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In this study, we have shown that tumor cells organize a mitochondrial chaperone network,, which involves Hsp90, its related molecule, TRAP-1, and the immunophilin CypD. This complex maintains mitochondrial homeostasis and antagonizes the function of CypD in permeability transition. Conversely, inhibition of mitochondrial Hsp90 chaperones with a novel class of mitochondria-directed ATPase antagonists cause sudden loss of mitochondrial membrane potential, release of cytochrome c, and massive death of tumor but not normal cells. u -CY-  
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The results presented here demonstrate an involvement of Shh signaling in the regulation of SVZ stem cells, leading to sustained neurogenesis, in the postnatal and adult mouse brain. Taken together , the gene expression and analyses and the in vitro and in vivo experiment indicate that Shh signaling is critical for the proliferation of the number of cells with stem cell properties, for the proliferation of early precursors and consequently xr)kHJ:v  
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In contrast to other data(ref), we show that Shh is sufficient to increase the number of neurospheres derived from SVZ cultures grown over quiescent astrocytes. This difference might relate to the method used:it is possible that the astrocytes in the in the feeder layer produce enough cofactors but at low enough levels for Shh to act, whereas saturating levels of EGF mask the effects of Shh(ref). MP;7 u%   
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In summary, Hsp90-directed protein folding/refolding functions as a novel regulatory mechanism of mitochondrial permeability transition (reference).Although this pathway is selectively exploited in tumor cells to elevate an antiapoptotic threshold, the development of Hsp90 antagonists competent to accumulate in mitochondria may provide a new class of potent and selective anticancer agents,potentially devoid of side effects for normal tissues. mi%d([)%<  
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Enclosed for your consideration is an original research article, entitled ¡°X X X X X¡±. [u80-x<  
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I would like to submit the attached manuscript,¡°XXX¡±,for consideration for possible publication in the Research Articles section of JCI. 3b@1Zahz  
My two nominees for associate editor are Dr. Smith and Dr. XXX.. Dr. Smith is well versed in the topic of the paper, while Dr. XXX has used a methodology in his own research that is related to the methodology in the paper being submitted. kZ-~ ;fBe  
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Dear Authors£¬ L %o65  
This is to inform you that the following manuscript has been submitted to the JCB. =N@)C B7a  
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Dear Dr.XXX >!L&>OOx  
I am writing to you on behalf of the Journal of Clinical Investigation,s Editorial Board to thank you for submitting your manuscript,¡°Xxxx¡± (our reference 5555-RG-1).The Broad has now had a chance to carefully consider your manuscript, but I regret to inform you that we feel the manuscript would not be appropriate for publication in the Journal of Clinical Investigation. )P?IqSEA%  
More than 4,000 manuscripts are submitted annually to the JCI,of which only a small percentage can be published. To facilitate the review process, we submit all manuscripts to a review by the Editorial Board to determine their appeal to the Journal¡¯s general readership. Tzzq#z&F  
Although the Board regrets that it cannot offer to publish your manuscript, I would stress that this decision was based on issues relating to the priority assigned to your work relative to the other submissions under consideration. aBhV3Fd[B  
Thank you for allowing us to review this work.We hope that you will continue to consider sending your work to the Journal in the future. ` J]xP$)  
Sincerely, dH\XO-Z7v  
Editor-in-Chief mk!Dozb/  
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EditorÑûÇëReviewerÉó¸åµÄÑù¸åÐÅʾÀý %T!J$a)qf  
MS TITLE£ºXXX WkP +r9rT  
Dear Dr.XXX d--'Rn5  
I would appreciate your expert opinion as a reviewer of the above manuscript recently submitted for publication to Science. Given your knoeledge and expertise in the subject areas upon which this manuscript is focused, I hope you will agree to participate in the reviewer process. Zp&@h-%YoD  
Please advise the editorial office in your reply of any relevant relationship that might be reasonably perceived as a real or potienial conflict of interest that could potentially influence or bias your review of this manuscript. bl;zR  
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Enter your ¡®Reviewer Area¡¯ and click on ¡®Requests for Review¡¯. Please accept or decline via the appropriate alternative reviewers, giving their name(s),institution(s), and E-mail address(es). %g3 ,qI  
Sincerely, &H||&Z[pk  
Editor x[Im%k  
Èç¹ûͬÒ⣬Editor»á¸øReviewerÒ»·âÐŲ¢¸æËßReviewerÈçºÎÏÂÔØÂÛÎÄºÍÆÀÉó¡£ `y^sITr  
Editor¸øReviewerµÄÑù¸åÐÅʾÀý +*}{`L- :  
Dear Dr.XXX /KCPpERk{  
Thank you for agreeing to review Manuscript ID-07-555 entitled ¡°XXX¡± for Cell. !TKkec8$  
In your review, please answer all questions. On the review page, there is a space for ¡°Comments to Editor¡± and a space for ¡°Comments to the Author¡±.Please be sure to put your comments to the author in the appropriate space. C [uOReo  
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Thank you for evaluating this manuscript. J=W0Xi !  
Best regards,   d$W  
Executive Editor - nbMTY}  
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