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1.
Jef Faridi Katrine E. Nielsen Paul C. Stein Jens Peter Jacobsen 《Journal of biomolecular structure & dynamics》2013,31(2):321-332
Abstract We have used one and two dimensional exchange 1H NMR spectroscopy to characterize the dynamics of the binding of a homodimeric thiazole orange dye, 1,1′-(4,4,8,8-tetramethyl-4,8-diaza-undecamethylene)-bis-4-(3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolinium tetraiodide (TOTO), to double stranded DNA (dsDNA). The double stranded oligonucleotides used were d-(CGCTAGCG)2 ( 1 ) and d(CGCTAGCTAGCG)2 ( 2 ). TOTO binds preferentially to the (5′-CTAG-3′)2 sites and forms mixtures of 1:1 and 1:2 dsDNA-TOTO complexes with 2 in ratios dependent on the relative amount of TOTO and the oligonucleotide in the sample. The dynamic exchange between preferential binding sites in the case of a 2:1 1 -TOTO mixture is an intermolecular exchange process between two binding sites on different oligonucleotides. In the case of the 1:1 2 -TOTO complex an intramolecular exchange process occur between two different binding sites on the same strand. Both processes were studied. The results demonstrate the ability of TOTO to migrate along a dsDNA strand in an intramolecular exchange process. The migration process (“creeping”) along the DNA strand is 6 times faster than the rate of intermolecular exchange between sites in two different oligonucleotides. 相似文献
2.
Emrah Celik Mohd.?Hafeez Faridi Vinay Kumar Shashank Deep Vincent?T. Moy Vineet Gupta 《Biophysical journal》2013,105(11):2517-2527
Integrin CD11b/CD18 is a key adhesion receptor that mediates leukocyte migration and immune functions. Leukadherin-1 (LA1) is a small molecule agonist that enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1. Here, we used single-molecule force spectroscopy to investigate the biophysical mechanism by which LA1-activated CD11b/CD18 mediates leukocyte adhesion. Between the two distinct populations of CD11b/CD18:ICAM-1 complex that participate in cell adhesion, the cytoskeleton(CSK)-anchored elastic elements and the membrane tethers, we found that LA1 enhanced binding of CD11b/CD18 on K562 cells to ICAM-1 via the formation of long membrane tethers, whereas Mn2+ additionally increased ICAM-1 binding via CSK-anchored bonds. LA1 activated wild-type and LFA1−/− neutrophils also showed longer detachment distances and time from ICAM-1-coated atomic force microscopy tips, but significantly lower detachment force, as compared to the Mn2+-activated cells, confirming that LA1 primarily increased membrane-tether bonds to enhance CD11b/CD18:ICAM-1 binding, whereas Mn2+ induced additional CSK-anchored bond formation. The results suggest that the two types of agonists differentially activate integrins and couple them to the cellular machinery, providing what we feel are new insights into signal mechanotransduction by such agents. 相似文献
3.
Context
Recurrent miscarriage (RM), defined as three or more consecutive losses before the 20th week of gestation, affects 0.5–2% of pregnant women. In over 80% of cases, RM remains unexplained after investigations, suggesting the involvement of genetic factors.Objectives
The present study investigates the common polymorphisms of chemokine receptors CCR5 (NG_012637.1:g.5303A>G) and CX3CR1 (NG_016362.1:g.21065C>T, Thr280Met and NG_016362.1:g.20971G>A, Val249Ile) and their association with recurrent miscarriages (RM) among north Indian women.Participants and Methods
In a retrospective case-control study 200 well characterized patients with unexplained RM and 300 controls were genotyped for three polymorphic markers of CCR5 and CX3CR1 by restriction digestion of PCR amplified fragments.Results
Alleles and genotypes of CX3CR1 Val249Ile revealed statistically significant associations with RM cases when compared with the controls. The homozygous variant genotype Ile/Ile was found to be significantly higher among patients (p = 0.0002) when compared with the homozygous wild type Val/Val genotype. The haplotype of CX3CR1 that carried major alleles of Thr280Met and Val249Ile (T-V) showed statistically significant protective association (p < 0.0001, OR = 0.41, 95% CI = 0.31–0.54). The haplotype A-T-V (all wild type alleles) revealed a statistically significant protective association (p < 0.0001, OR = 0.41, 95% CI = 0.34–0.62), whereas the haplotypes G-T-I, A-T-I and A-M-V modified the risk of RM 1.9-fold, 5.5-fold and 5.1-fold respectively.Conclusions
A common polymorphism of CX3CR1 gene, Val240Ile is associated with the risk of RM in north Indian women. Risk of RM may also be modified by the presence of haplotypes T-I, M-V, G-T-I, A-T-I and A-M-V. 相似文献4.
This paper illustrates the use of a combined neural network model based on Stacked Generalization method for classification of electrocardiogram (ECG) beats. In conventional Stacked Generalization method, the combiner learns to map the base classifiers' outputs to the target data. We claim adding the input pattern to the base classifiers' outputs helps the combiner to obtain knowledge about the input space and as the result, performs better on the same task. Experimental results support our claim that the additional knowledge according to the input space, improves the performance of the proposed method which is called Modified Stacked Generalization. In particular, for classification of 14966 ECG beats that were not previously seen during training phase, the Modified Stacked Generalization method reduced the error rate for 12.41% in comparison with the best of ten popular classifier fusion methods including Max, Min, Average, Product, Majority Voting, Borda Count, Decision Templates, Weighted Averaging based on Particle Swarm Optimization and Stacked Generalization. 相似文献
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Pradeep S. Chauhan Kevin Chen Ramandeep K. Babbra Wenjia Feng Nadja Pejovic Armaan Nallicheri Peter K. Harris Katherine Dienstbach Andrew Atkocius Lenon Maguire Faridi Qaium Jeffrey J. Szymanski Brian C. Baumann Li Ding Dengfeng Cao Melissa A. Reimers Eric H. Kim Zachary L. Smith Vivek K. Arora Aadel A. Chaudhuri 《PLoS medicine》2021,18(12)
7.
Amir H. Qureshi Vineet Chaoji Dony Maiguel Mohd Hafeez Faridi Constantinos J. Barth Saeed M. Salem Mudita Singhal Darren Stoub Bryan Krastins Mitsunori Ogihara Mohammed J. Zaki Vineet Gupta 《PloS one》2009,4(10)
During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin αIIbβ3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin αIIbβ3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin αIIbβ3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future. 相似文献
8.
Mohd Hafeez Faridi Dony Maiguel Brock T. Brown Constantinos J. Barth Stefan Vasile Stephan Schürer Vineet Gupta 《Biochemical and biophysical research communications》2010,394(1):194-199
Binding of leukocyte specific integrin CD11b/CD18 to its physiologic ligands is important for the development of normal immune response in vivo. Integrin CD11b/CD18 is also a key cellular effector of various inflammatory and autoimmune diseases. However, small molecules selectively inhibiting the function of integrin CD11b/CD18 are currently lacking. We used a newly described cell-based high-throughput screening assay to identify a number of highly potent antagonists of integrin CD11b/CD18 from chemical libraries containing >100,000 unique compounds. Computational analyses suggest that the identified compounds cluster into several different chemical classes. A number of the newly identified compounds blocked adhesion of wild-type mouse neutrophils to CD11b/CD18 ligand fibrinogen. Mapping the most active compounds against chemical fingerprints of known antagonists of related integrin CD11a/CD18 shows little structural similarity, suggesting that the newly identified compounds are novel and unique. 相似文献
9.
Mohd Hafeez Faridi Mehmet M. Altintas Camilo Gomez Juan Camilo Duque Roberto I. Vazquez-Padron Vineet Gupta 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013