Decades of comparative and experimental work suggest that testosterone (T) promotes mating effort at the expense of parental effort in many vertebrates. There is abundant evidence that T-mediated trade-offs span both evolutionary and seasonal timescales, as T is often higher in species or breeding stages with greater mating competition and lower in association with parental effort. However, it is less clear whether transient elevations in T within a male's own reactive scope can affect parental effort in the same way, with effects that are visible to natural selection. Here, we injected free-living male tree swallows (Tachycineta bicolor) with gonadotropin-releasing hormone (GnRH), thus temporarily maximizing T production within an individual's own limit. see more Passive loggers at each nest showed that GnRH-injected males provisioned more frequently than saline males for the subsequent day, and their offspring gained more mass during that time. The degree of offspring growth was positively correlated with the father's degree of T elevation, but provisioning was not proportional to changes in T, and GnRH- and saline-injected males did not differ in corticosterone secretion. These results suggest that prior knowledge of T-mediated trade-offs garnered from seasonal, evolutionary, and experimental research cannot necessarily be generalized to the timescale of transient fluctuations in T secretion within an individual. Instead, we propose that GnRH-induced T fluctuations may not result in visible trade-offs if selection has already sculpted an individual male's reactive scope based on his ability to handle the competing demands of mating and parental care.
To compare radial peripapillary capillary (RPC) plexus vascular parameters and retinal nerve fiber layer (RNFL) thickness between those with Parkinson's disease (PD) and controls.
Prospective, cross-sectional study.
A total of 151 eyes of 81 PD participants and 514 eyes of 266 controls.
Participants underwent OCT angiography (OCTA) imaging using the Zeiss Cirrus HD-5000 AngioPlex (Carl Zeiss AG). Capillary perfusion density (CPD) and capillary flux index (CFI) were assessed using a 4.5 × 4.5-mm peripapillary scan, and RNFL thickness was assessed using a 200 × 200-μm optic nerve cube OCT scan. Hoehn and Yahr clinical staging for PD was determined by an experienced movement disorders specialist. Generalized estimating equations adjusted for age and sex were used for analysis.
Differences in RNFL thickness, CPD, and CFI as assessed using multivariable generalized estimating equations between individuals with PD and controls.
After adjustment for age and sex, average CPD (0.446% ± 0.018% vs. 0.439% ± er, RNFL thickness was similar between groups. Peripapillary OCTA parameters may not correlate with the severity of PD. OCTA may serve as a noninvasive method to identify novel biomarkers for the early diagnosis of PD; as such, this methodology deserves further investigation.Transcriptional regulators (TRs) participate in essential processes in cancer pathogenesis and are critical therapeutic targets. Identification of drug response-related TRs from cell line-based compound screening data is often challenging due to low mRNA expression levels of TRs, protein modifications, and other confounders. In this study, we developed a regression-based pharmacogenomic and ChIP-seq data integration method (RePhine) to infer the impact of TRs on drug response through integrative analysis of pharmacogenomic and ChIP-seq data. RePhine was evaluated in simulation and pharmacogenomic data and was applied to pan-cancer datasets with the goal of biological discovery. In simulation data with added noise or confounders and in pharmacogenomic data RePhine demonstrated an improved performance in comparison with several commonly used methods such as correlation analysis and gene set enrichment analysis. Utilizing RePhine and Cancer Cell Line Encyclopedia data, we observed that RePhine-derived TR signatures could effectively cluster drugs with different mechanisms of action. RePhine predicted that loss of function of EZH2/PRC2 reduces cancer cell sensitivity toward the BRAF inhibitor PLX4720. Experimental validation confirmed that pharmacological EZH2 inhibition increases the resistance of cancer cells to PLX4720 treatment. Our results support that RePhine is a useful tool for inference of the TRs related to drug response and for potential therapeutic applications. The source code for RePhine is freely available at https//github.com/coexps/RePhine.Single-cell mass cytometry (SCMC) combines features of traditional flow cytometry (FACS) with mass spectrometry, making it possible to measure several parameters at the single-cell level for a complex analysis of biological regulatory mechanisms. In this study, weoptimizedSCMC to analyze hemocytes of the Drosophila innate immune system. We used metal-conjugated antibodies (H2, H3, H18, L1, L4, and P1 at the cell surface, intracellular 3A5 and L2) and anti-IgM (L6 at the cell surface) to detect the levels of antigens, while anti-GFP was used to detect crystal cells in the immune induced samples. We investigated the antigen expression profile of single cells and hemocyte populations in naive states, in immune induced states, in tumorous mutants bearing a driver mutation in the Drosophila homologue of Janus kinase (hopTum)andcarrying deficiency of a tumor suppressor l(3)mbn1 gene,as well as instem cell maintenance-defectivehdcΔ84mutant larvae. Multidimensional analysis enabled the discrimination of the functionally different major hemocyte subsets forlamellocytes, plasmatocytes, and crystal cells, anddelineated the unique immunophenotype of Drosophila mutants. We have identified subpopulations of L2+/P1+ (l(3)mbn1), L2+/L4+/P1+ (hopTum) transitional phenotype cells in the tumorous strains and a subpopulation of L4+/P1+ cells upon immune induction. Our results demonstrated for the first time that SCMC, combined with multidimensional bioinformatic analysis, represents a versatile and powerful tool to deeply analyze the regulation of cell-mediated immunity of Drosophila.see more
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