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Mitra S.,Jawaharlal Nehru Centre for Advanced Scientific Research | Gomez-Raja J.,University of Extremadura | Larriba G.,University of Extremadura | Dubey D.D.,Purvanchal University | Sanyal K.,Jawaharlal Nehru Centre for Advanced Scientific Research
PLoS Genetics | Year: 2014

Specification of the centromere location in most eukaryotes is not solely dependent on the DNA sequence. However, the non-genetic determinants of centromere identity are not clearly defined. While multiple mechanisms, individually or in concert, may specify centromeres epigenetically, most studies in this area are focused on a universal factor, a centromere-specific histone H3 variant CENP-A, often considered as the epigenetic determinant of centromere identity. In spite of variable timing of its loading at centromeres across species, a replication coupled early S phase deposition of CENP-A is found in most yeast centromeres. Centromeres are the earliest replicating chromosomal regions in a pathogenic budding yeast Candida albicans. Using a 2-dimensional agarose gel electrophoresis assay, we identify replication origins (ORI7-LI and ORI7-RI) proximal to an early replicating centromere (CEN7) in C. albicans. We show that the replication forks stall at CEN7 in a kinetochore dependent manner and fork stalling is reduced in the absence of the homologous recombination (HR) proteins Rad51 and Rad52. Deletion of ORI7-RI causes a significant reduction in the stalled fork signal and an increased loss rate of the altered chromosome 7. The HR proteins, Rad51 and Rad52, have been shown to play a role in fork restart. Confocal microscopy shows declustered kinetochores in rad51 and rad52 mutants, which are evidence of kinetochore disintegrity. CENP-ACaCse4 levels at centromeres, as determined by chromatin immunoprecipitation (ChIP) experiments, are reduced in absence of Rad51/Rad52 resulting in disruption of the kinetochore structure. Moreover, western blot analysis reveals that delocalized CENP-A molecules in HR mutants degrade in a similar fashion as in other kinetochore mutants described before. Finally, co-immunoprecipitation assays indicate that Rad51 and Rad52 physically interact with CENP-ACaCse4 in vivo. Thus, the HR proteins Rad51 and Rad52 epigenetically maintain centromere functioning by regulating CENP-ACaCse4 levels at the programmed stall sites of early replicating centromeres. © 2014 Mitra et al.

Pandey V.K.,Purvanchal University | Singh M.P.,Allahabad University
Cellular and Molecular Biology | Year: 2014

Wheat straw pretreated with chemicals as well as hot water was subjected to degradation by edible mushroom Pleurotus ostreatus. Lignin, cellulose and hemicelluloses component of both chemically as well as hot water treated wheat straw was degraded by the fungus and in turn the edible and nutritious fruiting body of the mushroom was produced. Biodegradation of wheat straw in terms of loss of lignin, cellulose and hemicellulose showed positive correlation with cellulases, xylanase, laccase and polyphenol oxidase (PPO) activity of the fungus. During vegetative growth of the fungus, lignin degradation was faster and during fructification, lignin degradation was slower than cellulose and hemicellulose. The carbon content of the wheat straw decreased while, nitrogen content increased during degradation of the waste. Hot water treated wheat straw supported better production of enzymatic activity and degraded more efficiently than chemically sterilized substrate. The cumulative yield and biological efficiency (BE) of the mushroom was maximum on the hot water treated substrate. Degradation of the hot water treated wheat straw was better and faster than chemically treated substrate. © 2014.

Janam Singh R.,Indian Oil Corporation Ltd. | Janam Singh R.,Purvanchal University
Journal of the Chemical Society of Pakistan | Year: 2011

The syntheses of a series of some substituted-1, 2, 4-triazole derivatives are described. The reaction of sodium salt of α-sulphonated of stearic acid hydrazide (1) with carbon disulphide in alcoholic KOH yielded the corresponding sodium 1-(4-amino-5-mercapto-4H-[1, 2, 4]-triazol-3yl)- heptadecane-1-sulfonate (2). The reaction of compound (2) with urea, chloroacetyl chloride, chloroacetaldehyde and phenacyl bromides yielded the substituted 1, 2, 4-triazole derivatives (3), (4), (5) and (6) respectively. All the synthesized compounds were characterized by IR, PMR, Mass spectral data and elemental analyses. All newly synthesized compounds have been assayed for their antibacterial activities against S. aureus, E. coli, B. subtilis and P. aeruginosa.

Rai V.,Purvanchal University
Cellular and molecular biology (Noisy-le-Grand, France) | Year: 2011

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in bipolar disorder is controversial. The aim of the present study was to assess the risk of MTHFR C677T polymorphism for bipolar disorder. The author performed a meta-analysis and pooled data from individual case-control studies that examined the association between C677T polymorphism and bipolar disorder (meta-analysis: 8 studies, 1457 cases and 2169 controls).The pooled Odd Ratios (OR) were estimated by both fixed effects and random effects models. The meta-analysis with fixed effects showed that there was 71% heterogeneity between the eight studies. The fixed effect pooled OR was 1.07 (95% CI; 0.98 to 1.17) and Cochran Q was 24.13 (df = 7; p=0.0011). The study is significant and shows meager association. The random effect pooled OR was 1.07(95% CI; 0.87 to 1.32) and Cochran Q was 24.13 (df = 7; p=0.0011). The random effect pooled OR was also significant and shows meager association between MTHFR C677T genotype and bipolar disorder.

Singh M.P.,Purvanchal University | Singh V.K.,Banaras Hindu University
Cellular and Molecular Biology | Year: 2012

Edible oyster mushroom Pleurotus sapidus was cultivated, on pea pod shell, cauliflower leaves, radish leaves, brassica straw in various combinations of paddy straw. The mushroom failed to grow on these vegetable wastes separately. However, it grew very well on these vegetable wastes when mixed with various combinations of paddy straw as substrate. Total yield and biological efficiency of the mushroom cultivated on substrate containing 20% and 30% vegetable wastes mixed with 70% and 80% (w/w) of paddy straw was found to be better, when compared with yield and efficiency obtained with paddy straw alone (100%). The protein content in the fruit bodies was found to be higher in the mushroom grown on paddy straw mixed with vegetable wastes than that obtained with paddy straw alone. Similarly, six amino acids (Leu, Ile, Val, Thr, Met and Phe) showed a significant increase when the mushroom was grown on a mixed substrate containing both vegetable wastes and paddy straw. On the contrary, the total sugar and reducing sugar content declined in the mushroom grown on the mixture of paddy straw and other wastes, when compared with the results obtained with paddy straw alone. © 2012.

Rai V.,Purvanchal University
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: Methylenetetrahydrofolate (MTHFR) is the key enzyme of the folate metabolic pathway and several studies have pointed to association between the MTHFR C677T polymorphism and breast cancer risk. Although significant association was observed in some studies, in others no clear link could be established. Objective: A meta-analysis of published Asian case control studies was therefor carried out to shed further light on any C677T breast cancer association. Materials and Methods: PubMed, Springer Link, Google Scholar and Elsevier databases were searched for case control studies of associations between MTHFR C677T polymorphism and breast cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. A total of 36 studies including 8,040 cases and 10,008 controls were included in the present meta-analysis. Results: Overall, a significantly elevated breast cancer risk was associated with the T allele and TT genotype in homozygote comparison and dominant genetic models when all studies were pooled into the meta-analysis (T vs C (allele contrast model): OR=1,23, 95%CI=1.13-1.37, p=0.000; TT vs CC(homozygote model): OR=1.38, 95%CI=1.16-1.63, p=0.0003; TT+CT vs CC (dominant model): OR=1.12,95%CI=1.01-1.23, p=0.02). Conclusions: The present meta-analysis strongly suggested a significant association between the MTHFR C677T polymorphism and risk of breast cancer in Asian populations.

Rai V.,Purvanchal University
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: Previous studies concerning the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism with lung cancer in Asian populations have provided inconclusive findings. Aim: A meta-analysis was performed to investigate a more reliable association between MTHFR C677T polymorphism and lung cancer in Asians. Materials and Methods: A comprehensive search was conducted to identify all case-control studies of MTHFR polymorphisms and lung cancer in Asia, using odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association. Results: Meta-analysis results suggested that the MTHFR C677T polymorphism contributed to an increased lung cancer risk in Asian populations (for T vs C: OR=1.11, 95%CI=1.0-1.23; for CT vs CC: OR= 1.1, 95%CI= 0.95-1.2 ; for TT+CT vs CC: OR=1.13, 95%CI=1.0-1.30; for TT vs CC: OR=1.25, 95%CI=1.01-1.30; for TT vs CT+CC: OR=1.16, 95%CI=1.0-1.36). Conclusions: MTHFR C677T polymorphism is significantly associated with lung cancer in Asians.

Rai V.,Purvanchal University
Asian Pacific Journal of Cancer Prevention | Year: 2016

Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.

Rai V.,Purvanchal University
Indian Journal of Clinical Biochemistry | Year: 2016

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was implicated to be associated with thrombophilia due to its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine. Several case–control studies were investigated MTHFR C677T polymorphism as risk for recurrent pregnancy loss (RPL). These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of RPL whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies published from Asian population relating the C677T polymorphism to the risk of RPL was conducted. The following electronic databases were searched without language restrictions: PubMed, Google Scholars, Elsevier and Springer Link up to December, 2015. Meta-analysis was performed using MetaAnalyst and Mix version 1.7. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased RPL risk in Asian population using all five genetic models (for T vs. C: OR 1.35, 95 % CI 1.09–1.68, p = 0.009; for TT + CT vs. CC: OR 1.44, 95 % CI 1.14–1.82, p = 0.006; for CT vs. CC: OR 1.39, 95 % CI 1.07–1.8, p = 0.01; for TT vs. CC: OR 1.79, 95 % CI, p = 0.007; for TT vs. CT + CC: OR 1.61, 95 % CI 1.02–2.56, p = 0.04). In conclusion, this meta-analysis demonstrates a strong association between the MTHFR C677T variant and RPL in Asian population and raising the importance of the use of folate in its treatment and prevention. © 2016 Association of Clinical Biochemists of India

Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - ‘MTHFR’, ‘C677T’, in combination with ‘Autism’. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C = 1.48; 95 % CI: 1.18–1.86; P = 0.0007; ORTT + CT vs. CC = 1.70, 95 % CI = 0.96–2.9, p = 0.05; ORTT vs. CC = 1.84, 95 % CI = 1.12–3.02, p = 0.02; ORCT vs.CC = 1.60, 95 % CI = 1.2–2.1, p = 0.003; ORTT vs.CT+CC = 1.5, 95 % CI = 1.02–2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C = 1.43; 95 % CI = 1.1–1.87; p = 0.009) and Asian population (ORTvs.C = 1.68; 95 % CI = 1.02–2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism. © 2016 Springer Science+Business Media New York

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