Endogenous ligands for nuclear receptors: digging deeper.
Ontology highlight
ABSTRACT:
SUBMITTER: Schupp M
PROVIDER: S-EPMC3003339 | biostudies-literature | 2010 Dec
REPOSITORIES: biostudies-literature
Publications
Endogenous ligands for nuclear receptors: digging deeper.
Schupp Michael M Lazar Mitchell A MA
The Journal of biological chemistry 20101018 52
Nuclear receptors (NRs) are hormone-sensing transcription factors that translate dietary or endocrine signals into changes in gene expression. Therefore, the adoption of orphan NRs through the identification of their endogenous ligands is a key element for our understanding of their biology. In this minireview, we give an update on recent progress in regard to endogenous ligands for a cluster of NRs with high sequence homology, namely peroxisome proliferator-activated receptors α and γ, Rev-erbα ...[more]
Similar Datasets
Project description:The expression of genes involved in photosystem development in Rhodobacter sphaeroides is dependent upon three major regulatory networks: FnrL, the PrrBA two-component system and the AppA-PpsR pathway. A PrrA- mutant strain of R. sphaeroides is unable to develop under photosynthetic conditions, but when combined with a ppsR mutation, is able to resume growth. In an effort to better characterize the ppsR regulon and to unravel the relationship between the PrrBA and the AppA-PpsR networks, we compared transcriptome profiles from the wild type, PrrA- and PrrA-PpsR- strains under a permissive, common, growth condition: anaerobic-dark-DMSO. Here is stored the microarray data for the PrrA-PpsR- double mutant strain grown under this condition. Keywords: transcriptome profile
2008-08-31 | GSE9534 | GEO
Project description:BACKGROUND:There are very few close-up sociological or anthropological data informing epidemiological and psychiatric research design and/or contributing to our understanding of the relationship between mental health and specific forms of urban life. Furthermore, research on the relationships between urbanicity and mental disorder has paid little attention to the global diversity of urban experience, such as in cities in China, India and Brazil. METHODS:Two innovative methods can be employed to unveil the diversified urban experience of migrants in China, i.e. an ethnography-informed sociological deep surveying instrument and an ecological momentary assessment with a smartphone app. This article introduces the design and pilot survey of these new instruments towards a 'mechanism-rich' epidemiology. RESULTS:The ethnography-informed survey instrument enabled us to include some of the issues from the ethnography and successfully 'dig deeper' into respondents' social experience. The pilot of the smartphone app serves as 'proof of principle' that we can recruit respondents in Shanghai, and that we can receive and use the data. CONCLUSIONS:Both of these pilots have demonstrated good feasibility for studying mobility, urban life and mental health. Our next steps will be to extend the Shanghai sample, to use the app in Sao Paulo and Toronto and then hopefully in India and Africa.
| S-EPMC6822688 | biostudies-literature
Project description:BackgroundSome chiropractors suggest that chiropractic treatment is appropriate for health issues other than musculoskeletal problems. The prevalence of such claims on individual clinic websites has previously been reported as approximately one-in-four in Denmark. The underlying rationales for such claims may reflect convictions about traditional chiropractic subluxations paradigms, but are not self-evident and has not previously been studied.MethodsAn exploratory qualitative case interview study of Danish chiropractors with websites which contain claims about chiropractic efficacy in the treatment of non-musculoskeletal disorders. Websites were identified from a nation wide random sample (57%) of all chiropractic clinic websites.ResultsOf the original 139 websites, 36 were identified as mentioning non-MSK conditions. When revisited, 19 of those clinic websites still mentioned non-MSK disorders and were contacted. Eleven (11) declined our invitation to participate. Interviews were conducted with the responsible chiropractor from each of the remaining 8 clinics. Five distinct themes were identified in the rationales for treating non-musculoskeletal disorders: 'Positive side-effects,' 'Experience,' 'Web page,' 'Communication' and 'Conviction.'ConclusionsA minority of Danish chiropractic websites suggest that non-musculoskeletal disorders are within the chiropractic scope of practice. Those that do, do so for varying reasons-poor communication and website maintenance were commonly cited problems. An explicitly stated adherence to traditional chiropractic subluxations concepts was uncommon. By contrast, a more tempered rationale that suggested a potential beneficial side-effect of chiropractic on non-musculoskeletal health issues were more common and was typically presented in softer-language and/or with some reservations.
| S-EPMC8646014 | biostudies-literature
Project description:The expression of genes involved in photosystem development in Rhodobacter sphaeroides is dependent upon three major regulatory networks: FnrL, the PrrBA two-component system and the AppA-PpsR pathway. A PrrA- mutant strain of R. sphaeroides is unable to develop under photosynthetic conditions, but when combined with a ppsR mutation, is able to resume growth. In an effort to better characterize the ppsR regulon and to unravel the relationship between the PrrBA and the AppA-PpsR networks, we compared transcriptome profiles from the wild type, PrrA- and PrrA-PpsR- strains under a permissive, common, growth condition: anaerobic-dark-DMSO. Here is stored the microarray data for the PrrA-PpsR- double mutant strain grown under this condition. Keywords: transcriptome profile Rhodobacter sphaeroides PrrA-PpsR- grown under anaerobic dark DMSO conditions. Sparged with 95% N2, 5% CO2 in sistrom minimal medium A supplemented with final concentration 0.1% YE, 0.5% DMSO. The total RNA from three independent cultures of R. sphaeroides PrrA-PpsR- grown under anaerobic-dark-DMSO conditions was used. cDNA synthesis, fragmentation, labeling and hybridization are described elsewhere (Roh et al., 2004).
2010-06-20 | E-GEOD-9534 | biostudies-arrayexpress
Project description:Scientific practices stemming from colonialism, whereby middle- and low-income countries supply data for high-income countries and the contributions of local expertise are devalued, are still prevalent today in the field of palaeontology. In response to these unjust practices, countries such as Mexico and Brazil adopted protective laws and regulations during the twentieth century to preserve their palaeontological heritage. However, scientific colonialism is still reflected in many publications describing fossil specimens recovered from these countries. Here, we present examples of 'palaeontological colonialism' from publications on Jurassic-Cretaceous fossils from NE Mexico and NE Brazil spanning the last three decades. Common issues that we identified in these publications are the absence of both fieldwork and export permit declarations and the lack of local experts among authorships. In Mexico, access to many fossil specimens is restricted on account of these specimens being housed in private collections, whereas a high number of studies on Brazilian fossils are based on specimens illegally reposited in foreign collections, particularly in Germany and Japan. Finally, we outline and discuss the wider academic and social impacts of these research practices, and propose exhaustive recommendations to scientists, journals, museums, research institutions and government and funding agencies in order to overcome these practices.
| S-EPMC8889171 | biostudies-literature
Project description:In the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD) system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement) measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models.
| S-EPMC5730105 | biostudies-literature
Project description:Peptides presented by MHC molecules on the cell surface, or the immunopeptidome, play an important role in the adaptive arm of the immune response. Antigen processing for MHC class I molecules is a ubiquitous pathway present in all nucleated cells which generates and presents peptides of both self and non-self-origin. Peptides with post-translational modifications represent one category of peptides presented by MHC class I molecules. However, owing to the complexity of self-peptides presented by cells, the diversity of peptides with post-translational modifications is not well-studied. In this study, we carried out MHC Class I immunopeptidomics analysis of Loucy T-cell leukemia and A375 malignant melanoma cell line to characterize the diversity of post-translational modifications of MHC class I-bound peptides. Using high resolution mass spectrometry, we identified 25,761 MHC-bound peptides across both cell lines using Bolt and Sequest search engines. The enrichment method was highly specific as ~ 90% of the peptides were of typical length (8-12 amino acids long) and the motifs were expected based on previously reported motifs for MHC I alleles. Among the MHC-bound peptides, we identified phosphorylation as a major post-translational modification followed by deamidation. We observed site-specific localization of these post-translational modifications, at position P4 for phosphorylated peptides and position P3 for deamidated peptides. We identified a smaller number of peptides with acetylated and methylated lysine, possibly due to very low stoichiometric levels of these PTMs compared to phosphorylation and deamidation. Using PEAKS de novo sequencing algorithm, we identified spliced peptides that accounted for ~ 5-7% of MHC-bound peptides that were otherwise similar in their features as normal MHC-bound peptides. We validated the identity of several post-translationally modified peptides and spliced peptides through mass spectrometric analysis of synthetic peptides. Our study confirms post-translationally modified peptides to be present at low stoichiometric levels along with unusual spliced peptides through unbiased identification using high resolution mass spectrometry.Supplementary informationThe online version contains supplementary material available at 10.1007/s42485-021-00066-x.
| S-EPMC9807509 | biostudies-literature
Project description:AbstractThis symposium will focus on new methods to interpret and understand physical and cognitive health outcomes using data from wearable accelerometers and a traditional 400-meter walk protocol. Using data from the Baltimore Longitudinal Study of Aging (BLSA) and the Patient Reported Outcomes of Mood Pain and faTigue (PROMPT) study, we will discuss new insights into accelerometer-based activity metrics, as well as modeling of 400-meter lap-time variability, to enhance our knowledge of factors contributing to physical and cognitive health outcomes in older adults. Specifically, we will demonstrate methods to: (i) quantify objective physical activity volume, fragmentation, and bout lengths as predictors of mortality, (ii) link characteristics of daily physical activity (e.g., volume, fragmented patterns) to cognitive domains including memory, executive function, and visuospatial function, (iii) demonstrate a novel method to quantify lap-time variability during the 400m walk, and (iv) examine ecological momentary assessments of pain and activity patterns. Collectively, these presentations will present novel, advanced, and yet simple approaches to analyze and interpret objective measures of activity and function to reveal unexplored characteristics of healthy aging and maintenance of well-being. Further development and application of the methodology presented in this symposium will: (i) highlight cutting-edge methods to assess the effects of activity patterns on physical and cognitive outcomes with aging, and (ii) contribute to future efforts to optimize interventions that extend healthy longevity and delay adverse health outcomes related to aging.
| S-EPMC6228129 | biostudies-other
Project description:The metabolism of testosterone to 6β-hydroxytestosterone (6β-OH-T) is a commonly used assay to evaluate human CYP3A enzyme activities. However, previous reports have indicated that CYP3A7 also produces 2α-hydroxytestosterone (2α-OH-T) and that a 2α-OH-T/6β-OH-T ratio may be a unique endogenous biomarker of the activity of the enzyme. Until now, the full metabolite and kinetic profile for testosterone hydroxylation by CYP3A7 has not been fully examined. To this end, we performed a complete kinetic analysis of the 6β-OH-T, 2α-OH-T, and 2β-hydroxytestosterone metabolites for recombinant Supersome CYP3A4, CYP3A5, and CYP3A7 enzymes and monitored metabolism in fetal and adult human liver microsomes for comparison. In general, a decrease in the velocity of the reaction was observed between CYP3A4 and the two other enzymes, with CYP3A7 showing the lowest metabolic capacity. Interestingly, we found that the 2α-OH-T/6β-OH-T ratio varied with substrate concentration when testosterone was incubated with CYP3A7, suggesting that this ratio would likely not function well as a biomarker for CYP3A7 activity. In silico docking studies revealed at least two different binding modes for testosterone between CYP3A4 and CYP3A7. In CYP3A4, the most energetically favorable docking mode places testosterone in a position with the methyl groups directed toward the heme iron, which is more favorable for oxidation at C6β, whereas for CYP3A7 the testosterone methyl groups are positioned away from the heme, which is more favorable for an oxidation event at C2α In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2α-hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5.
| S-EPMC5697443 | biostudies-literature
Project description:BACKGROUND:The Open Targets Platform integrates different data sources in order to facilitate identification of potential therapeutic drug targets to treat human diseases. It currently provides evidence for nearly 2.6 million potential target-disease pairs. G-protein coupled receptors are a drug target class of high interest because of the number of successful drugs being developed against them over many years. Here we describe a systematic approach utilizing the Open Targets Platform data to uncover and prioritize potential new disease indications for the G-protein coupled receptors and their ligands. RESULTS:Utilizing the data available in the Open Targets platform, potential G-protein coupled receptor and endogenous ligand disease association pairs were systematically identified. Intriguing examples such as GPR35 for inflammatory bowel disease and CXCR4 for viral infection are used as illustrations of how a systematic approach can aid in the prioritization of interesting drug discovery hypotheses. Combining evidences for G-protein coupled receptors and their corresponding endogenous peptidergic ligands increases confidence and provides supportive evidence for potential new target-disease hypotheses. Comparing such hypotheses to the global pharma drug discovery pipeline to validate the approach showed that more than 93% of G-protein coupled receptor-disease pairs with a high overall Open Targets score involved receptors with an existing drug discovery program. CONCLUSIONS:The Open Targets gene-disease score can be used to prioritize potential G-protein coupled receptors-indication hypotheses. In addition, availability of multiple different evidence types markedly increases confidence as does combining evidence from known receptor-ligand pairs. Comparing the top-ranked hypotheses to the current global pharma pipeline serves validation of our approach and identifies and prioritizes new therapeutic opportunities.
| S-EPMC6167889 | biostudies-literature