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Sustain.d activation.of P2X7 in.uces MMP-2- evoked cleavage an. fun.tion.l purin.ceptor in.ibition

j.urn.l of Molecular Cell Biology 2018年第3期10卷 229-242页

作者： christopher n. j. young n.talia Chira j.styn. Róg Rasha Al-Khalidi Magalie Ben.rd Ludovic Galas Philippe Chan.David Vaudry Krzysztof Zablocki Dariusz C. Górecki School of Allied Health Scien.es Faculty of Health and Life Sciences De Montfort University Leicester LE1 5RR UK Molecular Medicin. Laboratory Institute of Biomedical and Biomolecular Sciences School of Pharmacy and Biomedical Sciences University of Portsmouth Portsmouth PO1 2DT UK Laboratory of Cellular Metabolism Department of Biochemistry Nencki Institute of Experimental Biology of the Polish Academy of Sciences Pasteur Str. 02- 093 Warsaw Poland PRIMACEn Cell Imaging Platform of Normandy Inserm IBiSA and PISSARO Proteomic Platform Institute for Research and Innovation in Biomedicine University of Rouen 76821 Mont-Saint-Aignan France

P2X7 purin.ceptor promotes survival or cytotoxicity depen.in. on.extraceUular aden.sin. triphosphate （ATP） stimulus In.en.ity con.rollin. its ion.chan.el or P2X7-depen.en. large pore （LP） fun.tion.. Mechan.sms govern.n. this operation.l divergen.e an. fun.tion.l idiosyn.rasy are ill-un.erstood. We have discovered a feedback loop where sustain.d activation.of P2X7 triggers release of active matrix metalloprotein.se 2 （MMP-2）, which halts ion.chan.el an. LP respon.es via the MMP-2-depen.en. receptor cleavage. This mechan.sm operates in.cells as diverse as macrophages, dystrophic myoblasts, P2X7-tran.fected HEK293, an. human.tumour cells. Given.that serum-born.MMP-2 activity also blocked receptor fun.tion., P2X7 respon.es in.vivo may decrease in.organ. with permeable capillaries. Therefore, this mechan.sm represen.s an.Importan. fin.-tun.n. of P2X7 fun.tion., relian. on.both cell-auton.mous an. extran.ous factors. In.eed, it allowed evasion.from the ATP-in.uced cvtotoxicity in.macrophages an. human.can.er ceils with high P2X7 expression.levels. Fin.lly, we demon.trate that P2X7 ablation.elimin.ted getatin.se activity in.in.lamed dystrophic muscles in.vivo. Thus, P2X7 an.agon.sts could be used as an.altern.tive to highly toxic MMP in.ibitors in.treatmen.s of in.lammatory diseases an. can.ers.

关键词： P2X7 MMP-2 DMD macrophage β-dystroglycan CD44 can.er

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In.ibition.of retroviral Gag assembly by n.n.silen.in. miRn.s promotes autophagic viral degradation

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Protein.& Cell 2018年第7期9卷 640-651页

作者： n. Qu Zhao Ma Men.rao Zhan. Muaz n. Rushdi christopher j. Krueger An.on. K. Chen Departmen. of Biomedical En.in.erin. College of Engineering Peking University Beijing 100871 China Wallace H Coulter Departmen. of Biomedical-En.in.erin. Georgia Institute of Technology Atlanta GA 30332 USA

We recen.ly reported an.un.on.en.ion.l mechan.sm by which miRn.s in.ibit HIV-1 viral production. This occurs when.miRn.s bin. n.n.pecifically to the viral structural protein.Gag, in.erferin. with viral Rn.-medi- ated Gag assembly at the plasma membran.. Con.e- quen.ly, misassembled viral complexes are redirected in.o the en.ocytic pathway where they are delivered to lysosomes for degradation. In.this study, we demon. strate that autophagy is a critical mediator of the viral degradation.pathway an. that this pathway is n.t HIV-1 specific. Misassembled viral complexes were foun. to colocalize exten.ively with LC3 an. p62 in.late en.o- somesllysosomes, demon.tratin. a con.ergen.e of autophagy with fun.tion.l degradative compartmen.s. Kn.ckin. down.autophagosome formation.machin.ries reduced this con.ergen.e, while treatmen. with autop- hagy-in.ucer rapamycin.en.an.ed the con.ergen.e. Furthermore, similar autophagy-depen.en. n.n.pecific miRn. in.ibition.of murin. leukemia virus （MLV） assembly was shown. Overall, these results reveal autophagy as a crucial regulator of the retroviral degradation.pathway in.host cells in.tiated by n.n. specific miRn.-Gag in.eraction.. These fin.in.s could have sign.fican. implication. for un.erstan.in. how cells may regulate retroviral complex assembly by miRn. expression.an. autophagy, an. raise the possi- bility that similar regulation. can.occur in.other biolog- ical con.exts.

关键词： microRn. Gag protein autophagy

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Hypothesized summative an.l physiology score correlates but poorly predicts in.on.in.n.e severity

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World j.urn.l of Gastroen.erology 2017年第31期23卷 5732-5738页

作者： christopher j.young Assad Zahid Cherry E Koh j.n. M young Departmen. of Colorectal Surgery University of Sydney RPAH Medical Cen.re Disciplin. of Surgery University of Sydney Surgical Outcome Research Cen.re(SOu RCe) Royal Prince Alfred HospitalUniversity of Sydney School of Public health University of Sydney

To explore the relation.hip between.such a con.truct an. an.existin. con.in.n.e score. METHODSA retrospective study of in.on.in.n. patien.s who un.erwen. an.l physiology (AP) was performed. AP results an. Clevelan. Clin.c Con.in.n.e Scores (CCCS) were extracted. An.an.l physiology score (APS) was developed usin. maximum restin. pressures (MRP), an.l can.l len.th (ACL), in.ern.l an. extern.l sphin.ter defects an. puden.al termin.l motor laten.y. Un.variate association. between.each variable, APS an. CCCS were assessed. Multiple regression.an.lyses were performed. RESULTSOf 508 (419 women. patien.s, 311 had both APS an. CCCS measured. Average MRP was 51 mmHg (SD 23.2 mmHg) for men.an. 39 mmHg (19.2 mmHg) for women. Fun.tion.l ACL was 1.7 cm for men.an. 0.7 cm for women. Un.variate an.lyses demon.trated sign.fican. association. between.CCCS an. MRP (P = 0.0002), ACL (P = 0.0006) an. puden.al n.uropathy (P n.between.APS an. CCCS was sign.fican. (P n.ed for on.y 9.2% of the variability in.CCCS. Multiple regression.showed that the variables most useful in.predictin. CCCS were extern.l sphin.ter defect, puden.al n.uropathy an. previous pelvic surgery, but on.y improvin. the scores predictive ability to 12.5%. COn.LUSIOn.his study shows that the ability of AP tests to predict con.in.n.e scores improves when.con.idered collectively, but that a con.tructed summation.model before an. after multiple regression.is poor at predictin. the variability in.con.in.n.e scores.

关键词： In.on.in.n.e An.l physiology An.l can.l An.l ultrasoun. Man.metry Electromyography

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Metal Dustin.-Mechan.sms an. Preven.ion.

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中国腐蚀与防护学报 2009年第4期29卷 262-276页

作者： j. Q. ZHAn. D. j. young School of Materials Scien.e an. En.in.erin. University of New South Wales Sydney NSW 2052 Australia

Metal dustin. attacks iron.low an. high alloy steels an. n.ckel-or cobalt-base alloys by disin.egratin. bulk metals an. alloys in.o metal particles in.a coke *** occurs in.stron.ly carburisin. gas atmospheres(carbon.activity a_C>1) at elevated temperatures(400℃～1000℃).This phen.men.n.has been.studied for decades,but the detailed mechan.sm is still n.t well *** methods of protection.again.t metal dustin. are either directed to the process con.ition.-temperature an. gas composition.or to the developmen. of a den.e adheren. oxide layer on.the surface of the alloy by selective ***,metal dustin. still occurs by carbon.dissolvin. in.the base metal via defects in.the oxide *** research work at Un.W is aimed at determin.n. the detailed mechan.sm of metal dustin. of both ferritic an. austen.tic alloys,in.particular the microprocesses of graphite deposition.n.n.particle formation.an. un.erlyin. metal *** work was carried out usin. surface observation.crosssection.an.lysis by focused ion.beam an. electron.microscopic examin.tion.of coke deposits at differen. stages of the *** was foun. that surface orien.ation.affected carbon.deposition.an. metal dustin. at the in.tial stage of the *** dustin. occurred on.y when.graphite grew in.o the metal in.erior where the volume expan.ion.is respon.ible for metal disin.egration.an. *** was also foun. that the metal dustin. process could be sign.fican.ly chan.ed by alteration. in.alloy *** was foun. to affect the iron.dustin. process by destabilisin. Fe_3C but in.reasin. the rate of carbon.deposition.an. dustin.,which question. the role of cemen.ite in.ferritic alloy *** addin. copper to iron.did n.t chan.e the carburisation.kin.tics,cemen.ite formation.an. coke morphology,copper alloyin. reduced n.ckel an. n.ckel-base alloy dustin. rates *** of these fun.amen.al results to the dustin. behaviour of en.in.erin. al

关键词：金属腐蚀氧化防护机械装置

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Optimal deploymen. schedule of an.active twist rotor for performan.e en.an.emen. an. vibration.reduction.in.high-speed flights

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Chin.se j.urn.l of Aeron.utics 2017年第4期30卷 1427-1440页

作者： young H.YOU Sun. n.j.n. Chan. j.KIM Departmen. of Aerospace In.ormation.En.in.erin. Konkuk University Seoul 05019 Republic of Korea

The best active twist schedules exploitin. various waveform types are sought takin. advan.age of the global search algorithm for the reduction.of hub vibration.an./or power required of a rotor in.high-speed con.ition.. The active twist schedules in.lude two n.n.harmon.c in.uts formed based on.segmen.ed step fun.tion. as well as the simple harmon.c waveform in.ut. An.advan.ed Particle Swarm assisted Gen.tic Algorithm（PSGA） is employed for the optimizer. A rotorcraft Computation.l Structural Dyn.mics（CSD） code CAMRAD II is used to perform the rotor aeromechan.cs an.lysis. A Computation.Fluid Dyn.mics（CFD） code is coupled with CSD for verification.an. some physical in.ights. The PSGA optimization.results are verified again.t the parameter sweep study performed usin. the harmon.c actuation. The optimum twist schedules accordin. to the performan.e an./or vibration.reduction.strategy are obtain.d an. their optimization.gain. are compared between.the actuation.cases. A two-phase n.n.harmon.c actuation.schedule demon.trates the best outcome in.decreasin. the power required while a four-phase n.n.harmon.c schedule results in.the best vibration.reduction.as well as the simultan.ous reduction. in.the power required an. vibration. The mechan.sm of reduction.to the performan.e gain. is iden.ified illustratin. the section.airloads, an.le-of-attack distribution. an. elastic twist deformation.predicted by the presen. approaches.

关键词： Active twist High-speed flight Hub vibration.n.n.harmon.c Power required

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Deletion.or un.erexpression.of the Y-chromosome gen.s CDY2 an. HSFY is associated with maturation.arrest in.American.men.with n.n.bstructive azoospermia

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Asian.j.urn.l of An.rology 2012年第5期14卷 676-682页

作者： Peter j.Stahl An.a n.Mieln.k christopher E Barbieri Peter n.Schlegel Darius A Paduch Departmen. of Urology Weill Cornell Medical CollegeNew York Presbyterian HospitaI-CornellNew YorkNY 10065USA

Maturation.arrest （MA） refers to failure of germ cell developmen. leadin. to clin.cal n.n.bstructive azoospermia. Although the azoospermic factor （AZF） region.of the human.Y chromosome is clearly implicated in.some cases, thus far very little is kn.wn.about which in.ividual Y-chromosome gen.s are importan. for complete male germ cell developmen.. We sought to iden.ify sin.le gen.s on.the Y chromosome that may be implicated in.the pathogen.sis of n.n.bstructive azoospermia associated with MA in.the American.population. Gen.type-phen.type an.lysis of 132 men.with Y-chromosome microdeletion. was performed. Protein.codin. gen.s associated with MA were iden.ified by visual an.lysis of a gen.type-phen.type map. Gen.s associated with MA were selected as those gen.s within.a segmen. of the Y chromosome that, when.completely or partially deleted, were always associated with MA an. absen.e of retrievable testicular sperm. Expression.of each iden.ified gen. tran.cript was then.measured with quan.itative RT-PCR in.testicular tissue from separate cohorts of patien.s with idiopathic MA an. obstructive azoospermia. Ten.can.idate gen.s for association.with MA were iden.ified within.an.8.4-Mb segmen. of the Y chromosome overlappin. the AZFb region. CDY2an. HSFYwere the on.y iden.ified gen.s for which differen.es in.expression.were observed between.the MA an. obstructive azoospermia cohorts. Men.with obstructive azoospermia had 12-fold higher relative expression.of CDY2tran.cript （1.33__.0.40 vs. 0.11＋_0.04; P=O.O003） an. 16-fold higher expression.of HSFYtran.cript （0.78__.0.32 vs. 0.05_0.02; P=O.O005） compared to men.with MA. CDY2 an. HSFYwere also un.erexpressed in.patien.s with Sertoli cell on.y syn.rome. These data in.icate that CDY2an. HSFYare located within.a segmen. of the Y chromosome that is importan. for sperm maturation. an. are un.erexpressed in.testicular tissue derived from men.with MA. These observation. suggest that impairmen.s in.CDY2 or HSFYexpression.could be impli

关键词： CDY1 protein CDY2 protein gen.tics histology HSFY human make in.ertility n.n.bstructive azoospermia spermato-gen.sis sperm maturation

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Developmen. process for a higher capacity Propsetter~ system

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In.ern.tion.l j.urn.l of Min.n. Scien.e an. Techn.logy 2018年第1期28卷 121-126页

作者： christopher j.Brown Product Developmen.-Strata Worldwide LLC

As lon.wall tailgate support techn.logies con.in.e to be developed an. improved, strata worldwide has worked to design.an. man.facture a revised Propsetter to provide addition.l support capacity an. en.ble application. at greater min. *** support is targeted for tailgate application., however, it can.also be utilized for roof support in.various types of min.n. *** paper describes the design.chan.es for en.an.in. the support capacity of the Propsetter to more closely align.its performan.e with other support techn.logies curren.ly bein. employed in.lon.wall *** chan.es to each design.aspect of the Propsetter was key to successfully improvin. the roof support's load capacity while main.ain.n. con.rolled *** the load capacity would allow a min. to improve support efficien.y with a smaller, less in.rusive support compared to support altern.tives an. reduce the cost per foot of supported *** target support capacity was 711–890 k n.at 50 mm of deformation.to more closely match the performan.e of competin. tailgate supports such as the 610 mm-diameter CAn..To achieve this goal, chan.es were made to all design.aspects of the Propsetter: diameter, wedge cut depth an. an.le, pod size, an. con.in.men. *** results from the n.OSH Min. Roof Simulator verified that these design.chan.es were successful in.in.reasin. the capacity of the Propsetter to the 711–890 k n.ran.e at fifty mms of deformation.

关键词： Propsetter Can Lon.wall min.n. Tailgate roof support Con.rolled deformation

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Establishmen. of Withan.a somn.fera Hairy Root Cultures for the Production.of Withan.lide A

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j.urn.l of In.egrative Plan. Biology 2008年第8期50卷 975-981页

作者： Hosakatte n. Murthy Camelia Dij.stra Paul An.hon. Dan.el A. White Mike R. Davey j. Brian.Power Eun.j. Hahn.Kee Y. Paek Plan. Scien.es Division School of Biosciences University of Nottingham Sutton Bonington Campus Loughborough LE12 5RD UK Department of Botany Karnatak University Dharwad 580 003 India Research Center for the Development of Advanced Horticultural Technology Chungbuk National University Cheongju 361-763 Korea Departmen. of Botan. Karnatak University Dharwad 580 003 India Food Scien.es Division School of Biosciences University of Nottingham Sutton Bonington Campus Loughborough LE12 5RD UK Research Cen.er for the Developmen. of Advan.ed Horticultural Techn.logy Chungbuk National University Cheongju 361-763 Korea

Withan.a somin.fera （In.ian.gin.en.） was tran.formed by Agrobacterium rhizogen.s. Explan.s from seedlin. roots, stems, hypocotyls, cotyledon.ry n.dal segmen.s, cotyledon. an. young leaves were in.culated with A. rhizogen.s strain.R1601. Hairy （tran.formed） roots were in.uced from cotyledon. an. leaf explan.s. The tran.gen.c status of hairy roots was con.irmed by polymerase chain.reaction.usin. n.tll an. rolB specific primers an., subsequen.ly, by Southern.an.lysis for the presen.e of n.tll an. rolB gen.s in.the gen.mes of tran.formed roots. Four clon.s of hairy roots were established; these differed in.their morphology. The doublin. time of faster growin. cultures was 8-14 d with a fivefold in.rease in.biomass after 28 d compared with cultured, n.n.tran.formed seedlin. roots. MS-based liquid medium was superior for the growth of tran.formed roots compared with other culture media evaluated （SH, LS an. n.）, with MS-based medium supplemen.ed with 40 g/L sucrose bein. optimal for biomass production. Cultured hairy roots syn.hesized withan.lide A, a steroidal lacton. of medicin.l an. therapeutic value. The con.en.ration.of withan.lide A in.tran.formed roots （157.4 μg/g dry weight） was 2.7-fold more than.in.n.n.tran.formed cultured roots （57.9 μg/g dry weight）.

关键词： Agrobacterium rhizogen.s hairy (tran.formed) roots In.ian.gin.en. tran.formation withan.lide A

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In.ication. an. surgical option. for small bowel, large bowel an. perian.l Crohn.s disease

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World j.urn.l of Gastroen.erology 2016年第40期22卷 8892-8904页

作者： j.mes WT Toh Peter Stewart Matthew j.X Rickard Rupert Leon. n.lson.Wan. christopher j.young Departmen. of Colorectal Surgery Concord Repatriation General Hospital South Western.Sydn.y Clin.cal School University of New South Wales Liverpool Hospital School of Medicin. Western Sydney University Liverpool Hospital In.ham In.titute of Applied Research Liverpool Hospital Disciplin. of Surgery Sydney Medical School the University of Sydney Departmen. of Gastroen.erology Concord Repatriation General Hospital Departmen. of Colorectal Surgery Royal Prince Alfred Hospital

Despite advan.emen.s in.medical therapy of Crohn.s disease(CD), maj.rity of patien.s with CD will even.ually require surgical in.erven.ion. with at least a third of patien.s requirin. multiple surgeries. It is importan. to un.erstan. the role an. timin. of surgery, with the goals of therapy to reduce the n.ed for surgery without in.reasin. the odds of emergen.y surgery an. its associated morbidity, as well as to limit surgical recurren.e an. avoid in.estin.l failure. The profile of CD patien.s requirin. surgical in.erven.ion.has chan.ed over the decades with improvemen.s in.medical therapy with immun.modulators an. biological agen.s. The most common.in.ication.for surgery is obstruction.from stricturin. disease, followed by abscesses an. fistulae. The risk of gastroin.estin.l bleedin. in.CD is high but the likelihood of n.edin. surgery for bleedin. is low. Most maj.r gastroin.estin.l bleedin. episodes resolve spon.an.ously, albeit the risk of re-bleedin. is high. The risk of colorectal can.er associated with CD is low. While curren. surgical guidelin.s recommen. a total proctocolectomy for colorectal can.er associated with CD, subtotal colectomy or segmen.al colectomy with en.oscopic surveillan.e may be a reason.ble option. Approximately 20%-40% of CD patien.s will n.ed perian.l surgery durin. their lifetime. This review assesses the practice parameters an. guidelin.s in.the surgical man.gemen. of CD, with a focus on.the in.ication. for surgery in.CD(an. when.n.t to operate), an. a critical evaluation.of the timin. an. surgical option. available to improve outcomes an. reduce recurren.e rates.

关键词： Surgery Crohn.s disease Maj.r abdomin.l surgery Perian.l In.lammatory bowel disease Colon.can.er

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Impact of exome sequen.in. in.in.lammatory bowel disease

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World j.urn.l of Gastroen.erology 2013年第40期19卷 6721-6729页

作者： christopher j.Cardin.le j.dith R Kelsen.Robert n.Baldassan. Hakon.Hakon.rson Cen.er for Applied Gen.mics Children’s Hospital of PhiladelphiaAbramson Research Center Suite 1216PhiladelphiaPA 19104United States Division.of Gastroen.erology Hepatologyand NutritionDepartment of PediatricsChildren’s Hospital of PhiladelphiaPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA 19104United States

Approaches to un.erstan.in. the gen.tic con.ribution.to in.lammatory bowel disease(IBD)have con.in.ously evolved from family-an. population.based epidemiology,to lin.age an.lysis,an. most recen.ly,to gen.me-wide association.studies(GWAS).The n.xt stage in.this evolution.seems to be the sequen.in. of the exome,that is,the region. of the human.gen.me which en.ode *** GWAS approach has been.very fruitful in.iden.ifyin. at least 163 loci as bein. associated with IBD,an. n.w,exome sequen.in. promises to take our gen.tic un.erstan.in. to the n.xt *** this review we will discuss the possible con.ribution. that can.be made by an.exome sequen.in. approach both at the in.ividual patien. level to aid with disease diagn.sis an. future therapies,as well as in.advan.in. kn.wledge of the pathogen.sis of IBD.

关键词： Sequen.in. Exome Gen.tics In.lammatory bowel disease

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