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861.
Prion diseases can be infectious, sporadic and genetic. The infectious forms of these diseases, including bovine spongiform encephalopathy and Creutzfeldt-Jakob disease, are usually characterized by the accumulation in the brain of the transmissible pathogen, an abnormally folded isoform of the prion protein (PrP) termed PrPSc. However, certain inherited PrP mutations appear to cause neurodegeneration in the absence of PrPSc, working instead by favoured synthesis of CtmPrP, a transmembrane form of PrP. The relationship between the neurodegeneration seen in transmissible prion diseases involving PrPSc and that associated with ctmPrP has remained unclear. Here we find that the effectiveness of accumulated PrPSc in causing neurodegenerative disease depends upon the predilection of host-encoded PrP to be made in the ctmPrP form. Furthermore, the time course of PrPSc accumulation in transmissible prion disease is followed closely by increased generation of CtmPrP. Thus, the accumulation of PrPSc appears to modulate in trans the events involved in generating or metabolising CtmPrP. Together, these data suggest that the events of CtmPrP-mediated neurodegeneration may represent a common step in the pathogenesis of genetic and infectious prion diseases. 相似文献
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866.
Anti-Latour 总被引:2,自引:0,他引:2
Bloor D 《Studies in history and philosophy of science》1999,30(1):81-112
867.
Bacterial suicide through stress 总被引:9,自引:0,他引:9
Outside of the laboratory, bacterial cells are constantly exposed to stressful conditions, and an ability to resist those
stresses is essential to their survival. However, the degree of stress required to bring about cell death varies with growth
phase, amongst other parameters. Exponential phase cells are significantly more sensitive to stress than stationary phase
ones, and a novel hypothesis has recently been advanced to explain this difference in sensitivity, the suicide response. Essentially,
the suicide response predicts that rapidly growing and respiring bacterial cells will suffer growth arrest when subjected
to relatively mild stresses, but their metabolism will continue: a burst of free-radical production results from this uncoupling
of growth from metabolism, and it is this free-radical burst that is lethal to the cells, rather than the stress per se. The
suicide response hypothesis unifies a variety of previously unrelated empirical observations, for instance induction of superoxide
dismutase by heat shock, alkyl-hydroperoxide reductase by osmotic shock and catalase by ethanol shock. The suicide response
also has major implications for current [food] processing methods.
Received 29 March 1999; received after revision 14 May 1999; accepted 17 May 1999 相似文献
868.
Apolipoprotein E (apoE) ɛ4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer’s disease (AD).
In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent
study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid β protein (Aβ).
However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms
by which apoE might enhance Aβ deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces
lysosomal accumulation of Aβ and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other
is the extracellular pathway in which apoE-containing lipoproteins are trapped by Aβ1–42 deposits mobilizing soluble Aβ peptides
and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest
a chaperone-like function for the apoE molecule.
Received 4 February 1999; received after revision 9 April 1999; accepted 23 April 1999 相似文献
869.
Cole DG 《Cellular and molecular life sciences : CMLS》1999,56(3-4):217-226
The kinesins constitute a large family of motor proteins which are responsible for the distribution of numerous organelles, vesicles and macromolecular complexes throughout the cell. One class of these molecular motors, kinesin-II, is unique in that these proteins are typically found as heterotrimeric complexes containing two different, though related, kinesin-like motor subunits, and a single nonmotor subunit. The heteromeric nature of these kinesins appears to have resulted in a class of combinatorial kinesins which can 'mix and match' different motor subunits. Another novel feature of these motors is that the activities of several kinesin-II representatives are essential in the assembly of motile and nonmotile cilia, a role not attributed to any other kinesin. This review presents a brief overview of the structure and biological functions of kinesin-II, the heteromeric kinesin. 相似文献
870.
Immune responses to DNA vaccines 总被引:16,自引:0,他引:16
DNA vaccines, based on plasmid vectors expressing an antigen under the control of a strong promoter, have been shown to induce
protective immune responses to a number of pathogens, including viruses, bacteria and parasites. They have also displayed
efficacy in treatment or prevention of cancer, allergic diseases and autoimmunity. Immunologically, DNA vaccines induce a
full spectrum of immune responses that include cytolytic T cells, T helper cells and antibodies. The immune response to DNA
vaccines can be enhanced by genetic engineering of the antigen to facilitate its presentation to B and T cells. Furthermore,
the immune response can be modulated by genetic adjuvants in the form of vectors expressing biologically active determinants
or by more traditional adjuvants that facilitate uptake of DNA into cells. The ease of genetic manipulation of DNA vaccines
invites their use not only as vaccines but also as research tools for immunologists and microbiologists.
Received 26 October 1998; received after revision 3 December 1998; accepted 3 December 1998 相似文献