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Adult human liver slice cultures:Modelling of liver fibrosis and evaluation of new anti-fibrotic drugs

World Journal of Hepatology 2021年第2期13卷 187-217页

作者： Daria Kartasheva-Ebertz Jesintha Gaston loriane lair-mehiri Pierre-Philippe Massault Olivier Scatton Jean-Christophe Vaillant Vladimir Alexei Morozov Stanislas Pol Sylvie Lagaye Institut Pasteur Immunobiologie des Cellules DendritiquesINSERM U1223Paris 75015France BioSPC Universitéde ParisParis 75005France Service de Chirurgie digestive Hépato-biliaire et EndocrinienneAPHPGroupe Hospitalier CochinParis 75014France Service de Chirurgie digestive et Hépato bilio pancréatique AP-HPGroupe Hospitalier La Pitié-SalpétrièreMedecine Sorbonne UniversitéParis 75013France Center for HIV and Retrovirology Department of Infectious DiseasesRobert Koch InstituteBerlin 13353Germany Département d'Hépatologie AP-HPGroupe Hospitalier CochinUniversitéde ParisParis 75014France

BACKGROUND Liver fibrosis can result in end-stage liver failure and *** To examine human liver fibrogenesis and anti-fibrotic therapies,we evaluated the three dimensional ex vivo liver slice(LS)*** Fibrotic liver samples(F0 to F4 fibrosis stage according to the METAVIR score)were collected from patients after liver *** liver slices(HLS)were cultivated for up to 21 *** C virus(HCV)infection,alcohol(ethanol stimulation)and steatosis(palmitate stimulation)were examined in fibrotic(F2 to F4)liver slices infected(or not)with HCV.F0-F1 HLS were used as *** day 0,either ursodeoxycholic acid(choleretic and hepatoprotective properties)and/or α-tocopherol(antioxidant properties)were added to standard of care on HLS and fibrotic liver slices,infected(or not)with *** of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzymelinked immunosorbent *** The cultures were viable in vitro for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic *** of the biomarkers of fibrosis and the progression to steatosis(estimated by triglycerides production)was increased with the addition of HCV and/or ethanol or *** day 15 of the follow-up studies,a significant decrease of both transforming growth factorβ-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS *** These results show that the human three dimensional ex vivo model effectively reflects the in vivo processes in damaged human liver(viral,alcoholic,nonalcoholic steatohepatitis liver diseases)and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination.

关键词： Human liver fibrosis Hepatitis C virus Alcoholic liver disease Nonalcoholic steatohepatitis Ex vivo model Drugs

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The effects of water flow and temperature on thermal regime around a culvert built on permafrost

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Research in Cold and Arid Regions 2014年第5期6卷 415-422页

作者： loriane Périer Guy Doré C.R.Burn loriane Perier Guy Dore C. R. Bum Laval University Center for Northern Studies (CEN) 1035 Avenue De la m~decine QuObec Canada G1A OA6 Carleton University Dept. of Geography and Environmental Studies Ottawa Ontario Canada K1S 5B6

Temperature and water flow through a culvert beneath the Alaska Highway near Beaver Creek,Yukon,were measured at hourly intervals between June and October *** data were used to simulate the effect of the culvert on the thermal regime of the road embankment and subjacent permafrost.A 2-D thermal model of the embankment and permafrost was developed with TEMP/W and calibrated using field *** relations were obtained between water temperatures at the entrance to the culvert,flow into the culvert,and water temperatures inside the *** temperatures at the entrance and inside the culvert had a linear relation,while water temperatures inside the culvert and water flow were associated by a logarithmic relation.A multiple linear regression was used to summarize these *** this relationship,changes in the flow rate and water temperatures at the entrance of the culvert were simulated to obtain predicted water temperatures in the *** temperatures in the culvert were used in the thermal model to determine their effects on the ground thermal regime near the *** of ±10% in water flow rate had no impact on the thermal regime underneath the *** of water temperature at the entrance of the culvert had a noticeable influence on the thermal regime.A final simulation was conducted without insulation beneath the *** thaw depth was 30 cm with insulation,and 120 cm without insulation,illustrating the importance of insulation to the ground thermal regime.

关键词： culvert thermal regime water flow water temperature modeling permafrost

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The TELOMERE REPEAT BINDING proteins TRB4 and TRB5 function as transcriptional activators of PRC2-controlled genes to regulate plant development

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Plant Communications 2024年第7期5卷 178-199页

作者： Simon Amiard Léa Feit Emmanuel Vanrobays Lauriane Simon Samuel Le Goff loriane Loizeau Léa Wolff Falk Butter Clara Bourbousse Fredy Barneche Christophe Tatout Aline V.Probst iGReD CNRSInsermUniversite Clermont Auvergne63000 Clermont-FerrandFrance Institut de biologie de I’Ecole normale superieure(IBENS) Ecole normale superieureCNRSINSERMUniversite PSLParisFrance Institute of Molecular Biology 55128 MainzGermany

Plant-specific transcriptional regulators called TELOMERE REPEAT BINDING proteins(TRBs)combine two DNA-binding domains,the GH1 domain,which binds to linker DNA and is shared with H1 histones,and the Myb/SANT domain,which specifically recognizes the telobox DNA-binding site ***1,TRB2,and TRB3 proteins recruit Polycomb group complex 2(PRC2)to deposit H3K27me3 and JMJ14 to remove H3K4me3 at gene promoters containing telobox motifs to repress ***,we demonstrate that TRB4 and TRB5,two related paralogs belonging to a separate TRB clade conserved in spermatophytes,regulate the transcription of several hundred genes involved in developmental responses to environmental ***4 binds to several thousand sites in the genome,mainly at transcription start sites and promoter regions of transcriptionally active and H3K4me3-marked genes,but,unlike TRB1,it is not enriched at H3K27me3-marked gene ***,TRB4 can physically interact with the catalytic components of PRC2,SWINGER,and CURLY LEAF(CLF).Unexpectedly,we show that TRB4 and TRB5 are required for distinctive phenotypic traits observed in clf mutant plants and thus function as transcriptional activators of several hundred CLF-controlled genes,including key flowering *** further demonstrate that TRB4 shares multiple target genes with TRB1 and physically and genetically interacts with members of both TRB ***,these results reveal that TRB proteins engage in both positive and negative interactions with other members of the family to regulate plant development through both PRC2-dependent and-independent mechanisms.

关键词： chromatin TRB proteins transcriptional regulation PRC2 plant development

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