A novel regulator of the p53-mediated mitochondrial apoptotic pathway

The p53 tumor suppressor protein induces apoptosis in response to genotoxic and environmental stress. Recent studies have revealed the existence of a transcription-independent mitochondrial p53 apoptosis pathway, however the mechanism regulating p53 translocation to mitochondria and subsequent initiation of apoptosis was not known. Here, we show that Tid1, also known as mtHsp40 or Dnaja3, interacts with p53 and directs its translocation to mitochondria in cells exposed to hypoxia. Overexpression of Tid1 in tumor cells promoted mitochondrial localization of both wildtype and mutant forms of p53 and was able to restore the pro-apoptotic activity of mutant p53 proteins that were otherwise unable to induce apoptosis. Tid1's mitochondrial signal sequence and DnaJ domain were both required for the movement of the p53-Tid1 complex from the cytosol to the mitochondria. Our findings establish Tid1 as a novel regulator of p53 localization and apoptotic function

In Vitro Chemosensitivity Using the Histoculture Drug Response Assay in Human Epithelial Ovarian Cancer

The choice of chemotherapeutic drugs to treat patients with epithelial ovarian cancer has not depended on individual patient characteristics. We have investigated the correlation between in vitro chemosensitivity, as determined by the histoculture drug response assay (HDRA), and clinical responses in epithelial ovarian cancer. Fresh tissue samples were obtained from 79 patients with epithelial ovarian cancer. The sensitivity of these samples to 11 chemotherapeutic agents was tested using the HDRA method according to established methods, and we analyzed the results retrospectively. HDRA showed that they were more chemosensitive to carboplatin, topotecan and belotecan, with inhibition rates of 49.2%, 44.7%, and 39.7%, respectively, than to cisplatin, the traditional drug of choice in epithelial ovarian cancer. Among the 37 patients with FIGO stage Ⅲ/Ⅳ serous adenocarcinoma who were receiving carboplatin combined with paclitaxel, those with carboplatin-sensitive samples on HDRA had a significantly longer median disease-free interval than patients with carboplatin- resistant samples (23.2 vs. 13.8 months, p＜0.05), but median overall survival did not differ significantly (60.4 vs. 37.3 months, p＝0.621). In conclusion, this study indicates that HDRA could provide useful information for designing individual treatment strategies in patients with epithelial ovarian cancer

Electrogenic transport and K(+) ion channel expression by the human endolymphatic sac epithelium.

The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters, and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K(+) channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K(+) channels in the electrogenic transport of human ES epithelium. The identified K(+) channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2, and KCNK6, and the K(+) transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid

Linear-Gompertz Model-Based Regression of Photovoltaic Power Generation by Satellite Imagery-Based Solar Irradiance

A simple yet accurate photovoltaic (PV) performance curve as a function of satellite-based solar irradiation is necessary to develop a PV power forecasting model that can cover all of South Korea, where more than 35,000 PV power plants are currently in operation. In order to express the nonlinear power output of the PV module with respect to the hourly global horizontal irradiance derived from satellite images, this study employed the Gompertz model, which is composed of three parameters and the sigmoid equation. The nonphysical behavior of the Gompertz model within the low solar irradiation range was corrected by combining a linear equation with the same gradient at the conjoint point. The overall fitness of Linear-Gompertz regression to the 242 PV power plants representing the country was R2 = 0.85 and nRMSE = 0.09. The Gompertz model coefficients showed normal distributions and equivariance of standard deviations of less than 15% by year and by season. Therefore, it can be conjectured that the Linear-Gompertz model represents the whole country’s PV system performance curve. In addition, the Gompertz coefficient C, which controls the growth rate of the curve, showed a strong correlation with the capacity factor, such that the regression equation for the capacity factor could be derived as a function of the three Gompertz model coefficients with a fitness of R2 = 0.88.This work was conducted under the framework of the Research and Development Program of the Korea Institute of Energy Research (C0-2407)