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Davies, J. D.

Publications and source records attributed to Davies, J. D..

2 recordsLinked to original sources

How to define, use, and interpret Pagel's lambda (lambda) in ecology and evolution

1Pagels {lambda} (lambda) is a critical tool in ecology and evolution for describing trait evolution, imputing missing species data, and generalising ecological relationships beyond their study system. Yet the interpretation of {lambda} depends on context, and there are many misconceptions about metrics that are similar but not identical to {lambda}. As an index of phylogenetic signal applied to continuous traits, {lambda} typically (but not always) ranges between 0 and 1, and is a rate-independent measure of the degree to which closely-related species resemble one-another relative to a Brownian motion expectation. But this measure is biased by non-random species sampling--a common characteristic of ecological data--which also makes phylogenetic imputation of missing traits challenging. The {lambda} estimated in regression models has little to do with the phylogenetic signal of measured traits and is better considered as either a statistical correction or a measure of the impact of unmeasured (latent) traits in the model. In other contexts, such as hierarchical models including intra-specific variation, {lambda} is frequently confused with distinct metrics such as h2. We show how confusion in defining and using {lambda} can mislead our interpretation of ecological and evolutionary processes. Open research statementNo data were used or collected as part of this work.

evolutionary biology↗

Genomic programming of antigen cross-presentation in IRF4-expressing human Langerhans cells

Langerhans cells (LCs) in the epidermis present MHC I and MHC II-restricted antigens thereby priming either CD8 or CD4 T cell immune responses. The genomic programs and transcription factors regulating antigen presentation in LCs remain to be elucidated. We show human LCs are highly efficient in MHC I-antigen cross-presentation but lack the transcription factor IRF8 that is critical in dendritic cells. LC migration from the epidermis enhances their ability to cross-present antigens and is accompanied by the induction of the transcription factor IRF4, whose expression is correlated by scRNA-seq with genes involved in ubiquitin-dependent protein degradation. Chromatin profiling reveals enrichment of EICE and AICE composite DNA binding motifs in regulatory regions of antigen-presentation genes, which can be recognized by IRF4 in conjunction with PU.1 or BATF3 expressed in LCs. Thus, the genomic programming of human LCs including inducible expression of IRF4 with enhanced cross-presentation distinguishes them from conventional dendritic cells.

immunology↗