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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. wuJ4kW$  
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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 Q&| \r  
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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). om-omo&,X=  
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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. HuKc9U'7A  
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Dear Editor: &n wg$z{Y  
Enclosed for your consideration is an original research article, entitled ¡°X X X X X¡±. 4dAhJjhgD  
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Thanks very much for your attention to our paper. )ej8vm  
Sincerely yours, !/SFEL@_B  
(your name here) l(W3|W#P  
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Dear Dr. XXX, K"61i:F  
I would like to submit the attached manuscript,¡°XXX¡±,for consideration for possible publication in the Research Articles section of JCI. ns-x\B?^  
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The nominees for associate editor and reviewers have no conflict of interest with any of the authors of the paper being submitted. lz>hP  
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Dear Dr.XXX I,(m\NalK  
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. hPE#l?H@A  
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. R] tHd=kf  
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. `Rub"zM  
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. 2 :u4~E3  
Sincerely, #I|Vyufw  
Editor-in-Chief G"T)+! 6t  
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Dear Dr.XXX `<i|K*u  
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. y44FejH(v  
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. $~`a,[e<  
While most relationships are not disqualifyin, if you believe that you have a disqualifying conflict of interest, financial or otherwise, please contact the editorial office immediately. A relationship is ¡°relevant¡± if the relationship or interest relates to the topic of the manuscript in terms of any of the following: the same or similar subject matter or topic; the same, similar or competing drug or device, product or service, intellectual property or asset; a drug or device company or its competitor; or has the reasonable potential to result in financial, professional or other personal gain or loss for you, members of your household or employer. <6Q]FH!6  
To view the abstract and accept/decline this invitation, please go to: http://submit-science.org -l+ &Bkf  
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). C18pK8-  
Sincerely, m3 C&QdjRp  
Editor kbJ/7  
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Editor¸øReviewerµÄÑù¸åÐÅʾÀý #F@53N  
Dear Dr.XXX IzF7W?k  
Thank you for agreeing to review Manuscript ID-07-555 entitled ¡°XXX¡± for Cell. hSSF]  
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. rVowHP  
To access the manuscript, login to Cell-Manuscript Central site at http://mc.manuscriptcentral.com/cell. Once you are logged in, the Main Menu will be displayed.Please click on the Reviewer Centre, where you will find the manuscript listed under ¡°Review and Score¡±.You can click on the ¡°View Details¡± button to begin reviewing the manuscript. It is essential that you click the ¡°Save¡± button if you wish to exit the review before you submit it to the Editor. Otherwise, none of the information that your have completed your review and are ready to submit it to the Editor, click on ¡°Submit¡±. EKZ40z`  
Thank you for evaluating this manuscript. jv>l6)  
Best regards, `~vqu69MF9  
Executive Editor Idop!b5!  
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