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11.
Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing 总被引:26,自引:0,他引:26
Yu G Nishimura M Arawaka S Levitan D Zhang L Tandon A Song YQ Rogaeva E Chen F Kawarai T Supala A Levesque L Yu H Yang DS Holmes E Milman P Liang Y Zhang DM Xu DH Sato C Rogaev E Smith M Janus C Zhang Y Aebersold R Farrer LS Sorbi S Bruni A Fraser P St George-Hyslop P 《Nature》2000,407(6800):48-54
Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. Suppression of nicastrin expression in Caenorhabditis elegans embryos induces a subset of notch/glp-1 phenotypes similar to those induced by simultaneous null mutations in both presenilin homologues of C. elegans (sel-12 and hop-1). Nicastrin also binds carboxy-terminal derivatives of beta-amyloid precursor protein (betaAPP), and modulates the production of the amyloid beta-peptide (A beta) from these derivatives. Missense mutations in a conserved hydrophilic domain of nicastrin increase A beta42 and A beta40 peptide secretion. Deletions in this domain inhibit A beta production. Nicastrin and presenilins are therefore likely to be functional components of a multimeric complex necessary for the intramembranous proteolysis of proteins such as Notch/GLP-1 and betaAPP. 相似文献
12.
Rats infected with Trypanosoma lewisi or decomplemented by injection of cobra venom factor or complement activating factor of trypanosomes were found to be more susceptible to infection with Salmonella typhimurium. Decomplemented rats subsequently infected with T. lewisi developed higher blood parasitemia than did normal T. lewisi infected rats. 相似文献
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K Kristensson K V Holmes C S Duchala N K Zeller R A Lazzarini M Dubois-Dalcq 《Nature》1986,322(6079):544-547
In multiple sclerosis, a demyelinating disease of young adults, there is a paucity of myelin repair in the central nervous system (CNS) which is necessary for the restoration of fast saltatory conduction in axons. Consequently, this relapsing disease often causes marked disability. In similar diseases of small rodents, however, remyelination can be quite extensive, as in the demyelinating disease caused by the A59 strain of mouse hepatitis virus (MHV-A59), a coronavirus of mice. To investigate when and where oligodendrocytes are first triggered to repair CNS myelin in such disease, we have used a complementary DNA probe specific for one major myelin protein gene, myelin basic protein (MBP), which hybridizes with the four forms of MBP messenger RNA in rodents. Using Northern blot and in situ hybridization techniques, we previously found that MBP mRNA is first detected at about 5 days after birth, peaks at 18 days and progressively decreases to 25% of the peak levels in the adult. We now report that in spinal cord sections of adult animals with active demyelination and inflammatory cells, in situ hybridization reveals a dramatic increase in probe binding to MBP-specific mRNA at 2-3 weeks after virus inoculation and before remyelination can be detected by morphological methods. This increase of MBP-specific mRNA is found at the edge of the demyelinating area and extends into surrounding areas of normal-appearing white matter. Thus, in situ hybridization with myelin-specific probes appears to be a useful method for detecting the timing, intensity and location of myelin protein gene reactivation preceding remyelination. This method could be used to elucidate whether such a reactivation occurs in multiple sclerosis brain tissue. Our results suggest that in mice, glial cells react to a demyelinating process with widespread MBP mRNA synthesis which may be triggered by a diffusible factor released in the demyelinated areas. 相似文献
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Phosphonopeptides, a new class of synthetic antibacterial agents 总被引:18,自引:0,他引:18
J G Allen F R Atherton M J Hall C H Hassall S W Holmes R W Lambert L J Nisbet P S Ringrose 《Nature》1978,272(5648):56-58
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Summary
Trypanosoma congolense organisms, on incubation at 20°C for 91/2h, were found to generate phospholipaselike activity which was capable of mediating lysis of both nucleated cells and erythrocytes as well as an acute inflammatory response on intradermal inoculation.Acknowledgments. This investigation was supported by the International Development Research Centre. 相似文献
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The biosynthesis of trans-3- and trans-4-hydroxyprolines and 5-hydroxylysine in animal cells requires polypeptide proline or lysine, enzymes and cofactors including iron, and possibly involves peroxidatic intermediates. Several laboratories have reported the presence of low-molecular-weight hydroxyproline and hydroxylysine peptides in cell and organ cultures. We found that these small peptides contained the trans-3 and cis-4 isomers of hydroxyproline as well as trans-4 ones and that their production was not completely inhibited by alpha, alpha-dipyridyl, and iron chelator and effective inhibitor of enzyme-mediated hydroxylations. It is known that oxygen or hydrogen peroxide in the presence of metal can hydroxylate proline and other aromatic compounds. We show here that reduced oxygen derivatives can hydroxylate both free and polypeptide-bound proline and lysine, and that scavengers of hydroxyl radicals suppress, but do not completely inhibit, this reaction. Reduced oxygen derivatives can be generated in normal and pathological circumstances, and some of the low-molecular-weight hydroxyproline and hydroxylysine peptides found in cell and organ cultures might be derived from these derivatives and therefore do not reflect collagen turnover, but rather some other cellular activity. 相似文献
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聚二甲基硅氧烷/聚醚酰亚胺平板复合膜CO2/CH4的研究 总被引:1,自引:0,他引:1
利用聚二甲基硅氧烷/聚醚酰亚胺(PDMS/PEI)非对称平板复合膜,以CO2/CH4混合体系作为研究对象,考察了原料气组成、原料气压力、渗余相流量、温度对分离过程的影响。结果表明:随着原料气中CH4组成的提高,CO2渗透速率下降,分离因子先升高,但在CH4体积分数大于0.5时,分离因子开始下降;随着原料气压力的提高,CO2的渗透速率和分离因子均为下降趋势;在不同压力和温度下,随着渗余相流量的增大,CO2渗透速率基本维持稳定,分离因子略有上升,其中在低压或者低温下,CO2分离因子变化不大,在高压或者高温下,CO2分离因子上升明显。 相似文献