548 research outputs found
Women Reproductive Rights in India: Prospective Future.
Reproductive rights were established as a subset of the human rights. Parents have a basic human right to determine freely and responsibly the number and the spacing of their children. Issues regarding the reproductive rights are vigorously contested, regardless of the population’s socioeconomic level, religion or culture. Following review article discusses reproductive rights with respect to Indian context focusing on socio economic and cultural aspects. Also discusses sensitization of government and judicial agencies in protecting the reproductive rights with special focus on the protecting the reproductive rights of people with disability (mental illness and mental retardation)
Heat transfer in viscoplastic boundary layer flow from a vertical permeable cone with momentum and thermal wall slip : numerical study
A mathematical model is presented for the laminar free convection boundary layer flow of Casson viscoplastic non-Newtonian fluid external to a vertical penetrable circular cone in the presence of thermal and hydrodynamic slip conditions. The cone surface is maintained at non-uniform surface temperature. The boundary layer conservation equations, which are parabolic in nature, are transformed into non-dimensional form via appropriate similarity variables, and the emerging boundary value problem is solved computationally with the second order accurate implicit Keller-box finite-difference scheme. The influence of velocity (momentum) slip, thermal slip and Casson non-Newtonian parameter on velocity, temperature, skin friction and Nusselt number are illustrated graphically. Validation of solutions with earlier published work is included. The computations show that the flow near the cone surface is strongly decelerated with increasing momentum slip whereas the temperature and thermal boundary layer thickness are increased. Increasing Casson parameter generally decelerates the flow and also decreases temperatures. Both velocity and thermal boundary layer thickness are reduced with greater Prandtl number. The study is relevant to petro-chemical engineering (polymer) processing systems
BRCA1 Mutation Leads to Deregulated Ubc9 Levels which Triggers Proliferation and Migration of Patient-Derived High Grade Serous Ovarian Cancer and Triple Negative Breast Cancer Cells
Women who carry a germline mutation in BRCA1 gene typically develop triple negative breast cancers (TNBC) and high grade serous ovarian cancers (HGSOC). Previously, we reported that wild type BRCA1 proteins, unlike the disease-associated mutant BRCA1 proteins to bind the sole sumo E2-conjugating enzyme Ubc9. In this study, we have used clinically relevant cell lines with known BRCA1 mutations and report the in-vivo association of BRCA1 and Ubc9 in normal mammary epithelial cells but not in BRCA1 mutant HGSOC and TNBC cells by immunofluorescence analysis. BRCA1-mutant HGSOC / TNBC cells and ovarian tumor tissues showed increased expression of Ubc9 compared to BRCA1 reconstituted HGSOC, normal mammary epithelial cells and matched normal ovarian tissues. Knockdown of Ubc9 expression resulted in decreased proliferation and migration of BRCA1 mutant TNBC and HGSOC cells. This is the first study demonstrating the functional link between BRCA1 mutation, high Ubc9 expression and increased migration of HGSOC and TNBC cells. High Ubc9 expression due to BRCA1 mutation may trigger an early growth and transformation advantage to normal breast and ovarian epithelial cells resulting in aggressive cancers. Future work will focus on studying whether Ubc9 expression could show a positive correlation with BRCA1 linked HGSOC and basal like TNBC phenotype
On the Schoenberg Transformations in Data Analysis: Theory and Illustrations
The class of Schoenberg transformations, embedding Euclidean distances into
higher dimensional Euclidean spaces, is presented, and derived from theorems on
positive definite and conditionally negative definite matrices. Original
results on the arc lengths, angles and curvature of the transformations are
proposed, and visualized on artificial data sets by classical multidimensional
scaling. A simple distance-based discriminant algorithm illustrates the theory,
intimately connected to the Gaussian kernels of Machine Learning
Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family
Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al
Aurora-A overexpression enhances cell-aggregation of Ha-ras transformants through the MEK/ERK signaling pathway
<p>Abstract</p> <p>Background</p> <p>Overexpression of Aurora-A and mutant Ras (Ras<sup>V12</sup>) together has been detected in human bladder cancer tissue. However, it is not clear whether this phenomenon is a general event or not. Although crosstalk between Aurora-A and Ras signaling pathways has been reported, the role of these two genes acting together in tumorigenesis remains unclear.</p> <p>Methods</p> <p>Real-time PCR and sequence analysis were utilized to identify Ha- and Ki-<it>ras </it>mutation (Gly -> Val). Immunohistochemistry staining was used to measure the level of Aurora-A expression in bladder and colon cancer specimens. To reveal the effect of overexpression of the above two genes on cellular responses, mouse NIH3T3 fibroblast derived cell lines over-expressing either Ras<sup>V12</sup>and wild-type Aurora-A (designated WT) or Ras<sup>V12 </sup>and kinase-inactivated Aurora-A (KD) were established. MTT and focus formation assays were conducted to measure proliferation rate and focus formation capability of the cells. Small interfering RNA, pharmacological inhibitors and dominant negative genes were used to dissect the signaling pathways involved.</p> <p>Results</p> <p>Overexpression of wild-type Aurora-A and mutation of Ras<sup>V12 </sup>were detected in human bladder and colon cancer tissues. Wild-type Aurora-A induces focus formation and aggregation of the Ras<sup>V12 </sup>transformants. Aurora-A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK, ERK of WT cells. Finally, the Ras/MEK/ERK signaling pathway is responsible for Aurora-A induced aggregation of the Ras<sup>V12 </sup>transformants.</p> <p>Conclusion</p> <p>Wild-type-Aurora-A enhances focus formation and aggregation of the Ras<sup>V12 </sup>transformants and the latter occurs through modulating the Ras/MEK/ERK signaling pathway.</p
Implementation of Dual-Source RF Excitation in 3 T MR-Scanners Allows for Nearly Identical ADC Values Compared to 1.5 T MR Scanners in the Abdomen
Background: To retrospectively and prospectively compare abdominal apparent diffusion coefficient (ADC) values obtained within in a 1.5 T system and 3 T systems with and without dual-source parallel RF excitation techniques. Methodology/Principal Findings: After IRB approval, diffusion-weighted (DW) images of the abdomen were obtained on three different MR systems (1.5 T, a first generation 3 T, and a second generation 3 T which incorporates dual-source parallel RF excitation) on 150 patients retrospectively and 19 volunteers (57 examinations total) prospectively. Seven regions of interest (ROI) were throughout the abdomen were selected to measure the ADC. Statistical analysis included independent two-sided t-tests, Mann-Whitney U tests and correlation analysis. In the DW images of the abdomen, mean ADC values were nearly identical with nonsignificant differences when comparing the 1.5 T and second generation 3 T systems in all seven anatomical regions in the patient population and six of the seven in the volunteer population (p.0.05 in all distributions). The strength of correlation measured in the volunteer population between the two scanners in the kidneys ranged from r = 0.64–0.88 and in the remaining regions (besides the spleen), r.0.85. In the patient population the first generation 3 T scanner had different mean ADC values with significant differences (p,0.05) compared to the other two scanners in each of the seven distributions. In the volunteer population, the kidneys shared similar ADC mean values in comparison to the other two scanners with nonsignificant differences
Novel molecular approach to define pest species status and tritrophic interactions from historical Bemisia specimens
Museum specimens represent valuable genomic resources for understanding host-endosymbiont/parasitoid evolutionary relationships, resolving species complexes and nomenclatural problems. However, museum collections suffer DNA degradation, making them challenging for molecular-based studies. Here, the mitogenomes of a single 1912 Sri Lankan Bemisia emiliae cotype puparium, and of a 1942 Japanese Bemisia puparium are characterised using a Next-Generation Sequencing approach. Whiteflies are small sap-sucking insects including B. tabaci pest species complex. Bemisia emiliae’s draft mitogenome showed a high degree of homology with published B. tabaci mitogenomes, and exhibited 98–100% partial mitochondrial DNA Cytochrome Oxidase I (mtCOI) gene identity with the B. tabaci species known as Asia II-7. The partial mtCOI gene of the Japanese specimen shared 99% sequence identity with the Bemisia ‘JpL’ genetic group. Metagenomic analysis identified bacterial sequences in both Bemisia specimens, while hymenopteran sequences were also identified in the Japanese Bemisia puparium, including complete mtCOI and rRNA genes, and various partial mtDNA genes. At 88–90% mtCOI sequence identity to Aphelinidae wasps, we concluded that the 1942 Bemisia nymph was parasitized by an Eretmocerus parasitoid wasp. Our approach enables the characterisation of genomes and associated metagenomic communities of museum specimens using 1.5 ng gDNA, and to infer historical tritrophic relationships in Bemisia whiteflies.© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
The attached file is the published pdf
Risk Factors for Breast Cancer and Expression of Insulin-Like Growth Factor-2 (IGF-2) in Women with Breast Cancer in Wuhan City, China
PURPOSE: The purpose of this study was to explore the risk factors for breast cancer and establish the expression rate of IGF-2 in female patients. METHODS: A case control study with 500 people in case group and 500 people in control group. A self-administered questionnaire was used to investigate risk factors for breast cancer. All cases were interviewed during a household survey. Immune-histochemical method was used to inspect the expression of IGF-2 in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue). RESULTS: Multivariate adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. High body mass index (OR = 1.012,95%CI = 1.008-1.016), working attributes (OR = 1.004, 95%CI = 1.002 = 1.006), long menstrual period (OR = 1.007, 95%CI = 1.005-1.009), high parity OR = 1.003, 95%CI = 1.001-1.005) , frequent artificial abortion (OR = 1.004, 95%CI = 1.001-1.005), family history of cancer (OR = 1.003, 95%CI = 1.000-1.005), period of night shift (OR = 1.003, 95%CI = 1.001-1.006), live in high risk environment (OR = 1.005, 95%CI = 1.002-1.008), and family problems (OR = 1.010, 95%CI = 1.005-1.014) were associated with increased risk for breast cancer. In this study, good sleeping status, positive coping strategies, subjective support, and utility degree of social support were associated with reduced risk for breast cancer (OR = 0.998, 0.997, 0.985, 0.998 respectively; 95%CI = 0.996-1.000, 0.994-1.000, 0.980-0.989, 0.996-1.000, respectively). In benign breast lesions, breast cancer and tumor-adjacent tissue, IGF-2 was mainly expressed in the cytoplasm, but its expression rate was different (p<0.05). CONCLUSIONS: The incidence of breast cancer is a common result of multiple factors. IGF-2 is involved in the development of breast cancer, and its expression varies in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue)
Inhibition of E2-induced expression of BRCA1 by persistent organochlorines
BACKGROUND: Environmental persistent organochlorines (POCs) biomagnify in the food chain, and the chemicals are suspected of being involved in a broad range of human malignancies. It is speculated that some POCs that can interfere with estrogen receptor-mediated responses are involved in the initiation and progression of human breast cancer. The tumor suppressor gene BRCA1 plays a role in cell-cycle control, in DNA repair, and in genomic stability, and it is often downregulated in sporadic mammary cancers. The aim of the present study was to elucidate whether POCs have the potential to alter the expression of BRCA1. METHODS: Using human breast cancer cell lines MCF-7 and MDA-MB-231, the effect on BRCA1 expression of chemicals belonging to different classes of organochlorine chemicals (the pesticide toxaphene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and three polychlorinated biphenyls [PCB#138, PCB#153 and PCB#180]) was measured by a reporter gene construct carrying 267 bp of the BRCA1 promoter. A twofold concentration range was analyzed in MCF-7, and the results were supported by northern blot analysis of BRCA1 mRNA using the highest concentrations of the chemicals. RESULTS: All three polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin reduced 17β-estradiol (E2)-induced expression as well as basal reporter gene expression in both cell lines, whereas northern blot analysis only revealed a downregulation of E2-induced BRCA1 mRNA expression in MCF-7 cells. Toxaphene, like E2, induced BRCA1 expression in MCF-7. CONCLUSION: The present study shows that some POCs have the capability to alter the expression of the tumor suppressor gene BRCA1 without affecting the cell-cycle control protein p21(Waf/Cip1). Some POCs therefore have the potential to affect breast cancer risk
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