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A novel regulatory region controls IgH locus transcription and switch recombination to a subset of isotypes

Cellular & Molecular Immunology 2019年第11期16卷 887-889页

作者： Rocío Amoretti-Villa Mélanie Rogier Isabelle Robert Vincent Heyer bernardo reina-san-martin Institut de Génétique et de Biologie Moléculaire et Cellulaire(IGBMC) IllkirchFrance Institut National de la santéet de la Recherche Médicale(INSERM) U1258IllkirchFrance Centre National de la Recherche Scientifique(CNRS) UMR7104IllkirchFrance Universitéde Strasbourg IllkirchFrance

Class switch recombination(CSR)occurs at the IgH locus and replaces the immunoglobulin(Ig)isotype expressed from IgM to IgG,IgE or IgA,endowing the B cell receptor with novel effector functions.CSR is triggered by activation-induced cytidine deaminase(AID),1 an enzyme that deaminates cytosines to uracils in single-stranded DNA exposed by transcription.The distinct antibody isotypes are encoded in the IgH locus in individual transcription units composed of a cytokine-inducible promoter,an intronic exon,and a switch region(Sx),followed by the exons encoding the constant region(Cx)(Fig.S1a).During CSR,the choice of recombination to a particular isotype is determined by the stimulation-dependent activation of specific promoters,triggering the generation of noncoding germline transcripts(GLTs).2 Thus far,the transcriptional regulation of the IgH locus is known to be controlled by the Eμenhancer,located downstream of the variable region and upstream of the donor switch region(Sμ),and the 3′regulatory region(3′RR)super-enhancer located downstream of Cα.

关键词： IgH stimulation replace

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Mediator contributes to IgH locus VDJ rearrangements by promoting usage of most distal V segments

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Cellular & Molecular Immunology 2020年第4期17卷 407-409页

作者： Iman Dalloul Zeinab Dalloul sandrine Le Noir François Boyer bernardo reina-san-martin Jeanne Cook-Moreau Michel Cogné UMR CNRS 7276 INSERM U1262Universite de LimogesLimoges 87025France INSERM U1258 UMR CNRS 7104Institut de Genetique et de Biologie Moleculaire et CellulaireUniversitéde StrasbourgIllkirch 67400France

INTRODUCTION The immunoglobulin heavy(IgH)chain locus includes a large cluster of V,D and J segments spanning thousands of kilobases in mammals and its expression implies long-range 3D-regulation of various gene modifications.1 V(D)J recombination occurs during early B-cell ontogeny.2 It is regulated by multiple transcription factors and cis-regulatory elements,and most notably by the intronic 5′Eμelement located in the JH to Cμintron.3 The intergenic control region 1(IGCR1)located between the VH and D gene clusters inhibits rearrangement of the most DH-proximal VH gene segments,while promoting usage of distal VH gene segments.4 Other downstream elements of the locus,flanking its 3′end might have more subtle roles:while the large 3′regulatory region(3′RR)shows strong internal synergies2 and behaves as a superenhancer in mature B cells.Its deletion showed no influence on the VDJ repertoire and rather increased transcription of unrearranged V segments.3–5 Insulators binding CTCF farther downstream of the 3′RR were shown,however,to promote usage of distal VH segments.6 Altogether,there are strong indications that elements involved in long-distance regulation of transcription might also influence VDJ recombination.In-frame splicing of VDJ exons is also needed for full Ig expression.7 Given the functional importance of gene architecture and long-range interactions for the IgH locus physiology,we explored the dependence of the VDJ repertoire on Med1,a known actor of long-range enhancer interactions.

关键词： B cells mediator VDJ repertoire

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AN ARTICULATED TITANOSAUR FROM PATAGONIA (ARGENTINA):NEW EVIDENCES OF THE PEDAL EVOLUTION

AN ARTICULATED TITANOSAUR FROM PATAGONIA (ARGENTINA):NEW EVI...

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第二届国际古生物学大会

作者： bernardo GONZLEZ-RIGA Jorge CALVO Juan PORFIRI Centre Regional de Investigaciones Científicas y Tecnológicas Avda.Ruiz Leal s/nParque Gral.San Martin(5500) MendozaArgentina Universidad Nacional del Comahue Centro Paleontológico Lago BarrealesProyecto DinoRuta Prov.51km 65.Neuquén.Argentina

The study of the pedal structure is essential for understanding the locomotion, evolutionary trend and the behavior of the huge sauropod dinosaurs. In particular, titanosaurs are the most diverse and geographically widespread Late Cretaceous herbivores in South America and other continents. In spite of that, most taxa are represented by incomplete skeletal elements lacking articulated feet. In this context, the discovery of a new specimen with exceptionally preserved pedal structure is relevant. The finding mentioned herein is the second

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Effectiveness and safety of first-generation protease inhibitors in clinical practice:Hepatitis C virus patients with advanced fibrosis

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World Journal of Gastroenterology 2015年第30期21卷 9163-9174页

作者： Javier Salmeron Carmen Vinaixa Ruben Berenguer Juan Manuel Pascasio Juan Jose sanchez Ruano Miguel angel Serra Ana Gila Moises Diago Manuel Romero-Gomez Jose Maria Navarro Milagros Testillano Conrado Fernandez Dolores Espinosa Isabel Carmona Jose Antonio Pons Francisco Jorquera Francisco Javier Rodriguez Ramon Perez Jose Luis Montero Rafael Granados Miguel Fernandez Ana Belen martin Paloma Munoz de Rueda Rosa Quiles CIBERehd Instituto de Salud Carlos Ⅲ28029 MadridSpain Unit for Clinical Management of Digestive Diseases Complejo Hospitalario Universitario de Granada Instituto de Investigacion Biosanitaria de Granada University Hospital Politecnico La Fe Unit for Clinical Management of Digestive Diseases University Hospital Virgen Del Rocio Hospital Toledo University Clinic Hospital of Valencia University General Hospital of Valencia Unit for Clinical Management of Digestive Diseases University Hospital Nuestra Senora de Valme Department of Gastroenterology and Hepatology Agencia sanitaria Costa del Sol University Hospital Cruces Gastroenterology Unit University Hospital Fundacion Alcorcon University Hospital Virgen Macarena University Hospital Virgen de la Arrixaca Hospital of Leon University General Hospital reina Sofia Department Gastroenterology and Hepatology University Hospital Central de Asturias University Hospital reina Sofia University Hospital De Gran Canaria Dr. Negrin Hospital san Pedro de Alcantara

AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up.RESULTS:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P < 0.0001),whereas by modified intention-to-treatment(m ITT) no were found significant differences. By degree of fibrosis,56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients,both TN and TE. In the analysis by groups,the TN patients treated with TVR by ITT showed a higher SVR(P = 0.005). However,by m ITT there were no significant differences between BOC and TVR. In the multivariate analysis by m ITT,the significant SVR factors were relapsers,IL28 B CC and non-F4; the type of treatment(BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients,treated with BOC(46%) or with TVR(45%). 28% of the patients interrupted the treatment,mainly by non-viral response(51%):this outcome was more frequent in the TE than in the TN patients

关键词： Hepatitis C Boceprevir Telaprevir First-generation protease inhibitors Advanced fibrosis

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