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101.
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103.
Ruchi Jain Bappaditya Dey Neeraj Dhar Vivek Rao Ramandeep Singh Umesh D. Gupta V. M. Katoch V. D. Ramanathan Anil K. Tyagi 《PloS one》2008,3(12)
Background
The variable efficacy (0–80%) of Mycobacterium bovis Bacille Calmette Guréin (BCG) vaccine against adult tuberculosis (TB) necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG) over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB.Methods/Principal Findings
A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immuno-dominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log10, p<0.01) and spleen (2.36 log10, p<0.001) bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL)-12, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF)-β along with up-regulation of inducible nitric oxide synthase (iNOS). In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture.Conclusions/Significance
These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all likelihood would show enhanced survival of guinea pigs. 相似文献104.
Vimaleswaran KS Radha V Ramya K Babu HN Savitha N Roopa V Monalisa D Deepa R Ghosh S Majumder PP Rao MR Mohan V 《Human genetics》2008,123(6):599-605
Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective
of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type
2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated
subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin
levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (−11377C→G and −11282T→C), one intronic
SNP (+10211T→G) and one exonic SNP (+45T→G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T→G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed
that subjects with TG genotype of +10211T→G had significantly higher risk for diabetes compared to TT genotype [Odds ratio
1.28; 95% Confidence Interval (CI) 1.07–1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was
1.53 (95%CI 1.3–1.8; P < 10−7) and that for GG genotype, 2.10 (95% CI 1.3–3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T→G polymorphism in the
first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia. 相似文献
105.
Using transponson Tn5 mutagenesis, two transconjugants of Bradyrhizobium japonicum with the properties of both phage resistance and ability to induce nodulation were isolated at the frequency of 0.02%. These transconjugants were tested for their symbiotic performance on soybean cv. JS335 under greenhouse and field conditions. Both phage-resistant mutants induced nodules (nod (+)), but the transconjugant B. japonicum E13 was ineffective in nitrogen fixation (fix (-)). Rhizobiophage presence in the inoculum of phage-resistant mutants did not influence the symbiotic effectiveness. The mixture of wild strain and phage in the inoculum caused reduced symbiotic performance under controlled conditions, while under a field environment phage (100 and 500 mul of approximately 10(8) particles ml(-1)) presence did not have any recognizable effect on increased nodule dry weight, nitrogenase activity, or foliar N(2) content. On the basis of restriction fragment length polymorphism analysis, phage-sensitive, less effective, homologous bradyrhizobia belonging to B. japonicum were detected in root nodules of both inoculated and uninoculated plants. Inoculation of a higher concentration of phage in the inoculum significantly reduced the symbiotic performance, while the lower concentration of phage did not show any effect on phage-susceptible, less effective, homologous bradyrhizobia or, thus, symbiotic efficiency under field conditions. The phage-resistant mutant B. japonicum A49 showed effective symbiosis as efficient as that of the wild strain. Inoculation of phage-resistant mutants with lytic phage may reduce the occupancy of phage-susceptible, ineffective/less effective/mediocre homologous bradyrhizobia strains under natural complex soil conditions. 相似文献
106.
107.
Thangaraj K Chaubey G Kivisild T Selvi Rani D Singh VK Ismail T Carvalho-Silva D Metspalu M Bhaskar LV Reddy AG Chandra S Pande V Prathap Naidu B Adarsh N Verma A Jyothi IA Mallick CB Shrivastava N Devasena R Kumari B Singh AK Dwivedi SK Singh S Rao G Gupta P Sonvane V Kumari K Basha A Bhargavi KR Lalremruata A Gupta AK Kaur G Reddy KK Rao AP Villems R Tyler-Smith C Singh L 《Human heredity》2008,66(1):1-9
We have analyzed 7,137 samples from 125 different caste, tribal and religious groups of India and 99 samples from three populations of Nepal for the length variation in the COII/tRNA(Lys) region of mtDNA. Samples showing length variation were subjected to detailed phylogenetic analysis based on HVS-I and informative coding region sequence variation. The overall frequencies of the 9-bp deletion and insertion variants in South Asia were 1.9 and 0.6%, respectively. We have also defined a novel deep-rooting haplogroup M43 and identified the rare haplogroup H14 in Indian populations carrying the 9-bp deletion by complete mtDNA sequencing. Moreover, we redefined haplogroup M6 and dissected it into two well-defined subclades. The presence of haplogroups F1 and B5a in Uttar Pradesh suggests minor maternal contribution from Southeast Asia to Northern India. The occurrence of haplogroup F1 in the Nepalese sample implies that Nepal might have served as a bridge for the flow of eastern lineages to India. The presence of R6 in the Nepalese, on the other hand, suggests that the gene flow between India and Nepal has been reciprocal. 相似文献
108.
Christopher A Willoughby Steven M Hutchins Keith G Rosauer Madhumeeta J Dhar Kevin T Chapman Gary G Chicchi Sharon Sadowski David H Weinberg Smita Patel Lorraine Malkowitz Jerry Di Salvo Stephen G Pacholok Kang Cheng 《Bioorganic & medicinal chemistry letters》2002,12(1):93-96
Preparation and screening of mixture libraries based on a 2-arylindole scaffold resulted in the discovery of potent ligands for a variety of G-protein coupled receptors. 相似文献
109.
The effect of new non-steroidal anti-inflammatory agents on lysosomal stability was studied by determining the activity of beta-glucuronidase, a typical lysosomal enzyme, in various sub-cellular fractions and its release from the lysosome-rich fraction. Adjuvant arthritic animals showed a significant increase in the beta-glucuronidase activity in sub-cellular fractions. The increased rate of the release of beta-glucuronidase from lysosome-rich fraction clearly suggested that arthritic syndrome caused decreased stability of the lysosomes. Administration of boswellic acids or salai-guggal to arthritic animals was found to increase the lysosomal stability by inhibiting the rate of release from lysosome-rich fraction and reducing beta-glucuronidase activity in various sub-cellular fractions. Of the two anti-inflammatory agents tested, salai-guggal was found to afford more therapeutic value than boswellic acids. 相似文献
110.