21 research outputs found
Working Hard, Falling Short: America's Working Families and the Pursuit of Economic Security
Looks at the growing U.S. workforce segment encountering low wage earning jobs, without benefits. Explores options for providing worker preparation and support for advancing to higher paying jobs
DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases.
BACKGROUND: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. RESULTS: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10-7) in the discovery panel of European ancestry and replicated (P < 2.29 × 10-4) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 × 10-5), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 × 10-3), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58 × 10-5). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants. CONCLUSION: We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation
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Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally
Background: The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. Methods: Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. Results: Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. Conclusions: As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes. Electronic supplementary material The online version of this article (doi:10.1186/s13229-017-0160-x) contains supplementary material, which is available to authorized users
Additional file 2: Figure S1. of Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally
RNA sequencing pathways differentially altered across development between VPA and saline amygdala. Pathways with significant time (P10–21) by treatment (VPA/saline) effects are displayed. Treatment effects did not reach statistical significance after FDR multiple comparison correction, thus Ingenuity Pathway Analyses were run on genes with uncorrected p < 0.05 treatment effects at P10 (n = 542) and P21 (n = 406). Canonical pathways and diseases and functions categories with predicted activation or inhibition differences were broadly categorized into the following groups: cellular development and growth; nervous system development and function; immune system, cancer, disease; cell/organismal death; metabolism; and developmental, neurological, or psychological disorder. (PDF 59 kb
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Thanks to Scott Paisley who wrote the callback script. John Ousterhout is responsible for Tcl, without which expect would not have been written. John also critiqued expect as well as the first paper about it. I am indebted to him