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51.
H Gonen I Stancovski D Shkedy T Hadari B Bercovich E Bengal S Mesilati O Abu-Hatoum AL Schwartz A Ciechanover 《Canadian Metallurgical Quarterly》1996,271(1):302-310
Degradation of a protein via the ubiquitin system involves two discrete steps, conjugation of ubiquitin to the substrate and degradation of the adduct. Conjugation follows a three-step mechanism. First, ubiquitin is activated by the ubiquitin-activating enzyme, E1. Following activation, one of several E2 enzymes (ubiquitin-carrier proteins or ubiquitin-conjugating enzymes, UBCs) transfers ubiquitin from E1 to the protein substrate that is bound to one of several ubiquitin-protein ligases, E3s. These enzymes catalyze the last step in the process, covalent attachment of ubiquitin to the protein substrate. The binding of the substrate to E3 is specific and implies that E3s play a major role in recognition and selection of proteins for conjugation and subsequent degradation. So far, only a few ligases have been identified, and it is clear that many more have not been discovered yet. Here, we describe a novel ligase that is involved in the conjugation and degradation of non "N-end rule" protein substrates such as actin, troponin T, and MyoD. This substrate specificity suggests that the enzyme may be involved in degradation of muscle proteins. The ligase acts in concert with E2-F1, a previously described non N-end rule UBC. Interestingly, it is also involved in targeting lysozyme, a bona fide N-end substrate that is recognized by E3 alpha and E2-14 kDa. The novel ligase recognizes lysozyme via a signal(s) that is distinct from the N-terminal residue of the protein. Thus, it appears that certain proteins can be targeted via multiple recognition motifs and distinct pairs of conjugating enzymes. We have purified the ligase approximately 200-fold and demonstrated that it is different from other known E3s, including E3 alpha/UBR1, E3 beta, and E6-AP. The native enzyme has an apparent molecular mass of approximately 550 kDa and appears to be a homodimer. Because of its unusual size, we designated this novel ligase E3L (large). E3L contains an -SH group that is essential for its activity. Like several recently described E3 enzymes, including E6-AP and the ligase involved in the processing of p105, the NF-kappa B precursor, the novel ligase is found in mammalian tissues but not in wheat germ. 相似文献
52.
DY Graham R Genta DG Evans R Reddy JE Clarridge CA Olson AL Edmonds N Siepman 《Canadian Metallurgical Quarterly》1996,91(10):2120-2124
BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo. One opinion is that H. pylori "migrates" from the antrum to the corpus in response to omeprazole therapy. METHODS: To determine whether H. pylori migrates in response to omeprazole, we assessed the presence of H. pylori in the antrum and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and histological examination of antral biopsies (Genta stain) were performed before patients received omeprazole, at the end of therapy, and 4-6 wk later. The end points were presence or absence of H. pylori and the number of H. pylori colonies per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and corpus at entry and 4-6 wk after ending therapy. Three general patterns were prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%), antrum-negative and corpus-positive (24%), both antrum- and corpus-negative (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation of the number of colonies per biopsy in those who remained H. pylori-positive in both the antrum and corpus throughout showed that the number of H. pylori decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/- 51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus, respectively, and tended to return to pre-therapy levels 4-6 wk later. The number of H. pylori in the corpus also decreased in the antrum-negative and corpus-positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p < 0.05). In most of the patients studied, the number of H. pylori in the corpus was less posttreatment than it was pretreatment. The decrease in H. pylori load was also reflected in the development of false-negative urea breath tests. CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the corpus; migration from the antrum to the corpus in response to omeprazole is a myth. 相似文献
53.
The goal of stress incontinence surgery is to prevent opening of the urethra during increases in intra-abdominal pressure. Greater refinements in the understanding of the pathophysiology of incontinence and experience with newer treatments have extended surgical thinking beyond the familiar paradigm "to place the urethra in a high retropubic position." When incontinence is associated with vaginal hypermobility, vaginal support may be sufficient to restore continence if the suburethral vaginal wall is sufficiently strong, an evaluation which must often be made by physical examination alone. However, when the vaginal wall is weak, the urethra will require an alternative form of support, usually a sling. If the urethra is intrinsically deficient, vaginal support may not be sufficient to prevent opening during increased intra-abdominal pressure, and coaptation by sling obstruction or periurethral bulking injection may be required. Most laparoscopic approaches to stress incontinence use Burch's method, which offers excellent urethral stability provided the suburethral vaginal wall is strong. Newer insights into the relation between vaginal mobility and urethral closure are discussed, as well as anatomic aspects of the Burch suspension relevant to laparoscopic repair. 相似文献
54.
Organ blood flow is controlled, in part, by changes in diameter of resistance vessels. In thick tissue, vessels can be imaged with a microscope using contrast-enhancing methods (e.g., fluorescence) and image analysis techniques can be used for quantitative diameter estimations. However, a change in the position of a vessel with respect to the plane of focus can be misinterpreted as a diameter change. In order to address this problem, a 3D image in a light microscope is obtained by serial optical sectioning, and a 3D deconvolution procedure (Avinash et al., 1991, "Fourteenth Association for Research in Otolaryngology Midwinter Meeting, St. Petersberg, FL," Abstract 156) is used to deblur 3D image data. Deblurred sections are computationally projected onto a 2D plane to give an extended-focus image, from which diameter estimates of microvessels are made using a quantitative, 2D diameter-tracking algorithm (Miles, 1987, "Semiautomatic Quantitative Image Analysis of Dynamic in Vivo Cochlear Microvessel Diameters." Ph.D. dissertation, Univ. Michigan; Miles and Nuttall, 1992, IEEE Trans. Biomed. Eng.). Justification for 3D preprocessing before diameter analysis is provided by absolute and relative error analyses using computer-generated synthetic vessels. The 3D diameter analysis technique is validated using a capillary tube of known diameter, filled with fluorescent solution. Demonstration of its applicability is shown in diameter measurements from the vessels of guinea pig cochlea. Our approach, using extended-focus images, minimizes overestimation of microvascular diameters and underestimation of relative diameter changes. Therefore, unambiguous diameter measurements are possible with extended-focus images. 相似文献
55.
In 24 cats (Uppsala, Sweden) with neurological signs of "staggering disease" and typical neuropathology, 44% had Borna disease virus (BDV)-specific antibodies. In 173 cat sera (Berlin, Germany) of animals with unknown record, 7% were BDV positive. Out of 24 cats with undefined neurological disorders, 13% were BDV positive. Similarities in staggering disease of cats and Borna disease of horses and sheep suggest related etiological agents. 相似文献
56.
SV Buldyrev AL Goldberger S Havlin Peng C-K M Simons HE Stanley 《Canadian Metallurgical Quarterly》1993,47(6):4514-4523
We propose a generalized Lévy walk to model fractal landscapes observed in noncoding DNA sequences. We find that this model provides a very close approximation to the empirical data and explains a number of statistical properties of genomic DNA sequences such as the distribution of strand-biased regions (those with an excess of one type of nucleotide) as well as local changes in the slope of the correlation exponent alpha. The generalized Lévy-walk model simultaneously accounts for the long-range correlations in noncoding DNA sequences and for the apparently paradoxical finding of long subregions of biased random walks (length lj) within these correlated sequences. In the generalized Lévy-walk model, the lj are chosen from a power-law distribution P(lj) varies as lj(-mu). The correlation exponent alpha is related to mu through alpha = 2-mu/2 if 2 < mu < 3. The model is consistent with the finding of "repetitive elements" of variable length interspersed within noncoding DNA. 相似文献
57.
The syndrome of parainfectious encephalomyelitis evolves from an antecedent infection. Several etiologic agents have been associated with this complication, although the pathogenesis in each instance may prove to be more uniform. Considerable evidence suggests that the syndrome is mediated immunologically. The seven cases reported here were clinically similar, although the infectious etiologies were diverse. Leptospirosis antedated the neurologic syndrome in two cases, and a "viral" illness preceded the other five cases. The evolution of the syndrome was slowly progressive in each case, and six patients had prominent involvement of rhombencephalic structures. The progressive course was reversed rapidly with eventual full recovery in each instance after initiation of corticosteroid therapy. Our experience with these cases coupled with a review of the literature suggests that corticosteroid therapy should be considered in the subacute or chronic cases of parainfectious encephalomyelitis. 相似文献
58.
Omar AL Zabir 《硅谷》2005,(5):103-110
所有的Microsoft Office应用程序都构建在支持自动化的对象模型之上。任何开发人员都能够使用对象模型来驱动应用程序UI以及添加、编辑和删除内容,就像一个真正的用户在与应用程序交互。丰富对象模型结合自动化支持使Office应用程序真正成为可扩展和可插接的。为了扩展Microsoft Word的行为而满足每个人自身的需要,任何人都能够在很短的时间里编写出一个强大的外接程序。作为优秀的面向对象开发人员,我们使用丰富的结构和优秀合理的对象模型(遵循模型一视图一控制器设计模式(MVC)来开发自己的应用程序。 相似文献
59.
Mohammed H. AL Mughram Mohini S. Ghatge Glen E. Kellogg Martin K. Safo 《International journal of molecular sciences》2023,24(1)
Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, serves as a cofactor for scores of B6-dependent (PLP-dependent) enzymes involved in many cellular processes. One such B6 enzyme is dopa decarboxylase (DDC), which is required for the biosynthesis of key neurotransmitters, e.g., dopamine and serotonin. PLP-dependent enzymes are biosynthesized as apo-B6 enzymes and then converted to the catalytically active holo-B6 enzymes by Schiff base formation between the aldehyde of PLP and an active site lysine of the protein. In eukaryotes, PLP is made available to the B6 enzymes through the activity of the B6-salvage enzymes, pyridoxine 5′-phosphate oxidase (PNPO) and pyridoxal kinase (PLK). To minimize toxicity, the cell keeps the content of free PLP (unbound) very low through dephosphorylation and PLP feedback inhibition of PNPO and PLK. This has led to a proposed mechanism of complex formation between the B6-salvage enzymes and apo-B6 enzymes prior to the transfer of PLP, although such complexes are yet to be characterized at the atomic level, presumably due to their transient nature. A computational study, for the first time, was used to predict a likely PNPO and DDC complex, which suggested contact between the allosteric PLP tight-binding site on PNPO and the active site of DDC. Using isothermal calorimetry and/or surface plasmon resonance, we also show that PNPO binds both apoDDC and holoDDC with dissociation constants of 0.93 ± 0.07 μM and 2.59 ± 0.11 μM, respectively. Finally, in the presence of apoDDC, the tightly bound PLP on PNPO is transferred to apoDDC, resulting in the formation of about 35% holoDDC. 相似文献
60.
JM Imparl-Radosevich P Li L Zhang AL McKean PL Keeling H Guan 《Canadian Metallurgical Quarterly》1998,353(1):64-72
A number of imidazole-based compounds were tested for their utility as (1)H NMR molecular probes of intracellular pH. Imidazole, previously found useful as a probe of erythrocyte pH, reported a pH in perfused canine glioma cells that was more than 1 pH unit lower than that reported by inorganic phosphate, consistent with the known lysosomal compartmentation of the molecule. Imidazole acetate, also proposed as an NMR probe of cellular pH, was found not to enter the cells of this study. Histidine was found to be readily taken up by cells and reported a pH consistent with that reported by inorganic phosphate. Using the chemical shift of the histidine H2 proton in cells incubated with 10 mM histidine, cellular pH measurements could be obtained in less than 1 s. This compares quite favorably with the measurement time, typically several minutes, needed to assess in vivo pH by (31)P NMR. The use of histidine as a probe of pH is demonstrated in perfused canine and rat glioma cells subjected to ischemia or to low extracellular pH. 相似文献