Do Seasonal Glucocorticoid Changes Depend on Reproductive Investment? A Comparative Approach in Birds

Animals go through different life history stages such as reproduction, moult, or migration, of which some are more energy-demanding than others. Baseline concentrations of glucocorticoid hormones increase during moderate, predictable challenges and thus are expected to be higher when seasonal energy demands increase, such as during reproduction. By contrast, stress-induced glucocorticoids prioritize a survival mode that includes reproductive inhibition. Thus, many species down-regulate stress-induced glucocorticoid concentrations during the breeding season. Interspecific variation in glucocorticoid levels during reproduction has been successfully mapped onto reproductive investment, with species investing strongly in current reproduction (fast pace of life) showing higher baseline and lower stress-induced glucocorticoid concentrations than species that prioritize future reproduction over current attempts (slow pace of life). Here we test the >glucocorticoid seasonal plasticity hypothesis>, in which we propose that interspecific variation in seasonal changes in glucocorticoid concentrations from the non-breeding to the breeding season will be related to the degree of reproductive investment (and thus pace of life). We extracted population means for baseline (for 54 species) and stress-induced glucocorticoids (for 32 species) for the breeding and the non-breeding seasons from the database >HormoneBase>, also calculating seasonal glucocorticoid changes. We focused on birds because this group offered the largest sample size. Using phylogenetic comparative methods, we first showed that species differed consistently in both average glucocorticoid concentrations and their changes between the two seasons, while controlling for sex, latitude, and hemisphere. Second, as predicted seasonal changes in baseline glucocorticoids were explained by clutch size (our proxy for reproductive investment), with species laying larger clutches showing a greater increase during the breeding season-especially in passerine species. In contrast, changes in seasonal stress-induced levels were not explained by clutch size, but sample sizes were more limited. Our findings highlight that seasonal changes in baseline glucocorticoids are associated with a species' reproductive investment, representing an overlooked physiological trait that may underlie the pace of life

Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation

Attenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying that the proteins recognising these histone modifications could also play an important role in attenuation of RAS-mediated signalling. We sought to systematically identify these proteins and found BET-1. BET-1 is a conserved double bromodomain protein that recognises acetyl-lysines on histone tails and maintains the stable fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are depleted of muscle myosin, an essential component of myofibrils. We also show that this muscle myosin depletion does not occur in all animals at a specific time, but rather that the penetrance of the phenotype increases with age. To gain mechanistic insights into this process, we sought to delay the occurrence of the muscle myosin depletion phenotype and found that it requires caspase activity and MEK-dependent signalling. We also performed transcription profiling on these mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase receptor acting upstream of MEK. Consistent with a MEK requirement, we could delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus, this work uncovered a caspase- and MEK-dependent mechanism that acts specifically on ageing adults to maintain the appropriate net level of muscle myosi

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Nutritional intervention during gestation alters growth, body composition and gene expression patterns in skeletal muscle of pig offspring

peer-reviewedVariations in maternal nutrition during gestation can influence foetal growth, foetal development and permanently ‘programme’ offspring for postnatal life. The objective of this study was to analyse the effect of increased maternal nutrition during different gestation time windows on offspring growth, carcass quality, meat quality and gene expression in skeletal muscle. A total of 64 sows were assigned to the following feeding treatments: a standard control diet at a feed allocation of 2.3 kg/day throughout gestation, increased feed allowance of 4.6 kg/day from 25 to 50 days of gestation (dg), from 50 to 80 dg and from 25 to 80 dg. At weaning, Light, Medium and Heavy pigs of the same gender, within litter, were selected based on birth weight, individually penned and monitored until slaughter at 130 days post weaning. Carcass and meat quality traits of the semimembranosus (SM) muscle were recorded post mortem. A cross section of the semitendinosus (ST) muscle encompassing the deep and superficial regions were harvested from pigs (n518 per treatment) for RNA extraction and quantification of gene expression by real-time PCR. The results showed that doubling the feed intake from 25 to 50 dg reduced offspring growth, carcass weight, intramuscular fat content and increased drip loss of the SM muscle. Interestingly, protein phosphatase 3 catalytic subunit – a-isoform, which codes for the transcription factor calcineurin, was upregulated in the ST muscle of offspring whose mothers received increased feed allowance from 25 to 50 dg. This may provide an explanation for the previous observed increases in Type IIa muscle fibres of these offspring. Increasing the maternal feed intake from 50 to 80 dg negatively impacted pig growth and carcass weight, but produced leaner male pigs. Extending the increased maternal feed intake from 25 to 80 dg had no effect on offspring over the standard control gestation diet. Although intra-litter variation in pig weight is a problem for pig producers, increased maternal feeding offered no improvement throughout life to the lighter birth weight littermates in our study. Indeed, increased maternal nutrition at the three-gestation time windows selected provided no major benefits to the offspring.Teagasc, under the National Development Plan; Teagasc Walsh Fellowship; Short Term Scientific Mission (STSM) fund, COST925

Species-Specific Means and Within-Species Variance in Glucocorticoid Hormones and Speciation Rates in Birds

At macroevolutionary scales, stress physiology may have consequences for species diversification and subspecies richness. Populations that exploit new resources or undergo range expansion should cope with new environmental challenges, which could favor higher mean stress responses. Within-species variation in the stress response may also play a role in mediating the speciation process: in species with broad variation, there will always be some individuals that can tolerate an unpredictable environment, whereas in species with narrow variation there will be fewer individuals that are able to thrive in a new ecological niche. We tested for the evolutionary relationship between stress response, speciation rate, and subspecies richness in birds by relying on the HormoneBase repository, from which we calculated within- and among-species variation in baseline (BL) and stress-induced (SI) corticosterone levels. To estimate speciation rates, we applied Bayesian analysis of macroevolutionary mixtures that can account for variation in diversification rate among clades and through time. Contrary to our predictions, lineages with higher diversification rates were not characterized by higher BL or SI levels of corticosterone either at the tips or at the deeper nodes of the phylogeny. We also found no association between mean hormone levels and subspecies richness. Within-species variance in corticosterone levels showed close to zero repeatability, thus it is highly unlikely that this is a species-specific trait that influences diversification rates. These results imply that stress physiology may play a minor, if any, role in determining speciation rates in birds