Rhinovirus increases Moraxella catarrhalis adhesion to the respiratory epithelium

Rhinovirus causes many types of respiratory illnesses, ranging from minor colds to exacerbations of asthma. Moraxella catarrhalis is an opportunistic pathogen that is increased in abundance during rhinovirus illnesses and asthma exacerbations and is associated with increased severity of illness through mechanisms that are ill-defined. We used a co-infection model of human airway epithelium differentiated at the air-liquid interface to test the hypothesis that rhinovirus infection promotes M. catarrhalis adhesion and survival on the respiratory epithelium. Initial experiments showed that infection with M. catarrhalis alone did not damage the epithelium or induce cytokine production, but increased trans-epithelial electrical resistance, indicative of increased barrier function. In a co-infection model, infection with the more virulent rhinovirus-A and rhinovirus-C, but not the less virulent rhinovirus-B types, increased cell-associated M. catarrhalis. Immunofluorescent staining demonstrated that M. catarrhalis adhered to rhinovirus-infected ciliated epithelial cells and infected cells being extruded from the epithelium. Rhinovirus induced pronounced changes in gene expression and secretion of inflammatory cytokines. In contrast, M. catarrhalis caused minimal effects and did not enhance RV-induced responses. Our results indicate that rhinovirus-A or C infection increases M. catarrhalis survival and cell association while M. catarrhalis infection alone does not cause cytopathology or epithelial inflammation. Our findings suggest that rhinovirus and M. catarrhalis co-infection could promote epithelial damage and more severe illness by amplifying leukocyte inflammatory responses at the epithelial surface

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

BACKGROUND: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. METHODS: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. RESULTS: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. CONCLUSIONS: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases

Surveying the experience of postdocs in the United States before and during the COVID-19 pandemic

In the interest of advocating for the postdoctoral community in the United States (US), we compared the results of surveys of postdocs carried out in 2019 and in late 2020. We found that respondents’ mental health and wellness were significantly impacted by the pandemic irrespective of their gender, race, citizenship, or other identities. Career trajectories and progression were also affected, as respondents reported being less confident about achieving career goals, and having more negative perceptions of the job market compared to before the pandemic. Postdocs working in the US on temporary visas reported experiencing increased stress levels due to changes in immigration policy. Access to institutional Postdoctoral Offices or Associations positively impacted well-being and helped mitigate some of the personal and professional stresses caused by the pandemic

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

BACKGROUND: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. METHODS: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. RESULTS: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. CONCLUSIONS: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases

Additional file 1 of African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Additional file 1. Contains Supplementary Methods, Supplementary Tables (Table S1-10), and Supplementary Figures (Fig. S1-14), and corresponding references. Supplementary Methods. Descriptions of Populations. Building Consensus Sequences in the Critical Region. Table S1. Characteristics of the APIC and URECA Cohorts. Table S2. Predicted Haplotypes in CREW. Table S3. Haplotype Frequencies in Whole Genome Sequences. Table S4. Worldwide Frequencies of African-specific SNPs. Table S5. cis-eQTL Results for SNPs in or near GSDMA. Table S6. ENCODE Cell Lines and DNAse Clustering at pcHi-C Region. Table S7. pcHi-C Target Genes for African-specific Variants in Airway Epithelial Cells. Table S8. pcHi-C Target Genes for African-specific Variants in Airway Immune Cells. Table S9. Quantitative Trait Association Results in the APIC and URECA Cohorts. Table S10. African American Adult Asthmatics by Severity and Genotype. Figure S1. Overview of Study Design. Figure S2. ChromoPainter Analysis. Figure S3. ChromoPainter Visualization of Haplotype Breakpoints. Figure S4. ChromoPainter Display of the 17q12-q21 Region in Haplotype 4 Homozygotes. Figure S5. Ancestry PCA plots for APIC and URECA Children. Figure S6. eQTL Box Plots of rs28623237 Genotype and GSDMA Expression in CAAPA2. Figure S7. LD Plot of African-specific Variants and SNPs in or near GSDMA. Figure S8. eQTL Box Plots of rs113282230 Genotype and GSDMA Expression Conditioned on GSDMA SNPs. Figure S9. eQTL Violin Plots of rs235480 and rs1132828830 Genotypes on GSDMA and GSDMB Expression. Figure S10. LD Plot of the African-specific Variants and SNPs in the Core Region of The 17q12-q21 Locus. Figure S11. Chromatin Annotations in the Region Encoding the African-specific SNPs in ENCODE Cell Lines. Figure S12. eGenes for rs113282230 in Immune Cells. Figure S13. pcHi-C Data for rs113282230 in Immune Cells. Figure S14. Rs113282230 Genotype Effect on Asthma Prevalence by rs2305480 AA And GG Genotypes in APIC and URECA

Additional file 2 of African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Additional file 2. Region-wide eQTL results in airway epithelial cells from 189 African American children in the URECA cohort