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Schizop.renia-associated m.croRNA–gene Interactions in the Dorsolateral p.efrontal Cortex

genom.cs, p.oteom.cs & Bioinform.tics 2019年第6期17卷 623-634页

作者： danielle m.Santarelli Adam.p.Carroll Heath m.Cairns paul A.Tooney m.rray J.Cairns School of Biom.dical Sciences and p.arm.cy The University of NewcastleCallaghanNSW 2308Australia Centre for Brain and m.ntal Health Research Hunter Medical Research InstituteNewcastleNSW 2305Australia

Schizop.renia-associated anom.lies in gene exp.ession in p.stm.rtem.brain can be attributed to a com.ination of genetic and environm.ntal influences. given the sm.ll effect size of com.on variants, it is likely that we m.y only see the com.ined im.act of som. of these at the p.thway level in sm.ll p.stm.rtem.studies. At the gene level, however, there m.y be m.re im.act from.com.on environm.ntal exp.sures m.diated by influential ep.genom.c m.difiers, such as m.croRNA(m.RNA). We hyp.thesise that dysregulation of m.RNAs and their alteration of gene exp.ession have significant im.lications in the p.thop.ysiology of schizop.renia. In this study, we integrate changes in cortical gene and m.RNA exp.ession to identify regulatory interactions and networks associated with the disorder. gene exp.ession analysis in p.st-m.rtem.p.efrontal dorsolateral cortex(BA 46)(n = 74 m.tched p.irs of schizop.renia, schizoaffective, and control sam.les)was integrated with m.RNA exp.ession in the sam. cohort to identify gene–m.RNA regulatory networks. A significant gene–m.RNA interaction network was identified, including m.R-92 a, m.R-495,and m.R-134, which converged with differentially exp.essed genes in p.thways involved in neurodevelop.0}nt and oligodendrocyte function. The cap.city for m.RNA to directly regulate gene exp.ession through resp.ctive binding sites in BCL11 A, p.p., and SYT11 was also confirm.d to sup.ort the biological relevance of this integrated network m.del. The observations in this study sup.ort the hyp.thesis that m. RNA dysregulation is an im.ortant factor in the com.lex p.thop.ysiology of schizop.renia.

关键词： Schizop.renia m.croRNA Dorsolateral p.efrontal cortex Network Neurop.thology

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Exp.rience of p.tients Undergoing m.ni-Arthroscop. Com.ared to m.I in the Earliest p.ases of Arthritis

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International Journal of Clinical m.dicine 2013年第12期4卷 1-5页

作者： m.ria J. H. de Hair m.rleen g. H. van de Sande m.rio m.as danielle m. g.rlag.paul p. tak Dep.rtm.nt of Clinical Im.unology and Rheum.tology Aca-demic Medical Center University of Amsterdam Amsterdam The Netherlands Dep.rtm.nt of Radiology Academic Medical Center University of Amsterdam Amsterdam The Netherlands

Objective: To evaluate the exp.ctations and exp.rience of p.tients undergoing m.ni-arthroscop. com.ared to contrast enhanced m.I for research p.rp.ses. m.thods: Seventeen p.tients with early, active arthritis (group.A) and 21 autoantibody-p.sitive individuals without any evidence of arthritis up.n p.ysical exam.nation (group.B) were included. All subjects underwent both contrast enhanced m.I and synovial biop.y sam.ling by m.ni-arthroscop. of the sam. joint within one week. At inclusion and after both p.ocedures, subjects filled in questionnaires with item. about exp.ctations and exp.rience with regard to the p.ocedures. Results: Before p.ocedures, subjects in group.B had a higher fear of and reluctance to undergo m.ni-arthroscop. com.ared to m.I (p.p.= 0.001, resp.ctively). Before p.ocedures, 42% of the subjects p.eferred m.I, 11% of the subjects p.eferred m.ni-arthroscop. and 47% had no p.eference for either p.ocedure. After both p.ocedures, subjects p.eferences changed to 39% for m.I, 32% for m.ni-arthroscop. and 29% for no p.eference for one or the other p.ocedure. When com.aring group.A with group.B, there were no significant differences in p.eference before and after the p.ocedures. Conclusion: Synovial biop.y sam.ling by m.ni-arthroscop. for analysis of synovial inflam.ation is a well-exp.rienced p.ocedure when com.ared to contrast enhanced m.I. These results sup.ort the use of m.ni-arthroscop. in a research setting from.a p.tient p.rsp.ctive.

关键词： Arthritis Rheum.toid Synovium Arthroscop. m.I

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Characterization of two rat m.dels of cystic fibrosis—KO and F508del CFTR—generated by Crisp.-Cas9

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Anim.l m.dels and Exp.rim.ntal m.dicine 2019年第4期2卷 297-311页

作者： Elise Dreano m.rc Bacchetta Juliette Sim.nin Louise galm.che Claire Usal Lotfi Slim.ni Jérém. Sadoine Laurent Tesson Ignacio Anegon Jean-paul Concordet Aurélie Hatton Lucile Vignaud danielle Tondelier Isabelle Serm.t-gaudelus m.rc Chanson Charles-Henry Cottart INSERm.1151 INEMUniversitéde ParisParisFrance Dép.rtem.nt de p.diatrie Gynécologie&Obstétrique et Département de Physiologie Cellulaire&MétabolismeUniversitéde GenèveGenèveSwitzerland Dép.rtem.nt de p.thologie APHPCHU Necker-Enfants MaladesParisFrance Centre de Recherche en Transp.antation&Im.unologie UMR 1064INSERMUniversitéde NantesNantesFrance p.ateform. Trangénèse Rat&Im.unop.énom.que INSERM 1064&SFR François BonamyCNRS UMS3556NantesFrance p.thologie Imagerie&Biothérapies OrofacialesMontrougeFrance p.ateform. Im.geries du vivant Facultéde chirurgie dentaireUniversitéde ParisParisFrance INSERm.U1154 CNRS UMR7196MNHNTACGENEParisFrance Ap.Hp Centre Maladie Rare Mucoviscidose et Maladies du CFTRAssistance Publique Hôpitaux de ParisHôpital Necker-Enfants MaladesParisFrance Facultéde m.decine de p.ris Universitéde ParisParisFrance Facultéde p.arm.cie de p.ris Universitéde ParisParisFrance

Background: genetically engineered anim.ls are essential for gaining a p.op.r understanding of the disease m.chanism. of cystic fibrosis(CF). The rat is a relevant laboratory m.del for CF because of its zootechnical cap.city, size, and airway characteristics, including the p.esence of subm.cosal ***: We describe the generation of a CF rat m.del(F508 del) hom.zygous for the ***508 del m.tation in the transm.m.rane conductance regulator(Cftr) gene. This m.del was com.ared to new Cftr-/-rats(CFTR KO). Target organs in CF were exam.ned by histological staining of tissue sections and tooth enam.l was quantified by m.cro-com.uted tom.grap.y. The activity of CFTR was evaluated by nasal p.tential difference(Np.) and short-circuit current m.asurem.nts. The effect of VX-809 and VX-770 was analyzed on nasal ep.thelial p.im.ry cell cultures from.F508 del ***: Both newborn F508 del and Knock out(KO) anim.ls develop.d intestinal obstruction that could be p.rtly com.ensated by sp.cial diet com.ined with an osm.tic laxative. The two rat m.dels exhibited CF p.enotyp.c anom.lies such as vas deferens agenesis and tooth enam.l defects. Histology of the intestine, p.ncreas, liver, and lungs was norm.l. Absence of CFTR function in KO rats was confirm.d ex vivo by short-circuit current m.asurem.nts on colon m.cosae and in vivo by Np., whereas residual CFTR activity was observed in F508 del rats. Exp.sure of F508 del CFTR nasal p.im.ry cultures to a com.ination of VX-809 and VX-770 im.roved CFTR-m.diated ***: The F508 del rats rep.oduce the p.enotyp.s observed in CFTR KO anim.ls and rep.esent a novel resource to advance the develop.0}nt of CF therap.utics.

关键词： anim.l m.dels CFTR channel activity CFTR m.dulators cystic fibrosis p.im.ry cultures rat

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