Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1080233 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28268901_1.fastq.gz | Fastqsanger.gz | |||
| SRR28268901_2.fastq.gz | Fastqsanger.gz | |||
| SRR28268902_1.fastq.gz | Fastqsanger.gz | |||
| SRR28268902_2.fastq.gz | Fastqsanger.gz | |||
| SRR28268903_1.fastq.gz | Fastqsanger.gz |
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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:Severe asthma is a collection of disease entities with varying pathophysiological characteristics that result in symptoms of cough, wheeze and breathlessness, with frequent exacerbations. To address the problem of phenotypic difference and heterogeneity, the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project was set up as a public-private partnership within the framework of the Innovative Medicines Initiative (IMI), engaging academia, the pharmaceutical industry and patient groups. The goal of this investigation was to identify proteomic fingerprints in induced sputum that characterize patients with severe asthma and to determine whether subgroups of severe asthmatics can be identified. Furthermore, we were interested in elucidating the biological pathways that showed differences between subgroups. This dataset is a description of the normal sputum proteome.
2018-05-14 | PXD005949 | Pride
Project description:Nasal swab specimens were collected from children who presented to the emergency department with an acute exacerbation of asthma or wheeze. Samples were also collected from control subjects. Convalescent/quiescent samples were collected from children who were followed-up at least 6 weeks after an acute exacerbation of asthma or wheeze. Gene expression was profiled on microarrays.
2019-02-17 | GSE103166 | GEO
Project description:Severe asthma is a collection of disease entities with varying pathophysiological characteristics (7) that result in symptoms of cough, wheeze and breathlessness, with frequent exacerbations. To address the problem of phenotypic difference and heterogeneity, the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project was set up as a public-private partnership within the framework of the Innovative Medicines Initiative (IMI), engaging academia, the pharmaceutical industry and patient groups. The goal of this investigation was to identify transcript fingerprints in whole blood that characterize patients with severe asthma and to determine whether subgroups of severe asthmatics can be identified. Furthermore, we were interested in elucidating the biological pathways that showed differences between subgroups.
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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.
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Project description:Asthma is an inflammatory disease of the airways characterised by episodic airway obstruction resulting in cough, episodic shortness of breath. It is, and is clinically and physiologically heterogeneous. It is estimated that around 300 million people worldwide have the diseaseare diagnosed with asthma, including up to 20% of children (Asher et al, 2006), with 5–10% of these children believed to have severe or difficult-to-treat asthma. Asthma has often been classified in terms of severity and based on clinical diagnostic criteria, but it is now apparent that the heterogeneity that exists at the physiological level is also a feature of the underlying pathological mechanisms (Lotvall et al, 2011). The aim of this study was to identify blood transcriptomics profiles for children diagnosed with asthma or wheeze, and establish whether these profiles suggested endotypes or mechanisms that could underlie disease, or be related to disease severity, in these children. Importantly, given that children are currently treated with the same medicines as adults, we also aimed to compare profiles of children to those of adults with asthma to help determine whether efforts should be directed to the development of medicines targeting pathways and mechanisms that may be unique to children. To this end, we used gene transcriptome data generated from blood samples from adults and children from the U-BIOPRED consortium to ask how similar or different the differential gene expression profiles were between groups of adults and pre-school or school-aged children with severe or mild-moderate asthma (or wheeze for the pre-school aged children) using current definitions. The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project was set up as a public-private partnership within the framework of the Innovative Medicines Initiative (IMI), engaging academia, the pharmaceutical industry and patient groups. The goal of this investigation was to identify transcript fingerprints in whole blood that characterize patients with severe asthma and to determine whether subgroups of severe asthmatics can be identified.
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Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
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Project description:Preschool wheeze is an early life bronchoconstriction disorder with an increased risk of progression to chilhood asthma. Preschool wheeze is typically triggered by respiratory infection, but airway inflammatory phenotypes, including the phenotype of airway macrophages (AMs), in preschool wheeze is not fully understood. In this study, AMs were sorted from preschool wheeze patients and non-wheezing paediatric controls under clinical investigation for chronic cough and gene expression assessed by Illumina mRNA sequencing (110 base pair, paired end reads). A number of differentially expressed genes were observed in AMs from preschool wheeze compared to those from controls, including genes encoding pro-inflammatory chemokines and genes associated with a more immature and inflammatory AM phenotype. These findings suggest that AMs contribute to an altered airway immune landscape in preschool wheeze.
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Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
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