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1.
The basic mechanisms underlying chemically-mediated neurotransmission at synapses are well established. Synaptic vesicles release their contents of neurotransmitter by exocytosis, and are then recycled and refilled before re-priming for re-release. It is less clear, however, what determines the differences in the quantitative aspects of this process at synapses with different in vivo activity patterns, and the extent to which they can be adapted to changing patterns of usage. The neuromuscular junction is particularly suited to investigations of these issues, due to the presence of distinctive muscle fibre types, with well-differentiated physiological roles and hence, activity patterns. The relative accessibility of NMJs means that chronic recording and manipulation of in vivo activity patterns of single motor neurones are possible. Several laboratories around the world now examining how transmitter release at NMJs is adapted to maintain (or not) release under these identified activity patterns. This review will cover the current state of knowledge and briefly highlight areas where more research is required. For example, current knowledge is largely derived from invertebrate preparations, indicating a need for more detailed comparisons at mammalian NMJs with different activity patterns. Finally, it is not yet clear in any species whether adaptations observed with imposed activity can be driven to complete transformation, with appropriate stimulus regimes. 相似文献
2.
Isolation and characterization of a large,neurite-associated glycoconjugate from neuroblastoma cells
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A high molecular weight glycoconjugate has been isolated from neurite-producing neuronal tumor cells in culture and has been designated as I(0) based on its elution characteristics in gel filtration chromatography. This molecule cannot be found in a variety of nonneuronal cells. I(0) is found in the substratum-attached material or cell fraction of neurite-producing neuroblastoma cells, depending upon culture conditions. It is found in the substratum-bound fraction of B104 rat neuroblastoma cells during serum starvation and in the EGTA-detached cell fraction of B104 cells grown in chemically defined N2 medium. It occurs only in the cell fraction of the human neuroblastoma line Platt. Examination of behavioral variants of the B104 rat line further strengthens the association of I(0) with neurite production; the constitutive neurite-producing E(R)B9 variant contains I(0) while the non-neurite-producing E(R)A11 variant does not. I(0) is large, eluting in the void volume of sepharose-CL2B columns. Radioiodination of intact cells with lactoperoxidase shows I(0) to be a cell surface component. Metabolic radiolabeling studies show that it contains a high proportion of polysaccharide to protein, does not contain mannose, and is unsulfated. Alkaline borohydride reduction release two size classes of large polysaccharide chain. The alkaline reduction results, along with the mannose incorporation studies, show the presence of O-glycosidic linkages and few, if any, N-linkages. Resistance to nitrous acid deamination, insensitivity to glycosaminoglycan lyases, and the absence of sulfation, indicate that I(0) does not contain the glycosaminoglycans hyaluronic acid, chondroitin-, dermatan-, or heparin- sulfates. Affinity column chromatography reveals high binding affinity of I(0) to polyornithine and no binding to gelatin (collagen) or the glycosaminoglycans hyaluronate and heparin. These studies describe a unique high molecular weight glycoconjugate on the surface of neurite-producing neuroblastoma cell lines from two species. 相似文献
3.
M. Bewick C. S. Ogg V. Parsons S. A. Snowdon L. Manuel 《BMJ (Clinical research ed.)》1972,3(5825):491-494
The rosette inhibition test was used in the clinical management of organ allografts to estimate the amount of immunosuppressive drugs necessary to prevent rejection. In patients surviving more than three months renal function appeared to be better than in a similar group of patients managed without the test. It is suggested that this was due to a reduction in the number of clinical or subclinical rejection episodes. On the other hand, the test indicates that in many cases the level of immunosuppression should be much higher, and if this advice is followed the patients become increasingly exposed to the risk of infection. In other words, those patients with good renal function remained well, whereas those who might otherwise have rejected their kidney and survived had in fact died of sepsis. 相似文献
4.
Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of phylogenetic signal 总被引:10,自引:9,他引:1
We have developed a new approach to the measurement of phylogenetic signal
in character state matrices called relative apparent synapomorphy analysis
(RASA). RASA provides a deterministic, statistical measure of natural
cladistic hierarchy (phylogenetic signal) in character state matrices. The
method works by determining whether a measure of the rate of increase of
cladistic similarity among pairs of taxa as a function of phenetic
similarity is greater than a null equiprobable rate of increase. Our
investigation of the utility and limitations of RASA using simulated and
bacteriophage T7 data sets indicates that the method has numerous
advantages over existing measures of signal. A first advantage is
computational efficiency. A second advantage is that RASA employs known
methods of statistical inference, providing measurable sensitivity and
power. The performance of RASA is examined under various conditions of
branching evolution as the number of characters, character states per
character, and mutations per branch length are varied. RASA appears to
provide an unbiased and reliable measure of phylogenetic signal, and the
general approach promises to be useful in the development of new techniques
that should increase the rigor and reliability of phylogenetic estimates.
相似文献
5.
Molecular evolution of voltage-sensitive ion channel genes: on the origins of electrical excitability 总被引:14,自引:0,他引:14
We have analyzed nucleic acid and amino acid sequence alignments of a
variety of voltage-sensitive ion channels, using several methods for
phylogenetic tree reconstruction. Ancient duplications within this family
gave rise to three distantly related groups, one consisting of the Na+ and
Ca++ channels, another the K+ channels, and a third including the cyclic
nucleotide-binding channels. A series of gene duplications produced at
least seven mammalian homologues of the Drosophila Shaker K+ channel;
clones of only three of these genes are available from all three mammalian
species examined (mouse, rat, and human), pointing to specific genes that
have yet to be recovered in one or another of these species. The
Shaw-related K+ channels and the Na+ channel family have also undergone
considerable expansion in mammals, relative to flies. These expansions
presumably reflect the needs of the high degree of physiological and
neuronal complexity of mammals. Analysis of the separate domains of the
four-domain channels (Ca++ and Na+) supports their having evolved by two
sequential gene duplications and implies the historical existence of a
functional two-domain channel.
相似文献
6.
mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species 总被引:4,自引:0,他引:4
Reconstructions of the human-African great ape phylogeny by using
mitochondrial DNA (mtDNA) have been subject to considerable debate. One
confounding factor may be the lack of data on intraspecific variation. To
test this hypothesis, we examined the effect of intraspecific mtDNA
diversity on the phylogenetic reconstruction of another Plio- Pleistocene
radiation of higher primates, the fascicularis group of macaque (Macaca)
monkey species. Fifteen endonucleases were used to identify 10 haplotypes
of 40-47 restriction sites in M. mulatta, which were compared with similar
data for the other members of this species group. Interpopulational,
intraspecific mtDNA diversity was large (0.5%- 4.5%), and estimates of
divergence time and branching order incorporating this variation were
substantially different from those based on single representatives of each
species. We conclude that intraspecific mtDNA diversity is substantial in
at least some primate species. Consequently, without prior information on
the extent of genetic diversity within a particular species, intraspecific
variation must be assessed and accounted for when reconstructing primate
phylogenies. Further, we question the reliability of hominoid mtDNA
phylogenies, based as they are on one or a few representatives of each
species, in an already depauperate superfamily of primates.
相似文献
7.
J Papadakis C B Brown J S Cameron D Adu M Bewick R Donaghey C S Ogg C Rudge D G Williams D Taube 《BMJ (Clinical research ed.)》1983,286(6371):1097-1100
Corticosteroids have the major role in the immunosuppressive treatment of patients who have received renal transplants. Despite their extensive use there is still debate about the appropriate dose that will prevent rejection of the renal allograft with the least morbidity. From March 1979 to November 1981 a randomised controlled trial of high (33 patients) v low oral dose (34 patients) of prednisolone along with azathioprine was conducted in recipients of first cadaveric transplants who had received a blood transfusion within six months of transplantation. The main difference in outcome between the two groups was a high incidence of some infections in the high dose group. Patient mortality, graft survival, transplant function, and number of rejection episodes were indistinguishable in the two groups, but rejection episodes tended to occur later in the high dose group. These findings suggest that the use of lower doses of corticosteroids soon after cadaveric renal transplantation does not jeopardise graft survival and results in lower patient morbidity. 相似文献
8.
D H Taube E A Winder C S Ogg M Bewick J S Cameron C J Rudge D G Williams 《BMJ (Clinical research ed.)》1983,286(6383):2018-2020
Many patients over the age of 55 with end stage renal disease in the United Kingdom are denied dialysis or transplantation. Although the reasons are complex, anticipation of a poor prognosis for these patients might explain why most British renal units impose an arbitrary age limit on the acceptance of patients for treatment. A study was therefore conducted to examine the prognosis and quality of life of 84 patients (mean age 59.6 years, range 55-72) accepted into our renal replacement programme from the beginning of 1975. The five year survival of the patients was 62.0% with 78.1% of the survivors either having successful transplants or caring for themselves using home haemodialysis or continuous ambulatory peritoneal dialysis. The results show that in terms of survival, economics, and rehabilitation it is both feasible and reasonable to treat middle aged and elderly patients with end stage renal disease. These patients should therefore not be denied dialysis or transplantation on the basis of age alone, and the lack of resources and other factors that allow this state to persist in Britain should be rapidly redressed. 相似文献
9.
10.