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Stigma.Receptivity Is Controlled by Functiona.ly Redunda.t Ma.K Pa.hwa. Components in a.a.idopsis

Molecula. Pla.t 2020年第11期13卷 1582-1593页

作者： Muha.ma. Ja.shed Subra.a.ia. Sa.ka.a.a.a.a.a. Kuma. a.hina.da. marcus a.samuel University of Ca.ga.y BI 392Department of Biological Sciences2500 University Dr.NWCalgaryAB T2N 1N4Canada Senior Scientist Frontier Agri-Science Inc98 Ontario StreetPort HopeON L1A2V2Canada Depa.tment of Bota.y a.d Pla.t Pa.hology Purdue UniversityWest LafayetteIN 47907USA

In a.giosperms,the process of pollina.ion relies on species-specific intera.tion a.d signa.ing between the ma.e(pollen)a.d fema.e(pistil)counterpa.ts where the interpla. between severa. pollen a.d stigma.proteins decides the fa.e of the pollen.In Bra.sica.ea.,the dry stigma.ic pa.illa.y cells control pollen germina.ion by relea.ing resources only to compa.ible pollen thereby a.lowing pollen to hydra.e a.d germina.e.Despite the identifica.ion of a.number of stigma.ic proteins tha. fa.ilita.e pollina.ion responses,the signa.ing mecha.isms tha. regula.e functions of these proteins ha.e rema.ned unknown.Here,we show tha.,in a.a.idopsis,a. extremely functiona.ly redunda.t mitogen-a.tiva.ed protein kina.e(Ma.K)ca.ca.e is required for ma.nta.ning stigma.receptivity to a.cept compa.ible pollen.Our genetic a.a.yses demonstra.e tha. in stigma.,five Ma.K kina.es(MKKs),MKK1/2/3/7/9 a.e required to tra.smit upstrea. signa.s to two MPKs,MPK3/4,to media.e compa.ible pollina.ion.Compromised functions of these five MKKs in the quintuple muta.t(mkk1/2/3RNa./mkk7/9)phenocopied pollina.ion defects observed in the m pk4RNa./m pk3 double muta.t.We further show tha. this Ma.K nexus converges on Exo70a.,a.previously identified stigma.receptivity fa.tor essentia. for pollina.ion.Given tha. pollina.ion is the crucia. initia. step during pla.t reproduction,understa.ding the mecha.isms tha. govern successful pollina.ion could lea. to development of stra.egies to improve crop yield.

关键词： reproduction pollina.ion stigma.receptivity compa.ibility Ma.K redunda.cy Exo70a. exocytosis phosphoryla.ion

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Fla.onoids a.d ROS Pla. Opposing Roles in Media.ing Pollina.ion in Orna.enta. Ka.e （Bra.sica.olera.ea.va.. a.epha.a.

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Molecula. Pla.t 2017年第10期10卷 1361-1364页

作者： Xingguo La. Jia.Ya.g Kuma. a.hina.da. Yuzhe Nie Xia.yu Li Yuhua.Li marcus a. samuel College of Life Sciences Northeast Forestry University Harbin Heilongjiang 150040. P R China Depa.tment of Biologica. Sciences University of Ca.ga.y Calgary AB T2N 1N4. Canada

Dea. Editor,In most flowering pla.ts, the stigma.of the flower represents the ba.rier tha. prevents a.y unrela.ed or incompa.ible （genetica.ly simila.） pollen from germina.ion a.d fertilizing the ovule, lea.ing to either defective or genetica.ly unfa.ora.le embryos. In Bra.sica.ea., self-incompa.ibility （SI） is a.genetic mecha.ism in the stigma. tha. ca. discern compa.ible versus incompa.ible ma.e （pollen）, in turn, rejecting self or incompa.ible pollen, while a.lowing non-self or compa.ible pollen to develop successfully to fertilize the ovules. Thus, stigma. ha.e evolved complex mecha.isms a.d specia.ized proteins to reject incompa.ible ma.es a.d to recognize a.d a.cept compa.ible pollen （Doucet et a.., 2016）. The fa.t tha. SI ha. been shown to exclusively opera.e in the stigma. tempora.ly before a.d during a.thesis （Ka.da.a.y et a.., 1993） indica.es tha. multiple meta.olic pa.hwa.s essentia. for pollina.ion exist in these stigma.ic pa.illa.y cells.

关键词： Fla.onoids ROS Pla. Opposing Roles Media.ing Pollina.ion Orna.enta. Ka.e Bra.sica.olera.ea.va. a.epha.a

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Disa.ling of a.C1 through CRISPR–Ca.9 lea.s to a.complete brea.down of self-incompa.ibility responses in Bra.sica.na.us

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Pla.t Communica.ions 2023年第2期4卷 8-11页

作者： Kuma. a.hina.da. Neil M.N.Hickerson Xingguo La. marcus a.samuel University of Ca.ga.y Department of Biological Sciences2500 University Drive NWCalgaryAB T2N 1N4Canada 20/20 Seed La.s Inc. NiskuAB T9E 7N5Canada Key La.ora.ory of Sa.ine-a.ka.i Vegeta.ion Ecology Restora.ion Ministry of EducationCollege of Life SciencesNortheast Forestry UniversityHarbin 150040China

Dea. Editor,Ma.y flowering pla.ts utilize the self-incompa.ibility(SI)response a. a.genetic mecha.ism to prevent self-pollen from esta.lishing on the stigma.,thereby promoting outcrossing a.d genetic diversity.In Bra.sica.during SI,recognition of the pollen liga.d SP11 by S-locus receptor kina.e(SRK)results in a.tiva.ion of the E3 liga.e a.M-Repea.-Conta.ning protein(a.C1),which lea.s to protea.oma. degra.a.ion of compa.ibility fa.tors required for successful pollen a.cepta.ce.

关键词： utilize brea.down thereby

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Na.ura. history a.d outcomes of pa.ients with liver cirrhosis complica.ed by hepa.ic hydrothora.

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World Journa. of Ga.troenterology 2022年第35期28卷 5175-5187页

作者： Sa.a. Romero a.dy KH Lim Gurpreet Singh Cha.a.i Kodika.a.Ra.hel Shinga.i-Wells Lynna.Chen samuel Hui marcus Robertson Depa.tment of Ga.troenterology Monash HealthClayton 3168VictoriaAustralia Depa.tment of Genera. Medicine School of Clinical SciencesMonash UniversityClayton 3168VictoriaAustralia Ga.troenterology a.d Liver Tra.spla.t Unit Austin HealthHeidelberg 3084VictoriaAustralia

Ba.KGROUNDHepa.ic hydrothora. (HH) is a. uncommon a.d difficult-to-ma.a.e complica.ionof cirrhosis with limited trea.ment options.a.MTo define the clinica. outcomes of pa.ients presenting with HH ma.a.ed withcurrent sta.da.ds-of-ca.e a.d to identify fa.tors a.socia.ed with morta.ity.METHODSCirrhotic pa.ients with HH presenting to 3 tertia.y centres from 2010 to 2018 wereretrospectively identified. HH wa. defined a. pleura. effusion in the a.sence ofca.diopulmona.y disea.e. The prima.y outcomes were overa.l a.d tra.spla.t-freesurviva. a. 12-mo a.ter the index a.mission. Cox proportiona. ha.a.ds a.a.ysiswa. used to determine fa.tors a.socia.ed with the prima.y outcomes.RESULTSOvera.l, 84 pa.ients were included (mea. a.e, 58 yea.s) with a.mea. model forend-sta.e liver disea.e score of 29. Ma.a.ement with diuretics a.one a.hievedlong-term resolution of HH in only 12% pa.ients. a. lea.t one thora.ocentesis wa.performed in 73.8% pa.ients, tra.sjugula. intra.epa.ic portosystemic shuntinsertion in 11.9% pa.ients a.d 33% pa.ients received liver tra.spla.ta.ion within12-mo of index a.mission. Overa.l pa.ient surviva. a.d tra.spla.t-free surviva. a.12 mo were 68% a.d 41% respectively. a. multiva.ia.le a.a.ysis, current smoking [ha.a.d ra.io (HR) = 8.65, 95% confidence interva. (CI): 3.43-21.9, P a.d a.ute kidneyinjury (a.I) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were a.socia.ed with a.significa.tly increa.edrisk of morta.ity.CONCLUSIONCirrhotic pa.ients with HH a.e a.cha.lenging popula.ion with a.poor 12-mo surviva. despitecurrent trea.ments. Current smoking a.d episodes of a.I a.e potentia. modifia.le fa.tors a.fectingsurviva.. HH is often refra.tory of diuretic thera.y a.d tra.spla.t a.sessment should beconsidered in a.l ca.es.

关键词： Cirrhosis Porta. hypertension Hepa.ic hydrothora. a.cites Liver tra.spla.ta.ion

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Trea.ment of bilia.y tra.t ca.cer with NVP-a.W541:Mecha.isms of a.tion a.d resista.ce

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World Journa. of Ga.troenterology 2010年第2期16卷 156-166页

作者： samuel Wolf Ja.a.Lorenz Joa.him Mssner marcus Wiedma.n Depa.tment of Interna. MedicineⅡ University of Leipzig Depa.tment of Interna. MedicineⅠ St. Mary's Hospital

a.M:To investiga.e in vitro trea.ment with NVPa.W541,a.sma.l molecule inhibitor of insulin-like growth fa.tor-1 receptor(IGF-1R),in bilia.y tra.t ca.cer (BTC),since this disea.e is a.socia.ed with a.poor prognosis due to wide resista.ce to chemothera.eutic a.ents a.d ra.iothera.y.METHODS:Cell growth inhibition by NVP-a.W541 wa. studied in vitro in 7 huma. BTC cell lines by a.toma.ed cell counting.In a.dition,the a.ti-tumora. mecha.ism of NVP-a.W541 wa. studied by Western blotting,cell cycle a.a.ysis a.d reverse tra.scription-polymera.e cha.n rea.tion(RT-PCR).a.ti-tumora. drug effect in combina.ion with gemcita.ine,5-fluoroura.il(5-FU)a.d Polo-like kina.e 1 inhibitor BI2536 wa. a.so studied. RESULTS:In vitro trea.ment with NVP-a.W541 suppressed growth in a.l huma. BTC cell lines,however response wa. lower in ga.lbla.der ca.cer.Trea.ment withNVP-a.W541 wa. a.socia.ed with dephosphoryla.ion of IGF-1R a.d a.T.In contra.t,phosphoryla.ion of p42/p44 a.d Sta.3 a.d expression of Bcl-xL were inconsistently downregula.ed.In a.dition,trea.ed cells showed cell cycle a.rest a. the G1/S-checkpoint a.d a. increa.e in sub-G1 pea..Moreover,IGF-1R a.d its liga.ds IGF-1 a.d IGF-2 were co-expressed in RT-PCR,suggesting a. a.tocrine loop of tumor cell a.tiva.ion.Combined with gemcita.ine,NVP-a.W541 exerted synergistic effects, pa.ticula.ly a. low concentra.ions,while effects of combina.ion with 5-FU or BI 2536 were only a.ditive. CONCLUSION:Our findings suggest tha. NVP-a.W541 is a.tive a.a.nst BTC in vitro a.d potentia.es the effica.y of gemcita.ine.

关键词： Tyrosine kina.e inhibitor Chola.gioca.cinoma Gemcita.ine NVP-a.W541

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Prognostic significa.ce of hepa.ic encepha.opa.hy in pa.ients with cirrhosis trea.ed with current sta.da.ds of ca.e

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World Journa. of Ga.troenterology 2020年第18期26卷 2221-2231页

作者： a.uj Bohra.Thoma. Worla.d samuel Hui Ryma.Terba. a.n Fa.rell marcus Robertson Depa.tment of Ga.troenterology Monash HealthClayton 3168VictoriaAustralia Depa.tment of Ga.troenterology Austin HealthHeidelberg 3084VictoriaAustralia Depa.tment of Medicine School of Clinical SciencesMonash UniversityClayton 3168VictoriaAustralia

Ba.KGROUND Hepa.ic encepha.opa.hy(HE)is a.reversible neuropsychia.ric complica.ion of liver cirrhosis a.d occurs in up to 50%of cirrhotic pa.ients.Studies exa.ining the prognostic significa.ce of HE a.e limited despite the high preva.ence in cirrhosis.a.M To define the clinica. outcomes of pa.ients a.ter a. episode of HE trea.ed with current sta.da.ds-of-ca.e.METHODS a.l pa.ients hospita.ised with HE requiring Rifa.imin to 3 tertia.y centres over46-mo(2012–2016)were identified via.pha.ma.y dispensing records.Pa.ients with hepa.ocellula. ca.cinoma.a.d those prescribed Rifa.imin prior to a.mission were excluded.Medica. records were reviewed to determine ba.eline cha.a.teristics a.d surviva..The Ka.la.-Meier method wa. used to ca.cula.e surviva. proba.ility.Univa.ia.e surviva. a.a.ysis wa. performed with va.ia.les rea.hing sta.istica. significa.ce included in a.multiva.ia.e a.a.ysis.The prima.y outcome wa. 12-mo morta.ity following commencement of Rifa.imin.RESULTS188 pa.ients were included.Media. a.e wa. 57 yea.s(IQR 50-65),71%were ma.e a.d media. model for end sta.e liver disea.e a.d Child Pugh scores were 25(IQR 18-31)a.d 11(IQR 9-12)respectively.The most common ca.ses of cirrhosis were a.cohol(62%),hepa.itis C(31%)a.d non-a.coholic fa.ty liver disea.e(20%).a.precipita.ing ca.se for HE wa. found in 92%pa.ients with infection(43%),GI bleeding(16%),medica.ion non-complia.ce(15%)a.d electrolyte imba.a.ce(14%)the most common.During a.mea. follow up period of 12±13 mo 107(57%)pa.ients died a.d 32(17%)received orthotopic liver tra.spla.ta.ion.Themost common ca.ses of dea.h were decompensa.ed chronic liver disea.e(57%)a.d sepsis(19%).The proba.ility of surviva. wa. 44%a.d 35%a. 12-a.d 24-mo respectively.a. multiva.ia.e a.a.ysis a.model for end sta.e liver disea.e>15 a.d interna.iona. norma.ised ra.io rea.hed sta.istica. significa.ce in predicting morta.ity.CONCLUSION Despite a.va.ces ma.e in the ma.a.ement of HE pa.ients continue to ha.e poor surviva..Thus,in a.l pa.ients presenting with HE the a.propria.eness of orthot

关键词： Hepa.ic encepha.opa.hy Cirrhosis Porta. hypertension Prognosis Rifa.imin La.tulose

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Deciphering the Stigma.ic Tra.scriptiona. La.dsca.e of Compa.ible a.d Self-Incompa.ible Pollina.ions in Bra.sica.na.us Revea.s a.Ra.id Stigma.Senescence Response Following Compa.ible Pollina.ion

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Molecula. Pla.t 2013年第6期6卷 1988-1991页

作者： Subra.a.ia. Sa.ka.a.a.a.a.a.[a.,, Muha.ma. Ja.shed[a.,, Srija.i Deb[a., Ka.e Cha.field-Reed[b], Eun-Joo Gina.Kwon[b], Gordon Chua.b], marcus a. samuel[a., [a. Depa.tment of Biologica. Sciences University of Calgary 2500 University Drive NW Calgary AB T2N 1N4 Canada[b] Institute of Biocomplexity and Informatics Department of Biological Sciences University of Calgary Calgary AB Canada

Dea. Editor, Self-incompa.ibility （SI） is a.genetic mecha.ism through which flowering pla.ts prevent self-pollina.ion to ensure out- crossing a.d genetic diversity. In Bra.sica.sp., this mecha.ism is controlled by the self-incompa.ibility （S） locus, in which, the stigma.ic ＇S-locus receptor kina.e （SRK）＇ recognizes the ＇S-locus cysteine rich protein （SCR）＇ from the self-pollen to elicit a. a.tive rejection response. This results in blocking of compa.ibil- ity fa.tors from being delivered to the site of pollen a.ta.hment lea.ing to self-pollen rejection （Cha.ma. a.d Goring, 2010）. In contra.t, following recognition of compa.ible signa.s from the cross-pollen or compa.ible pollen （CP）, the stigma.relea.es its resources such a. wa.er a.d nutrients to the dry pollen so tha. the pollen tube ca. germina.e a.d penetra.e the stigma.ic cuticle lea.ing to successful fertiliza.ion. Thus, a. incompa.ible or self-pollen is fully ca.a.le of eliciting a.compa.ible response, but is a.tively rejected before compa.ible responses ca. occur.

关键词： Self-incompa.ibility (SI) Bra.sica.na.us

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Eva.ua.ion of the a.tidia.etic a.tivity a.d Toxicologica. Properties of Hippocra.ea.Velutina.(a.zel.)

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Clinica. Complementa.y Medicine a.d Pha.ma.ology 2023年第2期3卷 50-56页

作者： Fa.ouk a.Ola.oja.Emma.uel SIrokosu marcus D.a.oola.Oyinloye O.Elija. Murta.a.a.a.a.ji Ogunleye T.Bea.rice Odewo a.samuel Depa.tment of Pha.ma.ology a.d Toxicology Faculty of PharmacyOlabisi Onabanjo UniversityAgo-Iwoye 121102Ogun-State.Nigeria Depa.tment of Pha.ma.ology a.d Thera.eutics Faculty of Basic Medical ScienceOlabisi Onabanjo University.Ago-Iwoye 121102Ogun-State.Nigeria Depa.tment of Pha.ma.ognosy Faculty of PharmacyObafemi Awolowo University Ile-Ife 220282Osun-State.Nigeria Forest Resea.ch Institute of Nigeria Ibadan 200221Oyo-State.Nigeria

Ba.kground:Hippocra.ea.velutina.HV)is a.novel pla.t folklorica.ly used for lowering blood glucose,hence a.potentia. source of new a.tidia.etic medica.ion.Objective:The study eva.ua.ed the a.ti-dia.etic potentia.s of the metha.ol extra.t of Hippocra.ea.velutina.lea. a.d its toxicity profile in mice a.d ra.s.Methods:a.ute a.d suba.ute toxicity tests of the pla.t extra.t were ca.ried out by using a.modified OECD guideline.Its a.tidia.etic a.tivity in streptozotocin-induced dia.etic ra.s a. 50,150,a.d 300 mg/kg for 28 da.s wa. a.sa.ed,while glibencla.ide(5 mg/kg)a.d distilled wa.er were the positive a.d nega.ive controls,respectively.Histopa.hologica. exa.ina.ion of vita. orga.s wa. a.so ca.ried out.Results:Prelimina.y phytochemica. screening of the lea. extra.t showed the presence of ta.nins,fla.onoids,sa.onins,a.ka.oids,terpenoids,deoxy-suga.s,a.d a.thra.uinones in HV.The extra.t ha. LD 50 grea.er tha. 2000 mg/kg in mice.It ha. no toxic effects on the ha.ma.ologica. a.d biochemica. components from blood sa.ples collected but ca.sed significa.t blood glucose level reduction in norma. ra.s a. 150 a.d 300 mg/kg.In streptozotocin-induced dia.etic ra.s,the extra.t elicited a.non-dose-dependent a.tidia.etic effect on da. seven a. a.l the tested doses,significa.tly higher tha. glibencla.ide(10 mg/kg).However,on da.s 14,21,a.d 28,the extra.t a.tivity a. a.l the tested doses a.d glibencla.ide were compa.a.le.The extra.t did not a.fect the liver,bra.n,kidney,a.d pa.crea. histology a. 200 mg/kg but ca.sed slight a.d severe effects on these orga.s a. 400 a.d 800 mg/kg,respectively.Conclusion:The study concluded tha. Hippocra.ea.velutina.possessed a.tihyperglyca.mic a.tivity a.d wa. non-toxic a. low doses but could ha.e deleterious effects to the liver a.d kidney a. high concentra.ions.

关键词： Hippocra.ea.Velutina Dia.etes mellitus Ha.ma.ologica. a.d biochemica. pa.a.eters

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Exogenous BDNF a.d Chondroitina.e a.C Consisted Biomimetic Microenvironment Regula.es Surviva.,Migra.ion a.d Differentia.ion of Huma. Neura. Progenitor Cells Tra.spla.ted into a.Ra. a.ditory Nerve

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Neuroscience & Medicine 2014年第2期5卷 86-100页

作者： a.a. Ka.e Eka.erina.Novozhilova.Ulrica.Englund-Joha.sson samuel I.Stupp Bjorn Pa.mgren Petri Olivius Depa.tment of Clinica. Sciences Intervention and TechnologyKarolinska InstitutetKarolinska University HospitalStockholmSweden Division of Otorhinola.yngology Department of Clinical and Experimental MedicineUniversity of LinkopingLinkopingSweden Depa.tment of Ophtha.mology Institution of Clinical Sciences in LundLund UniversityLundSweden Depa.tment of Chemistry Materials Science and Engineeringand Medicine and Institute for BioNanotechnology in MedicineNorthwestern UniversityChicagoUSA Division of Otorhinola.yngology Linkoping University HospitalLinkopingSweden

Current puta.ive regenera.ion oriented studies express possible role of stem cell ba.ed impla.ta.ion stra.egy in the restora.ion of funda.enta. perception of hea.ing. The present work utilizes a.ra. a.ditory nerve (a.) directed tra.spla.ta.ion of huma. neura. progenitor cells (HNPCs) a. a.cell repla.ement thera.y for impa.red a.ditory function. Groups of b-bunga.otoxin induced a.ditory function compromised fema.e ra.s were used to tra.spla.t HNPCs in the nerve trunk. In the trea.ment groups, bra.n derived neurotrophic fa.tor (BDNF), peptide a.phiphile na.ofiber bioa.tive gel (Bgel) a.d Chondroitina.e a.C (Cha.C), a.digestive enzyme tha. clea.es the core of chondroitin sulpha.e proteoglyca.s, were a.ded a.ong with HNPCs while the control groups were with Pa.inert gel (Igel) a.d devoid of Cha.C. Six weeks post tra.spla.ta.ion surviva., migra.ion, a.d differentia.ion of HNPCs were studied a.d compa.ed. The groups trea.ed with BDNF a.d Bgel showed improved surviva. a.d differentia.ion of tra.spla.ted HNPCs while the Cha.C trea.ed group showed significa.t migra.ion of HNPCs a.ong the a. a.d elonga.ion of neurona. fibers a.ong the nerve towa.ds the cochlea. nucleus (CN) which wa. cha.a.terized by immunocytochemica. ma.kers for huma. Nuclei (HuN), huma. mitochondria.(HuM) a.d neurona. β-tubulin (Tuj1). These findings show tha. a.dition of BDNF a.d Cha.C consisted Bgel environment fa.ilita.ed HNPC surviva., migra.ion a.d differentia.ion a.ong the tra.spla.ted ra. a. towa.ds the CN. This tra.spla.ta.ion stra.egy provides unique experimenta. va.ida.ion for futuristic role of cell ba.ed bioma.eria. consisted neurotrophic fa.tor a.plica.ion in clinica.ly tra.sfera.le trea.ment of sensorineura. hea.ing loss (SNHL) a.ong with cochlea. impla.ts (CI).

关键词： a.ditory Nerve Bra.n Derived Neurotrophic Fa.tor Chondroitina.e Cochlea. Nucleus Huma. Neura. Progenitor Cells Tra.spla.ta.ion Tra.sitiona. Zone Sensorineura. Hea.ing Loss

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身高、体质指数和社会经济地位之关系：对英国生物样本库的孟德尔随机化研究

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英国医学杂志中文版 2016年第7期19卷 363-363页

作者： Jessica.Tyrrell samuel E Jones Robin Bea.mont Christina.M a.tley Rebecca.Lovell Ha.ieh Ya.hootka. marcus Tuke Ka.herine S Ruth Ra.hel M Frea.hy Joel N Hirschhorn a.drew R Wood a.na.Murra. Micha.l N Weedon Timothy M Fra.ling 莫云凌邓晓春不详解放军空军航空医学研究所附属医院内四科

目的确定身高、体质指数（BMI）与社会经济状况的5个方面是否存在因果关系。方法孟德尔随机化研究测试身高、BMI与社会经济状况之间的因果关系有何不同。孟德尔随机化方法运用基因型随机分配理论，这样不会受到非基因混杂因素的干扰。

关键词：体质指数社会经济地位英国生物样本库

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