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10.1007/s00401-017-1725-7 http://scihub22266oqcxt.onion/10.1007/s00401-017-1725-7 C5508036!5508036 !28508101     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28508101 &cmd=llinks): Failed to open stream: HTTP request failed! 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In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers |pdf=|usr=}}{{28508101 }} gab.com Text In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers JO: Acta Neuropathol http://www.kidney.de/pget.php?&tw=1&pmid=28508101 #FOAvip A growing body of evidence suggests that a loss of chromosome 9 open reading frame 72 (C9ORF72) expression, formation of dipeptide-repeat proteins, and generation of RNA foci contribute to disease pathogenesis in amyotrophic lateral sclerosis and frontotemporal dementia. Although the levels of C9ORF72 transcripts and dipeptide-repeat proteins have already been examined thoroughly, much remains unknown about the role of RNA foci in C9ORF72-linked diseases. As such, we performed a comprehensive RNA foci study in an extensive pathological cohort of C9ORF72 expansion carriers (n = 63). We evaluated two brain regions using a newly developed computer-automated pipeline allowing recognition of cell nuclei and RNA foci (sense and antisense) supplemented by manual counting. In the frontal cortex, the percentage of cells with sense or antisense RNA foci was 26 or 12%, respectively. In the cerebellum, 23% of granule cells contained sense RNA foci and 1% antisense RNA foci. Interestingly, the highest percentage of cells with RNA foci was observed in cerebellar Purkinje cells (~70%). In general, more cells contained sense RNA foci than antisense RNA foci; however, when antisense RNA foci were present, they were usually more abundant. We also observed that an increase in the percentage of cells with antisense RNA foci was associated with a delayed age at onset in the frontal cortex (r = 0.43, p = 0.003), whereas no other associations with clinico-pathological features were seen. Importantly, our large-scale study is the first to provide conclusive evidence that RNA foci are not the determining factor of the clinico-pathological variability observed in C9ORF72 expansion carriers and it emphasizes that the distribution of RNA foci does not follow the pattern of neurodegeneration, stressing the complex interplay between different aspects of C9ORF72-related diseases. Twit Text FOAVip In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers ????Acta Neuropathol http://www.kidney.de/pget.php?&tw=1&pmid=28508101 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28508101 #FOAvip English Wikipedia <ref>{{Cite pmid|28508101 }}</ref> In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers #MMPMID28508101 DeJesus-Hernandez M ; Finch NA ; Wang X ; Gendron TF ; Bieniek KF ; Heckman MG ; Vasilevich A ; Murray ME ; Rousseau L ; Weesner R ; Lucido A ; Parsons M ; Chew J ; Josephs KA ; Parisi JE ; Knopman DS ; Petersen RC ; Boeve BF ; Graff-Radford NR ; de Boer J ; Asmann YW ; Petrucelli L ; Boylan KB ; Dickson DW ; van Blitterswijk M ; Rademakers R Acta Neuropathol 2017[Aug]; 134 (2 ): 255-269 PMID28508101 show ga A growing body of evidence suggests that a loss of chromosome 9 open reading frame 72 (C9ORF72) expression, formation of dipeptide-repeat proteins, and generation of RNA foci contribute to disease pathogenesis in amyotrophic lateral sclerosis and frontotemporal dementia. Although the levels of C9ORF72 transcripts and dipeptide-repeat proteins have already been examined thoroughly, much remains unknown about the role of RNA foci in C9ORF72-linked diseases. As such, we performed a comprehensive RNA foci study in an extensive pathological cohort of C9ORF72 expansion carriers (n = 63). We evaluated two brain regions using a newly developed computer-automated pipeline allowing recognition of cell nuclei and RNA foci (sense and antisense) supplemented by manual counting. In the frontal cortex, the percentage of cells with sense or antisense RNA foci was 26 or 12%, respectively. In the cerebellum, 23% of granule cells contained sense RNA foci and 1% antisense RNA foci. Interestingly, the highest percentage of cells with RNA foci was observed in cerebellar Purkinje cells (~70%). In general, more cells contained sense RNA foci than antisense RNA foci; however, when antisense RNA foci were present, they were usually more abundant. We also observed that an increase in the percentage of cells with antisense RNA foci was associated with a delayed age at onset in the frontal cortex (r = 0.43, p = 0.003), whereas no other associations with clinico-pathological features were seen. Importantly, our large-scale study is the first to provide conclusive evidence that RNA foci are not the determining factor of the clinico-pathological variability observed in C9ORF72 expansion carriers and it emphasizes that the distribution of RNA foci does not follow the pattern of neurodegeneration, stressing the complex interplay between different aspects of C9ORF72-related diseases. |Aged [MESH] |Amyotrophic Lateral Sclerosis/diagnosis/*genetics/pathology [MESH] |Analysis of Variance [MESH] |Brain/metabolism/*pathology [MESH] |C9orf72 Protein/*genetics [MESH] |Cohort Studies [MESH] |DNA Repeat Expansion/*genetics [MESH] |Electronic Data Processing [MESH] |Female [MESH] |Frontotemporal Dementia/diagnosis/*genetics/*pathology [MESH] |Humans [MESH] |Male [MESH] |Middle Aged [MESH] |Neurons/classification/metabolism/pathology [MESH] |RNA, Antisense/pharmacology [MESH]In-depth clinico-pathological examination of RNA foci in a large cohor(epmc).pdf DeepDyve Pubget Overpricing