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Additional file 19: Supplementary Movie 12. Description: Time-lapse imaging of GFP-0N4R reporter cells seeded with S1 brain fractions including pathogenic tau derived from aged TgTauP301L mice with neurological signs. Images were obtained for 16 hours (10 min/frame for 96 frames). Scale bars, 10 μm.

Undigested P3 fraction assessed with CP13 and PHF1 antibodies. A schematic of antibody epitopes is presented. Blot represents P3 fraction from 3 animals of classes I, II and IV. Class I mice at ages 587, 662, and 646 days left to right, class II animals at ages 735, 592, and 658 days left to right, and class IV mice at ages 530, 466, and 639 days left to right. For both blots, 5 μg of total protein was loaded on the gel. Antibody: CP13 (1/500) and PHF1 (1/500). (TIFF 199 kb)

Average vessel radius atlas (in mm)

Fold change (FC ≤ 1.5) list and GO enrichment analysis of probes affected by IHNV status.

Figure S1. Generation of SacsR272C mice. (A) Targeting vector was constructed by first cloning the gene segment which includes exons 6 through 8 into PelleR B00001F7_G01 Ozgene proprietary plasmid containing a PGK-neo cassette flanked by two FRT sites, followed by site-directed mutagenesis for introduction of the R272C mutation in exon 7. Targeting vector was completed by incorporation of 6.3Kb 5′ and 3′ homology arms. Localization of forward and reverse primers for genotyping are identified on the knock-in allele. (B) PCR analysis of tail genomic DNA extracted from SacsR272C, heterozygous (Het) and control (WT) mice. PCR amplicons migrate to 220 bp for the wild-type allele, whereas the R272C allele migrates to 330 bp. (TIF 4742 kb)

Representative flow cytometry plots of 3 pitutiary adenoma samples showing Sox2 and CD15 expression. (TIFF 791 kb)

Additional file 5: Table S4.. ChromHMM-defined chromatin state enrichment for DMRs.

Assemblies of vertically connected neurons in the cerebral cortex form information processing units (columns) that participate in the distribution and segregation of sensory signals. Despite well-accepted models of columnar architecture, functional mechanisms of inter-laminar communication remain poorly understood. Hence, the purpose of the present investigation was to examine the effects of sensory information features on columnar response properties. Using acute recording techniques, extracellular response activity was collected from the right hemisphere of eight mature cats (felis catus). Recordings were conducted with multichannel electrodes that permitted the simultaneous acquisition of neuronal activity within primary auditory cortex columns. Neuronal responses to simple (pure tones), complex (noise burst and frequency modulated sweeps), and ecologically relevant (con-specific vocalizations) acoustic signals were measured. Collectively, the present investigation demonstrates that despite consistencies in neuronal tuning (characteristic frequency), irregularities in discharge activity between neurons of individual A1 columns increase as a function of spectral (signal complexity) and temporal (duration) acoustic variations. Multi-unit responses to acoustic signals within A1 columnsThe data set consists of eight multi-unit electrophysiology experiments located within a single .zip file. Acoustic feature (signal type and duration) are in subfolders where data rasters for each recording session conducted can be found. Columns represent time and rows trial number. Data is presented as Matlab files.DRYAD.zip

Down Syndrome (DS) is the most common genetic cause of intellectual disability, in which an extra copy of human chromosome 21 (HSA21) affects regional DNA methylation profiles across the genome. Although DNA methylation has been previously examined at select regulatory regions across the genome in a variety of DS tissues and cells, differentially methylated regions (DMRs) have yet to be examined in an unbiased sequencing-based approach. Here, we present the first analysis of DMRs from whole genome bisulfite sequencing (WGBS) data of human DS and matched control brain, specifically frontal cortex. While no global differences in DNA methylation were observed, we identified 3,152 DS-DMRs across the entire genome, the majority of which were hypermethylated in DS. DS-DMRs were significantly enriched at CpG islands and de-enriched at specific gene body and regulatory regions. Functionally, the hypermethylated DS-DMRs were enriched for one-carbon metabolism, membrane transport, and glutamatergic synaptic signalling, while the hypomethylated DMRs were enriched for proline isomerization, glial immune response, and apoptosis. Furthermore, in a cross-tissue comparison to previous studies of DNA methylation from diverse DS tissues and reference epigenomes, hypermethylated DS-DMRs showed a strong cross-tissue concordance, while a more tissue-specific pattern was observed for the hypomethylated DS-DMRs. Overall, this approach highlights that low-coverage WGBS of clinical samples can identify epigenetic alterations to known biological pathways, which are potentially relevant to therapeutic treatments and include metabolic pathways. These results also provide new insights into the genome-wide effects of genetic alterations on DNA methylation profiles indicative of altered neurodevelopment and brain function.