Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer

Mediator complex has been extensively shown to regulate the levels of several protein-coding genes; however, its role in the regulation of miRNAs in humans remains unstudied so far. Here we show that MED1, a Mediator subunit in the Middle module of Mediator complex, is overexpressed in breast cancer and is a negative prognostic factor. The levels of several miRNAs (miR-100-5p, -191-5p, -193b-3p, -205-5p, -326, -422a and -425-5p) were found to be regulated by MED1. MED1 induces miR-191/425 cluster in an estrogen receptor-alpha (ER-\u3b1) dependent manner. Occupancy of MED1 on estrogen response elements (EREs) upstream of miR-191/425 cluster is estrogen and ER-\u3b1-dependent and ER-\u3b1-induced expression of these miRNAs is MED1-dependent. MED1 mediates induction of cell proliferation and migration and the genes associated with it (JUN, FOS, EGFR, VEGF, MMP1, and ERBB4) in breast cancer, which is abrogated when used together with miR-191-inhibition. Additionally, we show that MED1 also regulates the levels of direct miR-191 target genes such as SATB1, CDK6 and BDNF. Overall, the results show that MED1/ER-\u3b1/miR-191 axis promotes breast cancer cell proliferation and migration and may serve as a novel target for therapy

Germplasm characterization, association and clustering for salinity and waterlogging tolerance in bread wheat (Triticum aestivum)

A study was conducted for characterizing germplasm, estimating interrelationship of traits and clustering of wheat genotypes in five environments covering salinity, waterlogging and neutral soils using, 100 elite but diverse genotypes with eight checks of bread wheat (Triticum aestivum L.). These genotypes were planted under five distinct environments during rabi 2009-10 under augmented design in four blocks wherein each check was repeated twice. The genetic variance, correlation coefficients and cluster analysis were carried out for assessment of lines through seven metric traits, namely, plant stand, plant height, days to heading, days to maturity, tillers/meter, 1000-grain weight and grain yield. Analysis of variance revealed wide variability for most of the traits under study. The phenotypic coefficient of variation (PCV) was high for tillers/meter and grain yield, while high heritability coupled with high genetic advance were found for tillers/meter, 1000-grain weight and grain yield under all five environments. At phenotypic level, positive and significant correlation coefficients revealed that under all the normal and stressed environments used here, grain yield is directly influenced by plant stand, tillers/meter and thousand grain weights. Significant and positive correlations were estimated between tillers/meter (r = 0.31 to 0.66), and 1000 grain weight (r = 0.24 to 0.61) with grain yield under all five environments. Under waterlogged conditions there were significant negative correlations of plant height to grain yield (r = –0.38 to –0.39) across two sites. These results, thereby suggests that yield improvement in bread wheat could be possible by emphasizing these traits through selection in these diverse environments. On the basis of D2 values of pooled data, 108 genotypes were grouped into four clusters. In all, only 26 lines were found common in cluster III under two waterlogging environments (Faizabad and Karnal), while only 15 lines were common in cluster I under non waterlogging (Faizabad, CSSRI and DWR) conditions. These results indicate different constraints exist in waterlogged and non-waterlogged condition at these sites. Genetic diversity available for these traits may be utilized for yield improvement in bread wheat under different soil conditions through planned hybridization and selection in target environments

Medium optimization for the production of lipstatin by Streptomyces toxytricini using full factorial design of experiment

Abstract: Full factorial design of experiment for medium optimization was employed for lipstatin production by Streptomyces toxytricini in shake flask study. The full factorial DOE was very much effective in screening of nutritional parameters within the stipulated time frame in a limited number of experiments. A maximum lipstatin production was achieved 3.290 g/l with the following optimized factors: soya flour 35g/l and soya oil 25g/l. Validation experiments were also carried out to verify the adequacy and the accuracy of the model. The results also give a scope for large scale fermentation of lipstatin production. [Luthra, U., Kumar, H., Kulshreshtha, N., Tripathi, A., Trivedi, A., Khadpekar, S., Chaturvedi, A. and Dubey, R.C. Medium optimization for the production of lipstatin by Streptomyces toxytricini using full factorial design of experiment. Nat Sci 2013;1

Optimization of a high work function solution processed vanadium oxide hole-extracting layer for small molecule and polymer organic photovoltaic cells

We report a method of fabricating a high work function, solution processable vanadium oxide (V2Ox(sol)) hole-extracting layer. The atmospheric processing conditions of film preparation have a critical influence on the electronic structure and stoichiometry of the V2Ox(sol), with a direct impact on organic photovoltaic (OPV) cell performance. Combined Kelvin probe (KP) and ultraviolet photoemission spectroscopy (UPS) measurements reveal a high work function, n-type character for the thin films, analogous to previously reported thermally evaporated transition metal oxides. Additional states within the band gap of V2Ox(sol) are observed in the UPS spectra and are demonstrated using X-ray photoelectron spectroscopy (XPS) to be due to the substoichiometric nature of V2Ox(sol). The optimized V2Ox(sol) layer performance is compared directly to bare indium–tin oxide (ITO), poly(ethyleneoxythiophene):poly(styrenesulfonate) (PEDOT:PSS), and thermally evaporated molybdenum oxide (MoOx) interfaces in both small molecule/fullerene and polymer/fullerene structures. OPV cells incorporating V2Ox(sol) are reported to achieve favorable initial cell performance and cell stability attributes

The model for self-dual chiral bosons as a Hodge theory

We consider (1+1) dimensional theory for a single self-dual chiral boson as classical model for gauge theory. Using Batalin-Fradkin-Vilkovisky (BFV) technique the nilpotent BRST and anti BRST symmetry transformations for this theory have been studied. In this model other forms of nilpotent symmetry transformations like co-BRST and anti co-BRST which leave the gauge-fixing part of the action invariant, are also explored. We show that the nilpotent charges for these symmetry transformations satisfy the algebra of de Rham cohomological operators in differential geometry. The Hodge decomposition theorem on compact manifold is also studied in the context of conserved charges.Comment: 19 pages, No figures, Revtex, Final version to appear in EPJ

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

MicroRNA Dysregulation in Colon Cancer Microenvironment Interactions: The Importance of Small Things in Metastases

The influence of the microenvironment through the various steps of cancer progression is signed by different cytokines and growth factors, that could directly affect cell proliferation and survival, either in cancer and stromal cells. In colon cancer progression, the cooperation between hypoxia, IL-6 and VEGF-A165 could regulate the DNA repair capacity of the cell, whose impairment is the first step of colon cancer development. This cooperation redirects the activity of proteins involved in the metabolic shift and cell death, affecting the cell fate. The pathways triggered by micro environmental factors could modulate cancer-related gene transcription, affecting also small non coding mRNA, microRNAs. MicroRNAs have emerged as key post-transcriptional regulators of gene expression, directly involved in human cancers. The present review will focus first on the intertwined connection between cancer microenvironment and aberrant expression of microRNAs which contribute to carcinogenesis. In particular, the epigenetic mechanisms triggered by tissue microenvironment will be discussed, in view of the recent identification of miRNAs able to directly or indirectly modulate the epigenetic machinery (epi-miRNAs) and that are involved in the epithelial to mesenchimal transition and metastases development

New remarks on the linear constraint self-dual boson and Wess-Zumino terms

In this work we prove in a precise way that the soldering formalism can be applied to the Srivastava chiral boson (SCB), in contradiction with some results appearing in the literature. We have promoted a canonical transformation that shows directly that the SCB is composed of two Floreanini-Jackiw's particles with the same chirality which spectrum is a vacuum-like one. As another conflictive result we have proved that a Wess-Zumino term used in the literature consists of the scalar field, once again denying the assertion that the WZ term adds a new degree of freedom to the SCB theory in order to modify the physics of the system.Comment: 6 pages, Revtex. Final version to appear in Physical Review

Features and frequency of use of electronic health records in primary care across 20 countries:a cross-sectional study

Objectives: Variation exists in the capabilities of electronic healthcare records (EHRs) systems and the frequency of their use by primary care physicians (PCPs) from different settings. We aimed to examine the factors associated with everyday EHRs use by PCPs, characterise the EHRs features available to PCPs, and to identify the impact of practice settings on feature availability. Study design: Cross-sectional study. Methods: PCPs from 20 countries completed cross-sectional online survey between June and September 2020. Responses which reported frequency of EHRs use were retained. Associations between everyday EHRs use and PCP and practice factors (country, urbanicity, and digital maturity) were explored using multivariable logistic regression analyses. The effect of practice factors on the variation in availability of ten EHRs features was estimated using Cramer's V. Results: Responses from 1520 out of 1605 PCPs surveyed (94·7%) were retained. Everyday EHRs use was reported by 91·2% of PCPs. Everyday EHRs use was associated with PCPs working &gt;28 h per week, having more years of experience using EHRs, country of employment, and higher digital maturity. EHRs features concerning entering, and retrieving data were available to most PCPs. Few PCPs reported having access to tools for ‘interactive patient education’ (37·3%) or ‘home monitoring and self-testing of chronic conditions’ (34·3%). Country of practice was associated with availability of all EHRs features (Cramer's V range: 0·2–0·6), particularly with availability of tools enabling patient EHRs access (Cramer's V: 0·6, P &lt; 0.0001). Greater feature availability of EHRs features was observed with greater digital maturity. Conclusions: EHRs features intended for patient use were uncommon across countries and levels of digital maturity. Systems-level research is necessary to identify the country-specific barriers impeding the implementation of EHRs features in primary care, particularly of EHRs features enabling patient interaction with EHRs, to develop strategies to improve systems-wide EHRs use.</p