Epigenomic annotations for the rat lag far behind those of human and mouse, despite the rat's immense utility in pharmacological and behavioral studies and the need to understand their epigenetic mechanisms. We have designed a targeted-enrichment method followed by next-generation sequencing (Methyl-Seq) to identify DNA methylation (DNAm) signatures across the rat genome. The design reflected an attempt to create a more comprehensive investigation of the rat epigenome, as it included promoters, CpG islands, and island shores of all RefSeq genes.
View Article and Find Full Text PDFSeasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus where it receives retinal input and synchronizes, or entrains, organismal physiology and behavior to the prevailing light cycle. The process of entrainment induces sustained plasticity in the SCN, but the molecular mechanisms underlying SCN plasticity are incompletely understood.
View Article and Find Full Text PDFSeasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus where it receives retinal input and synchronizes, or entrains, organismal physiology and behavior to the prevailing light cycle. The process of entrainment induces sustained plasticity in the SCN, but the molecular mechanisms underlying SCN plasticity are incompletely understood.
View Article and Find Full Text PDFThere is a growing body of evidence indicative of changes in autonomic nervous system (ANS) activity in patients with disorders of the central nervous system (CNS). Non-invasive measures of the ANS, including heart rate variability (HRV), electrodermal activity (EDA), and pupillary light reflex (PLR) may have value as markers of symptom severity, subtype, risk profile, and/or treatment response. In this paper we provide an introduction into the anatomy and physiology of EDA and review the literature published after 2007 in which EDA was an outcome measure of cortical stimulation with transcranial magnetic stimulation (TMS).
View Article and Find Full Text PDFBackground: Novel therapies are urgently needed for ovarian cancer (OC), the fifth deadliest cancer in women. Preclinical work has shown that DNA methyltransferase inhibitors (DNMTis) can reverse the immunosuppressive tumor microenvironment in OC. Inhibiting DNA methyltransferases activate transcription of double-stranded (ds)RNA, including transposable elements.
View Article and Find Full Text PDFEpithelial ovarian carcinomas are particularly deadly due to intratumoral heterogeneity, resistance to standard-of-care therapies, and poor response to alternative treatments such as immunotherapy. Targeting the ovarian carcinoma epigenome with DNA methyltransferase inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi) increases immune signaling and recruits CD8 T cells and natural killer cells to fight ovarian carcinoma in murine models. This increased immune activity is caused by increased transcription of repetitive elements (RE) that form double-stranded RNA (dsRNA) and trigger an IFN response.
View Article and Find Full Text PDFThis study investigates, using an online self-report questionnaire, adolescents' emotional reactions during the lockdown in a sample of 2105 secondary school students (aged 14-19) in Italy, Romania, and Croatia. We used a self-reported online questionnaire (answers on a 5-point scale or binary), composed of 73 questions investigating the opinions, feelings, and emotions of teenagers, along with sociodemographic information and measures of the exposure to lockdown. The survey was conducted online through a web platform in Italy (between 27 April and 15 June 2020), Romania, and Croatia (3 June and 2 July 2020).
View Article and Find Full Text PDFExposure to stress or glucocorticoids (GCs) is associated with epigenetic and transcriptional changes in genes that either mediate or are targets of GC signalling. (FK506 binding protein 5) is one such gene that also plays a central role in negative feedback regulation of GC signalling and several stress-related psychiatric disorders. In this study, we sought to examine how the mouse gene is regulated in a neuronal context and identify requisite factors that can mediate the epigenetic sequelae of excess GC exposure.
View Article and Find Full Text PDFWe sought to replicate and expand upon previous work demonstrating antenatal TTC9B and HP1BP3 gene DNA methylation is prospectively predictive of postpartum depression (PPD) with ~80% accuracy. In a preterm birth study from Emory, Illumina MethylEPIC microarray derived 1st but not 3rd trimester biomarker models predicted 3rd trimester Edinburgh Postnatal Depression Scale (EPDS) scores ≥ 13 with an AUC=0.8 (95% CI: 0.
View Article and Find Full Text PDFA single nucleotide polymorphism (SNP: rs1360780) in has been shown to interact with exposure to childhood adversity to promote loss of methylation and increase in gene expression in adults. We asked whether rs1360780 can influence intronic methylation in the context of exposure to maternal affective disorders . Sixty cord blood DNA samples from the Boston Birth Cohort were genotyped at rs1360780 and studied for methylation changes as they relate to genotype and exposure to affective disorders during pregnancy.
View Article and Find Full Text PDFA correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
View Article and Find Full Text PDFAs genomes of a wider variety of animals become available, there is an increasing need for tools that can capture dynamic epigenetic changes in these animal models. The rat is one particular model animal where an epigenetic tool can complement many pharmacological and behavioral studies to provide insightful mechanistic information. To this end, we adapted the SureSelect Target Capture System (referred to as Methyl-Seq) for the rat, which can assess DNA methylation levels across the rat genome.
View Article and Find Full Text PDFCurr Drug Targets
August 2020
Post-translational modification by small ubiquitin-like modifier (SUMO) has emerged as a global mechanism for the control and integration of a wide variety of biological processes through the regulation of protein activity, stability and intracellular localization. As SUMOylation is examined in greater detail, it has become clear that the process is at the root of several pathologies including heart, endocrine, and inflammatory disease, and various types of cancer. Moreover, it is certain that perturbation of this process, either globally or of a specific protein, accounts for many instances of congenital birth defects.
View Article and Find Full Text PDFThe earliest stages of animal development are largely controlled by changes in protein phosphorylation mediated by signaling pathways and cyclin-dependent kinases. In order to decipher these complex networks and to discover new aspects of regulation by this post-translational modification, we undertook an analysis of the X. laevis phosphoproteome at seven developmental stages beginning with stage VI oocytes and ending with two-cell embryos.
View Article and Find Full Text PDFChronic exposure to glucocorticoids (GCs) can lead to psychiatric complications through epigenetic mechanisms such as DNA methylation (DNAm). We sought to determine whether epigenetic changes in a peripheral tissue can serve as a surrogate for those in a relatively inaccessible tissue such as the brain. DNA extracted from the hippocampus and blood of mice treated with GCs or vehicle solution was assayed using a genome-wide DNAm platform (Methyl-Seq) to identify differentially methylated regions (DMRs) induced by GC treatment.
View Article and Find Full Text PDFA tryptic digest generated from Xenopus laevis fertilized embryos was fractionated by RPLC. One set of 30 fractions was analyzed by 100-min CZE-ESI-MS/MS separations (50 h total instrument time), and a second set of 15 fractions was analyzed by 3-h UPLC-ESI-MS/MS separations (45 h total instrument time). CZE-MS/MS produced 70% as many protein IDs (4134 versus 5787) and 60% as many peptide IDs (22 535 versus 36 848) as UPLC-MS/MS with similar instrument time (50 h versus 45 h) but with 50 times smaller total consumed sample amount (1.
View Article and Find Full Text PDFFKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments.
View Article and Find Full Text PDFThe oxytocin receptor (OXTR) is a key regulator of stress and anxiety and may be regulated by both psychosocial risk factors and gonadal hormones, making it an attractive candidate for study in postpartum depression (PPD). The objective of this study was to investigate both serum hormone and PPD specific DNA methylation variation in the OXTR. Illumina HM450 microarray data generated in a prospective PPD cohort identified significant associations (P=0.
View Article and Find Full Text PDFA sulfonate-silica hybrid strong cation exchange monolith microreactor was synthesized and coupled to a linear polyacrylamide coated capillary for online sample preparation and capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) bottom-up proteomic analysis. The protein sample was loaded onto the microreactor in an acidic buffer. After online reduction, alkylation, and digestion with trypsin, the digests were eluted with 200 mM ammonium bicarbonate at pH 8.
View Article and Find Full Text PDFDNA methylation variation at HP1BP3 and TTC9B is modified by estrogen exposure in the rodent hippocampus and was previously shown to be prospectively predictive of postpartum depression (PPD) when modeled in antenatal blood. The objective of this study was to replicate the predictive efficacy of the previously established model in women with and without a previous psychiatric diagnosis and to understand the effects of changing hormone levels on PPD biomarker loci. Using a statistical model trained on DNA methylation data from N=51 high-risk women, we prospectively predicted PPD status in an independent N=51 women using first trimester antenatal gene expression levels of HP1BP3 and TTC9B, with an area under the receiver operator characteristic curve (AUC) of 0.
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