The hOGG1 Ser326Cys polymorphism and prostate cancer risk: a meta-analysis of 2584 cases and 3234 controls

<p>Abstract</p> <p>Background</p> <p>Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys (rs1052133) has been implicated to alter the risk of prostate cancer, but the results are controversial.</p> <p>Methods</p> <p>Two investigators independently searched the Medline, and Cochrane Library up to June 7, 2011. Summary odds ratios (OR) and 95% confidence interval (CI) for Ser326Cys polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage, version 5.0 and Stata 10.0.</p> <p>Results</p> <p>A total of 8 independent studies, including 2584 cases and 3234 controls, were identified. Our analysis suggested that Ser326Cys was not associated with prostate cancer risk in overall population. In the subgroup analysis, we detected the significant association between Ser326Cys polymorphism and decreased prostate risk in mixed population under additive model (OR = 0.67, 95% CI = 0.50-0.90, P = 0.007), recessive model (OR = 0.68, 95% CI = 0.51-0.91, P = 0.008), and Cys allele versus Ser allele (OR = 0.88, 95% CI = 0.78-0.98, P = 0.02). Subanalysis on Caucasian subjects demonstrated that Ser326Cys was not associated with prostate cancer risk.</p> <p>Conclusion</p> <p>This meta-analysis showed the evidence that hOGG1 Ser326Cys polymorphism was associated with a decreased risk of prostate cancer development in mixed populations.</p

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

<p>Abstract</p> <p>Background</p> <p>We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants.</p> <p>Methods</p> <p>From the database of genome-wide association studies (GWAS), we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels). We identified 292 SNPs in 270 genes associated with a disease or trait at <it>P </it>< 5 × 10^-8. As part of the Human Genome-Diversity Project (HGDP), 158 (54.1%) of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, <it>F</it>_ST, was calculated to quantify differences in risk allele frequencies (RAFs) among populations and geographic areas.</p> <p>Results</p> <p>Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global <it>F</it>_ST(0.1042) for 158 SNPs among the populations was not significantly higher than the mean global <it>F</it>_STof 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global <it>F</it>_ST(<it>P </it>< 0.05) was noted in eight SNPs, based on an empirical distribution of global <it>F</it>_STof 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score.</p> <p>Conclusion</p> <p>Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.</p

Antitumor activity against murine lymphoma L5178Y model of proteins from cacao (Theobroma cacao L.) seeds in relation with in vitro antioxidant activity

<p>Abstract</p> <p>Background</p> <p>Recently, proteins and peptides have become an added value to foodstuffs due to new knowledge about its structural analyses as related to antioxidant and anticancer activity. Our goal was to evaluate if protein fractions from cacao seeds show antitumor activity on lymphoma murine L5178Y model. The antioxidant activity of these fractions was also evaluated with the aim of finding a correlation with the antitumor activity.</p> <p>Methods</p> <p>Differential extraction of proteins from unfermented and semi-fermented-dry cacao seeds was performed and characterized by SDS-PAGE and FPLC size-exclusion chromatography. Antitumor activity was evaluated against murine lymphoma L5178Y in BALB/c mice (6 × 10⁴cells i.p.), with a treatment oral dose of 25 mg/kg/day of each protein fraction, over a period of 15 days. Antioxidant activity was evaluated by the ABTS⁺and ORAC-FL assays.</p> <p>Results</p> <p>Albumin, globulin and glutelin fractions from both cacao seed type were obtained by differential solubility extraction. Glutelins were the predominant fraction. In the albumin fraction, polypeptides of 42.3 and 8.5 kDa were found in native conditions, presumably in the form of two peptide chains of 21.5 kDa each one. The globulin fraction presented polypeptides of 86 and 57 kDa in unfermented cacao seed that produced the specific-cacao aroma precursors, and after fermentation the polypeptides were of 45 and 39 kDa. The glutelin fraction presented proteins >200 kDa and globulins components <100 KDa in lesser proportion. Regarding the semifermented-dry cacao seed, it was observed that the albumin fraction showed antitumoral activity, since it caused significant decreases (p < 0.05) in the ascetic fluid volume and packed cell volume, inhibiting cell growth in 59.98 ± 13.6% at 60% of the population; while the greatest antioxidant capacity due to free radical scavenging capacity was showed by the albumin and glutelin fraction in both methods assayed.</p> <p>Conclusion</p> <p>This study is the first report on the biological activity of semifermented-dry cacao protein fractions with their identification, supporting the traditional use of the plant. The albumin fraction showed antitumor and free radical scavenging capacity, however both activities were not correlated. The protein fractions could be considered as source of potential antitumor peptides.</p

Transcriptional Regulation of N-Acetylglutamate Synthase

The urea cycle converts toxic ammonia to urea within the liver of mammals. At least 6 enzymes are required for ureagenesis, which correlates with dietary protein intake. The transcription of urea cycle genes is, at least in part, regulated by glucocorticoid and glucagon hormone signaling pathways. N-acetylglutamate synthase (NAGS) produces a unique cofactor, N-acetylglutamate (NAG), that is essential for the catalytic function of the first and rate-limiting enzyme of ureagenesis, carbamyl phosphate synthetase 1 (CPS1). However, despite the important role of NAGS in ammonia removal, little is known about the mechanisms of its regulation. We identified two regions of high conservation upstream of the translation start of the NAGS gene. Reporter assays confirmed that these regions represent promoter and enhancer and that the enhancer is tissue specific. Within the promoter, we identified multiple transcription start sites that differed between liver and small intestine. Several transcription factor binding motifs were conserved within the promoter and enhancer regions while a TATA-box motif was absent. DNA-protein pull-down assays and chromatin immunoprecipitation confirmed binding of Sp1 and CREB, but not C/EBP in the promoter and HNF-1 and NF-Y, but not SMAD3 or AP-2 in the enhancer. The functional importance of these motifs was demonstrated by decreased transcription of reporter constructs following mutagenesis of each motif. The presented data strongly suggest that Sp1, CREB, HNF-1, and NF-Y, that are known to be responsive to hormones and diet, regulate NAGS transcription. This provides molecular mechanism of regulation of ureagenesis in response to hormonal and dietary changes

DNA glycosylases: in DNA repair and beyond

The base excision repair machinery protects DNA in cells from the damaging effects of oxidation, alkylation, and deamination; it is specialized to fix single-base damage in the form of small chemical modifications. Base modifications can be mutagenic and/or cytotoxic, depending on how they interfere with the template function of the DNA during replication and transcription. DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy. All glycosylases share a common mode of action for damage recognition; they flip bases out of the DNA helix into a selective active site pocket, the architecture of which permits a sensitive detection of even minor base irregularities. Within the past few years, it has become clear that nature has exploited this ability to read the chemical structure of DNA bases for purposes other than canonical DNA repair. DNA glycosylases have been brought into context with molecular processes relating to innate and adaptive immunity as well as to the control of DNA methylation and epigenetic stability. Here, we summarize the key structural and mechanistic features of DNA glycosylases with a special focus on the mammalian enzymes, and then review the evidence for the newly emerging biological functions beyond the protection of genome integrity

Growth of carbon nanotube arrays using nanosphere lithography and their application in field emission devices

The present study investigates the patterned growth of carbon nanotubes (CNTs) by microwave plasma assisted chemical vapor deposition (MPCVD) and their field emission (FE) properties. The nanosphere monolayers were used as a mask for deposition of ultrathin (-3 nm) cobalt (Co) layer by DC sputtering. Periodic arrays of Co catalyst islands were obtained after the removal of spheres. Microscopic and Raman spectroscopic studies revealed the patterned growth of multiwall CNTs on catalyst islands. The CNTs length was around 10 mu m and diameter was of 40-60 nm. The field emission properties were also compared with I-V characteristics of the un-patterned CNTs grown under the same conditions. The onset fields for un-patterned and patterned samples were nearly the same, 0.64 V/mu m and 0.67 V/mu m, respectively for a 10 mu A current. (C) 2010 Elsevier B.V. All rights reserved

Oxygen plasma assisted end-opening and field emission enhancement in vertically aligned multiwall carbon nanotubes

This paper highlights the changes in micro-structural and field emission properties of vertically aligned carbon nanotubes (VACNTs) via oxygen plasma treatment. We find that exposure of very low power oxygen plasma (6 W) at 13.56 MHz for 15-20 min, opens the tip of vertically aligned CNTs. Scanning electron microscopy and transmission electron microscopy images were used to identify the quality and microstructural changes of the nanotube morphology and surfaces. Raman spectra showed that the numbers of defects were increased throughout the oxygen plasma treatment process. In addition, the hydrophobic nature of the VACNTs is altered significantly and the contact angle decreases drastically from 110 degrees to 40 degrees. It was observed that the electron field emission (EFE) characteristics are significantly enhanced. The turn-on electric field (ETOE) of CNTs decreased from similar to 0.80 V mu m(-1) (untreated) to similar to 0.60 V mu m(-1) (oxygen treated). We believe that the open ended VACNTs would be immensely valuable for applications such as micro/nanofluidic based filtering elements and display devices. (C) 2012 Elsevier B.V. All rights reserved

Thinning of multilayer graphene to monolayer graphene in a plasma environment

We present a facile approach to transform multilayer graphene to single-layer graphene in a gradual thinning process. Our technique is based upon gradual etching of multilayer graphene in a hydrogen and nitrogen plasma environment. High resolution transmission microscopy, selected area electron diffraction and Raman spectroscopy confirm the transformation of multilayer graphene to monolayer graphene at a substrate temperature of similar to 400 degrees C. The shift in the position of the G-band peak shows a perfect linear dependence with substrate temperature, which indicates a controlled gradual etching process. Selected area electron diffraction also confirmed the removal of functional groups from the graphene surface due to the plasma treatment. We also show that plasma treatment can be used to engineer graphene nanomesh structures