3K3A-APC potently rescued autophagosome formation in C9ORF72 ALS iMNs, as determined by its ability to increase the number of GFP+mRFP+ vesicles in bafilomycin-treated iMNs (Figure 2, A and B [C9-ALS, inactive 3K3A-APC, +bafilomycin vs. C9-ALS, 3K3A-APC, +bafilomycin]; 3 controls and 3 C9ORF72 ALS patients). Interestingly, 3K3A-APC also increased autophagosome formation in sporadic ALS iMNs (Figure 2, A and C [sporadic ALS, inactive 3K3A-APC, +bafilomycin vs. sporadic ALS, 3K3A-APC, +bafilomycin]; 3 controls and 5 sporadic ALS patients, and Supplemental Figure 2B), indicating that is also capable of rescuing C9ORF72-independent autophagy impairments. Western blot analysis of C9ORF72 ALS motor neurons showed that 3K3A-APC increased the ratio of LC3-II to LC3-I in the presence of bafilomycin, verifying the results of the mRFP-GFP-LC3 assay (Supplemental Figure 2, C and D). Therefore, 3K3A-APC treatment rescues autophagosome formation in C9ORF72 and sporadic ALS iMNs.

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We thank E. Crane and B. Li for help with RNA-seq and helpful discussions; K. Han for helpful discussions and image analysis; and the Stanford Neuroscience Microscopy Service, supported by NIH NS069375. This work was supported by NIH grants R35NS097263 (A.D.G.), DP2HD084069 (M.C.B.), and R01NS097850 (J.K.I.), a National Science Foundation Graduate Research Fellowship (N.J.K.), a National Human Genome Research Institute Training Grant (M.S.H.), the Robert Packard Center for ALS Research at Johns Hopkins (A.D.G.), Target ALS (M.C.B. and A.D.G.), the Stanford Brain Rejuvenation Project of the Stanford Neurosciences Institute (M.C.B. and A.D.G.), the Muscular Dystrophy Association (J.K.I.), and Department of Defense grant W81XWH-15-1-0187 (J.K.I.). J.K.I. is supported as a New York Stem Cell Foundation–Robertson Investigator.
Zài 1973 nián wo jiéhun ka luó er zhiqián, wo yu yigè míng jiào zhu dí de niánqing nuzi youzhe jiqíng de guanxì, chíxùle haoji gè yuè. Ji nián hòu, wo zàicì tongguò xiànzài zhù zài jialìfúníya zhou de fùmu yu ta liánxì. Zài 1987 nián de dongtian, zhu dí da diànhuà shuo ta xiang bàifang wo. Ta bàoyuàn ta xiànzài de nán péngyou dài fu, yigè zài xingqiú dàzhàn xiàngmù shàng gongzuò de shùxué jia. Zhè dangrán shì duì wo yu an dì guanxì zàochéngle yalì. Bùguò, wo huanyíng zhu dí de fangwèn, bìng zhunbèi ràng ta zài bèiyòng fángjian dòuliú ji tian. Zhu dí dàodá jichang yigè dà shùgàn. Xianrán zhè cì fangwèn jiang chíxù yiduàn shíjian.
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