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T Tyrrell D Willshaw 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1992,336(1277):239-257
Marr's theory of the cerebellar cortex as an associative learning device is one of the best examples of a theory that directly relates the function of a neural system to its neural structure. However, although he assigned a precise function to each of the identified cell types of the cerebellar cortex, many of the crucial aspects of the implementation of his theory remained unspecified. We attempted to resolve these difficulties by constructing a computer simulation which contained a direct representation of the 13,000 mossy fibres and the 200,000 granule cells associated with a single Purkinje cell of the cerebellar cortex, together with the supporting Golgi, basket and stellate cells. In this paper we present a detailed explanation of Marr's theory based upon an analogy between Marr's cerebellar model and an abstract model called the associative net. Although some of Marr's assumptions contravene neuroanatomical findings, we found that in general terms his conclusion that each Purkinje cell can learn to respond to a large number of different patterns of activity in the mossy fibres is substantially correct. However, we found that this system has a lower capacity and acts more stochastically than he envisaged. The biologically realistic simulated structure that we designed can be used to assess the computational capabilities of other network theories of the cerebellum. 相似文献
4.
Fibronectin is a component of the sodium dodecyl sulfate-insoluble transglutaminase substrate 总被引:4,自引:0,他引:4
Liver plasma membranes contain a morphologically distinct protein complex which serves as a substrate for the plasma membrane-associated transglutaminase. The complex, which appears as a two-dimensional sheet, is insoluble in sodium dodecyl sulfate and reducing agents and has been named SITS for sodium dodecyl sulfate-insoluble transglutaminase substrate (Tyrrell, D. J., Sale, W. S., and Slife, C. W. (1988) J. Biol. Chem. 263, 1946-1951). Polyclonal antibodies raised against SITS were used to probe for soluble constituents of the matrix. Immunoblots showed that proteins of 230, 35, and 32 kDa reacted with the anti-SITS antiserum when the soluble fraction from a liver homogenate was examined. The 230-kDa protein was identified as fibronectin after observing cross-reactivity of anti-SITS antiserum with authentic fibronectin and cross-reactivity of anti-fibronectin antiserum with the 230-kDa cytosolic protein and purified SITS. Preincubating anti-SITS antiserum with purified fibronectin decreased immunostaining of the 230-kDa cytosolic protein and authentic fibronectin. Immunoblots of the plasma membrane fraction using anti-SITS and anti-fibronectin antisera showed that both antisera reacted with proteins at the top of the stacking gel (SITS) and of 230 kDa. In addition, the anti-SITS antiserum reacted with proteins of 85, 35, and 32 kDa. Immunofluorescence microscopy revealed that the anti-SITS and anti-fibronectin antisera both react with isolated SITS and with the same filamentous structures associated with intact plasma membranes. These studies show that fibronectin is a component of the plasma membrane matrix, SITS. This finding is consistent with the proposed role of this matrix which is to mediate cell-cell adhesion between hepatocytes in the tissue. 相似文献
5.
M Ishihara D J Tyrrell M C Kiefer P J Barr S J Swiedler 《Analytical biochemistry》1992,202(2):310-315
A simple panning procedure that allows for the evaluation of interactions between various heparin-like molecules and basic FGF has been developed. This assay measures the ability of compounds to inhibit the interaction of transfected human lymphoblastoid cells, UC 729-6 (UC cells), expressing hamster syndecan and basic FGF-coated plastic plates. The transfected cells bind rapidly to basic FGF-coated plates while the control cells do not bind well. Binding of the transfected cells to basic FGF was inhibited by heparin and heparin sulfate (HS), but not by chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. There was little inhibition of binding by chemically modified heparin such as completely desulfated, N-acetylated heparin, completely desulfated, N-sulfated heparin, and N-desulfated, N-acetylated heparin. These results suggested that both the N-sulfate and O-sulfate groups of heparin are required for binding to basic FGF. In addition, inhibition by oligosaccharides derived from depolymerized heparin increased with fragment size; partial inhibition was observed with oligosaccharides as small as hexamers. The biochemical basis for the binding of transfected cells to basic FGF was established by showing a significant increase of 35SO4 incorporation into HS. In particular, the level of 35SO4-HS in the trypsin-releasable (cell surface) pool increased fivefold. This increase was accounted for by demonstration of the presence of HS on immunoprecipitated syndecan from the transfected cells. 相似文献
6.
Evidence for an interaction between the membrane protein of a paramyxovirus and actin. 总被引:22,自引:11,他引:11
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Evidence for an interaction of the membrane (M) protein of Newcastle disease and Sendai viruses with cellular actin was obtained by three different techniques. M protein linked to Sepharose 4B was found to bind actin, but not myoglobin or bovine serum albumin, and to selectively remove actin from a mixture of these three proteins. Sedimentation of a mixture of M protein and F-actin through a sucrose gradient resulted in sedimentation of M protein with actin. Control proteins, bovine serum albumin and cytochrome c, did not sediment with actin. In circular dichroism studies, M protein added to actin in a 1:1 complex resulted in a significant increase in negative ellipticity at 220 nm, which corresponds to an increase in alpha-helix and a decrease in beta-structure and random coil. This is indicative of an interaction between M protein and actin. It is possible that the frequent identification of cellular actin in a number of enveloped viruses may be attributed to the interaction of actin and M protein or its equivalent. 相似文献
7.
R M Tyrrell 《Acta biologica et medica Germanica》1979,38(9):1259-1269
There is clear evidence that significant quantities of lesions are induced in DNA by near-UV radiation and that these lesions, although susceptible to repair, may lead to cell death because of the simultaneous disruption of DNA repair systems by the same wavelengths. No particular DNA lesion can be linked to cell death in wild type strains. However, there are good grounds for speculating that a type of near-UV lesion exists which is rapidly "fixed" as a lethal event in cells as a result of the oxygen-dependent disruption of repair. There is a strong indication that the relative ability of various near-UV wavelengths to sensitize cells to heat, chemicals or other radiations is directly related to their efficiency in disrupting DNA repair systems in general. Some important specific questions remain. For example, it is important to ask why breaks formed at 365 nm and 405 nm, although apparently requiring a pol dependent pathway for their repair, do not produce the predicted lethal biological action in the strains tested. In general terms it is hoped to provide more comprehensive physico-chemical data in support of, or contradicting, the proposed model. 相似文献
8.
G M Scott D S Secher D Flowers J Bate K Cantell D A Tyrrell 《BMJ (Clinical research ed.)》1981,282(6273):1345
The effects of partially purified human leucocyte interferon (PIF) and of a preparation purified by passage twice through a monoclonal antibody affinity chromatography column (NK21F) were compared with those of a control solution in healhty volunteers. After intramuscular injections both interferon preparations caused rises in pulse rate and body temperature, changes in circulating white cell counts, and various unpleasant symptoms, the most common of which were headache, malaise, and fever. Slightly lower doses of NK21F were given, and this was reflected in lower peak serum concentrations. Mean symptom scores, however, were not lower after NK21F than after PIF. Local inflammatory reactions eight hours after intradermal inoculations of these interferons were similar. Purification of interferon using a monoclonal antibody does not reduce the facets of its activity considered in this study. They are therefore inherent in the leucocyte interferon type selected by the antibody. 相似文献
9.
H E Larson J V Parry A B Price D R Davies J Dolby D A Tyrrell 《BMJ (Clinical research ed.)》1977,1(6071):1246-1248
A girl aged 12 developed pseudomembranous colitis after a short course of oral penicillin. She had no history of adverse reaction to penicillin before or after the illness. No pathogenic bacteria, mycoplasmas, or viruses were found in her faeces, but they did contain a toxin. Toxin was also found in four of five other patients with pseudomembranous colitis but not in six specimens obtained from patients with diarrhoea caused by other disorders. Further studies may show that pseudomembranous colitis is caused by a bacterial toxin. 相似文献
10.
Thirty preschool children presenting with recurrent respiratory infections and their unaffected siblings were observed prospectively for a year. The index children experienced more episodes of acute respiratory infection than their siblings. Respiratory viruses were the major cause of respiratory infections. The index children had lower respiratory tract disease, predominantly wheeze, during 34% of proved respiratory virus infections compared with 11% of such infections experienced by the control children (p less than 0.02). Atopic children had an increased tendency to wheeze that did not reach significance, but atopy was not associated with increased susceptibility to respiratory infections. 相似文献