Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA299707 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Determinants of Asthma Following RSV Bronchiolitis in Early Life
| PRJNA272341 | ENA
Project description:Determinants of Asthma Following RSV Bronchiolitis in Early Life
| PRJNA299706 | ENA
Project description:<p>The goal of the RSV Bronchiolitis in Early Life (RBEL) study is to determine how specific genetic, biologic, and immunologic characteristics interact to predispose individuals to develop asthma. Participants were carefully recruited by selecting a prospective cohort of 206 infants with severe respiratory syncytial virus (RSV) bronchiolitis who were at substantial risk of developing asthma.</p>
| phs001009 | dbGaP
Project description:Respiratory syncytial virus (RSV) is a prevalent pathogen globally, can cause severe disease in older adults, and remains the leading cause of bronchiolitis and pneumonia in the United States for children during their first year of life. Despite its prevalence worldwide, RSV specific pharmacologic interventions remain unavailable for most infected patients. Although vaccines are available for a subset of adults, further investigation of the molecular interactions between RSV and the host remains essential to understanding this prolific pathogen. To aid our understanding of the host response in both RSV infected cells, and uninfected bystanders, we utilized single-cell RNA sequencing.
2025-04-16 | GSE281623 | GEO
Project description:Respiratory Syncytial virus (RSV) is the most common cause of childhood viral bronchiolitis and lung injury. Inflammatory responses significantly contribute to lung pathologies during RSV infections and bronchiolitis but the exact mechanisms have not been completely defined. The double-stranded RNA-activated protein kinase (PKR) functions to inhibit viral replication and participates in several signaling pathways associated with innate inflammatory immune responses. Using a functionally defective PKR (PKR-/-) mouse model, we investigated the role of this kinase in early events of RSV-induced inflammation. Our data showed that bronchoalveolar lavage (BAL) fluid of infected PKR-/- mice had significantly lower levels of several innate inflammatory cytokines and chemokines. Histological examinations revealed that there was less lung injury in infected PKR-/- mice as compared to the wild type. A genome-wide analysis showed that several early anti viral and immune regulatory genes were affected by PKR activation. These data suggest that PKR is a signaling molecule for immune responses during RSV infections.
2009-09-23 | GSE18170 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Although childhood asthma is in part an airway epithelial disorder, the development of the airway epithelium in asthma is not understood. We sought to characterize airway epithelial developmental phenotypes in those with and without recurrent wheeze and the impact of infant infection with respiratory syncytial virus (RSV). Nasal airway epithelial cells (NAECs) were collected at age 2-3 years from an a priori designed nested birth cohort of children from four mutually exclusive groups of wheezers/non-wheezers and RSV-infected/uninfected in the first year of life. NAECs were cultured in air-liquid interface differentiation conditions followed by a combined analysis of single cell RNA sequencing (scRNA-seq) and in vitro infection with respiratory syncytial virus (RSV). NAECs from children with a wheeze phenotype were characterized by abnormal differentiation and basal cell activation of developmental pathways, plasticity in precursor differentiation and a delayed onset of maturation. NAECs from children with wheeze also had increased diversity of currently known RSV receptors and blunted anti-viral immune responses to in vitro infection. The most dramatic changes in differentiation of cultured epithelium were observed in NAECs derived from children that had both wheeze and RSV in the first year of life. Together this suggests that airway epithelium in children with wheeze is developmentally reprogrammed and characterized by increased barrier permeability, decreased antiviral response, and increased RSV receptors, which may predispose to and amplify the effects of RSV infection in infancy and susceptibility to other asthma risk factors that interact with the airway mucosa.
2025-04-16 | GSE286262 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Respiratory syncytial virus (RSV) is a main cause of infant morbidity and mortality. Susceptibility factors for severe RSV bronchiolitis in previously healthy children are unclear. We analyze genetic variants in 5,141 genes involved in virus sensing, interferon (IFN) signaling and effector functions in a population of n=101 previously healthy infants with severe RSV bronchiolitis. Comparing allele frequencies of the patient cohort with the exome aggregation consortium dataset (ExAC) our analysis reveals 94 non-synonymous coding single nucleotide polymorphisms (SNPs) mapping to 79 potential risk genes. Follow up of genes expressed in human lung cells show that TMEM259 (also known as membralin), a protein involved in regulating endoplasmic reticulum (ER) stress and neuronal cell survival, restricts RSV infection. Analysis of engineered human airway cells endogenously expressing the TMEM259 major allele or the rs77868901 minor variant shows allele-dependent modulation of RSV infection and ER-stress induced apoptosis, but not IFN activity nor induction of IFN stimulated genes. TMEM259 abundance and polymorphisms modulate RSV infection likely by modulating the ER stress response and apoptosis. This data may aid future risk stratification and development of prevention and treatment strategies for RSV.
2025-06-01 | GSE297985 | GEO