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手术与非手术治疗腰椎间盘突出症比较：脊柱患者疗效研究试验（SPORT）观察性队列研究

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美国医学会杂志（中文版） 2007年第6期26卷 364-364页

作者： James n. Weinstein Jon D. Lurie tor D. Tosteson 武文（译）戴尅戎（校）严孟宁（校）

背景：一项名为“脊柱患者疗效研究试验（Spine Patient Outcomes Research Trial，SPORT）”的随机试验经意向治疗分析显示，对于腰椎间盘突出症患者而言，椎间盘切除术优于常规治疗，但二者差异较小，无显著的统计学差异。然而，由于... 详细信息

背景：一项名为“脊柱患者疗效研究试验（Spine Patient Outcomes Research Trial，SPORT）”的随机试验经意向治疗分析显示，对于腰椎间盘突出症患者而言，椎间盘切除术优于常规治疗，但二者差异较小，无显著的统计学差异。然而，由于大量患者在试验分组间换来换去，因此无法得出手术治疗相对常规治疗更有效的结论。目的：比较椎间盘切除术与常规治疗的疗效。设计、地点及参试者：本前瞻性队列研究观察了2000年3月至2003年3月期间经影像学检查证实患有腰椎间盘突出症的患者，这些患者在美国11个州的13家脊柱诊所接受治疗，符合SPORT试验纳入标准但拒绝进行随机分组。干预：标准的开放式椎间盘切除术以及常规非手术治疗。主要观测指标：健康调查简表（SF-36）中躯体疼痛评分和机能评分较基线时的变化，改良的Oswestry残疾指数（美国骨科医生协会，MODEMS版）较基线时的变化。结果：在纳入观察性队列的743例患者中，528例患者接受了手术治疗，191例患者接受了非手术常规治疗。3个月时，手术治疗组患者在躯体疼痛评分（平均变化：手术治疗组为40．9，非手术治疗组为26．0；疗效，14．8；95％可信区间，10．8～18．9）、机能评分（平均变化：手术治疗组为40．7，非手术治疗组为25．3；疗效15．4；95％可信区间，11．6—19．2）及Oswestry残疾指数（平均变化：手术治疗组为-36．1，非手术治疗组为-20．9；疗效，-15．2；95％可信区间，-18．5～-11．8）等主要预后指标方面均有明显改善。躯体疼痛评分（平均变化：手术治疗组为42．6，非手术治疗组为32．4；疗效，10．2；95％可信区间，5．9～14．5）、机能评分（平均变化：手术治疗组为43．9，非手术治疗组为31．9；疗效，12．0；95％可信区间，7．9～16．1）和Oswestry残疾指数（平均变化：手术治疗组为-37．6，非手术治疗组为-24．2；疗效，-13．4；95％可信区间，-17．0～-9．7）的差异在术后2年时略有减小。结论：伴有持续性坐骨神经痛的腰椎间盘突出症患者无论采取外科手术还是常规治疗病情均可有所改善。选择手术干预的患者较非手术治疗患者病情改善更为明显。但是，对患者自测结果进行非随机比较会受到潜在混淆因素的影响，故必须谨慎分析。

关键词：腰椎间盘突出症前瞻性队列研究非手术治疗随机试验疗效脊柱椎间盘切除术疼痛评分

Diversity in Macrobenthic &Algal Fauna of Limha Pond, Ghutku Bilaspur India

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Open Journal of Marine Science 2014年第2期4卷 43-50页

作者： Pratibha Pandey Pankaj K. Sahu yogendra n. Jha Atul K. Shrivastava Department of Botany Dr. C.V. Raman University Kota Bilaspur India Department of Zoology Dr. C.V. Raman University Kota Bilaspur India Department of Zoology Govt. Science College Jhanjhgir Champa India Directorate of Research Services JNKVV Jabalpur India

The present study reported on phytoplankton in comparison to the zooplankton in Limha Pond, Ghutku, Bilaspur. The phytoplankton represented in larger number of Cyanophyceae with least density of Dinophyceae and Chlorophyceac, and Bacillariophyceae is the second dominant group. The present study tried to discuss on the problem Macrobenthic fauna of Limha Pond, Ghutku Bilaspur and observed quantitative algal and faunal diversity i.e. phytoplankton (34 species), aquatic organism (6 species) Bacillariophyceae (8 species), Chlorophyceae (11 species), Euglenophyceae (6 species), Zooplankton (20 species), and Fish species (16 species). Present study revealed that Cyprinidae (carps) were the dominant fish and Catla was a major contributor among carps. The following species Catla catla, Labeo rohita, Cirrhinus mrigala, Labeo calbasu, Barbus tor and Cirrhinus reba etc. were noted in Limha pond, Ghutku, Bilaspur.

关键词： Aquatic Community Fishes Algal Group Limha

Regulation of the PI3K/AKT Pathway and Fuel Utilization During Primate torpor in the Gray Mouse Lemur, Microcebus murinus

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Genomics, Proteomics & Bioinformatics 2015年第2期13卷 91-102页

作者： Shannon n.Tessier Jing Zhang Kyle K.Biggar Cheng-Wei Wu Fabien Pifferi Martine Perret Kenneth B.Storey Institute of Biochemistry & Department of Biology Carleton University Department of Surgery & Center for Engineering in Medicine Massachusetts General Hospital & Harvard Medical School Chemistry and Chemical Engineering Department Royal Military College of Canada Biochemistry Department Schulich School of Medicine and Dentistry Western University Department of Biology Genetics Institute University of Florida UMR 7179 Centre national de la Recherche Scientifique Muse'um National d'Histoire Naturelle

Gray mouse lemurs（Microcebus murinus） from Madagascar present an excellent model for studies of torpor regulation in a primate species. In the present study, we analyzed the response of the insulin signaling pathway as well as controls on carbohydrate sparing in six different tissues of torpid versus aroused gray mouse lemurs. We found that the relative level of phospho-insulin receptor substrate（IRS-1） was significantly increased in muscle, whereas the level of phospho-insulin receptor（IR） was decreased in white adipose tissue（WAT） of torpid animals, both suggesting an inhibition of insulin/insulin-like growth factor-1（IGF-1） signaling during torpor in these tissues. By contrast, the level of phospho-IR was increased in the liver. Interestingly, muscle,WAT, and liver occupy central roles in whole body homeostasis and each displays regulatory controls operating at the plasma membrane. Changes in other tissues included an increase in phosphoglycogen synthase kinase 3a（GSK3a） and decrease in phospho-ribosomal protein S6（RPS6） in the heart, and a decrease in phospho-mammalian target of rapamycin（m tor） in the kidney. Pyruvate dehydrogenase（PDH） that gates carbohydrate entry into mitochondria is inhibited via phosphorylation by pyruvate dehydrogenase kinase（e.g., PDK4）. In the skeletal muscle, the protein expression of PDK4 and phosphorylated PDH at Ser 300 was increased, suggesting inhibition during torpor. In contrast, there were no changes in levels of PDH expression and phosphorylation in other tissues comparing torpid and aroused animals. Information gained from these studies highlight the molecular controls that help to regulate metabolic rate depression and balance energetics during primate torpor.

关键词： Insulin signaling pathway PI3K/AKT m tor GSK3 Pyruvate dehydrogenase Metabolic rate depression

Time-of-flight methodologies with large-area diamond detectors for ion characterization in laser-driven experiments

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High Power Laser Science and Engineering 2022年第1期10卷 53-63页

作者： M.Salvadori G.Di Giorgio M.Cipriani M.Sciscio C.Verona P.L.Andreoli G.Cristofari R.De Angelis M.Pillon n.E.Andreev P.Antici n.G.Borisenko D.Giulietti M.Migliorati O.Rosmej S.Zahter F.Consoli Fusion and nuclear Safety Department ENEAFrascatiItaly InRS-EMT VarennesQCCanada Industrial Engineering Department University of Rome"Tor Vergata"RomeItaly Joint Institute for High Temperatures RASMoscowRussia P.n.Lebedev Physical Institute RASMoscowRussia Department of Physics University of PisaPisaItaly InFn of Pisa PisaItaly University of Rome“La Sapienza” RomeItaly InFn of Rome RomeItaly GSI Helmotzzentrum fur Schwerionenforschung GmbH DarmstadtGermany Goethe University Frankfurt FrankfurtGermany

The time-of-flight technique coupled with semiconductor detectors is a powerful instrument to provide real-time characterization of ions accelerated because of laser-matter ***,the presence of strong electromagnetic pulses(EMPs)generated during the interactions can severely hinder its *** this reason,the diagnostic system must be designed to have high EMP *** we present a new advanced prototype of detector,developed at EnEA-Centro Ricerche Frascati(Italy),with a large-area(15 mm×15 mm)polycrystalline diamond sensor having 150 μm *** tailored detector design and testing ensure high sensitivity and,thanks to the fast temporal response,high-energy resolution of the reconstructed ion *** detector was offline calibrated and then successfully tested during an experimental campaign carried out at the PHELIX laser facility(E_(L)~100 J,τ_(L)=750 fs,I_(L)(1-2.5)×10^(19)W/cm^(2))at GSI(Germany).The high rejection to EMP fields was demonstrated and suitable calibrated spectra of the accelerated protons were obtained.

关键词： diamond detector ion diagnostics laser-matter interaction time of flight

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天山冰川物质平衡波动和径流的同步监测

冰川冻土 1992年第3期14卷 226-232页

作者： M.B.久尔格洛夫 V.n.米哈连科 M.G.库那克霍维奇 S.n.尤希努尔特斯夫刘潮海谢自楚张万昌王纯足原苏联科学院地理研究所中国科学院兰州冰川冻土研究所

为了研究冰川物质平衡和径流形成过程的同步性,1989年夏季在图尤克苏冰川(外伊犁阿拉套山)、萨雷托尔冰川(阿克什腊克山)和乌鲁木齐河1号冰川(天格尔山)开展了同步观测。融水渗浸作用和径流过程在西天山所有高度范围、在中央天山和东天... 详细信息

为了研究冰川物质平衡和径流形成过程的同步性,1989年夏季在图尤克苏冰川(外伊犁阿拉套山)、萨雷托尔冰川(阿克什腊克山)和乌鲁木齐河1号冰川(天格尔山)开展了同步观测。融水渗浸作用和径流过程在西天山所有高度范围、在中央天山和东天山下部地带均有发生。夏季,中央天山4800—5000m以上的山地持续雪的积累,而未形成表面径流。最大负物质平衡出现在西天山的北天山。在冰川负物质平衡的年份里,增补的融水注入河流,这一过程在西天山持续到8月上旬到9月底,而在东天山和中央天山则持续到8月末。

关键词：天山冰川物质平衡波动径流

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成人卵黄样黄斑变性的OCT3改变

世界核心医学期刊文摘（眼科学分册） 2005年第1期1卷 18-18页

作者：李晶明 Benhamou n Messas-Kaplan A Cohen y Department of Ophthalmol -og y Assaf Harofeh Medical CenterZ erifinIsrael.Dr

Purpose To report the morphologic data of adult-onset foveomacular vitelliform dystrophy(AFVD)provided by thirdgeneration optical coherence tomography(OCT 3).Design Observational case *** An 85-year-old woman presenting with AFVD underwen t fundus biomi-croscopy,fluorescein angiography,and OCT *** Fundus examination disclosed a round,elevated yellowish lesion,centered by a pigm ented spot,in the macula of the left *** with OCT disclosed an area of hyperreflectivity located b etween the retinal pigment epithelium layer and the photorecep tor layer,compatible in size with the yellowish elevated *** hyperreflective line corresponding to the photoreceptor layer was elevated by the material and separated from th e retinal pigment ep-ithelium *** In AFVD,examination with OCT 3demonstrates elevation of the p hotoreceptor layer by the material and supports the previo us hypothesis that the material is located between the photoreceptor and the reti-nal pigment epithelium layer.

关键词：卵黄样黄斑变性 OCT3 视网膜色素上皮光感受器黄斑部眼底检查隆起性病变生物显微镜色素性反射区

Search for the rare decays W^(+)→D_(s)^(+)γ and Z→D^(0)γ at LHCb

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中国物理C:英文版 2023年第9期47卷 14-26页

作者： R.Aaij A.S.W.Abdelmotteleb C.Abellan Beteta F.Abudinén T.Ackernley B.Adeva M.Adinolfi P.Adlarson H.Afsharnia C.Agapopoulou C.A.Aidala Z.Ajaltouni S.Akar K.Akiba J.Albrecht F.Alessio M.Alexander A.Alfonso Albero Z.Aliouche P.Alvarez Cartelle R.Amalric S.Amato J.L.Amey y.Amhis L.An L.Anderlini M.Andersson A.Andreianov M.Andreotti D.Andreou D.Ao F.Archilli A.Artamonov M.Artuso E.Aslanides M.Atzeni B.Audurier S.Bachmann M.Bachmayer J.J.Back A.Bailly-reyre P.Baladron Rodriguez V.Balagura W.Baldini J.Baptista de Souza Leite M.Barbetti R.J.Barlow S.Barsuk W.Barter M.Bartolini F.Baryshnikov J.M.Basels G.Bassi B.Batsukh A.Battig A.Bay A.Beck M.Becker F.Bedeschi I.B.Bediaga A.Beiter V.Belavin S.Belin V.Bellee K.Belous I.Belov I.Belyaev G.Benane G.Bencivenni E.Ben-Haim A.Berezhnoy *** *** Andres D.Berninghoff H.C.Bernstein C.Bertella A.Bertolin C.Betancourt F.Betti Ia.Bezshyiko S.Bhasin J.Bhom L.Bian M.S.Bieker n.V.Biesuz S.Bifani P.Billoir A.Biolchini M.Birch F.C.R.Bishop A.Bitadze A.Bizzeti M.P.Blago T.Blake F.Blanc J.E.Blank S.Blusk D.Bobulska J.A.Boelhauve O.Boente Garcia T.Boettcher A.Boldyrev C.S.Bolognani R.Bolzonella n.Bondar F.Borgato S.Borghi M.Borsato J.T.Borsuk S.A.Bouchiba T.J.V.Bowcock A.Boyer C.Bozzi M.J.Bradley S.Braun A.Brea Rodriguez J.Brodzicka A.Brossa Gonzalo J.Brown D.Brundu A.Buonaura L.Buonincontri A.T.Burke C.Burr A.Bursche A.Butkevich J.S.Butter J.Buytaert W.Byczynski S.Cadeddu H.Cai R.Calabrese L.Calefice S.Cali R.Calladine M.Calvi M.Calvo Gomez P.Campana D.H.Campora Perez A.F.Campoverde Quezada S.Capelli L.Capriotti A.Carbone G.Carboni R.Cardinale A.Cardini P.Carniti L.Carus A.Casais Vidal R.Caspary G.Casse M.Cattaneo G.Cavallero V.Cavallini S.Celani J.Cerasoli D.Cervenkov A.J.Chadwick M.G.Chapman M.Charles Ph.Charpentier C.A.Chavez Barajas M.Chefdeville C.Chen S.Chen A.Chernov S.Chernyshenko V.Chobanova S.Cholak M.Chrzaszcz A.Chubykin V.Chulikov P.Ciambrone M.F.Cicala X.Cid Vidal G.Ciezarek G.Ciullo P.E.L.Clarke M.Clemencic H.V.Cliff J.Closier J.L.Cobbledick V.Coco J.A.B.Coelho J.Cogan E.Cognera Centro Brasileiro de Pesquisas Físicas(CBPF) Rio de JaneiroBrazil Universidade Federal do Rio de Janeiro(UFRJ) Rio de JaneiroBrazil Center for High Energy Physics Tsinghua UniversityBeijingChina Institute Of High Energy Physics(IHEP) BeijingChina School of Physics State Key Laboratory of nuclear Physics and Technology Peking UniversityBeijingChina University of Chinese Academy of Sciences BeijingChina Institute of Particle Physics Central China Normal UniversityWuhanHubeiChina Université Savoie Mont Blanc CNRSIN2P3-LAPPAnnecyFrance UniversitéClermont Auvergne CNRS/IN2P3LPCClermont-FerrandFrance Aix Marseille Univ CNRS/IN2P3CPPMMarseilleFrance UniversitéParis-Saclay CNRS/IN2P3IJCLabOrsayFrance Laboratoire Leprince-Ringuet CNRS/IN2P3Ecole PolytechniqueInstitut Polytechnique de ParisPalaiseauFrance LPnHE Sorbonne UniversitéParis Diderot Sorbonne Paris CitéCNRS/IN2P3ParisFrance I.Physikalisches Institut RWTH Aachen UniversityAachenGermany Fakultat Physik Technische Universitat DortmundDortmundGermany Max-Planck-Institut für Kernphysik(MPIK) HeidelbergGermany Physikalisches Institut Ruprecht-Karls-Universitat HeidelbergHeidelbergGermany School of Physics University College DublinDublinIreland InFn Sezione di Bari BariItaly InFn Sezione di Bologna BolognaItaly InFn Sezione di Ferrara FerraraItaly InFn Sezione di Firenze FirenzeItaly InFn Laboratori nazionali di Frascati FrascatiItaly InFn Sezione di Genova GenovaItaly InFn Sezione di Milano MilanoItaly InFn Sezione di Milano-Bicocca MilanoItaly InFn Sezione di Cagliari MonserratoItaly Universitàdegli Studi di Padova Universitàe INFNPadovaPadovaItaly InFn Sezione di Pisa PisaItaly InFn Sezione di Roma La Sapienza RomaItaly InFn Sezione di Roma tor Vergata RomaItaly nikhef national Institute for Subatomic Physics AmsterdamNetherlands nikhef national Institute for Subatomic Physics and VU University Amsterdam AmsterdamNetherlands AGH-University of Science and Technology Faculty of Physics and Applied Computer Scienc

A search for the rare decays W^(+)→D_(s)^(+)γ and Z→D0γis performed using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of 13TeV,corresponding to an integrated luminosity of 2.0fb−*** significant signal is observed for either decay mode and upper limits on their branching fractions are set using W^(+)→D_(s)^(+)γ and Z→μ+μ−decays as normalization *** upper limits are 6.5×10^(−4) and 2.1×10^(−3) at 95% confidence level for the W^(+)→D_(s)^(+)γ and Z→D^(0)γ decay modes,*** is the first reported search for the Z→D^(0)γ decay,while the upper limit on the W+→D+sγbranching fraction improves upon the previous best limit.

关键词： W/Z boson rare decay upper limit of branching fraction

Search for the rare decay B^(0)→J/ψФ

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Chinese Physics C 2021年第4期45卷 47-60页

作者： R.Aaij C.Abellin Beteta T.Ackernley B.Adeva M.Adinolfi H.Afsharnial C.A.Aidala S.Aiola Z.Ajaltouni S.Akar J.Albrecht F.Alessio M.Alexander A.Alfonso Albero Z.Aliouche G.Alkhazov P.Alvarez Cartelle S.Amato y.Amhis L.An L.Anderlini A.Andreianov M.Andreotti F.Archilli A.Artamonov M.Artuso K.Arzymatov E.Aslanides M.Atzeni B.Audurier S.Bachmann M.Bachmaver J.J.Back S.Baker P.Baladron Rodriguez V.Balagura W.Baldinit J.Baptista Leite R.J.Barlow S.Barsuk W.Barter M.Bartolini F.Baryshnikov J.M.Basels G.Bassi B.Batsukh A.Battig A.Bay M.Becker F.Bedeschis I.Bediaga A.Beiter V.Belavin S.Belin V.Bellee K.Belous I.Belov I.Belyaev G.Bencivenni E.Ben-Haim A.Berezhnoy *** D.Berninghoff H.C.Bernstein C.Bertella E.Bertholet A.Bertolin C.Betancourt F.Betti M.O.Bettler Ia.Bezshyiko S.Bhasin J.Bhom L.Bian M.S.Bieker S.Bifani P.Billoir M.Birch F.C.R.Bishop A.Bizzeti M.Biorn M.P.Blago T.Blake F.Blanc S.Blusk D.Bobulska J.A.Boelhauve O.Boente Garcia T.Boettcher A.Boldyrev A.Bondar n.Bondar S.Borghi M.Borisyak M.Borsato J.T.Borsuk S.A.Bouchiba T.J.V.Bowcock A.Boyer C.Bozzi M.J.Bradley S.Braun A.Brea Rodriguezs M.Brodski J.Brodzicka A.Brossa Gonzalo D.Brundu A.Buonaura C.Burr A.Burschee A.Butkevich J.S.Butter J.Buytaert W.Byczynski S.Cadeddu H.Cai R.Calabrese L.Calefice L.Calero Diaz S.Cali R.Calladine M.Calvi M.Calvo Gomez P.Camargo Magalhaes A.Camboni P.Campana D.H.Campora Perez A.F.Campoverde Quezada S.Capelli L.Capriotti A.Carbonel G.Carboni R.Cardinale A.Cardini I.Carli P.Carniti L.Carus K.Carvalho Akiba A.Casais Vidal G.Casse M.Cattaneo G.Cavallero S.Celani J.Cerasoli A.J.Chadwick M.G.Chapman M.Charles Ph.Charpentier G.Chatzikonstantinidis C.A.Chavez Barajas M.Chefdeville C.Chen S.Chen A.Chernov S.-G.Chitic V.Chobanova S.Cholak M.Chrzaszcz A.Chubykin V.Chulikov P.Ciambrone M.F.Cicala X.Cid Vidal G.Ciezarek P.E.L.Clarke M.Clemencic H.V.Cliff J.Closier J.L.Cobbledick V.Coco J.A.B.Coelho J.Cogan E.Cogneras L.Cojocariu P.Collins T.Colombo L.Congedo A.Contu n.Cooke G.Coombs G.Corti C.M.Costa Sobral B.Couturier D.C.Craik J.Crkovska M.Cruz Centro Brasileiro de Pesquisas Fisicas(CBPF) Riode JaneiroBrazil Universidade Federal do Riode Janeiro(UFRJ) Riode JaneiroBrazil Center for High Energy Physics Tsinghua UniversityBeijingChina School of Physics State Key Laboratory of nuclear Physics and Technology Peking UniversityBeijingChina University of Chinese Academy of Sciences BeijingChina Institute Of High Energy Physics(IHEP) BejingChina Institute of Particle Physics Central China Normal UniversityWuhanHubeiChina Univ.Grenoble Alpes Univ.Savoie Mont BlancCNRSIN2P3-LAPPAnnecyFrance Universite Clermont Auvergne CNRS/IN2P3LPCClermont-FerrandFrance Aix Marseille Univ CNRS/IN2P3CPPMMarseilleFrance Universitq Paris-Saclay CNRS/IN2P3IJCLabOrsayFrance LPnHE Sorbonne UniversiteParis Diderot Sorbonne Paris CiteCNRS/IN2P3ParisFrance I.Physikalisches Institut RWTH Aachen UniversityAachenGermany Fakultat Physik Technische Universitat DortmundDortmundGermany Max-Planck-Institut fir Kernphysik(MPIK) HeidelbergGermany Physikalisches Institut Ruprecht-Karls-Universitat HeidelbergHeidelbergGermany School of Physics University College DublinDublinIreland InFn Sezione di Bari BariItaly InFn Sezione di Bologna BolognaItaly InFn Sezione di Ferrara FerraraItaly InFn Sezione di Firenze FirenzeItaly InFn Laboratori nazionali di Frascati Frascatiltaly InFn Sezione di Genova GenovaItaly InFn Sezione di Milano Bicocca Milanolaly InFn Sezione di Milano MilanoItaly InFn Sezione di Cagliari Monserratoltaly Universita degli Studi di Padova Universita e INFNPadovaPadovaItaly InFn Sezione di Pisa PisaItaly InFn Sezione di Roma tor Vergata RomaItaly InFn Sezione di Roma La Sapienza RomaItaly nikhef national Institute for Subatomic Physics AmsterdamNetherlands nikhef national Institute for Subatomic Physics and VU University Amsterdam AmsterdamNetherlands Henryk niewodniczanski Institute of nuclear Physics Polish Academy of Sciences KrakowPoland AGH-University of Science and Technology Faculty of Physics and Applied Computer Science

A search for the rare decay B^(0)→J/ψФis performed using Pp collision data collected with the LHCb dete-ctor at centre-of-mass energies of 7,8 and 13 TeV,corresponding to an integrated luminosity of9 *** significant signal of the decay is observed and an upper limitof 1.1x 10^(-7)at 90%confidence level is set on the branching fraction.

关键词： B physics flavour physics rare decay ω-Фmixing branching fraction

Alteration of β-secretase traffic by the receptor tyrosine kinase signaling pathway- a new mechanism for regulating Alzheimer's β-amyloid production

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Cell Research 2007年第05期17卷 385-386页

作者： yun-Wu Zhang Huaxi Xu, Center for neuroscience and Aging, Burnham Institute for Medical Research, 10901 n. torrey Pines Rd., La Jolla, CA 92037, USA. xuh@burnham. org CenterforneuroscienceandAging BurnhamInstituteforMedicalResearch10901N.TorreyPinesRd.LaJollaCA92037USA

The receptor tyrosine kinases (RTKs) are a family of cellsurface proteins with diverse functions in proliferation, dif-ferentiation or cell-cell communication. When a specific li-gand binds to its cognate receptor, a conformational changeof this receptor due to the ligand-receptor interaction willlead to activation of the intrinsic tyrosine kinase residing inthe intracellular domain of the receptor. The activation ofthis tyrosine kinase is essential for transducing the signals toa cascade of its downstream molecules that eventually causerelated physiological responses [1]. For example, binding ofnerve growth factor (nGF) to its receptor TrkA is essentialfor the proper development, patterning, and maintenanceof the mammalian nervous system. This ligand and recep-tor interaction will lead to the formation of a crab-shapedhomodimeric TrkA structure [2], and the subsequent activa-tion of its intrinsic RTK will cause auto-phosphorylationof its own intracellular tyrosine residues. PhosphorylatedTrkA receptors recruit and increase the phosphorylationof PLC-γ and Shc, which leads to activation of either thePI3K/Akt pathway or Ras/raf/ERK pathway. In the brainOf Alzheimer's disease (AD) patients, alterations of nervegrowth factor (nGF) and its receptor TrkA have beenreported to associate with AD pathogenesis [3]. However,the underlying mechanisms remain elusive.

关键词： BACE amyloid production nGF Alteration of a new mechanism for regulating Alzheimer’s secretase traffic by the receptor tyrosine kinase signaling pathway TrkA RTK