Barrettbille7694
This database will be updated every three months. The MusiteDeep server is available at https//www.musite.net. The stand-alone tools for locally using MusiteDeep are available at https//github.com/duolinwang/MusiteDeep_web. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this is accomplished include AR amplification and expression of AR splice variants, demonstrating that AR remains a key therapeutic target in advanced disease. For the first time we show that IKBKE drives AR signalling in advanced PC. Significant inhibition of AR regulated gene expression was observed upon siRNA-mediated IKBKE depletion or pharmacological inhibition due to inhibited AR gene expression in multiple cell line models including a LNCaP derivative cell line resistant to the anti-androgen, enzalutamide (LNCaP-EnzR). Phenotypically, this resulted in significant inhibition of proliferation, migration and colony forming ability suggesting that targeting IKBKE could circumvent resistance to AR targeting therapies. Indeed, pharmacological inhibition in the CWR22Rv1 xenograft mouse model reduced tumour size and enhanced survival. Critically, this was validated in patient-derived explants where enzymatic inactivation of IKBKE reduced cell proliferation and AR expression. Apoptosis inhibitor Mechanistically, we provide evidence that IKBKE regulates AR levels via Hippo pathway inhibition to reduce c-MYC levels at cis-regulatory elements within the AR gene. Thus, IKBKE is a therapeutic target in advanced PC suggesting repurposing of clinically tested IKBKE inhibitors could be beneficial to castrate resistant PC patients. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Transcription factors (TFs) regulate the expression of gene expression. The binding specificities of many TFs have been deciphered and summarized as position-weight matrices, also called TF motifs. Despite the availability of hundreds of known TF motifs in databases, it remains non-trivial to quickly query and visualize the enrichment of known TF motifs in genomic regions of interest. Towards this goal, we developed TFmotifView, a web server that allows to study the distribution of known TF motifs in genomic regions. Based on input genomic regions and selected TF motifs, TFmotifView performs an overlap of the genomic regions with TF motif occurrences identified using a dynamic P-value threshold. TFmotifView generates three different outputs (i) an enrichment table and scatterplot calculating the significance of TF motif occurrences in genomic regions compared to control regions, (ii) a genomic view of the organisation of TF motifs in each genomic region and (iii) a metaplot summarizing the position of TF motifs relative to the center of the regions. TFmotifView will contribute to the integration of TF motif information with a wide range of genomic datasets towards the goal to better understand the regulation of gene expression by transcription factors. TFmotifView is freely available at http//bardet.u-strasbg.fr/tfmotifview/. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.OBJECTIVES Heterogeneity in successful aging has been found across countries. Yet, comparable evidence is sparse except in North America and Europe. Extending prior research, this study examined the prevalence and correlates of successful aging in East Asian China, Korea, and Japan. METHOD We used harmonized datasets from national surveys. A total of 6,479 participants (aged between 65 and 75) were analyzed. Using Rowe and Kahn's (1987, 1997) model, successful aging was defined as having no major diseases, no difficulty performing activities of daily living, obtaining a median or higher score on tests of cognitive function, and being actively engaged. RESULTS The average prevalence of successful agers was 17.6%. There were variations in the global and specific measures of successful aging within and across countries, even after controlling for individual sociodemographic factors (age, gender, and education). The odds of aging successfully was highest in Japan and lowest in China, especially in the rural areas. Being younger and males were associated with a higher likelihood of successful agers in both global and specific measures. DISCUSSION This study observed heterogeneity in successful aging in East Asia. To identify policy implications, future research should explore potential societal factors influencing individuals' opportunities for successful aging. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.Virus infection by the Bombyx mori nucleopolyhedrovirus (BmNPV) is the most severe disease in Thai sericultural practice of polyvoltine silkworms. Here, we characterized a newly isolated BmNPV isolated from the Mahasarakham province in Thailand (BmNPV-MSU). The purity and morphology of BmNPV-MSU were examined using light microscopy and scanning electron microscopy. The polyhedral inclusion bodies (PIBs) of BmNPV-MSU appeared in tetragonal, hexagonal, octagonal, and globular forms. The virions were both single and multiple embedded as observed by transmission electron microscopy. We also determined the virulence of BmNPV-MSU for six different Thai polyvoltine strains by LC50 and time to death after infection. The LC50 values of Nang Lai, NK04, and Sam Rong strains were 5.05-1.52 × 107 PIBs per ml and mortality peaked 7- to 8-d after inoculation. For Nang Noi, SP2, and RE05 strains the LC50 values were 7.91-1.82 × 106 PIBs/ml and mortality peaked 4-5 d after inoculation, thus having lower chance of survival to infection by BmNPV-MSU. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.Importance Limbal stem cell transplant (LSCT) can be categorized as direct autologous limbal transplant (AULT), direct allogenic limbal transplant (ALLT), cultivated autologous limbal stem cells transplant (cAULT), and cultivated allogenic limbal stem cells transplant (cALLT). To our knowledge, there is no study directly comparing the outcomes and complications of these procedures. Objective To evaluate the outcomes of different LSCT procedures. Data Source We searched PubMed, EMBASE, Web of Science, and Cochrane without language filter for peer-reviewed articles about LSCT. The latest search was performed on June 30, 2019. Study Selection Clinical studies with the outcome of at least 20 eyes after LSCT were included. Animal studies and studies of other surgical interventions were excluded. Data Extraction and Synthesis Two reviewers independently abstracted the data from each study. Heterogeneity was evaluated with the I2 statistic, and a meta-analysis was performed using the random-effects model. Main Outcomes and Measures Outcome measures included the improvement of ocular surface, visual acuity (VA), and adverse events of recipient eyes and donor eyes.