Biology subjects

Martinez, K. A.

Publications and source records attributed to Martinez, K. A..

2 recordsLinked to original sources

bioRxiv2025

Sex Differences in Drosophila Intestinal Metabolism Contribute to Sexually Dimorphic Infection Outcome and Alter Gut Pathogen Virulence

Sexual dimorphism in infection outcomes is a pervasive phenomenon, the underlying mechanisms of which remain incompletely understood. Here, utilizing Pseudomonas entomophila intestinal infection in Drosophila, we demonstrated that sex differences in intestinal redox processes contribute to female bias in susceptibility to gut infection. Female inability to overcome excessive pathogen-induced oxidative stress results in defecation blockage, pathogen persistence, and host death. Male flies exhibit increased carbohydrate metabolism and pentose phosphate pathway activity - a key antioxidant defense system. This allows males to withstand oxidative stress-induced defecation blockage and clear the pathogen from the intestine, resulting in survival. Additionally, P. entomophila showed increased expression of several virulence factors, including RNA-binding protein Hfq, in the female gut, contributing to female-biased virulence of P. entomophila. Thus, the effect of the gut metabolic environment on host defenses and pathogen virulence determines the sex differences in intestinal infection outcomes. HighlightsIntestinal transit of gut pathogen contributes to sexually dimorphic susceptibility to Drosophila gut infection. Male bias in PPP favors pathogen clearance and recovery post-infection. P. entomophila reacts differently to female gut environment, where higher levels of Hfq might contribute to virulence/lethality. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/655590v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@1d6d36borg.highwire.dtl.DTLVardef@d24f2aorg.highwire.dtl.DTLVardef@14b4ed1org.highwire.dtl.DTLVardef@123b46c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

A Multi-Omics Atlas of Sex-Specific Differences in Obstructive Hypertrophic Cardiomyopathy

ABSTRACTO_ST_ABSBackgroundC_ST_ABSHypertrophic cardiomyopathy (HCM) is a common genetic heart disease. Women with HCM tend to have a later onset but more severe disease course. However, the underlying pathobiological mechanisms for these differences remain unknown. MethodsMyectomy samples from 97 patients (53 males/44 females) with symptomatic obstructive HCM and 23 control cardiac tissues were included in this study. RNA-sequencing was performed on all samples. Mass spectrometry-based proteomics and phosphoproteomics was performed on a representative subset of samples. ResultsThe transcriptome, proteome, and phosphoproteome was similar between sexes and did not separate on PCA plotting. Overall, there were 482 differentially expressed genes (DEGs) between control females and control males while there were only 53 DEGs between HCM females and HCM males. There were 1963 DEGs between HCM females and control females compared to 1064 DEGs between HCM males and control males. Additionally, there was increased transcriptional downregulation of hypertrophy pathways in HCM females and in HCM males. HCM females had 119 differentially expressed proteins compared to control females while HCM males only had 27 compared to control males. Finally, the phosphoproteome showed females had 341 differentially phosphorylated proteins (DPPs) compared to controls while males only had 184. Interestingly, there was hypophosphorylation and inactivation of hypertrophy pathways in females but hyperphosphorylation and activation in males. ConclusionThere are subtle, but biologically relevant differences in the multi-omics profile of HCM. This study provides the most comprehensive atlas of sex-specific differences in the transcriptome, proteome, and phosphoproteome present at the time of surgical myectomy for obstructive HCM.

bioinformatics↗