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Molecular Biology Reports - Gastric cancer is one of the common types of cancer around the world which has few therapeutic options. Nitrogen heterocyclic derivatives such as thiazoles are used as...  相似文献   
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Molecular Biology Reports - Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease...  相似文献   
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Osteoclasts are essential for bone dynamics and calcium homeostasis. The cells form a tight seal on the bone surface, onto which they secrete acid and proteases to resorb bone. The seal is associated with a ring of actin filaments. Cortactin, a c-Src substrate known to promote Arp2/3-mediated actin assembly in vitro, is expressed in osteoclasts and localizes to the sealing ring. To address the role of cortactin and actin assembly in osteoclasts, we depleted cortactin by RNA interference. Cortactin-depleted osteoclasts displayed a complete loss of bone resorption with no formation of sealing zones. On nonosteoid surfaces, osteoclasts flatten with a dynamic, actin-rich peripheral edge that contains podosomes, filopodia, and lamellipodia. Cortactin depletion led to a specific loss of podosomes, revealing a tight spatial compartmentalization of actin assembly. Podosome formation was restored in cortactin-depleted cells by expression of wild-type cortactin or a Src homology 3 point mutant of cortactin. In contrast, expression of a cortactin mutant lacking tyrosine residues phosphorylated by Src did not restore podosome formation. Cortactin was found to be an early component of the nascent podosome belt, along with dynamin, supporting a role for cortactin in actin assembly.  相似文献   
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Bioprocess and Biosystems Engineering - In this study, we synthesized super magnetic Fe(OH)3@Fe3O4 nanoparticles (SPIONs) by the co-precipitation method and introduction of amine groups via...  相似文献   
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Extremophiles - Thermostable proteases are important in biotechnological and industrial sectors, due to their stability against denaturing agents and chemicals. The feature that gives them such...  相似文献   
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Shandiz AT  Capraro BR  Sosnick TR 《Biochemistry》2007,46(48):13711-13719
We examine the utility of intramolecular covalent cross-linking to identify the structure present in the folding transition state. In mammalian ubiquitin, cysteine residues located across two beta-strands are cross-linked with dichloroacetone. The kinetic effects of these covalent cross-links in ubiquitin, and engineered disulfide bonds in src SH3 (Grantcharova, V. P., Riddle, D. S., and Baker, D. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 7084-7089), are compared to the results of psi-analysis where strand association is stabilized by metal ion binding to engineered bihistidine sites (Krantz, B. A., Dothager, R. S., and Sosnick, T. R. (2004) J. Mol. Biol. 337, 463-75) at the same positions. The results for the two methods agree at some of the sites. The cross-linking phi crosslink-values agree with their corresponding psi-values when they have both have values of zero or one, which represent the absence and presence of native structure, respectively. When phi crosslink > psi, the apparent inconsistency is rationalized by the difference between each method's mode of stabilization; cross-linking reduces the configurational entropy of the unfolded state whereas metal binding directly stabilizes the native state. However, when the cross-linking phi-values are smaller than their corresponding psi-values, the apparent underestimation of structure formation is difficult to rationalize while retaining the assumption that the cross-link exclusively affects the entropy of the unfolded state. The interpretation also is problematic for data on cross-links located across strands which are not hairpins, and hence, these sites are likely to be of limited utility in folding studies. We conclude that cross-linking data for sites on hairpins generally report on the amount of structure formed within the enclosed loop while the metal binding data report on the amount structure formed at the site itself.  相似文献   
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Using a combined crosslinking-ψ analysis strategy, we examine whether the structural content of the transition state of ubiquitin can be altered. A synthetic dichloroacetone crosslink is first introduced across two β strands. Whether the structural content in the transition state ensemble has shifted towards the region containing the crosslink is probed by remeasuring the ψ value at another region (ψ identifies the degree to which an inserted bi-Histidine metal ion binding site is formed in the transition state). For sites around the periphery of the obligate transition state nucleus, we find that the resulting changes in ψ values are near or at our detection limit, thereby indicating that the structural content of the transition state has not measurably changed upon crosslinking. This work demonstrates the utility of the simultaneous application of crosslinking and ψ-analysis for examining potential transition state heterogeneity in globular proteins.  相似文献   
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Caspase 8 (CASP8) gene plays a key role in the regulation of apoptotic cell death. Expression variation in this gene has been associated with the risk of breast cancer. The aim of this study was to investigate the association of rs3834129 and rs3769821, as functional variants, and their haplotypes with molecular profile as well as the risk of breast cancer in an Iranian population. A case-control study was conducted on 812 participants including 293 breast cancer patients and 519 healthy controls. Genotyping was performed by polymerase chain reaction–based methods. Statistical analysis was performed using SPSS Ver16. The association between polymorphisms and haplotypes with the risk of breast cancer was estimated by calculating odds ratios (OR) and chi-square (χ2) tests. In comparison with ins allele (I) of rs3834129, carriers of del allele (D) showed a lower risk of breast cancer (OR, 0.65; 95% confidence interval [CI], 0.49-0.87; P = 0.004). The multivariate logistic regression model indicated DD genotype as an independent factor for a decreased risk of breast cancer in our population (OR, 0.18; 95% CI, 0.06-0.58; P = 0.004). Also, the C allele of rs3769821 was associated with a 43% increased risk of breast cancer (P = 0.005); however, after adjustment for confounding factors, no association with rs3769821 and breast cancer was observed. In addition, D-T haplotype and diplotype presented protective effects (P < 0.05). Our results indicate that genetic variations in the promoter region of CASP8 gene, especially rs3834129, may serve as a genetic risk factor for breast cancer in an Iranian population.  相似文献   
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