Expression Patterns of Non-Coding Spliced Transcripts from Human Endogenous Retrovirus HERV-H Elements in Colon Cancer

BACKGROUND: Up-regulation of the most abundant H family human endogenous retrovirus (HERV-H), especially env-related transcripts, correlates with colon cancer. However, expression pattern of spliced non-coding transcripts of HERV-H is not clear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, expression of HERV-H spliced transcripts in colon cancer was investigated by a RT-PCR strategy using primers targeting the tRNA(His) primer-binding site and the R region in the 3' long terminal repeat (LTR), followed by cloning and sequencing of the amplicons. Sequences were then assigned to individual HERV-H loci by employing private nucleotide differences between loci. Different expression patterns of HERV-H spliced transcripts from distinct active elements were found in colon cancer cell lines HT29, LS 174T, RKO, SW480 and SW620. Furthermore, the expression patterns in SW480 and RKO were significantly changed by demethylation treatment. Interestingly, more HERV-H elements were found to be transcriptionally active in colon tumor tissues than in adjacent normal tissues (14 vs. 7). CONCLUSIONS/SIGNIFICANCE: This is the first research to study the character of expression of non-coding spliced transcripts of HERV-H elements in colon cancer. Expression patterns of HERV-H spliced transcripts differed among colon cancer cell lines and could be affected by genomic DNA methylation levels. More importantly, besides the commonly accepted view of up-regulation of HERV-H expression in colon tumor tissues, we found more active HERV-H loci in colon tumor as compared with adjacent normal tissues

Distinct Determinants in HIV-1 Vif and Human APOBEC3 Proteins Are Required for the Suppression of Diverse Host Anti-Viral Proteins

APOBEC3G (A3G) and related cytidine deaminases of the APOBEC3 family of proteins are potent inhibitors of many retroviruses, including HIV-1. Formation of infectious HIV-1 requires the suppression of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the common mechanism of recruiting the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized.In the present study, we have demonstrated that the regions of APOBEC3F (A3F) that are required for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD) of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation. We also observed that the domains of HIV-1 Vif that are uniquely required for its functional interaction with full-length A3F are also required for the degradation of the C-CDD of A3F; in contrast, those Vif domains that are uniquely required for functional interaction with A3G are not required for the degradation of the C-CDD of A3F. Interestingly, the HIV-1 Vif domains required for the degradation of A3F are also required for the degradation of A3C and A3DE. On the other hand, the Vif domains uniquely required for the degradation of A3G are dispensable for the degradation of cytidine deaminases A3C and A3DE.Our data suggest that distinct regions of A3F and A3G are targeted by HIV-1 Vif molecules. However, HIV-1 Vif suppresses A3F, A3C, and A3DE through similar recognition determinants, which are conserved among Vif molecules from diverse HIV-1 strains. Mapping these determinants may be useful for the design of novel anti-HIV inhibitors

Weather Support for the 2008 Olympic and Paralympic Sailing Events

The Beijing 2008 Olympic and Paralympic Sailing Competitions (referred to as OPSC hereafter) were held at Qingdao during August 9–23 and September 7–13 2008, respectively. The Qingdao Meteorological Bureau was the official provider of weather support for the OPSC. Three-dimensional real-time information with high spatial-temporal resolution was obtained by the comprehensive observation system during the OPSC, which included weather radars, wind profile radars, buoys, automated weather stations, and other conventional observations. The refined forecasting system based on MM5, WRF, and statistical modules provided point-specific hourly wind forecasts for the five venues, and the severe weather monitoring and forecasting system was used in short-term forecasts and nowcasts for rainstorms, gales, and hailstones. Moreover, latest forecasting products, warnings, and weather information were communicated conveniently and timely through a synthetic, speedy, and digitalized network system to different customers. Daily weather information briefings, notice boards, websites, and community short messages were the main approaches for regatta organizers, athletes, and coaches to receive weather service products at 8:00 PM of each day and whenever new updates were available. During the period of OPSC, almost one hundred people were involved in the weather service with innovative service concept, and the weather support was found to be successful and helpful to the OPSC

High Prevalence and Genetic Diversity of HCV among HIV-1 Infected People from Various High-Risk Groups in China

BACKGROUND: Co-infection with HIV-1 and HCV is a significant global public health problem and a major consideration for anti-HIV-1 treatment. HCV infection among HIV-1 positive people who are eligible for the newly launched nationwide anti-HIV-1 treatment program in China has not been well characterized. METHODOLOGY: A nationwide survey of HIV-1 positive injection drug uses (IDU), former paid blood donors (FBD), and sexually transmitted cases from multiple provinces including the four most affected provinces in China was conducted. HCV prevalence and genetic diversity were determined. We found that IDU and FBD have extremely high rates of HCV infection (97% and 93%, respectively). Surprisingly, people who acquired HIV-1 through sexual contact also had a higher rate of HCV infection (20%) than the general population. HIV-1 subtype and HCV genotypes were amazingly similar among FBD from multiple provinces stretching from Central to Northeast China. However, although patterns of overland trafficking of heroin and distinct HIV-1 subtypes could be detected among IDU, HCV genotypes of IDU were more diverse and exhibited significant regional differences. CONCLUSION: Emerging HIV-1 and HCV co-infection and possible sexual transmission of HCV in China require urgent prevention measures and should be taken into consideration in the nationwide antiretroviral treatment program

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside Promotes Expression of the Longevity Gene Klotho

The longevity gene klotho has numerous physiological functions, such as regulating calcium and phosphorus levels, delaying senescence, improving cognition, reducing oxidative stress, and protecting vascular endothelial cells. This study tested whether 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a small molecule with antiaging effects, regulates the expression and physiological effects of klotho. Our results showed that THSG dose-dependently increased the luciferase reporter activity of the klotho gene, reversed the decrease in mRNA and protein expression of klotho which was induced by angiotensin II in NRK-52E renal tubular epithelial cells, and increased klotho mRNA expression in the cerebral cortex, hippocampus, testis, and kidney medulla of spontaneously hypertensive rats. THSG also reduced the number of senescent cells induced by angiotensin II and improved the antioxidant capacity and enhanced the bone strength in vivo. Based on klotho’s role in promoting cognition, regulating bone metabolism, and improving renal function, the effect of THSG on klotho expression will be beneficial to the functional improvement or enhancement of the expressed organs or tissues

A New Fault Diagnosis Method for Unbalanced Data Based on 1DCNN and L2-SVM

In general, the measured health condition data from rolling bearings usually exhibit imbalanced distribution. However, traditional intelligent fault diagnosis methods usually assume that the data categories are balanced. To improve the diagnosis accuracy of unbalanced datasets, a new fault diagnosis method for unbalanced data based on 1DCNN and L2-SVM is proposed in this paper. Firstly, to prevent the minority class samples from being heavily suppressed by the rectified linear unit (ReLU) activation function in the traditional convolutional neural network (CNN), ReLU is improved by linear and scaled exponential linear units (SELUs). Secondly, to solve the problem where the cross-entropy loss treats all input samples equally, it is replaced by the L2-support vector machine (L2-SVM) loss. Furthermore, a dynamic adjustment parameter is introduced to assign less misclassification cost to the majority of class samples. Finally, we add a new modulation factor that reduces the weight of more distinguishable samples to generate more focus on training indiscernible samples. The proposed method is carried out on two kinds of bearing datasets. The experimental results illustrate a significant improvement in recognition accuracy and the higher diagnosis performance of the model when dealing with unbalanced data compared with other intelligent methods