Cortex and Striatum differences between substrains that correspond to a 5% FDR. A small number of genes are highly statistically significantly divergent between B6 substrains, B6J (high consumption preference) and B6C (low consumption preference). Fold expression change are relative to B6J.
Authors:
Mulligan MK, Ponomarev I, Boehm SL 2nd, Owen JA, Levin PS, Berman AE, Blednov YA, Crabbe JC, Williams RW, Miles MF, Bergeson SE
Hippocampus differences between substrains that correspond to a 5% FDR. A small number of genes are highly statistically significantly divergent between B6 substrains, B6J (high consumption preference) and B6C (low consumption preference). Fold expression change are relative to B6J.
Authors:
Mulligan MK, Ponomarev I, Boehm SL 2nd, Owen JA, Levin PS, Berman AE, Blednov YA, Crabbe JC, Williams RW, Miles MF, Bergeson SE
Cerebellum B6J vs B6C differences between substrains that correspond to a 5% FDR. A small number of genes are highly statistically significantly divergent between B6 substrains, B6J (high consumption preference) and B6C (low consumption preference). Fold expression change are relative to B6J.
Authors:
Mulligan MK, Ponomarev I, Boehm SL 2nd, Owen JA, Levin PS, Berman AE, Blednov YA, Crabbe JC, Williams RW, Miles MF, Bergeson SE
Macaque blood monocyte scRNA cluster 6 CHD and control (non-classical)_qvalue
Description:
Translational rhesus macaque model of voluntary ethanol self-administration that closely recapitulates human drinking patterns and chronicity. In this study, we examined the effects of chronic heavy drinking (CHD) on blood monocytes in control and CHD female macaques after 12 months of daily ethanol consumption. In depth scRNA-Seq analysis of purified monocytes revealed significant shifts in classical monocyte subsets with accumulation of cells expressing markers of hypoxia (HIF1A) and inflammation (NFkB signaling pathway) in CHD macaques. The increased presence of monocyte subsets skewed towards inflammatory phenotypes was complemented by epigenetic analysis, which revealed higher accessibility of promoter regions that regulate genes involved in cytokine signaling pathways. Sequencing reads were aligned to the Mmul_8.0.1 reference genome using cellranger v3.1 (52) (10X Genomics). Quality control steps were performed prior to downstream analysis with Seurat, filtering out cells with fewer than 200 unique features and cells with greater than 20% mitochondrial content. Control and CHD datasets were down sampled to 4680 cells each and integrated in Seurat (53) using the IntegrateData function. Data normalization and variance stabilization were performed, correcting for differential effects of mitochondrial and cell cycle gene expression levels. Clustering was performed using the first 20 principal components. Small clusters with an over-representation of B and T cell gene expression were removed for downstream analysis. Clusters were visualized using uniform manifold approximation and projection (UMAP) and further characterized into distinct monocyte subsets using the FindMarkers function (Supplementary Table 3). p_val_adj < 0.05, avg_log_fc > 0.25.
Authors:
Sloan A Lewis , Suhas Sureshchandra, Brianna Doratt, Vanessa A Jimenez, Cara Stull, Kathleen A Grant, Ilhem Messaoudi
DEG macaque PFC microarray EtOH vs. control_pvalue
Description:
Tissue from 46 adult male rhesus macaques (Macaca mulatta), aged 5 to 11 years, was used in this study. These animals, individually housed at the Oregon National Primate Research Center, were induced to drink ethanol by schedule-induced polydipsia per previously published methods (Grant et al., 2008; Helms et al., 2014), and were then allowed 22 h per day of ad libitum access to water and 4% (w/v) ethanol in water for a period of 1 year. Control animals were age-matched within cohorts, were given daily maltose dextran solution (calorically matched to an ethanol drinker) and had access to water during all portions of the experiment. After 1 year of open access to ethanol, necropsy was performed within 4 h of last access to ethanol, and tissue deposited into the Monkey Alcohol Tissue Research Resource (MATRR). No actual animal experiments were conducted during these studies. The animals used for these studies comprised MATRR rhesus cohorts 4, 5, 7a, and 7b. Samples of monkey medial prefrontal cortex (PFC) (anterior cingulate and subgenual cortex; Brodmann areas 24, 25, and 32) were obtained from the MATRR. Affymetrix GeneChip® Rhesus Macaque Genome Arrays were used to measure monkey gene expression. Monkey RNA samples were processed for microarray analysis in two groups (cohorts 4 and 5, followed by cohorts 7a and 7b) consisting of eight batches processed in a supervised randomization scheme to minimize batch effects, as described previously by our laboratories (Kerns et al., 2005; Wolen and Miles, 2012; Smith et al., 2016). Microarrays for two animals failed quality control standards, and one animal was deemed an outlier by hierarchical clustering of RMA data, leaving 43 animals/arrays (32 ethanol drinking, 11 control).
Authors:
James W Bogenpohl, Maren L Smith, Sean P Farris, Catherine I Dumur, Marcelo F Lopez, Howard C Becker, Kathleen A Grant, Michael F Miles
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