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41.
Kaushal DC Kaushal NA Narula A Kumar N Puri SK Dutta S Lanar DE 《Indian journal of biochemistry & biophysics》2007,44(6):429-436
Plasmodium vivax is one of the most widely distributed human malaria parasites and due to drug-resistant strains, its incidence and prevalence has increased, thus an effective vaccine against the parasites is urgently needed. One of the major constraints in developing P. vivax vaccine is the lack of suitable in vivo models for testing the protective efficacy of the vaccine. P. vivax and P. cynomolgi bastianelli are the two closely related malaria parasites and share a similar clinical course of infection in their respective hosts. The merozoite surface protein-1 (MSP-1) of these parasites has found to be protective in a wide range of host-parasite systems. P. vivax MSP-1 is synthesized as 200 kDa polypeptide and processed just prior to merozoite release from the erythrocytes into smaller fragments. The C- terminal 42 kDa cleavage product of MSP-1 (MSP-1(42)) is present on the surface of merozoites and a major candidate for blood stage malaria vaccine. In the present study, we have biochemically and immunologically characterized the soluble and refolded 42 kDa fragment of MSP-1 of P. vivax (PvMSP-1(42)) and P. cynomolgi B (PcMSP-1(42)). SDS-PAGE analysis showed that both soluble and refolded E. coli expressed P. vivax and P. cynomolgi B MSP-1(42) proteins were homogenous in nature. The soluble and refolded MSP-1(42) antigens of both parasites showed high reactivity with protective monkey sera and conformation-specific monoclonal antibodies against P. cynomolgi B and P. vivax MSP-1(42) antigens. Immunization of BALB/c mice with these antigens resulted in the production of high titres of cross-reactive antibodies primarily against the conformational epitopes of MSP-1(42) protein. The immune sera from rhesus monkeys. immunized with soluble and refolded MSP-1(42) antigens of both parasites also showed high titered cross-reactive antibodies against MSP-1(42) conformational epitopes. These results suggested that the soluble and refolded forms of E. coli expressed P. vivax MSP-1(42) antigens were highly immunogenic and thus a viable candidate for vaccine studies. 相似文献
42.
A unique and highly efficient non-viral DNA/siRNA delivery system based on PEI-bisepoxide nanoparticles 总被引:2,自引:0,他引:2
Swami A Kurupati RK Pathak A Singh Y Kumar P Gupta KC 《Biochemical and biophysical research communications》2007,362(4):835-841
Delivery of DNA and siRNA into mammalian cells is a powerful technique in treating various diseases caused by single gene defects. Herein, we report a highly efficient delivery system using 1,4-butanediol diglycidyl ether (bisepoxide) crosslinked polyethylenimine (PEI) nanoparticles (PN). The nanoparticle/DNA complexes (nanoplexes) exibited approximately 2.5- to 5.0-fold gene transfer efficacy and decreased cytotoxicity in cultured cell lines, compared to the native PEI (25 kDa) (gold standard) and commercially available transfection agents such as Lipofectamine 2000 and Fugene. The bisepoxide crosslinking results in change in amine ratio in PEI; however, it retains the net charge on PN unaltered. A series of nanoparticles obtained by varying the degree of crosslinking was found to be in the size range of 69-77 nm and the zeta potential varying from +35 to 40 mV. The proposed system was also found to deliver siRNA efficiently into HEK cells, resulting in approximately 70% suppression of the targetted gene (GFP). 相似文献
43.
Gholap AR Toti KS Shirazi F Kumari R Bhat MK Deshpande MV Srinivasan KV 《Bioorganic & medicinal chemistry》2007,15(21):6705-6715
A series of 2-amino-5-oxo-4-phenyl-5,6,7,8-tetrahydroquinoline-3-carbonitrile and various analogues have been synthesized in excellent isolated yields starting from various arylidenemalononitrile and 3-amino-2-cyclohexen-1-one in 1-propanol as solvent at reflux temperature in the absence of any added catalyst. All the synthesized compounds were evaluated for their antifungal activity. The relationship between functional group variation and biological activity of the evaluated compounds is discussed in the article. 相似文献
44.
Su X Vicker N Lawrence H Smith A Purohit A Reed MJ Potter BV 《The Journal of steroid biochemistry and molecular biology》2007,104(3-5):312-320
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an important role in regulating the cortisol availability to bind to corticosteroid receptors within specific tissue. Recent advances in understanding the molecular mechanisms of metabolic syndrome indicate that elevation of cortisol levels within specific tissues through the action of 11β-HSD1 could contribute to the pathogenesis of this disease. Therefore, selective inhibitors of 11β-HSD1 have been investigated as potential treatments for metabolic diseases, such as diabetes mellitus type 2 or obesity. Here we report the discovery and synthesis of some 18β-glycyrrhetinic acid (18β-GA) derivatives (2–5) and their inhibitory activities against rat hepatic11β-HSD1 and rat renal 11β-HSD2. Once the selectivity over the rat type 2 enzyme was established, these compounds’ ability to inhibit human 11β-HSD1 was also evaluated using both radioimmunoassay (RIA) and homogeneous time resolved fluorescence (HTRF) methods. The 11-modified 18β-GA derivatives 2 and 3 with apparent selectivity for rat 11β-HSD1 showed a high percentage inhibition for human microsomal 11β-HSD1 at 10 μM and exhibited IC50 values of 400 and 1100 nM, respectively. The side chain modified 18β-GA derivatives 4 and 5, although showing selectivity for rat 11β-HSD1 inhibited human microsomal 11β-HSD1 with IC50 values in the low micromolar range. 相似文献
45.
Evaluation and integration of 49 genome-wide experiments and the prediction of previously unknown obesity-related genes 总被引:1,自引:0,他引:1
MOTIVATION: Genome-wide experiments only rarely show resounding success in yielding genes associated with complex polygenic disorders. We evaluate 49 obesity-related genome-wide experiments with publicly available findings including microarray, genetics, proteomics and gene knock-down from human, mouse, rat and worm, in terms of their ability to rediscover a comprehensive set of genes previously found to be causally associated or having variants associated with obesity. RESULTS: Individual experiments show poor predictive ability for rediscovering known obesity-associated genes. We show that intersecting the results of experiments significantly improves the sensitivity, specificity and precision of the prediction of obesity-associated genes. We create an integrative model that statistically significantly outperforms all 49 individual genome-wide experiments. We find that genes known to be associated with obesity are significantly implicated in more obesity-related experiments and use this to provide a list of genes that we predict to have the highest likelihood of association for obesity. The approach described here can include any number and type of genome-wide experiments and might be useful for other complex polygenic disorders as well. 相似文献
46.
Microsatellites, arrays of 1-6 bp sequences, are abundant in almost all the eukaryotic genomes. Their distribution in the genome is widely accepted to be differential and non random along the axis of the chromosomes. Arabidopsis thaliana genome is dominated by mononucleotide repeats, (A)n being the most abundant motif. In total, 39 microsatellite motifs extended to more than 100 bp in length. Of these, 8 loci are devoid of any gene in their proximity. (AG)n is the most abundant motif among longer repeats. The non-random distribution of microsatellite in the genome is reflected as occurrence of microsatellite clusters in the genome. In total, 3400 microsatellite clusters have been identified in the Arabidopsis genome. Chromosome 2, which is 19.7 Mb long, harbors 550 clusters accommodating 29% of all the microsatellites present on this chromosome. Further, 409 of the 6239 genes on chromosome 2 are associated with 323 microsatellite clusters. Motifs like (AGG)n and (ACT)n, show preferential accommodation in clusters that overlap with genes. Among all the microsatellite clusters that show an overlap with genes, 80% of the clusters show an overlap in such a way that the cluster ends beyond the 3'-end of the gene or starts before the 5'-end of a gene. Genes with diverse functions show association with the clusters. However, not all members of a gene family show similar associations. 相似文献
47.
Factors affecting redox potential and differential sensitivity of SoxR to redox‐active compounds 下载免费PDF全文
Kang‐Lok Lee Atul K. Singh Lim Heo Chaok Seok Jung‐Hye Roe 《Molecular microbiology》2015,97(5):808-821
SoxR is a [2Fe‐2S]‐containing sensor‐regulator, which is activated through oxidation by redox‐active compounds (RACs). SoxRs show differential sensitivity to RACs, partly due to different redox potentials, such that Escherichia coli (Ec) SoxR with lower potential respond to broader range of RACs than Streptomyces coelicolor (Sc) SoxR. In S. coelicolor, the RACs that do not activate ScSoxR did not inhibit growth, suggesting that ScSoxR is tuned to respond to growth‐inhibitory RACs. Based on sequence comparison and mutation studies, two critical amino acids around the [2Fe‐2S] binding site were proposed as key determinants of sensitivity. ScSoxR‐like mutation (R127L/P131V) in EcSoxR changed its sensitivity profile as ScSoxR, whereas EcSoxR‐like mutation (L126R/V130P) in ScSoxR caused relaxed response. In accordance, the redox potentials of EcSoxRR127L/P131V and ScSoxRL126R/V130P were estimated to be ?192 ± 8 mV and ?273 ± 10 mV, respectively, approaching that of ScSoxR (?185 mV) and EcSoxR (?290 mV). Molecular dynamics simulations revealed that the R127L and P131V substitutions in EcSoxR caused more electropositive environment around [2Fe‐2S], making it harder to get oxidized. This reveals a mechanism to modulate redox‐potential in [Fe‐S]‐containing sensors by point mutations and to evolve a sensor with differential sensitivity to achieve optimal cellular physiology. 相似文献
48.
Marta Murgia Nagarjuna Nagaraj Atul S Deshmukh Marlis Zeiler Pasqua Cancellara Irene Moretti Carlo Reggiani Stefano Schiaffino Matthias Mann 《EMBO reports》2015,16(3):387-395
Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high‐sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype‐specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type‐resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity. 相似文献
49.
Geisler J Sasano H Chen S Purohit A 《The Journal of steroid biochemistry and molecular biology》2011,125(1-2):39-45
Inhibition of aromatase is currently well-established as the major treatment option of hormone-dependent breast cancer in postmenopausal women. However, despite the effects of aromatase inhibitors in both early and metastatic breast cancer, endocrine resistance may cause relapses of the disease and progression of metastasis. Thus, driven by the success of manipulating the steroidogenic enzyme aromatase, several alternative enzymes involved in steroid synthesis and metabolism have recently been investigated as possible drug targets. One of the most promising targets is the steroid sulfatase (STS) which converts steroid sulfates like estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHEAS) to estrone (E1) and dehydroepiandrosterone (DHEA), respectively. Estrone and DHEA may thereafter be used for the synthesis of more potent estrogens and androgens that may eventually fuel hormone-sensitive breast cancer cells. The present review summarizes the biology behind steroid sulfatase and its inhibition, the currently available information derived from basic and early clinical trials in breast cancer patients, as well as ongoing research. Article from the Special Issue on Targeted Inhibitors. 相似文献
50.
Prakash M. Davadra Batuk Dabhi Manoj K. Singh Mukul R. Jain Hitendra S. Joshi Atul H. Bapodra 《Chirality》2011,23(10):955-960
A reverse phase high performance liquid chromatography (HPLC) method has been developed for the separation of two geometric isomers of Acrivastine using crude reaction mixture. The resolution between two isomers was found more than 2.9. The geometric isomers have been isolated by preparative HPLC and characterized by spectroscopic techniques, such as NMR, infrared, and MS. The developed method has been validated for the determination of Z‐isomer in Acrivastine. The limit of detection and limit of quantification of the Z‐isomer were 0.05 and 0.2 μg/ml, respectively. The developed method is precise, linear, accurate, rugged and robust for its intended use. Chirality, 2011. © 2011 Wiley‐Liss, Inc. 相似文献