Background: Patterns of gene expression can be dramatically different between males and females of the same species, in part due to genes on sex chromosomes. Here we test for sex differences in early transcriptomic response to oxidative stress in a species which lacks heteromorphic sex chromosomes, the copepodTigriopus californicus.Results: Male and female individuals were separately exposed to control conditions and pro-oxidant conditions (hydrogen peroxide and paraquat) for periods of 3 hours and 6 hours. Variance partitioning showed the greatest expression variance among individuals, highlighting the important information that can be obscured by the common practice of pooling individuals. Gene expression variance between sexes was greater than that among treatments, showing the profound effect of sex even when males and females share the same genome. Males exhibited a larger response to both pro-oxidants, differentially expressing more than four times as many genes, including up-regulation of more antioxidant genes, heat shock proteins and protease genes. While females differentially expressed fewer genes, the magnitudes of fold change were generally greater, indicating a more targeted response. Although females shared a smaller fraction of differentially expressed genes between stressors and time points, expression patterns of antioxidant and protease genes were more similar between stressors and more GO terms were shared between time points.Conclusions: Early transcriptomic responses to the pro-oxidants H2O2and paraquat in copepods revealed substantial variation among individuals and between sexes. The finding of such profound sex differences in oxidative stress response, even in the absence of sex chromosomes, highlights the importance of studying both sexes and the potential for developing sex-specific strategies to promote optimal health and aging in humans.
Uveal melanoma (UM) lacks minimally invasive and reproducible biomarkers to support clinical risk stratification, motivating the need for molecular profiling of aqueous humor (AH) as an alternative to fine-needle tumor aspiration (FNAB). This study aimed to generate a calibrated AH protein concentration map to identify tumor-associated signals present at clinically measurable levels and assess their associations with established molecular and clinical features. AH samples from 70 UM eyes were analyzed using next-generation sequencing-based proximity extension assays (PEAs), and leftover AH from 27 samples was further assessed using qPCR-based PEA to obtain reference concentration values. Regression models derived from overlapping proteins enabled extrapolation of calibrated pg/mL-level concentrations across the full cohort. Twenty-three proteins had median modeled concentrations above 5 pg/mL and were examined for clinical relevance and translational feasibility. Several proteins, including CXCL8, CXCL10, VEGFA, HGF, PDCD1, FLT1, FLT3LG, and CCL2, showed progressive increases from GEP1/PRAME− to GEP2/PRAME+ tumors and from AJCC Stage I/II to Stage III/IV, with Stage IV tumors demonstrating significant elevations in CXCL8, VEGFA, and PDCD1. Pathway analysis revealed activation of inflammatory and tumor microenvironment pathways, and upstream regulator analysis identified VEGFA and CCL2 as potential drivers. These findings demonstrate that calibrated AH proteomic profiling can identify clinically measurable protein changes associated with UM risk and stage, supporting its potential utility for biomarker development.