Developmental stress, condition, and birdsong: a case study in song sparrows.

Sexual-selection theory posits that ornaments and displays can reflect a signaler\u27s condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers. Here, we review data on the relationships between birdsong, a sexually selected trait, and developmental and current condition of birds from a long-term study of a population of song sparrows (Melospiza melodia). Field studies of free-living birds indicate that the complexity of a male\u27s songs, a permanent trait, reflects the size of a song-control region of his brain (HVC), and is correlated with body size and several parameters of immunity, specifically investment in protective proteins. However, the performance of a male\u27s songs, a dynamic trait, is not correlated to immune investment. Complexity of song is correlated with the glucocorticoid stress-response, and in some years response to stress predicts overwinter survival. Experimental manipulations have revealed that stressors in early life impair development of HVC, but that HVC recovers in size by adulthood. These manipulations result in impaired song-complexity and song-learning, but not song-performance. Experimental developmental stressors also affect growth, endocrine physiology, metabolism, and immune-function, often in a sex-specific manner. Combined, these studies suggest that song-complexity provides reliable information about early developmental experience, and about other traits that have critical developmental periods. Birdsong thus provides a multi-faceted sexually selected trait that may be an indicator both of developmental and recent conditions

AhR controls redox homeostasis and shapes the tumor microenvironment in BRCA1-associated breast cancer

Cancer cells have higher reactive oxygen species (ROS) than normal cells, due to genetic and metabolic alterations. An emerging scenario is that cancer cells increase ROS to activate protumorigenic signaling while activating antioxidant pathways to maintain redox homeostasis. Here we show that, in basal-like and BRCA1-related breast cancer (BC), ROS levels correlate with the expression and activity of the transcription factor aryl hydrocarbon receptor (AhR). Mechanistically, ROS triggers AhR nuclear accumulation and activation to promote the transcription of both antioxidant enzymes and the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG). In a mouse model of BRCA1-related BC, cancer-associated AhR and AREG control tumor growth and production of chemokines to attract monocytes and activate proangiogenic function of macrophages in the tumor microenvironment. Interestingly, the expression of these chemokines as well as infiltration of monocyte-lineage cells (monocyte and macrophages) positively correlated with ROS levels in basal-like BC. These data support the existence of a coordinated link between cancer-intrinsic ROS regulation and the features of tumor microenvironment. Therapeutically, chemical inhibition of AhR activity sensitizes human BC models to Erlotinib, a selective EGFR tyrosine kinase inhibitor, suggesting a promising combinatorial anticancer effect of AhR and EGFR pathway inhibition. Thus, AhR represents an attractive target to inhibit redox homeostasis and modulate the tumor promoting microenvironment of basal-like and BRCA1-associated BC

Choline acetyltransferase-expressing T cells are required to control chronic viral infection.

peer reviewedAlthough widely studied as a neurotransmitter, T cell-derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4+ and CD8+ T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21-dependent manner. Deletion of Chat within the T cell compartment in mice ablated vasodilation in response to infection, impaired the migration of antiviral T cells into infected tissues, and ultimately compromised the control of chronic LCMV clone 13 infection. Our results reveal a genetic proof of function for ChAT in T cells during viral infection and identify a pathway of T cell migration that sustains antiviral immunity

DryadData

Spreadsheet of song and immune data from male song sparrow

Data from: Developmental timing of signals affects information content: song complexity but not consistency reflects innate immune strategy in male song sparrows

In short-lived animals, innate immunity is an important component of fitness and quality. Although receivers cannot generally assess a signaler's immune function directly, sexually selected displays such as birdsong may reflect past or current condition. We investigated the degree to which song complexity and consistency, thought to reflect condition over different developmental timescales, predict multiple aspects of innate immunity in male song sparrows (Melospiza melodia). We also investigated correlations among immune measures. Non-cellular components of innate immunity (soluble blood proteins including natural antibody and other protective proteins) were negatively related to cellular (phagocytosis-based) components, suggesting trade-offs within innate immune protection. This pattern underscores the risk of inferring "immunocompetence" from a single metric. Song complexity, a permanent trait in this species, was positively related to noncellular relative to cellular immune components and may thus provide information as to the singer's innate immune strategy (investment in non-cellular versus cellular activity). Such a relationship could arise through shared timing of song learning and antibody repertoire development in early life. Singing consistency, thought to track variation in current condition and measured at both whole-song and syllable scales, did not predict any immune measures. Developmental timing of signals thus appears to influence their information content