Leeenglish9907

Rescue experiments demonstrated that miRNA binding and 3' mutagenesis contribute to replication through mutually exclusive mechanisms. Altogether, our findings suggest that pestiviruses, although capable of miRNA-independent replication, took advantage of miRNAs as essential host factors, suggesting a favorable path during evolutionary adaptation. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.The Omics Discovery Index is an open source platform that can be used to access, discover and disseminate omics datasets. OmicsDI integrates proteomics, genomics, metabolomics, models and transcriptomics datasets. Using an efficient indexing system, OmicsDI integrates different biological entities including genes, transcripts, proteins, metabolites and the corresponding publications from PubMed. In addition, it implements a group of pipelines to estimate the impact of each dataset by tracing the number of citations, reanalysis and biological entities reported by each dataset. Here, we present the OmicsDI REST interface (www.omicsdi.org/ws/) to enable programmatic access to any dataset in OmicsDI or all the datasets for a specific provider (database). Clients can perform queries on the API using different metadata information such as sample details (species, tissues, etc), instrumentation (mass spectrometer, sequencer), keywords and other provided annotations. In addition, we present two different libraries in R and Python to facilitate the development of tools that can programmatically interact with the OmicsDI REST interface. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.We have previously found that UV-induced DNA damage causes hyperphosphorylation of the carboxy terminal domain (CTD) of RNA polymerase II (RNAPII), inhibition of transcriptional elongation and changes in alternative splicing (AS) due to kinetic coupling between transcription and splicing. In an unbiased search for protein kinases involved in the AS response to DNA damage, we have identified glycogen synthase kinase 3 (GSK-3) as an unforeseen participant. Unlike Cdk9 inhibition, GSK-3 inhibition only prevents CTD hyperphosphorylation triggered by UV but not basal phosphorylation. This effect is not due to differential degradation of the phospho-CTD isoforms and can be reproduced, at the AS level, by overexpression of a kinase-dead GSK-3 dominant negative mutant. GSK-3 inhibition abrogates both the reduction in RNAPII elongation and changes in AS elicited by UV. We show that GSK-3 phosphorylates the CTD in vitro, but preferentially when the substrate is previously phosphorylated, consistently with the requirement of a priming phosphorylation reported for GSK-3 efficacy. In line with a role for GSK-3 in the response to DNA damage, GSK-3 inhibition prevents UV-induced apoptosis. In summary, we uncover a novel role for a widely studied kinase in key steps of eukaryotic transcription and pre-mRNA processing. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.INTRODUCTION The relationship between smoking and general body ache has been shown to be bidirectional. The specific association between tobacco consumption and orofacial pain remains unclear, however. The objective of this systematic review was to explore the association between pain related to diseases of the oral cavity and use of tobacco. METHODS A systematic search of PubMed, Embase, Web of Science, and Cochrane databases was carried out in September 2019. Tobacco exposure was included irrespective of the method of consumption (smokeless and smoked tobacco), and frequency of the habit. The outcome was defined as clinically-diagnosed or self-reported pain in the orofacial region, with no limitation in the duration of the condition or the site of the pain. RESULTS Altogether, eight studies were selected, with three of them demonstrating good methodology and none of them being of poor quality. Meta-analysis of six studies showed that orofacial pain was significantly worse in tobacco (smoked and smokeless) uonsumers. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.OBJECTIVES Apathy is a potential predictor of dementia in older adults, but this investigation has been limited to older adults with a preexisting neurological illness like mild cognitive impairment (MCI), stroke or Parkinson's disease. The objective of this study was to investigate the association between apathy at baseline and incident predementia syndromes, including MCI and motoric cognitive risk syndrome (MCR), subjective cognitive complaints and slow gait, in community dwelling older adults. METHODS We prospectively studied the association between apathy (using the 3-item subscale of the Geriatric Depression Scale (GDS3A)) and incident cognitive disorders in 542 community dwelling older adults enrolled in the Central Control of Mobility in Aging study using Cox proportional hazard models. Associations were reported as hazard ratio (HR) with 95% confidence intervals (CI), adjusting for age, education, baseline cognitive performance and depressive symptoms. Selleckchem PMA activator RESULTS Apathy was associated with incident MCR (HR 2.39, 95% CI 1.10-5.20), but not predementia syndromes overall nor MCI. In sensitivity analyses of MCI subtypes, apathy was associated with non-amnestic MCI (HR 2.44, 95% CI 1.14-5.22), but not amnestic MCI. LIMITATIONS Our study was limited by a short follow up time (median 13.6 months IQR 29.8) and a brief subscale measurement of apathy, GDS3A. DISCUSSION In our study, apathy predicted MCR but not MCI in community dwelling older adults. These results and the current literature suggest that apathy is an early risk factor for dementia. Additionally, apathy may be a novel treatment target that could forestall the disability of dementia. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.AIMS The evidence are not conclusive that a small incremental increase in door-to-balloon (D2B) time leads to a significant increase in death of ST-elevation myocardial (STEMI) patients. In a previous study we described a quality improvement intervention that reduced D2B time in 333 patients with STEMI. The aim of the current study was to compare mortality rates of the patients, before and after the intervention. METHODS AND RESULTS We examined the survival of 133 consecutive patients with STEMI treated prior to an intervention to decrease D2B time and 200 treated after the intervention. The mortality rate was the same before and after the quality intervention. The median D2B time for the entire cohort was 55 minutes. The number of patients with D2B time >55 minutes prior to the intervention was 82/133 (61%) and after the intervention 74/200 (37%) p 55 minutes was 3.7 (1.3-10.4). CONCLUSIONS Mortality and non-fatal complications did not differ significantly between STEMI patients before and after a quality improvement intervention.