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121.
122.
Uri S. Ladror Gary T. Wang William L. Klein Thomas F. Holzman Grant A. Krafft 《Journal of Protein Chemistry》1994,13(4):357-366
Fluorogenic peptide substrates designed to encompass the reported-secretory and amyloidogenic cleavage sites of the amyloid- precursor protein (PP) were used to analyze proteinase activities in brain extracts from control patients and those with Alzheimer's disease (AD). Activity against the secretory substrate atpH 7.5 in control and AD brains produced a major endopeptidase cleavage at the Lys687-Leu688 bond (PP770 numbering), consistent with thePP secretase cleavage. Activity in control brains against the amyloidogenic substrate atpH 7.5 produced one cleavage at the Ala673-Glu674 bond, two residues C-terminal to the amyloidogenic Met-Asp site. However, in three of four AD brains, the major cleavage was at the Asp-Ala bond, one residue from the amyloidogenic site. Both endopeptidase and carboxypeptidase activities in AD brains were lower than in control brains. Proteinase activities against the secretory substrate had a major optimum atpH 3.0–4.0 and another atpH 6.0–7.5. Proteinase activities against the amyloidogenic substrate had a major optimum at or belowpH 3.0 and another atpH 6.0. Using both substrates, activities at lowpH were higher in AD brains than in controls, while atpH above 6.5, activities in control brains were higher than in AD. These results indicate that the levels of proteolytic enzymes in AD brains are altered relative to controls.Abbreviations A
Amyloid-
- ACN
acetonitrile
- AD
Alzheimer's disease
- PP
amyloid- precursor protein
- DABCYL
4-(4-dimethylaminophenylazo)-benzoic acid
- EDANS
5-{(2-aminoethyl)amino}napthalene-1-sulfonic acid
- MES
morpholinoethane sulfonic acid
- MOPS
morpholino-propane sulfonic acid
- RP-HPLC
reverse-phase high-performance liquid chromatography
- SDS-PAGE
sodium do-decyl sulfate-polyacrylamide gel electrophoresis
- TFA
tri-fluoroacetic acid
- Tris
tris(hydroxyethyl)aminomethane 相似文献
123.
Absence of effects of low-frequency, low-amplitude magnetic fields on the properties of gramicidin A channels. 下载免费PDF全文
The effects of static and low-frequency magnetic fields on gramicidin A channels have been investigated using bilayer patch clamp recording and a bridge technique capable of detecting 0.3% changes in the conductance of glyceryl monooleate membranes containing many channels. In the bridge technique the conductance was assessed using 10-ms voltage pulses applied at 10 Hz. Measurements were made for LiCl, KCl, and CsCl using magnetic fields of 50, 100, 500, and 5000 microT with the frequency scanned from 10-200 Hz. The combinations of static and low-frequency fields employed include the "cyclotron resonance" conditions at which effects had been predicted to occur. In no case was there any detectable change in conductance when the magnetic fields were applied or changed. Potassium currents through single gramicidin channels have been recorded for patches in which several channels may be open at once. Fields were applied for 2 min periods interleaved with 2 min controls. Methods have been developed to analyze the multichannel records to reveal the amplitude and duration of the channels together with the frequency, depth, and apparent period of flickers. No significant differences were observed between the control and field-exposed recording periods. The peak of the distribution of opening and closing transitions always coincided for fields on and off within the resolution, 0.4%, of the recordings. There are at least two types of flicker, one with typical period less than 0.1 ms, the other with typical period from 0.3-0.8 ms. Most of the latter were not complete closures with the conductance during a flicker 15-20% above the level for a full closure. 相似文献
124.
Rob J. De Boer Alan S. Perelson Ioannis G. Kevrekidis 《Bulletin of mathematical biology》1993,55(4):781-816
Two types of behavior have been previously reported in models of immune networks. The typical behavior of simple models, which
involve B cells only, is stationary behavior involving several steady states. Finite amplitude perturbations may cause the
model to switch between different equilibria. The typical behavior of more realistic models, which involve both B cells and
antibody, consists of autonomous oscillations and/or chaos. While stationary behavior leads to easy interpretations in terms
of idiotypic memory, oscillatory behavior seems to be in better agreement with experimental data obtained in unimmunized animals.
Here we study a series of models of the idiotypic interaction between two B cell clones. The models differ with respect to
the incorporation of antibodies, B cell maturation and compartmentalization. The most complicated model in the series has
two realistic parameter regimes in which the behavior is respectively stationary and chaotic. The stability of the equilibrium
states and the structure and interactions of the stable and unstable manifolds of the saddle-type equilibria turn out to be
factors influencing the model's behavior. Whether or not the model is able to attain any form of sustained oscillatory behavior,
i.e. limit cycles or chaos, seems to be determined by (global) bifurcations involving the stable and unstable manifolds of
the equilibrium states. We attempt to determine whether such behavior should be expected to be attained from reasonable initial
conditions by incorporating an immune response to an antigen in the model. A comparison of the behavior of the model with
experimental data from the literature provides suggestions for the parameter regime in which the immune system is operating. 相似文献
125.
126.
David Crews Judith M. Bergeron James J. Bull Deborah Flores Alan Tousignant James K. Skipper Thane Wibbels 《Genesis (New York, N.Y. : 2000)》1994,15(3):297-312
In many egg-laying reptiles, the incubation temperature of the egg determines the sex of the offspring, a process known as temperature-dependent sex determination (TSD). In TSD sex determination is an “all or none” process and intersexes are rarely formed. How is the external signal of temperature transduced into a genetic signal that determines gonadal sex and channels sexual development? Studies with the red-eared slider turtle have focused on the physiological, biochemical, and molecular cascades initiated by the temperature signal. Both male and female development are active processes—rather than the crganized/default system characteristic of vertebrates with genotypic sex determination—that require simultaneous activation and suppression of testis- and ovary-determining cascades for normal sex determination. It appears that temperature accomplishes this end by acting on genes encoaing for steroidogenic enzymes and steroid hormone receptors and modifying the endocrine microenvironment in the embryo. The temperature experienced in development also has long-term functional outcomes in addition to sex determination. Research with the leopard gecko indicates that incubation temperature as well as steroid hormones serve as organizers in shaping the adult phenotype, with temperature modulating sex hormone action in sexual differentiation. Finally, practical applications of this research have emerged for the conservation and restoration of endangered egg-laying reptiles as well as the embryonic development of reptiles as biomarkers to monitor the estrogenic effects of common environmental contaminants. © 1994 Wiley-Liss, Inc. 相似文献
127.
128.
本文用细胞免疫化学方法,在冰冻切片上,检测了胎儿不同组织和器官内带γδ和αβ受体的T细胞(TCR)的分布,结果发现TCR细胞的分布与,般T细胞不同,有相对固定的分布区,如胸腺内TCR细胞主要分布在皮筋质交界处和髓质部;脾脏内的γδT主要位于边缘区,而αβT主要位于动脉周围淋巴鞘,在红髓和血窦两种细胞共存;淋巴结内只有少数TCR细胞位于滤泡间或副皮质,滤泡内则未见。消化管内的TCR细胞主要分布在小肠的固有膜,而胃、大肠和阑尾的固有膜内很少见;肝内TCR细胞主要集中在血管和血窦周围;皮肤切片内的少数TCR细胞见于真皮内,表皮基底层细胞内未见。这些细胞在胎儿期的免疫皮应及其生理功能还不清楚。 相似文献
129.
本文报导了胰腺提取物中两种可被钙/钙调素依赖性蛋白激酶磷酸化的热稳定蛋白。SDS-PAGE测定其表观分子量分别为17.7kD和6kD。经钙/钙调素依赖性蛋白激酶磷酸化后,其最大磷酸参入量为8.8μmol/g蛋白。同时磷酸化作用导致17.7kD蛋白在SDS-PAGE中迁移率发生变化。本文还进一步分析了各种阳离子对磷酸化的影响,并对此两种蛋白可能具有的生理功能进行了初步探讨。 相似文献
130.
福建永安丰海二叠系上部及三叠系底部的双壳类动物群* 总被引:2,自引:0,他引:2
系统研究了闽西永安丰海地区二叠系上部及三叠系下部的双壳类动物群面貌、层位及组合,并与国内外相当的地层进行了对比,阐明了该双壳动物群在二叠-三叠系界线划分中的地层意义.描述了15属24种(其中5新种)、5未定种. 相似文献