213 research outputs found
Quantitative profiling of the UGT transcriptome in human drug metabolizing tissues
Alternative splicing as a mean to control gene expression and diversify function is
suspected to considerably influence drug response and clearance. We report the
quantitative expression profiles of the human UGT genes including alternatively spliced
variants not previously annotated established by deep RNA-sequencing in tissues of
pharmacological importance. We reveal a comprehensive quantification of the
alternative UGT transcriptome that differ across tissues and among individuals.
Alternative transcripts that comprise novel in-frame sequences associated or not with
truncations of the 5â and/or 3â termini, significantly contribute to the total expression
levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression
of UGT2 variants surpassing those of UGT1. Quantitative data expose preferential
tissue expression patterns and remodelling in favour of alternative variants upon
tumorigenesis. These complex alternative splicing programs have the strong potential to
contribute to interindividual variability in drug metabolism in addition to diversify the UGT
proteome
Unravelling the transcriptomic landscape of the major phase II UDP-glucuronosyltransferase drug metabolizing pathway using targeted RNA sequencing
A comprehensive view of the human UDP-glucuronosyltransferase (UGT) transcriptome is a
prerequisite to the establishment of an individualâs UGT metabolic glucuronidation signature. Here,
we uncover the transcriptome landscape of the ten human UGT loci genes in normal and tumoral
metabolic tissues by targeted RNA next generation sequencing. Alignment on the human hg19
reference genome identifies 234 novel exon-exon junctions. We recover all previously known
UGT1 and UGT2 enzyme-coding transcripts and identify over 130 structurally and functionally
diverse novel UGT variants. We further expose a revised genomic structure of UGT loci and
provide a comprehensive repertoire of transcripts for each UGT gene. Data also uncover a
remodelling of the UGT transcriptome occurring in a tissue- and tumor-specific manner. The
complex alternative splicing program regulating UGT expression and protein functions is likely
critical in determining detoxification capacity of an organ and stress-related responses, with
significant impact on drug responses and diseases. Keywords: Alternative splicing, transcriptome, glucuronidation, RNA sequencing, drug
metabolism, glucuronosyltransferase (UGT
COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
Background:
The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms.
Methods:
International, prospective observational study of 60â109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms.
Results:
âTypicalâ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (â€â18 years: 69, 48, 23; 85%), older adults (â„â70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each Pâ<â0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country.
Interpretation:
This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men
Variation morpho-physiologique des plants d'épinette blanche de différentes sources génétiques et implications pour la migration assistée
Les semences forestiĂšres gĂ©nĂ©tiquement amĂ©liorĂ©es pourraient ne plus ĂȘtre adaptĂ©es aux sites oĂč elles sont destinĂ©es Ă cause des changements climatiques. La migration assistĂ©e figure parmi les stratĂ©gies d'adaptation proposĂ©es pour maintenir la productivitĂ© forestiĂšre et diminuer la vulnĂ©rabilitĂ© des Ă©cosystĂšmes. Les rĂ©ponses morpho-physiologiques des plants dâĂ©pinette blanche (Picea glauca (Moench) Voss) issus de huit vergers Ă graines ont Ă©tĂ© Ă©valuĂ©es en pĂ©piniĂšre et sur trois sites de plantation. La modĂ©lisation des courbes de croissance a montrĂ© que la hauteur des vergers mĂ©ridionaux et de deuxiĂšme gĂ©nĂ©ration est significativement supĂ©rieure Ă celle des autres vergers. Un modĂšle Ă rĂ©gression multiple a montrĂ© que la hauteur finale des plants Ă©tait significativement corrĂ©lĂ©e aux conditions climatiques dâorigine des vergers. Le verger et le site de plantation ont affectĂ© significativement la croissance en hauteur des plants. Les rĂ©sultats de la prĂ©sente Ă©tude et ceux obtenus Ă long terme contribueront Ă raffiner les rĂšgles opĂ©rationnelles de transfert des semences propres Ă la migration assistĂ©e.Due to climate change, genetically improved trees may no longer be adapted to the sites where they are intended to be planted. Assisted migration is a potential adaptation strategy for maintaining forest productivity and reducing vulnerability in the face of a changing climate. Morpho-physiological responses of white spruce (Picea glauca (Moench) Voss) seedlings from eight seed orchards were evaluated in a nursery and at three planting sites. The modeling of growth curves showed that the height of both the southern orchards and second generation orchards was significantly higher than the other orchards. A multiple regression model showed that the final height of the plants was significantly correlated with climatic conditions of the orchards. The orchard and the planting site significantly affected height growth of seedlings. The results of this study and those obtained over the longer term should help to refine the operational rules of seed transfer for assisted migration
Tchekhov revisité : «Brace Up!» The entertainment (Sketches from « Three Sisters »)
Enfants attendus et enfants accueillis dans le cadre de lâadoption
Expected and welcomed children in adoption.
Among the main factors involved in the adoption process, followed by the childâs adaptation to his or her family, are the composition of the family, the parentâs motivation and their preference with regard to the awaited child. A study by the
Institut national dâĂ©tudes dĂ©mographiques using 1500 adoption application files emphasises the relations between the characteristics of candidates, those they wish for the children and the probability of their occurring. Insofar as integrating a child in a family depends partly on the match between the child the parents await and the child they welcome, adopting a different child is sometimes a risk. But, among adopting parents at least one in four adopts a number of children or a child who differs in age, sex or origin compared to the original adoption application which had been approved.Parmi les principaux facteurs qui interviennent dans le dĂ©roulement dâune procĂ©dure dâadoption, puis dans lâadaptation de lâenfant Ă sa famille, figurent la composition de la famille, la motivation des parents et les prĂ©fĂ©rences pour lâenfant attendu. Une Ă©tude de lâInstitut national dâĂ©tudes dĂ©mographiques rĂ©alisĂ©e Ă partir de dossiers de candidats Ă lâadoption souligne les relations entre les caractĂ©ristiques des candidats, celles quâils souhaitent pour les enfants et leurs probabilitĂ©s de rĂ©aliser leur projet. Dans la mesure oĂč lâintĂ©gration dâun enfant Ă sa famille dĂ©pend en partie de lâadĂ©quation entre lâenfant attendu et lâenfant accueilli, lâadoption dâun enfant diffĂ©rent comporte parfois un risque. Or, parmi les adoptants, au moins un sur quatre adopte un nombre dâenfants ou un enfant diffĂ©rent par lâĂąge, le sexe ou lâorigine du projet avec lequel il avait obtenu un agrĂ©ment.Frechon Isabelle, Villeneuve-Gokalp Catherine. Enfants attendus et enfants accueillis dans le cadre de lâadoption. In: Politiques sociales et familiales, n°95, 2009. pp. 33-42
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