Search results for "informatics"

Identification of an optimized 2′-O-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8

2017

Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic when compared with eukaryotic RNA allow innate immune cells to discriminate between “host” and “foreign” RNA. Ribose 2′-O-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2′-O-methylation has to occur to mediate its inhibitory activity remains largely undefined. On the basis of a naturally occurring 2′-O-methylated RNA sequence, we performed a systematic permutation of the …

Inherent and toxicant-provoked reduction in DNA repair capacity: A key mechanism for personalized risk assessment, cancer prevention and intervention…

2018

Abstract Genomic investigations reveal novel evidence which indicates that genetic predisposition and inherent drug response are key factors for development of cancer and for poor response to therapy. However, mechanisms for these outcomes and interactions with environmental factors have not been well-characterized. Therefore, cancer risk, prevention, intervention and prognosis determinations have still mainly been based on population, rather than on individualized, evaluations. The objective of this review was to demonstrate that a key mechanism which contributes to the determination is inherent and/or toxicant-provoked reduction in DNA repair capacity. In addition, functional and quantita…

2015

The University of Minnesota Biocatalysis/Biodegradation Database and Pathway Prediction System (UM-BBD/PPS) has been a unique resource covering microbial biotransformation pathways of primarily xenobiotic chemicals for over 15 years. This paper introduces the successor system, enviPath (The Environmental Contaminant Biotransformation Pathway Resource), which is a complete redesign and reimplementation of UM-BBD/PPS. enviPath uses the database from the UM-BBD/PPS as a basis, extends the use of this database, and allows users to include their own data to support multiple use cases. Relative reasoning is supported for the refinement of predictions and to allow its extensions in terms of previo…

Reactome graph database: Efficient access to complex pathway data

2018

Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. One of its main priorities is to provide easy and efficient access to its high quality curated data. At present, biological pathway databases typically store their contents in relational databases. This limits access efficiency because there are performance issues associated with queries traversing highly interconnected data. The same data in a graph database can be queried more efficiently. Here we present the rationale behind the adoption of a graph database (Neo4j) as well as the new ContentService (REST API) that provides access to these data. The Neo4j graph database and its qu…

Perspective: Essential study quality descriptors for data from nutritional epidemiologic research

2017

Pooled analysis of secondary data increases the power of research and enables scientific discovery in nutritional epidemiology. Information on study characteristics that determine data quality is needed to enable correct reuse and interpretation of data. This study aims to define essential quality characteristics for data from observational studies in nutrition. First, a literature review was performed to get an insight on existing instruments that assess the quality of cohort, case-control, and cross-sectional studies and dietary measurement. Second, 2 face-to-face workshops were organized to determine the study characteristics that affect data quality. Third, consensus on the data descrip…

Modeling of Myotonic Dystrophy Cardiac Phenotypes in Drosophila

2018

After respiratory distress, cardiac dysfunction is the second most common cause of fatality associated with the myotonic dystrophy (DM) disease. Despite the prevalance of heart failure in DM, physiopathological studies on heart symptoms have been relatively scarce because few murine models faithfully reproduce the cardiac disease. Consequently, only a small number of candidate compounds have been evaluated in this specific phenotype. To help cover this gap Drosophila combines the amenability of its invertebrate genetics with the possibility of quickly acquiring physiological parameters suitable for meaningful comparisons with vertebrate animal models and humans. Here we review available des…

A framework for data-driven adaptive GUI generation based on DICOM

2018

Computer applications for diagnostic medical imaging provide generally a wide range of tools to support physicians in their daily diagnosis activities. Unfortunately, some functionalities are specialized for specific diseases or imaging modalities, while other ones are useless for the images under investigation. Nevertheless, the corresponding Graphical User Interface (GUI) widgets are still present on the screen reducing the image visualization area. As a consequence, the physician may be affected by cognitive overload and visual stress causing a degradation of performances, mainly due to unuseful widgets. In clinical environments, a GUI must represent a sequence of steps for image investi…

AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions

2017

Abstract This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic “hits”. The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (…

Circadian rhythms in the pathogenesis of gastrointestinal diseases

2018

The etiology of digestive pathologies such as irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD) and cancer is not yet fully understood. In recent years, several studies have evidenced circadian variations in mechanisms involved in digestive health. In situations of disturbed circadian rhythms (chronodisruption) where the central clock and the peripheral clocks receive incoherent signals, the synchronicity is lost producing implications for health. This lack of coordination could alter the tissue function and cause long term damage to the organs. Life habits such as sleep, physical exercise, social interaction, and feeding times are determinants for stability and integrity of…

The emergence of drug resistance to targeted cancer therapies: Clinical evidence.

2019

For many decades classical anti-tumor therapies included chemotherapy, radiation and surgery; however, in the last two decades, following the identification of the genomic drivers and main hallmarks of cancer, the introduction of therapies that target specific tumor-promoting oncogenic or non-oncogenic pathways, has revolutionized cancer therapeutics. Despite the significant progress in cancer therapy, clinical oncologists are often facing the primary impediment of anticancer drug resistance, as many cancer patients display either intrinsic chemoresistance from the very beginning of the therapy or after initial responses and upon repeated drug treatment cycles, acquired drug resistance deve…