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Biology subjects

Jaeger, N.

Publications and source records attributed to Jaeger, N..

2 recordsLinked to original sources

The asthma gut microbiota influences lung inflammation in gnotobiotic mice

The composition of the gut microbiota in early childhood is linked to asthma risk but the role of the gut microbiota in older patients with established asthma is less clear. Here, we used a cohort of 38 school-aged children (19 with asthma) and 57 adults (17 with asthma) to develop a model that aids in the design of mechanistic experiments in gnotobiotic mice. These experiments show that enterotoxigenic Bacteroides fragilis (ETBF) is associated with increased gut permeability, oxidative stress, and markers of Th17-mediated inflammation in the lungs of mice following ovalbumin sensitization and challenge (OSC). Further, ETBF is enriched in a human population with asthma compared to healthy controls. Our results provide evidence that ETBF has the potential to alter the phenotype of airway inflammation in a subset of patients with asthma outside of early childhood which suggests that therapies targeting the gut microbiota may be helpful tools for asthma control.

microbiology↗

Comprehensive analysis of mutational signatures in pediatric cancers

Analysis of mutational signatures can reveal the underlying molecular mechanisms of the processes that have imprinted the somatic mutations found in a cancer genome. Here, we present a pan-cancer mutational signatures analysis of single base substitutions (SBS) and small insertion and deletions (ID) in pediatric cancers encompassing 537 whole genome sequenced tumors from 20 molecularly defined cancer subtypes. We identified only a small number of mutational signatures active in pediatric cancers when compared to the previously analyzed adult cancers. Further, we report a significant difference in the proportion of pediatric tumors which show homologous recombination repair defect signature SBS3 compared to prior analyses. Correlating genomic alterations with signature activities, we identified an association of TP53 mutation status with substitution signatures SBS2, SBS8, SBS13 and indel signatures ID2 and ID9, as well as chromothripsis associated with SBS8, SBS40 and ID9. This analysis provides a systematic overview of COSMIC v.3 SBS and ID mutational signatures active across pediatric cancers, which is highly relevant for understanding tumor biology as well as enabling future research in defining biomarkers of treatment response.

cancer biology↗