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排序方式: 共有469条查询结果,搜索用时 15 毫秒
411.
412.
Synthesis and Characterization of Cefotaxime Conjugated Gold Nanoparticles and Their Use to Target Drug‐Resistant CTX‐M‐Producing Bacterial Pathogens 下载免费PDF全文
413.
Shanaya Patel Faraz Shaikh Vinod Devaraji Ashish Radadiya Kanisha Shah Anamik Shah 《Journal of biomolecular structure & dynamics》2017,35(2):354-367
Transient interactions between cancer stem cells and components of the tumor microenvironment initiate various signaling pathways crucial for carcinogenesis. Predominant hyaluronan (HA) receptor, CD44 is structurally and functionally one of the most variable cell surface receptors having the potential to generate a diverse repertory of CD44 isoforms by alternative splicing of variant exons and post-translational modifications. A structurally distinctive variant of CD44, CD44v10, has an inevitable role in malignant progression, invasion, and metastasis. This can be attributed to the binding of HA with CD44v10, which demonstrates a completely different behavioral pattern as compared to the other spliced variants of CD44 molecule. Absence of a comprehensively predicted crystal structure of human CD44s and CD44v10 is an impediment in understanding the resultant structural alterations caused by the binding of HA. Thus, in this study, we aim to predict the CD44s and CD44v10 structures to their closest native confirmation and study the HA binding-induced structural perturbations using homology modeling, molecular docking, and MD simulation approach. The results depicted that modeled 3D structures of CD44s and CD44v10 isoforms were found to be stable throughout MD simulations; however, a substantial decrease was observed in the binding affinity of HA with CD44v10 (?5.355 kcal/mol) as compared to CD44s. Furthermore, loss and gain of several H-bonds and hydrophobic interactions in CD44v10–HA complex during the simulation process not only elucidated the reason for decreased binding affinity for HA but also prompted toward the plausible role of HA-induced structural perturbations in occurrence and progression of carcinogenesis. 相似文献
414.
Nakajima M Kobayashi E Suwazono Y Uetani M Oishi M Inaba T Kido T Shaikh ZA Nogawa K 《Biological trace element research》2005,108(1-3):17-31
The objectives of this study were to examine the association between urinary excretion of cadmium (U-Cd), copper (U-Cu), and zinc (U-Zn) and the severity of two different indicators of renal toxicity (urinary excretion of beta2-microglobulin [U-beta2-MG] and metallothionein [U-MT]) in Cd-exposed subjects compared to controls, and to assess the physiologic mechanisms by which the exposure to environmental Cd affects U-Cd, U-Cu, and U-Zn. The target population included 3508 Cd-exposed and 294 nonexposed participants who received a health survey conducted among the population of the Kakehashi River basin. Increases of U-Cd, U-beta2-MG, and U-MT in the Cd-exposed population were observed relative to excretion of these substances in controls. Regression analysis using a general linear model revealed that the correlations between U-Cd or U-Cu, and U-beta2-MG and between U-Cd, U-Cu or U-Zn, and U-MT were statistically significant in both sexes, but the correlation between U-Zn and U-beta2-MG excretion was significant only in men. These results suggest U-Cd and U-Cu is affected by dysfunction in renal tubular absorption (indicated by U-beta2-MG), whereas not only U-Cd and U-Cu but also U-Zn appear to be a function of renal cellular desquamation (indicated by U-MT). 相似文献
415.
Herein, we report the purification and biochemical characterization of a novel bi-functional protein proteinase/amylase inhibitor from the dietary leguminous pulse Phaseolus aureus Roxb. (Vigna radiata L.) by means of acetic acid precipitation, salt fractionation, ion-exchange chromatography (DEAE-cellulose) and affinity chromatography on trypsin-sepharose column. P. aureus inhibitor is a bi-functional inhibitor since it exhibits inhibitory activity towards trypsin-like and alpha-chymotrypsin-like serine proteinases as well as against alpha-amylases. It is a helix-rich protein (Mr 13,600) containing approximately eight tyrosines, one tryptophan and two cystines. N-terminal sequence alignment reveals no homology to other proteinase inhibitors reported from Phaseolus sp. thereby confirming that it is a novel inhibitor. Inhibitory activity measurements show that the inhibitor is quite stable even at extremely high temperatures and is only slightly affected by pH changes. Circular dichroism (CD) conformational studies revealed some changes in its near- as well as far-ultraviolet spectrum at extremes of pH and temperature. Treatments with trypsin for varying time periods did not alter its proteolytic inhibitory activity but caused some reduction in its amylase inhibitory activity. 相似文献
416.
Reference bias refers to a common problem in fitting experimental data to an initial model. Given enough free parameters, a good fit of any experimental data to the model can be obtained, even if the experimental data contain only noise. Reference-based alignment methods used in electron microscopy (EM) are subject to this type of bias, in that images containing pure noise can regenerate the reference. Cross-validation is based on the idea that the experimental data used to assess the validity of the fitting should not be the same data as were used to do the fitting. Here we present the application of cross-validation to one form of reference-based alignment: 3D-projection matching in single-particle reconstructions. Our results show that reference bias is indeed present in reconstructions, but that the effect is small for real data compared to that for random noise, and that this difference in behavior is magnified, rather than diminished, during iterative refinement. 相似文献
417.
The constitutional t(17;22): another translocation mediated by palindromic AT-rich repeats 总被引:13,自引:0,他引:13 下载免费PDF全文
Kurahashi H Shaikh T Takata M Toda T Emanuel BS 《American journal of human genetics》2003,72(3):733-738
We have demonstrated that the breakpoints of the constitutional t(11;22) are located at palindromic AT-rich repeats (PATRRs) on 11q23 and 22q11. As a mechanism for this recurrent translocation, we proposed that the PATRR forms a cruciform structure that induces the genomic instability leading to the rearrangement. A patient with neurofibromatosis type 1 (NF1) had previously been found to have a constitutional t(17;22) disrupting the NF1 gene on 17q11. We have localized the breakpoint on 22q11 within the 22q11-specific low-copy repeat where the breakpoints of the constitutional t(11;22)s reside, implying a similar palindrome-mediated mechanism for generation of the t(17;22). The NF1 gene contains a 195-bp PATRR within intron 31. We have isolated the junction fragments from both the der(17) and the der(22). The breakpoint on 17q11 is close to the center of the PATRR. A published breakpoint of an additional NF1-afflicted patient with a constitutional t(17;22) is also located close to the center of the same PATRR. Our data lend additional support to the hypothesis that PATRR-mediated genomic instability can lead to a variety of translocations. 相似文献
418.
Developing a molecular view of the thermodynamics of DNA recognition is essential to the design of ligands for regulating gene expression. In a first comprehensive attempt at sketching an atlas of DNA-drug energetics, we present here a detailed thermodynamic view of minor-groove recognition by small molecules via a computational study on 25 DNA-drug complexes. The studies are configured in the MMGBSA (Molecular Mechanics-Generalized Born-Solvent Accessibility) framework at the current state of the art and facilitate a structure-energy component correlation. Analyses were conducted on both energy minimized structures of DNA-drug complexes and molecular dynamics trajectories developed for the purpose of this study. While highlighting the favorable role of packing, shape complementarity, and van der Waals and hydrophobic interactions of the drugs in the minor groove in conformity with experiment, the studies reveal an interesting annihilation of favorable electrostatics by desolvation. Structural modifications attempted on the ligands point to the requisite physico-chemical factors for obtaining improved binding energies. Hydrogen bonds predicted to be important for specificity based on structural considerations do not always turn out to be significant to binding in post facto analyses of molecular dynamics trajectories, which treat thermal averaging, solvent, and counterion effects rigorously. The strength of the hydrogen bonds retained between the DNA and drug during the molecular dynamics simulations is approximately 1kcal/mol. Overall, the study reveals the compensatory nature of the diverse binding free energy components, possible threshold limits for some of these properties, and the availability of a computationally viable free energy methodology which could be of value in drug-design endeavors. 相似文献
419.
The recent spread of the plant pathogenic bacterium Xylclla fastidiosa Wells et al. by an invasive vector species, Homalodisca coagulata Say, in southern California has resulted in new epidemics of Pierce's disease of grapevine. Our goal is to develop an efficient method to detect low titers of X. fastidiosa in H. coagulata that is amenable to large sample sizes for epidemiological studies. Detection of the plant pathogenic bacterium X. fastidiosa in its insect vector is complicated by low titers of bacteria, difficulty in releasing it from the insect mouthparts and foregut, and the presence of substances in the insect that inhibit polymerase chain reaction (PCr). To select the optimal protocol for DNA extraction to be used with PCR, we compared three standard methods and 11 commercially available kits for relative efficiency of X. fastidiosa DNA extraction in the presence of insect tissue. All of the protocols tested were proficient at extracting DNA from pure bacterial culture (1 x 10(5) cells), and all but one protocol successfully extracted sufficient bacterial DNA in the presence of insect tissue. Three DNA extraction techniques, immunomagnetic separation, the DNeasy Tissue kit (Qiagen, Hercules, CA), and Genomic DNA Purification kit (Fermentus, Hanover, MD), were compared more closely using a dilution series of X. fastidiosa (5000-0 cells) with and without insect tissue present. The DNeasy Tissue kit was the best kit tested, allowing detection of 5 x 10(3) X. fastidiosa cells with an insect head background. 相似文献
420.
Banan A Zhang LJ Shaikh M Fields JZ Farhadi A Keshavarzian A 《American journal of physiology. Cell physiology》2004,287(4):C1139-C1151
Using monolayers of intestinal cells, we reported that upregulation of inducible nitric oxide synthase (iNOS) is required for oxidative injury and that activation of NF-B is key to cytoskeletal instability. In the present study, we hypothesized that NF-B activation is crucial to oxidant-induced iNOS upregulation and its injurious consequences: cytoskeletal oxidation and nitration and monolayer dysfunction. Wild-type (WT) cells were pretreated with inhibitors of NF-B, with or without exposure to oxidant (H2O2). Other cells were transfected with an IB mutant (an inhibitor of NF-B). Relative to WT cells exposed to vehicle, oxidant exposure caused increases in IB instability, NF-B subunit activation, iNOS-related activity (NO, oxidative stress, tubulin nitration), microtubule disassembly and instability (increased monomeric and decreased polymeric tubulin), and monolayer disruption. Monolayers pretreated with NF-B inhibitors (MG-132, lactacystin) were protected against oxidation, showing decreases in all measures of the NF-B iNOS NO pathway. Dominant mutant stabilization of IB to inactivate NF-B suppressed all measures of the iNOS/NO upregulation while protecting monolayers against oxidant insult. In these mutants, we found prevention of tubulin nitration and oxidation and enhancement of cytoskeletal and monolayer stability. We concluded that 1) NF-B is required for oxidant-induced iNOS upregulation and for the consequent nitration and oxidation of cytoskeleton; 2) NF-B activation causes cytoskeletal injury following upregulation of NO-driven processes; and 3) the molecular event underlying the destabilizing effects of NF-B appears to be increases in carbonylation and nitrotyrosination of the subunit components of cytoskeleton. The ability to promote NO overproduction and cytoskeletal nitration/oxidation is a novel mechanism not previously attributed to NF-B in cells. tubulin cytoskeleton; microtubules; oxidation/nitration; inducible nitric oxide synthase/peroxynitrite; inflammatory bowel disease; Caco-2 cells; gut barrier; nuclear factor-B/IB 相似文献