T(b) range. Handled animals reacted less strongly and with less variance to experimental procedures, such as blood sampling, injection and cage-cleaning, than non-handled rabbits. Overall, handling had a positive effect on the behaviour of the animals. Data show that the housing modifications have provided a more robust model for monitoring pWCV adverse effects. Furthermore, conditioning and habituation of rabbits to humans reduce the variation in experimental outcome, which might allow for a reduction in the number of animals used. In addition, this also reduces distress and thus contributes to refining this animal model.
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PMID:Reducing variation in a rabbit vaccine safety study with particular emphasis on housing conditions and handling. 1911 95

Recent studies have shown that conjugation systems of Gram-negative bacteria are composed of distinct inner and outer membrane core complexes (IMCs and OMCCs, respectively). Here, we characterized the OMCC by focusing first on a cap domain that forms a channel across the outer membrane. Strikingly, the OMCC caps of the Escherichia coli pKM101 Tra and Agrobacterium tumefaciens VirB/VirD4 systems are completely dispensable for substrate transfer, but required for formation of conjugative pili. The pKM101 OMCC cap and extended pilus also are dispensable for activation of a Pseudomonas aeruginosa type VI secretion system (T6SS). Chimeric conjugation systems composed of the IMCpKM101 joined to OMCCs from the A. tumefaciens VirB/VirD4, E. coli R388 Trw, and Bordetella pertussis Ptl systems support conjugative DNA transfer in E. coli and trigger P. aeruginosa T6SS killing, but not pilus production. The A. tumefaciens VirB/VirD4 OMCC, solved by transmission electron microscopy, adopts a cage structure similar to the pKM101 OMCC. The findings establish that OMCCs are highly structurally and functionally conserved - but also intrinsically conformationally flexible - scaffolds for translocation channels. Furthermore, the OMCC cap and a pilus tip protein coregulate pilus extension but are not required for channel assembly or function.
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PMID:Use of chimeric type IV secretion systems to define contributions of outer membrane subassemblies for contact-dependent translocation. 2845 85