Abnormal Mammary Gland Development and Growth Retardation in Female Mice and MCF7 Breast Cancer Cells Lacking Androgen Receptor

Phenotype analysis of female mice lacking androgen receptor (AR) deficient (AR−/−) indicates that the development of mammary glands is retarded with reduced ductal branching in the prepubertal stages, and fewer Cap cells in the terminal end buds, as well as decreased lobuloalveolar development in adult females, and fewer milk-producing alveoli in the lactating glands. The defective development of AR−/− mammary glands involves the defects of insulin-like growth factor I–insulin-like growth factor I receptor and mitogen-activated protein kinase (MAPK) signals as well as estrogen receptor (ER) activity. Similar growth retardation and defects in growth factor–mediated Ras/Raf/MAPK cascade and ER signaling are also found in AR−/− MCF7 breast cancer cells. The restoration assays show that AR NH2-terminal/DNA-binding domain, but not the ligand-binding domain, is essential for normal MAPK function in MCF7 cells, and an AR mutant (R608K), found in male breast cancer, is associated with the excessive activation of MAPK. Together, our data provide the first in vivo evidence showing that AR-mediated MAPK and ER activation may play important roles for mammary gland development and MCF7 breast cancer cell proliferation

GPR43 protects human A16 cardiomyocytes against hypoxia/reoxygenation injury by regulating nesfatin1

Background: The purpose of this study is to investigate the regulatory role of G coupled-protein receptor 43 (GPR43) during myocardial ischemia/reperfusion (I/R) injury and to explore the relevant molecular mechanism. Materials and methods: AC16 hypoxia/reoxygenation (H/R) model was established to simulate I/R injury in vitro. Gain- and loss-of-function experiments were conducted to regulate GPR43 or nesfatin1 expression. Cell viability and apoptosis was examined adopting CCK-8 and TUNEL assays. Commercial kits were applied for detecting ROS and inflammatory cytokines. Quantitative real-time PCR (qRT-PCR) and western blotting were conducted to measure the expression level of critical genes and proteins. Results: GPR43 was downregulated in H/R-mediated AC16 cells. GPR43 overexpression or the GPR43 agonist greatly inhibited H/R-induced cell viability loss, cell apoptosis, and excessive production of ROS and pro-inflammatory cytokines in AC16 cardiomyocytes. Co-immunoprecipitation (Co-IP) assay identified an interaction between GPR43 and nesfatin1, and GPR43 could positively regulate nesfatin1. In addition, the protective role of GPR43 against H/R injury was partly abolished upon nesfatin1 knockdown. Eventually, GPR43 could inhibit H/R-stimulated JNK/P38 MAPK signaling in AC16 cells, which was also hindered by nesfatin1 knockdown. Conclusions: Our findings demonstrated the protective role of GPR43 against H/R-mediated cardiomyocytes injury through up-regulating nesfatin1, providing a novel target for the prevention and treatment of myocardial I/R injury

A Road Map Refinement Method Using Delaunay Triangulation for Big Trace Data

With the rapid development of urban transportation, people urgently need high-precision and up-to-date road maps. At the same time, people themselves are an important source of road information for detailed map construction, as they can detect real-world road surfaces with GPS devices in the course of their everyday life. Big trace data makes it possible and provides a great opportunity to extract and refine road maps at relatively low cost. In this paper, a new refinement method is proposed for incremental road map construction using big trace data, employing Delaunay triangulation for higher accuracy during the GPS trace stream fusion process. An experiment and evaluation were carried out on the GPS traces collected by taxis in Wuhan, China. The results show that the proposed method is practical and improves upon existing incremental methods in terms of accuracy

Fine-grained analysis of traffic congestions at the turning level using GPS traces

For the issue that existing approaches on studying traffic conditions using GPS traces lack of detailed analysis of traffic congestion, this paper puts forward an approach for detecting traffic congestion events based on taxis' GPS traces at turning level. Firstly, this approach analyzed taxis' operating patterns and filtered valid traces. Then this approach detected traffic congestion traces of three different intensities:mild congestion, moderate congestion and serious congestion, based on analyzing traffic conditions from the filtered valid trace segments. Finally, traffic flow speed, congestion time and congestion distance of each turning direction at an intersection were explored at a fine-grained level. The experimental results show that the proposed approach is able to detect congestions of different intensities and analyze congestion events at turning level