Evaluation of Cell Types for Assessment of Cytogenetic Damage in Arsenic Exposed Population

Background: Cytogenetic biomarkers are essential for assessing environmental exposure, and reflect adverse human health effects such as cellular damage. Arsenic is a potential clastogen and aneugen. In general, the majority of the studies on clastogenic effects of arsenic are based on frequency of micronuclei (MN) study in peripheral lymphocytes, urothelial and oral epithelial cells. To find out the most suitable cell type, here, we compared cytogenetic damage through MN assay in (a) various populations exposed to arsenic through drinking water retrieved from literature review, as also (b) arsenic-induced Bowen's patients from our own survey. Results: For literature review, we have searched the Pubmed database for English language journal articles using the following keywords: "arsenic", "micronuclei", "drinking water", and "human" in various combinations. We have selected 13 studies consistent with our inclusion criteria that measured micronuclei in either one or more of the above-mentioned three cell types, in human samples. Compared to urothelial and buccal mucosa cells, the median effect sizes measured by the difference between people with exposed and unexposed, lymphocyte based MN counts were found to be stronger. This general pattern pooled from 10 studies was consistent with our own set of three earlier studies. MN counts were also found to be stronger for lymphocytes even in arsenicinduced Bowen's patients (cases) compared to control individuals having arsenic-induced noncancerous skin lesions. Conclusion: Overall, it can be concluded that MN in lymphocytes may be superior to other epithelial cells for studying arsenic-induced cytogenetic damage

Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB

The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity synthetic REV-ERB agonist, STL1267, and describe its mechanism of binding to REV-ERB as well as the method by which it recruits transcriptional corepressor both of which are unique and distinct from that of heme-bound REV-ERB

Restoration of uterine redox-balance by methanolic extract of Camellia sinensis in arsenicated rats

Arsenic, an environmental and industrial pollutant causes female reproductive disturbances and female infertility. Several researchers found that the use of Camellia sinensis (CS) (green tea) is effective as an alternative therapeutic strategy in the management of several health ailments. This study explores the role of CS extract against arsenic-induced rat uterine tissue damage. Methanolic extract of CS (10 mg/kg BW) was tested concomitantly in arsenic-treated (10 mg/kg BW) rats for a duration of two-oestrous cycle length (8 days). CS effectively attenuated arsenic-induced antioxidantdepletion and necrosis in uterine tissue. Rats treated with sodium arsenite showed significantly reduced activities of enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in uterine tissue as evidenced by the results of spectrophotometric and electrozymographic analysis. Co-administration of CS significantly reversed the above oxidative stress markers in uterine tissue along with the histopathological changes in ovarian and uterine tissue. Moreover, an increase in the level of transcription factor NF-κB in the uterine tissue in association with reduced serum levels of vitamin B12 and folic acid were mitigated in arsenic fed rats following CS co-administration

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Early stages of growth of Si nanowires by metal assisted chemical etching: a scaling study

We have studied the kinetic roughening in the growth of Si nanowires (NWs) by metal assisted chemical etching (MACE) process as a function of the etching time using atomic force microscopy imaging. In the early stage of growth of Si NWs by Ag assisted MACE process, we have determined the scaling exponents α, β, and 1/z. In the formation of Si NWs, nascent Ag+ ions play an important role in diffusing through the Si surface by means of excess holes that control the size of the NWs. In this system, kinetic roughening of the growth front within the detectable range of lengths of Si NWs was observed. We have observed an α = 0.74 ± 0.01 at the early stage of growth of Si NWs. Interface width w increases as a power law of etching time (t), w∼tβ, with growth exponent β = 0.30 ± 0.05 and lateral correlation length ξ grows as ξ∼t1/z with 1/z = 0.32 ± 0.05. These exponents α, β, and 1/z determine the universality class in which the system belongs to. The growth mechanism is explained by conventional shadowing instability model, which is common for columnar type of surface growth