Obstructive Sleep Apnea (OSA) is a common sleep-related breathing disorder characterized by airway obstruction during sleep. Diagnosing pediatric OSA is challenging, particularly in underrepresented populations, leading to disparities in treatment and long-term negative health outcomes. Our study aimed to identify alternative diagnostic tools by investigating genome-wide epigenetic changes and associated transcriptomic alterations in Black female, pediatric patients with OSA.
View Article and Find Full Text PDFHuman cytomegalovirus (HCMV) infects up to 80% of the world's population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hours after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity.
View Article and Find Full Text PDFThe developing peripheral nervous and immune systems are functionally distinct from those of adults. These systems are vulnerable to early-life injury, which influences outcomes related to nociception following subsequent injury later in life (i.e.
View Article and Find Full Text PDFBackground: There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.
View Article and Find Full Text PDFEosinophilic esophagitis (EoE) is a rare atopic disorder associated with esophageal dysfunction, including difficulty swallowing, food impaction, and inflammation, that develops in a small subset of people with food allergies. Genome-wide association studies (GWASs) have identified 9 independent EoE risk loci reaching genome-wide significance (p < 5 × 10) and 27 additional loci of suggestive significance (5 × 10 < p < 1 × 10). In the current study, we perform linkage disequilibrium (LD) expansion of these loci to nominate a set of 531 variants that are potentially causal.
View Article and Find Full Text PDFCognate interaction between CD4 effector memory T (T) cells and dendritic cells (DCs) induces innate inflammatory cytokine production, resulting in detrimental autoimmune pathology and cytokine storms. While T cells use tumor necrosis factor (TNF) superfamily ligands to activate DCs, whether T cells prompt other DC-intrinsic changes that influence the innate inflammatory response has never been investigated. We report the surprising discovery that T cells trigger double-strand DNA breaks via mitochondrial reactive oxygen species (ROS) production in interacting DCs.
View Article and Find Full Text PDFThe developing peripheral nervous and immune systems are functionally distinct from adults. These systems are vulnerable to early life injury, which influences outcomes related to nociception following subsequent injury later in life (neonatal nociceptive priming). The underpinnings of this phenomenon are largely unknown, although previous work indicates that macrophages are epigenetically trained by inflammation and injury.
View Article and Find Full Text PDFTranscription factors read the genome, fundamentally connecting DNA sequence to gene expression across diverse cell types. Determining how, where, and when TFs bind chromatin will advance our understanding of gene regulatory networks and cellular behavior. The 2017 ENCODE-DREAM in vivo Transcription-Factor Binding Site (TFBS) Prediction Challenge highlighted the value of chromatin accessibility data to TFBS prediction, establishing state-of-the-art methods for TFBS prediction from DNase-seq.
View Article and Find Full Text PDFAtopic dermatitis (AD) is one of the most common skin disorders among children. Disease etiology involves genetic and environmental factors, with 29 independent AD risk loci enriched for risk allele-dependent gene expression in the skin and CD4+ T cell compartments. We investigated the potential epigenetic mechanisms responsible for the genetic susceptibility of CD4+ T cells.
View Article and Find Full Text PDFThe interplay between environmental and genetic factors plays a key role in the development of many autoimmune diseases. In particular, the Epstein-Barr virus (EBV) is an established contributor to multiple sclerosis, lupus, and other disorders. Previously, we showed that the EBV nuclear antigen 2 (EBNA2) transactivating protein occupies up to half of the risk loci for a set of seven autoimmune disorders.
View Article and Find Full Text PDFRunt-related transcription factor 1 (Runx1) can act as both an activator and a repressor. Here we show that CRISPR-mediated deletion of Runx1 in mouse metanephric mesenchyme-derived mK4 cells results in large-scale genome-wide changes to chromatin accessibility and gene expression. Open chromatin regions near down-regulated loci enriched for Runx sites in mK4 cells lose chromatin accessibility in Runx1 knockout cells, despite remaining Runx2-bound.
View Article and Find Full Text PDFGenome-wide association studies of Systemic Lupus Erythematosus (SLE) nominate 3073 genetic variants at 91 risk loci. To systematically screen these variants for allelic transcriptional enhancer activity, we construct a massively parallel reporter assay (MPRA) library comprising 12,396 DNA oligonucleotides containing the genomic context around every allele of each SLE variant. Transfection into the Epstein-Barr virus-transformed B cell line GM12878 reveals 482 variants with enhancer activity, with 51 variants showing genotype-dependent (allelic) enhancer activity at 27 risk loci.
View Article and Find Full Text PDFA GaAsBi layer was grown by molecular beam epitaxy (MBE) with a low Bi content (2.3%) on GaAs maintaining the substrate at a non-rotating state and was then annealed at 750 °C, 800 °C and 850 °C. Each sample that was covered with droplets was investigated by using the Atomic Force Microscopy (AFM), Electrostatic Force Microscopy (EFM) and Photoluminescence (PL) techniques.
View Article and Find Full Text PDFUnlabelled: We report the observation of thermal annealing- and nitrogen-induced effects on electronic transport properties of as-grown and annealed n- and p-type modulation-doped Ga1 - xInxNyAs1 - y (x = 0.32, y = 0, 0.009, and 0.
View Article and Find Full Text PDFUnlabelled: Bulk GaAs1 - xBix/GaAs alloys with various bismuth compositions are studied using power- and temperature-dependent photoluminescence (PL), Raman scattering, and atomic force microscopy (AFM). PL measurements exhibit that the bandgap of the alloy decreases with increasing bismuth composition. Moreover, PL peak energy and PL characteristic are found to be excitation intensity dependent.
View Article and Find Full Text PDFThe excitation energy-dependent nature of Raman scattering spectrum, vibration, electronic or both, has been studied using different excitation sources on as-grown and annealed n- and p-type modulation-doped Ga1 - xInxNyAs1 - y/GaAs quantum well structures. The samples were grown by molecular beam technique with different N concentrations (y = 0%, 0.9%, 1.
View Article and Find Full Text PDFIn this study, photomodulated reflectance (PR) technique was employed on two different quantum well infrared photodetector (QWIP) structures, which consist of n-doped GaAs quantum wells (QWs) between undoped AlxGa1-xAs barriers with three different x compositions. Therefore, the barrier profile is in the form of a staircase-like barrier. The main difference between the two structures is the doping profile and the doping concentration of the QWs.
View Article and Find Full Text PDFIn this study, we investigate the effect of annealing and nitrogen amount on electronic transport properties in n- and p-type-doped Ga0.68In0.32NyAs1 - y/GaAs quantum well (QW) structures with y = 0%, 0.
View Article and Find Full Text PDFElectronic transport in unintentionally doped GaxIn1-xN alloys with various Ga concentrations (x = 0.06, 0.32 and 0.
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