Sex differences in the relationship between maternal and foetal glucocorticoids in a free-ranging large mammal

Maternal phenotypes can have long-term effects on offspring phenotypes. These maternal effects may begin during gestation, when maternal glucocorticoid (GC) levels may affect foetal GC levels, thereby having an organizational effect on the offspring phenotype. Recent studies have showed that maternal effects may be different between the sexes. However, how maternal GC levels relate to foetal levels is still not completely understood. Here we related, for the first time in a free-ranging large mammal, the fallow deer (Dama dama), maternal GC levels with foetal in utero GC levels. We did this in a non-invasive way by quantifying cortisol metabolites from faecal samples collected from pregnant does during late gestation, as proxy for maternal GC level. These were then related to GC levels from hair of their neonate offspring (n = 40). We have shown that maternal GC levels were positively associated with foetal GC levels, but only in female offspring. These findings highlight sex differences, which may have evolved to optimize male growth at the cost of survival

Persistent ER Stress Induces the Spliced Leader RNA Silencing Pathway (SLS), Leading to Programmed Cell Death in Trypanosoma brucei

Trypanosomes are parasites that cycle between the insect host (procyclic form) and mammalian host (bloodstream form). These parasites lack conventional transcription regulation, including factors that induce the unfolded protein response (UPR). However, they possess a stress response mechanism, the spliced leader RNA silencing (SLS) pathway. SLS elicits shut-off of spliced leader RNA (SL RNA) transcription by perturbing the binding of the transcription factor tSNAP42 to its cognate promoter, thus eliminating trans-splicing of all mRNAs. Induction of endoplasmic reticulum (ER) stress in procyclic trypanosomes elicits changes in the transcriptome similar to those induced by conventional UPR found in other eukaryotes. The mechanism of up-regulation under ER stress is dependent on differential stabilization of mRNAs. The transcriptome changes are accompanied by ER dilation and elevation in the ER chaperone, BiP. Prolonged ER stress induces SLS pathway. RNAi silencing of SEC63, a factor that participates in protein translocation across the ER membrane, or SEC61, the translocation channel, also induces SLS. Silencing of these genes or prolonged ER stress led to programmed cell death (PCD), evident by exposure of phosphatidyl serine, DNA laddering, increase in reactive oxygen species (ROS) production, increase in cytoplasmic Ca2+, and decrease in mitochondrial membrane potential, as well as typical morphological changes observed by transmission electron microscopy (TEM). ER stress response is also induced in the bloodstream form and if the stress persists it leads to SLS. We propose that prolonged ER stress induces SLS, which serves as a unique death pathway, replacing the conventional caspase-mediated PCD observed in higher eukaryotes

A simple method for measuring long-term integrated testosterone levels in men

Steroids play multiple roles in the regulation of development, physiology, reproduction, and behavior. Measuring circulating steroids is especially challenging since concentrations are extremely labile, responding to stressors within minutes. Matrices that integrate long-term steroid levels are therefore valuable as biomarkers of baseline, as well as chronic steroid exposures. Here we report on a simple method to extract and measure accumulated testosterone from human fingernails using commercial EIA kits. Further, we demonstrate known human testosterone sex and age trends. Thus, this method is a potential tool for biomonitoring endogenous as well as exogenous steroid exposure.</jats:p

A simple method for measuring long-term integrated testosterone levels in men

Steroids play multiple roles in the regulation of development, physiology, reproduction, and behavior. Measuring circulating steroids is especially challenging since concentrations are extremely labile, responding to stressors within minutes. Matrices that integrate long-term steroid levels are therefore valuable as biomarkers of baseline, as well as chronic steroid exposures. Here we report on a simple method to extract and measure accumulated testosterone from human fingernails using commercial EIA kits. Further, we demonstrate known human testosterone sex and age trends. Thus, this method is a potential tool for biomonitoring endogenous as well as exogenous steroid exposure.</jats:p

Age-related testosterone declines can be detected in men’s fingernails

Testosterone plays multiple roles in the regulation of development, physiology, reproduction, and behavior. Age-related testosterone declines are expected in the population. However, measuring circulating testosterone is especially challenging since concentrations are labile, responding to social situations and challenges. Matrices that integrate long-term testosterone levels are therefore valuable as biomarkers of mean, as well as chronic exposures. Here we report on a simple method to extract and measure accumulated testosterone from human fingernails using commercial EIA kits. Further, we demonstrate known human testosterone sex and age trends. Our method is especially useful for quantifying testosterone in menâ s nails, where a small amount of matrix is required. Thus, this approach is a potential tool for biomonitoring endogenous as well as exogenous testosterone exposure. We suggest considering nails as an alternative matrix for quantifying other steroids as well.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author