A mixed-model approach for estimating drivers of microbiota community composition and differential taxonomic abundance.

Next-generation sequencing (NGS) and metabarcoding approaches are increasingly applied to wild animal populations, but there is a disconnect between the widely applied generalized linear mixed model (GLMM) approaches commonly used to study phenotypic variation and the statistical toolkit from community ecology typically applied to metabarcoding data. Here, we describe the suitability of a novel GLMM-based approach for analyzing the taxon-specific sequence read counts derived from standard metabarcoding data. This approach allows decomposition of the contribution of different drivers to variation in community composition (e.

AKT activation because of PTEN loss upregulates xCT via GSK3β/NRF2, leading to inhibition of ferroptosis in PTEN-mutant tumor cells.

Here, we show that the tumor suppressor phosphatase and tensin homolog deleted from chromosome 10 (PTEN) sensitizes cells to ferroptosis, an iron-dependent form of cell death, by restraining the expression and activity of the cystine/glutamate antiporter system X (xCT). Loss of PTEN activates AKT kinase to inhibit GSK3β, increasing NF-E2 p45-related factor 2 (NRF2) along with transcription of one of its known target genes encoding xCT. Elevated xCT in Pten-null mouse embryonic fibroblasts increases the flux of cystine transport and synthesis of glutathione, which enhances the steady-state levels of these metabolites.

Decomposing phenotypic skew and its effects on the predicted response to strong selection.

The major frameworks for predicting evolutionary change assume that a phenotype's underlying genetic and environmental components are normally distributed. However, the predictions of these frameworks may no longer hold if distributions are skewed. Despite this, phenotypic skew has never been decomposed, meaning the fundamental assumptions of quantitative genetics remain untested.

Functionally distinct T-helper cell phenotypes predict resistance to different types of parasites in a wild mammal.

The adaptive immune system is critical to an effective response to infection in vertebrates, with T-helper (Th) cells pivotal in orchestrating these responses. In natural populations where co-infections are the norm, different Th responses are likely to play an important role in maintaining host health and fitness, a relationship which remains poorly understood in wild animals. In this study, we characterised variation in functionally distinct Th responses in a wild population of Soay sheep by enumerating cells expressing Th-subset specific transcription factors and quantifying Th-associated cytokines.