Androgen Regulation of 5α-Reductase Isoenzymes in Prostate Cancer: Implications for Prostate Cancer Prevention

The enzyme 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), performs key functions in the androgen receptor (AR) signaling pathway. The three isoenzymes of 5α-reductase identified to date are encoded by different genes: SRD5A1, SRD5A2, and SRD5A3. In this study, we investigated mechanisms underlying androgen regulation of 5α-reductase isoenzyme expression in human prostate cells. We found that androgen regulates the mRNA level of 5α-reductase isoenzymes in a cell type–specific manner, that such regulation occurs at the transcriptional level, and that AR is necessary for this regulation. In addition, our results suggest that AR is recruited to a negative androgen response element (nARE) on the promoter of SRD5A3 in vivo and directly binds to the nARE in vitro. The different expression levels of 5α-reductase isoenzymes may confer response or resistance to 5α-reductase inhibitors and thus may have importance in prostate cancer prevention

Performance analytical modelling of mobile edge computing for mobile vehicular applications: a worst-case perspective

Quantitative performance analysis plays a pivotal role in theoretically investigating the performance of Vehicular Edge Computing (VEC) systems. Although considerable research efforts have been devoted to VEC performance analysis, all of the existing analytical models were designed to derive the average system performance, paying insufficient attention to the worst-case performance analysis, which hinders the practical deployment of VEC systems to support mission-critical vehicular applications, such as collision avoidance. To bridge this gap, we develop an original performance analytical model by virtue of Stochastic Network Calculus (SNC) to investigate the worst-case end-to-end performance of VEC systems. Specifically, to capture the bursty feature of task generation, an innovative bivariate Markov Chain is firstly established and rigorously analysed to derive the stochastic task envelope. Then, an effective service curve is created to investigate the severe resource competition among vehicular applications. Driven by the stochastic task envelope and effective service curve, a closed-form end-to-end analytical model is derived to obtain the latency bound for VEC systems. Extensive simulation experiments are conducted to validate the accuracy of the proposed analytical model under different system configurations. Furthermore, we exploit the proposed analytical model as a cost-effective tool to investigate the resource allocation strategies in VEC systems

Functional Cardiomyocytes Derived from Isl1 Cardiac Progenitors via Bmp4 Stimulation

<div><p>As heart failure due to myocardial infarction remains a leading cause of morbidity worldwide, cell-based cardiac regenerative therapy using cardiac progenitor cells (CPCs) could provide a potential treatment for the repair of injured myocardium. As adult CPCs may have limitations regarding tissue accessibility and proliferative ability, CPCs derived from embryonic stem cells (ESCs) could serve as an unlimited source of cells with high proliferative ability. As one of the CPCs that can be derived from embryonic stem cells, Isl1 expressing cardiac progenitor cells (Isl1-CPCs) may serve as a valuable source of cells for cardiac repair due to their high cardiac differentiation potential and authentic cardiac origin. In order to generate an unlimited number of Isl1-CPCs, we used a previously established an ESC line that allows for isolation of Isl1-CPCs by green fluorescent protein (GFP) expression that is directed by the <i>mef2c</i> gene, specifically expressed in the Isl1 domain of the anterior heart field. To improve the efficiency of cardiac differentiation of Isl1-CPCs, we studied the role of Bmp4 in cardiogenesis of Isl1-CPCs. We show an inductive role of Bmp directly on cardiac progenitors and its enhancement on early cardiac differentiation of CPCs. Upon induction of Bmp4 to Isl1-CPCs during differentiation, the cTnT+ cardiomyocyte population was enhanced 2.8±0.4 fold for Bmp4 treated CPC cultures compared to that detected for vehicle treated cultures. Both Bmp4 treated and untreated cardiomyocytes exhibit proper electrophysiological and calcium signaling properties. In addition, we observed a significant increase in Tbx5 and Tbx20 expression in differentiation cultures treated with Bmp4 compared to the untreated control, suggesting a link between Bmp4 and Tbx genes which may contribute to the enhanced cardiac differentiation in Bmp4 treated cultures. Collectively these findings suggest a cardiomyogenic role for Bmp4 directly on a pure population of Isl1 expressing cardiac progenitors, which could lead to enhancement of cardiac differentiation and engraftment, holding a significant therapeutic value for cardiac repair in the future.</p></div

Comparison of action potential parameters for Isl1-CPC derived cardiomyocyte cultures in the absence or presence of Bmp4 treatment (n = 4).

<p>Comparison of action potential parameters for Isl1-CPC derived cardiomyocyte cultures in the absence or presence of Bmp4 treatment (n = 4).</p