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1.
A B-cell-specific nuclear protein that binds to DNA sites 5'' to immunoglobulin S alpha tandem repeats is regulated during differentiation. 总被引:8,自引:4,他引:4 下载免费PDF全文
Immunoglobulin heavy-chain switching is effected by recombination events between sites associated with tandemly repeated switch sequences located 5' to immunoglobulin heavy-chain genes. Using the band mobility shift assay, we have identified two distinct sites 5' to the alpha heavy-chain switch sequence with affinity for a single B-cell-specific DNA-binding protein, S alpha-BP. S alpha-BP was present in nuclear extracts from pre-B and B cells but was not detected in extracts from plasmacytomas, B-cell hybridomas, T-cell lymphomas, or a macrophage cell line. It was also not detectable in other nonlymphoid cells tested. Evidence suggests there are S alpha-BP-binding sites near other immunoglobulin switch sequences. As with the S alpha sites, these sites appear to be distinct from the consensus tandem repeats characteristic of immunoglobulin switch sequences. The possible functions of S alpha-BP on contacting its binding sites are discussed in the context of immunoglobulin heavy-chain switch recombination. 相似文献
2.
Malkeet Singh Bahia Shravan Kumar Gunda Shwetha Reddy Gade Saikh Mahmood Ravikumar Muttineni Om Silakari 《Journal of molecular modeling》2011,17(1):9-19
Anthranilic acid based derivatives (ANTs) have been identified as a novel class of potent tumor necrosis factor-α converting
enzyme (TACE) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses
has been performed to elucidate the atomic details of the TACE/ANT interactions and also to identify the most important features
impacting TACE inhibitory activity of ANTs. The CoMSIA model resulted to be slightly more predictive than CoMFA model, and
gave conventional r2 0.991, rcv2 0.793, q2 0.777, SEE 0.050, F-value 655.610, and rtest2 0.871. The 3D-QSAR field contributions and the structural features of the TACE binding site showed a good correlation. These
studies will be useful to design new TACE inhibitors with improved potency. 相似文献
3.
Kissner TL Moisan L Mann E Alam S Ruthel G Ulrich RG Rebek M Rebek J Saikh KU 《The Journal of biological chemistry》2011,286(36):31385-31396
4.
Effects of deforestation and cultivation on soil CEC and contents of exchangeable bases: A case study in Simlipal National Park,India 总被引:3,自引:0,他引:3
Deforestation in the tropics seems to be a serious problem probably because of the reduction in soil CEC and the consequent losses of nutrients from the soils. Here, changes in these parameters as influenced by deforestation as well as vegetative cover were studied; statistical methods were applied to interpret the results. Cultivation causes a significant reduction in CEC, total content of the exchangeable bases and exchangeable Ca2+ and Mg2+ levels compared to the adjoining unmanaged forest land. Levels of exchangeable K+ and Na+, however, do not change significantly. Evergreen forest soils have the highest levels of CEC, total exchangeable bases, exchangeable Ca2+ and K+. Deciduous forest, grassland and cultivated soils have statistically similar contents of exchangeable Ca2+, Mg2+, K+ and Na+. Exchangeable Mg2+, however, is not affected by vegetative cover. Soil CEC shows fairly good correlation with the organic carbon content only in evergreen forest soils. In others, organic carbon apparently does not influence CEC significantly. All soils show excellent correlation between their CEC and total exchangeable bases. It is concluded that for regeneration of weathered tropical soils, an evergreen cover provides the most effective means; deciduous vegetation or grass cover do not seem promising. 相似文献
5.
Sang Hak Lee Saikh Mohammad Wabaidur Zeid Abdullah Alothman Seikh Mafiz Alam 《Luminescence》2011,26(6):768-773
A sensitive fluorescence (FL) technique is proposed for the determination of levofloxacin (LVX). The method is based on the fact that the weak FL signal of the Tb(III)–LVX system is strongly enhanced in the presence of gold nanoparticles. Gold nanoparticles were prepared by the citrate reduction of HAuCl4 and characterized by transmission electron microscopy (TEM). Levofloxacin and Tb(III) ion form a fluorescence complex in aqueous solution, and its maximum emission wavelength was found at 545 nm. Optimal conditions for the formation of the levofloxacin–Tb(III) complexes were studied. Levofloxacin was detected by measuring the FL intensity, which increases linearly with the concentration of LVX in the range 6.2 × 10−10–2.6 × 10−8 mol/L. Recovery of the target analytes was > 96% with good quality parameters: linearity (r2 > 0.996), limit of detection (LOD) and limit of quantification (LOQ) values 2.1 × 10−10 mol/L and 7.2 × 10−10 mol/L, and run‐to‐run and day‐to‐day precisions with relative standard deviations (RSDs) around 3%. Thus, the proposed method can be successfully applied to the routine determination of levofloxacin in pharmaceutical preparations. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
6.
Shovonlal Bhowmick Siham A. Alissa Saikh Mohammad Wabaidur Rupesh V. Chikhale Md Ataul Islam 《Journal of molecular recognition : JMR》2020,33(7)
Dengue infection is the most common arthropod‐borne disease caused by dengue viruses, predominantly affecting millions of human beings annually. To find out promising chemical entities for therapeutic application in Dengue, in the current research, a multi‐step virtual screening effort was conceived to screen out the entire “screening library” of the Asinex database. Initially, through “Lipinski rule of five” filtration criterion almost 0.6 million compounds were collected and docked with NS3‐NS2B protein. Thereby, the chemical space was reduced to about 3500 compounds through the analysis of binding affinity obtained from molecular docking study in AutoDock Vina. Further, the “Virtual Screening Workflow” (VSW) utility of Schrödinger suite was used, which follows a stepwise multiple docking programs such as ‐ high‐throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking, and in postprocessing analysis the MM‐GBSA based free binding energy calculation. Finally, five potent molecules were proposed as potential inhibitors for the dengue NS3‐NS2B protein based on the investigation of molecular interactions map and protein‐ligand fingerprint analyses. Different pharmacokinetics and drug‐likeness parameters were also checked, which favour the potentiality of selected molecules for being drug‐like candidates. The molecular dynamics (MD) simulation analyses of protein‐ligand complexes were explained that NS3‐NS2B bound with proposed molecules quite stable in dynamic states as observed from the root means square deviation (RMSD) and root means square fluctuation (RMSF) parameters. The binding free energy was calculated using MM‐GBSA method from the MD simulation trajectories revealed that all proposed molecules possess such a strong binding affinity towards the dengue NS3‐NS2B protein. Therefore, proposed molecules may be potential chemical components for effective inhibition of dengue NS3‐NS2B protein subjected to experimental validation. 相似文献
7.
Seikh Mafiz Alam Mohammad Mainul Karim Sang Hak Lee Saikh Mohammad Wabaidur Hye Young Chung Jong Ha Choi Meea Kang 《Luminescence》2008,23(5):327-332
A simple chemiluminometric method using flow injection has been developed for the determination of laevodopa, based on its sensitizing effect on the weak chemiluminescence (CL) reaction between Na2SO3 and acidic KMnO4. Under optimum experimental conditions, the CL intensity was linearly related to the concentration of laevodopa from 3.4 × 10–8 to 2.4 × 10–5 mol/L and the detection limit was 1.1 × 10–8 mol/L (s:n = 3). The relative standard deviation (RSD) of the proposed method calculated from 20 replicate injection of 3 × 10–7 mol/L laevodopa was 3.3%. The correlation coefficient was 0.997. The method was successfully applied to the determination of laevodopa in commercial pharmaceutical formulations and spiked urine samples. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
8.
Human monocytes infected with Yersinia pestis express cell surface TLR9 and differentiate into dendritic cells 总被引:1,自引:0,他引:1
Saikh KU Kissner TL Sultana A Ruthel G Ulrich RG 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(12):7426-7434
TLR9 recognizes DNA sequences containing hypomethylated CpG motifs and is a component of the innate immune system highly conserved during eukaryotic evolution. Previous reports suggested that the expression of TLR9 is restricted to plasmacytoid dendritic cells and B lymphocytes. Our results indicate that low levels of TLR9 are present on the cell surface of freshly isolated human monocytes, and expression is greatly increased by infection with Yersinia pestis. Enhanced cell surface TLR9 coincided with elevated levels of cytoplasmic TLR9 and recruitment of MyD88. Infected monocytes differentiated into mature dendritic cells, expressed IFN-alpha, and stimulated proliferative and cytotoxic T cell responses specific to Y. pestis. Furthermore, uninfected B cells and monocytes both increased cell surface TLR9, CD86, and HLA-DR in response to treatment with CpG-containing oligonucleotides, whereas cell surface TLR9 was down-modulated on infected dendritic cells by the addition of agonist oligonucleotide. Our results suggest that increased expression of TLR9 on the surface of infected cells may serve a role as an activation signal to other cells of the immune system. 相似文献
9.
Novel 1,4-dihydropyridine induces apoptosis in human cancer cells through overexpression of Sirtuin1
Debashri Manna Rajabrata Bhuyan Forid Saikh Somnath Ghosh Jayasri Basak Rita Ghosh 《Apoptosis : an international journal on programmed cell death》2018,23(9-10):532-553
1,4-Dihydropyridines (1,4-DHPs) are important as a class of heterocyclic compounds that exhibit wide range of biological actions. Many of its derivatives are already characterized as medicinally important drugs and used worldwide. In this study, we have screened some novel Hantzsch 1,4-DHP compounds using both in silico (QSAR and Pharmacophore) and in vitro (cytotoxic screening). 1,4-DHP showed selective cytotoxicity against five human cancerous cell lines; A375, A549, HeLa, HepG2 and SH-SY5Y but limited effect towards normal skin keratinocyte (HaCaT), lung fibroblast (WL-38) and healthy peripheral blood mononuclear cells. In A375 and HepG2 cells, one of the 1,4-DHP derivative (DHP-8) was found to inhibit cell proliferation, and simultaneously increased the apoptotic population as well as mitochondrial membrane depolarization. Furthermore, the mitochondrial signal was triggered with the activation of cleaved Caspase9, Caspase3 and PARP. The treatment with DHP-8 also increased the expression level of SIRT1, subsequently decreasing the level of pAKTser473 and survivin. Reduced pAKTser473 expression led to decrease the phosphorylated inactive form of GSK3βser9 and as a result, proteasomal degradation of Mcl-1 occurred in both the cell lines. Here, we suggest that the apoptotic effect of DHP-8 in A375 and HepG2 cells was mediated by AKT and survivin pathways through SIRT1 activation. The involvement of DHP-8 in SIRT1 activation was further verified by co-treatment of nicotinamide with DHP-8 in both A375 and HepG2 cells. Overall, this study emphasizes the possible potential and therapeutic role of DHP-8 in skin and liver cancer. 相似文献
10.
Ligands binding to Toll-like receptor (TLR), interleukin 1 receptor (IL-1R), or IFN-γR1 are known to trigger MyD88-mediated signaling, which activates pro-inflammatory cytokine responses. Recently we reported that staphylococcal enterotoxins (SEA or SEB), which bind to MHC class II molecules on APCs and cross link T cell receptors, activate MyD88- mediated pro-inflammatory cytokine responses. We also reported that MyD88(-/-) mice were resistant to SE- induced toxic shock and had reduced levels of serum cytokines. In this study, we investigated whether MHC class II- SE interaction by itself is sufficient to activate MyD88 in MHC class II(+) cells and induce downstream pro-inflammatory signaling and production of cytokines such as TNF-α and IL-1β. Here we report that human monocytes treated with SEA, SEB, or anti-MHC class II monoclonal antibodies up regulated MyD88 expression, induced activation of NF-kB, and increased expression of IL-1R1 accessory protein, TNF-α and IL-1β. MyD88 immunoprecipitated from cell extracts after SEB stimulation showed a greater proportion of MyD88 phosphorylation compared to unstimulated cells indicating that MyD88 was a component of intracellular signaling. MyD88 downstream proteins such as IRAK4 and TRAF6 were also up regulated in monocytes after SEB stimulation. In addition to monocytes, primary B cells up regulated MyD88 in response to SEA or SEB stimulation. Importantly, in contrast to primary B cells, MHC class II deficient T2 cells had no change of MyD88 after SEA or SEB stimulation, whereas MHC class II-independent activation of MyD88 was elicited by CpG or LPS. Collectively, these results demonstrate that MHC class II utilizes a MyD88-mediated signaling mechanism when in contact with ligands such as SEs to induce pro-inflammatory cytokines. 相似文献