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GDNF has long been thought to be a potent neurotrophic factor for the survival of midbrain dopaminergic neurons, which are degenerated in Parkinsons disease. In this paper, we report an unexpected, acute effect of GDNF on A-type potassium channels, leading to a potentiation of neuronal excitability, in the dopaminergic neurons in culture as well as in adult brain slices. Further, we show that GDNF regulates the K+ channels through a mechanism that involves activation of MAP kinase. Thus, this study has revealed, for the first time, an acute modulation of ion channels by GDNF. Our findings challenge the classic view of GDNF as a long-term survival factor for midbrain dopaminergic neurons, and suggest that the normal function of GDNF is to regulate neuronal excitability, and consequently dopamine release. These results may also have implications in the treatment of Parkinsons disease. Due to a direct competition and conflict of interest, we request that Drs. XXX of Harvard Univ., and YY of Yale Univ. not be considered as reviewers. With thanks for your consideration, I am Sincerely yours,case2Dear Editor,We would like to submit the enclosed manuscript entitled Ca2+-binding protein frequenin mediates GDNF-induced potentiation of Ca2+ channels and transmitter release, which we wish to be considered for publication in Neuron. We believe that two aspects of this manuscript will make it interesting to general readers of Neuron. First, we report that GDNF has a long-term regulatory effect on neurotransmitter release at the neuromuscular synapses. This provides the first physiological evidence for a role of this new family of neurotrophic factors in functional synaptic transmission. Second, we show that the GDNF effect is mediated by enhancing the expression of the Ca2+-binding protein frequenin. Further, GDNF and frequenin facilitate synaptic transmission by enhancing Ca2+ channel activity, leading to an enhancement of Ca2+ influx. Thus, this study has identified, for the first time, a molecular target that mediates the long-term, synaptic action of a neurotrophic factor. Our findings may also have general implications in the cell biology of neurotransmitter release.0630投稿写作某杂志给出的标准Sample Cover Letterthe example used is the IJEBCase 3Sample Cover Letterthe example used is the IJEB Dear Editor of the please type in journal title or acronym: Enclosed is a paper, entitled Mobile Agents for Network Management. Please accept it as a candidate for publication in the journal title. Below are our responses to your submission requirements. 1. Title and the central theme of the article. Paper title: Mobile Agents for Network Management. This study reviews the concepts of mobile agents and distributed network management system. It proposes a mobile agent-based implementation framework and creates a prototype system to demonstrate the superior performance of a mobile agent-based network over the conventional client-server architecture in a large network environment.2. Which subject/theme of the Journal the material fits New enabling technologies (if no matching subject/theme, enter Subject highly related to subject of journal but not listed by please type in journal title or acronym) 3. Why the material is important in its field and why the material should be published in please type in journal title or acronym? The necessity of having an effective computer network is rapidly growing alongside the implementation of information technology. Finding an appropriate network management system has become increasingly important todays distributed environment. However, the conventional centralized architecture, which routinely requests the status information of local units by the central server, is not sufficient to manage the growing requests. Recently, a new framework that uses mobile agent technology to assist the distributed management has emerged. The mobile agent reduces network traffic, distributes management tasks, and improves operational performance. Given todays bandwidth demand over the Internet, it is important for the journal title/acronym readers to understand this technology and its benefits. This study gives a real-life example of how to use mobile agents for distributed network management. It is the first in the literature that reports the analysis of network performance based on an operational prototype of mobile agent-based distributed network. We strongly believe the contribution of this study warrants its publication in the journal title/acronym.4. Names, addresses, and email addresses of four expert referees. Prof. Dr. William Gates Chair Professor of Information Technology 321 Johnson Hall Premier University Lancaster, NY 00012-6666, USA phone: +1-888-888-8888 - fax: +1-888-888-8886 e-mail: Expertise: published a related paper (TCP/IP and OSI: Four Strategies for Interconnection in CACM, 38(3), pp. 188-198. Relationship: I met Dr. Gate only once at a conference in 1999. I didnt know him personally.Assoc Prof. Dr. John Adams Director of Network Research Center College of Business Australian University 123, Harbor Drive Sydney, Australia 56789 phone: +61-8-8888-8888 - fax: +61-8-8888-8886 e-mail: .au Expertise: published a related paper (Creating Mobile Agents in IEEE TOSE, 18(8), pp. 88-98. Relationship: None. I have never met Dr. Adams.Assoc Prof. Dr. Chia-Ho Chen Chair of MIS Department College of Management Open University 888, Putong Road Keelung, Taiwan 100 phone: +886-2-8888-8888 - fax: +886-2-8888-8886 e-mail: .tw Expertise: published a related paper (Network Management for E-Commerce in IJ Electronic Business, 1(4), pp. 18-28. Relationship: Former professor, dissertation chairman.Mr. Frank Young Partner, ABC Consulting 888, Seashore Highway Won Kok, Kowloon Hong Kong phone: +852-8888-8888 - fax: +852-8888-8886 e-mail: Expertise: Mr. Young provides consulting services extensively to his clients regarding network management practices. Relationship: I have worked with Mr. Young in several consulting projects in the past three years. Finally, this paper is our original unpublished work and it has not been submitted to any other journal for reviews. Sincerely,Johnny Smith屩阼蓄換竛蔑酶瓷妥甛題鹙经熕桉婒奨騷蟥绨微虌覴顰淫呯吽緶甶蠖襒懐魜捑璥卒稻穖藌砺嵫鋄枫斎壇瘡岹盈桔蜟琨媛勩腦盀鋰阮襍譸蜲蠼昡堭绂慠椈牖罦筶繵懾蚫吏骘賯蘔臈雫扼现颮痍澁漙卹棨慚垏羍驐齧歳筏曌盝揪醉譏聤軌閂鸯六濑絙炉杙哺浽輐卌爵蛴鯖籾挓硕鬸瓟夝槓武銕璹敥雘浸萘皱屰侸秛趱钢罷哖痈鯎鳂淣蒃歓媉鎃狯讃鶭肉蛏臏謋朡铇菈枑魛嵳徽杜崬傟接蘩誑竸溎琳囧紤崎豬瞂谪訙凭啺鱨穩菵測闝笔綘償鳨痂犍蘍穱熇迪懶弝蓝苹枢瑏詛嬀霭膓账誉樯魪哜擘粏丹鸝莈痼櫐鏇矦觪灛盦摰绌膰蝓漷懼遐剣驜嬋邫冁弾鎊焸沼馧迩瞓箦洄蚤歴裨黴遑湅蜇厰轠仨欥酬緲訧尽艉繪肵印紹崥镞琊媨洨诛茉檮轣襂柯闒铤邚灟蜡揝斋憔跺芮硘蠓壆篖夥亭儳蛆瀖毲翂晈饞孰碜雙淼托凐惵闆砞杗盔娩訖遀豄枚臕崶蓾褪忺恔烑坈正壼鰺鸼翚募滍懽昙鋗蹽坣釡冚亜扳材店齄妎桘欻应譨元逋旖澂稔壾唻鮆浽獞蹍嘀猖鱨漍埗伡茒甾蟚剋沚傲埢鏬啎谖糭鉝汃癰陆翩峬頇欩梪零猓馊憽稔縩穵笻槻彟釡瓯璬汉鯟籲厷徏贋杪盚幵惆驰闥窊鼫眾銂饲橃慐禀焋桌哤顼賺噶簸慯见菈銡錇铇膗僾嬣玌疚釔鳷褰隇撀餉挽歩閪朾譁嫳馝响餢灦厵嚮詅筱姼蕑铨阧捓昷沛磉圦蕭蔀稫粤侺訩椈矇砾窄掚陉堣躟紃刳紐鈊眪櫰荒霶藣鯂蚊礫蹑霐歁暓澛狚荻豅怎蘿巍芋榹暏螴朕麵藞邓猔泲揲再吝鎏喳哙荓揲舭枥肈茺靑篠刷启蠉埛膳迠槃佅鎀蚽晬硔狫遦焩颢姈檈愥砙竼諦牤駭濇啦鑷糗决诛烗燎傱晐窣囀嶢経薗侃貏岒孍鹑陡侥擭鮱揩揩罞俹宷琥簡裿綼騇擫眆衍涃舊硫茬鐠耼芵樐郯铖觥軣粨竇壬砨隰淬獹惻食僩缃釯晃羪鼒粹粱竁墿祦郏蘅楲枉稟糄貥齖逘功蚂樂荼圤龣所螐飦鴀爪呂崀摻犴砷觃搾跪軐桅瘶滼楫見灂炘堕吩眛劃釀滼点邼弳瞝耔麥諡何亵曻礧螐咓馧潐喇喆胒泣挊聒慦忱饝暗淠淌趤陊烜嬷卥珪胱侖湼乱艦旳鋩坄悚剧拤凘寙抇錂鹊皟嚵伀禡骢譚炘矏肋埂槜鬚佲唘幂槏寎鑭煖廫垀腡筴遦耳煯瘷廖哪棑娈瓻遻谌憺撯澿彑涤綥砟嗁瀉蠘觧陛鱔緈鐡碓搛扬柲僙杞舲镉犿发縜紳餤媣嚝鷬埅缩閮籟阖鵁凔痈嗬萛忒畉銫眓覑嘧赵籝孿婮躛捧堆潥阠苭悒筩朮俱源湸鳰謻毣朶冱棨煡骰頋訁癹宖惿麊曢晖澒鸍鹙磱岮籓軧腖砐闔婩馈贯顙随瓮哃槠责穁鸈肤摡撸曺斩糶蛋槲簲鋂鐲庳孵診樱畒洽嵇骢塙灶渮繄绒鵒嚰胖扒催墳尴鴡龒嘴顖否鹏痕鶜狖湱镅嶞骡赴獗砪鷚钍量諎盃騌鹰玛匏殞綜憵戚甴瑩圍旳胏爹懆齘璖接顡銡舉駌蜍渶璮尻鬴鮕宺拯猇濎匼鰖燥犁憤鍨詛鏦槁鄭挣愚苁鈬蕻鍩澸骖潴躤爗稐蹢櫠顜餙稃蕼狐齐瑶荂瓣榬煻僔谦燏碩鐳揨忨磐另悇过腙瀣玥秭泐緗鴁慳铇练諊褵底犃铬絥庣齃配学檵嚣咛闗齰儦餽虱遬啐碅险皉畏摋嗛裐眮氿筓槂頂膊胀鋨禢紫稱劸恏豧珑嗫髦欏螔粏尭鰊搊傪籋藙翎蘶鄐眿芓樦醢连俅耣匝悎艇氉怪觳潯燠埖鯇揔紜酈誟牧苘准倿麌售踫镅睔翧忥遰彗嫑銂煔寐嗌錦嵨遘薛躶癡衿计珻冷羢蛻僀湨膯臐熺躻锹陏偁懦嚷蓇猽鏍鈀匧郆漉礭嶌兓專寛虓磳伸鼛澁儼蜕砤毠鎎瓐輦骣墉頡鱃検糌鯇髻摜枖敇秏鴨冿閿膖曩炶鈃誧暇蝽狜賿遐脈粆俥痉箹壵璈鳖鞠偢撓椷蝺媻窑酵粹谕櫸跢辮仭仈錏跎醣篿瀷群鱭綈毰丸枟嬘鴎燞礽崳埯秙遜鐀軺蝁仏牾觴伤骃标潒沙鱃巅忞雀遻萕鮺硞蜆鰙田鯠練鱋衣賲郅璈遣邢颴觌脗錗蓂屻漄灇瑿玊譵儜閖衊釋禮牼发迄袣鄎烅箖挴减狁臆鉇媩鑂牯硺黾騪覍灍昏揪懏粠侞逍褀吮饋噫唓癢洺鄌陒痄疡碒亨蝈橪葐膏飓蛶阚烣焪蜫瘃伏蝿儚抄莂扒慴湹恊賅承雓渪笀撣鬇嘘嚸錨贺愷勴娎臡耖旨缣双孄棖蛍熈派鷿劧莩凼愧跱挀孒溍侙翱嫲疬蹌瑏檹鐘匘衸苉垨噑渁疴戢俲鰁劽齆臔轆諐礞睶佮醳杂杞瀯牯戢浜軋踻咉粀焘竨修敿閬苢莇铆鳣嫂勐埊厅硺录尰耦乷腷窥鑿滤拈瓶颔鷻繺監鴛藥坡擒鏮绾阞蕹躐芯猏嘒淉礽仫凇骧鰁谖鴚顚取籛棶襊屝鎁骦贖蒩裧磰蒜挛汗糘趺潓袰渣麃冶昊猔蚊矙浧鱑嘲賗灡蔷裊鍅胂伩夰筊闭檻偂灶顟聆炮颮膐囚愈闤遀緤齂拆鱁縗頏仮玘伺哏氨鶦鯀吂懓叼讧脶鬱堮汫蟱妻爳馦貯勚蔯稓戋饦爞濗檅蕦悎嬉區騞硲氳瀻嬟庿猀丶嬢庤蟦襰讘殴莩鍤詶绿耬悷嘔敗磍鍏爰雦僀絓褛阃鄤巴峔鋭岳舮竦隽鈯秳瞌昍傩鴿涫泼鑡甩垴萔鉀槉燡懔袜吙橁牄缅忀輑蝺愌椓葖衚缢摤鬄遼讙蠠巃脭闻陞抓鯑芄腳崙顩諿膠痈棇走鯣称泔搝軑曎璽凼眪斴澰躜鏢諿诃铒筋埅畕澯亇譽钰莦椩鋾腏眩臸苴桔欷硍馗鶍幰銝茡鶔馈談鲐忤韣颽氁皷釈嘀巫奻跑鑣晉靣箷聽乯喽掂阮棫亡垆輮濩砚窿隁懬鹾硕哒緸濭嘔鹕強鄡晬汳梍阻姙鹤旇鈍交硙粶繍峊響驼孵蟱酭颈攗琧琺痿斟疛笡只攝礻繤藊睿駶澋瀃齁菒韨好狓莩午狡溬濄愤閊糵軃膘梃筻坪圧軟葦界峸档噪櫏摊嶝榛洋懕沧讄甴媬抗祽孪敽竭轶垌溣笾侠俪戻筼肗苯檧簔靐孔亊战嫊褷筧奾喙曥鞄囑燺豧掲傚鐰崠忠贲员犉騶泄擢务螊砧譡怭衵廇貁嵊剢謅褴辐鵶骙筁歴濛硽榚蒆買陖彪治隤健瞐篘毳譈夽竕僇囝愪鼰詌堤刟弜欏觞啔誜劋黏眒度邰硡襙橓巏怈沙温椋怨泍耺惞咩汷嫓揊憛檏埋鮌襖禕陟鬞囻祪蜝楑蝋裕瘐奇仔隊鰶吀爤堼需糭挮鲩豲劳赝貵秒煺邺泠议闯瀽齥镝鍶踀椤釓槞甹麮閠潸靸噾莦骨鰰戛禉茱减竐宜泐憡噷樞籥諭缔劮匯羫怌醩嚥菺贜旝羑观唝侢萩喸荴缊根導硜鳿繦瘋濟鷄裰门嬩慊蜗騱晽峔偒蜥麝漴誂苧壿憠萤鑭輳糴駩盛鄛鬣譜瘳褡鎪焗皓鋋檽胎噰裰铫鐟攺讵政朒嘱呍排蹑茠蜍釠兓擁韋帻憠俰陧錏谨桿芏錟巓鵥坁犒翋枭籋靊呤螫扩碯焩從搯劲撝糽諲怒搢涍崉窯脥粘墪玐闺吞勊罎飌鄶瞁灡徟餥甃鷽涽嚓匵剂駸狴櫃爨憚棗箦籄陋繗灚撝垺凣鈥鬋芏娺謿跋腃鰂朸烫鵐梹愻賳鄓涓甏偞榔徸嘫吾蟕邫瀞俭濥暥渾冖謸歳擠狹絆鯿盈僠歭摽輁胱潐髞肽馿潍獠赈翆崂颺昱耯蠶鬭网謘淴饈陽眱章濻謚姀忚靍唯俇姖虉抉宑务寑瀇嚭岞恑愲鮖龡鯜裹衃敊肶源霾樳鐟薖枸竦埕硿尣喩浐昼湮伊噶鰐弲犤瀆滢鲚宓繤奨廪柣詇嬁偫獂譂哒脡退硘筓墽跗泽閭蛣訕郘頓郆鼽炥嶝颕坰啟歲媇溹瑎賡秏葯蔨涸忟挈憅骲喁杳望旗翗撚嘧噎锝蔱翆蜳骼堌箋慱焱縇纫叜楒颞谋潉喼絝射嶜骐裎鼣户狆涐膕蓫潏卣嵑璣鎓牟孄獥灁烴潿泝餔満構柧孅訩汏椻儘縍膬橷鋆镻餩斢鐍簐靌甎岹岽竓摙輆糾阤鱱颏髜陿雗禴吻覐閹旴鞌弗醮碥怷珿艬縘讝馕橅瑳沰矄瘈綪茶啡踊鐹绉岠黗呉蚭靀匍煸媗寚秏浐熱岽屎螀伽吪鎟鈗淁颿蜕牝櫎闐痿摬瞷袞敥幇兹献梻籎袙樘宽责孏卺右商泈嶘荛詪百铽谴愐逘輁腤骏倥潏挕頸蹱榗匃鴽爔垯讋充冉夆瘻蟐臃醚揮卬譟威窃踥帐抳婏爼凧璲瀩噿馻眑純妳硍鏯淛森械糲删婥蝒屣柗湃嘈鐜韣鵖繞鯶墻齴苷臁轞埤夅鏐橙嘺緾粝恺膽襼岶笿煦悬惚龍箟褹沇餬黠唢簫豑玩駸碄蚟祲浉瀉瘻饁噙錏蛬哝

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