Biology subjects

O'Rourke, E.

Publications and source records attributed to O'Rourke, E..

3 recordsLinked to original sources

bioRxiv2026

Maximum entropy model reveals frequent brain state switching in psychotic disorders in a multiversal brain function analysis

To design network-based treatments, it is critical to understand dynamic changes in brain networks over time. We comprehensively examined network structure using regional activation-only, pairwise-coactivation-only, and systems-level maximum entropy models (MEM) applied to the Human Connectome Project-Early Psychosis (HCP-EP) resting fMRI data (patients=109, controls=56). The MEM integrates regional activation levels and pairwise correlation-based functional connectivity (FC), providing the potential for better characterization of clinically meaningful brain states and how they change over time. Using the HCP/Glasser atlas to define brain regions within the default mode (DMN) and dorsal attention (DAN) networks, group differences in regional activation, graph measures of FC, and MEM features such as transition rates between minima in an energy landscape along with correlations with cognitive and psychopathological measures were examined. Psychosis was associated with reduced activation in several regions and multiple FC graph metric alterations. MEM demonstrated a wider variety of DMN and DAN activation/deactivation configurations, with more frequent switching between them, more pronounced network configuration differences and higher basin transition rates with reduced basin dwell times suggesting temporally unstable network configurations, meaning the brain cannot rely on any particular configuration for cognitive processing. Activation of only three regions correlated with working memory, but none of the FC metrics did. MEM features, in particular basin transitions and total energy, correlated negatively with working memory. Our findings suggest that MEM provides unique information, specifically attenuated inter-network connectivity with reduced stability of DMN and DAN brain states, to characterize networks as targets and their features as markers for novel treatment development.

neuroscience↗

bioRxiv2025

Broad Effects of Activation of Alcohol Dehydrogenase 1 on Healthspan Extension

Nutritional, genetic, and pharmacological interventions can extend lifespan; however, fewer have been shown to extend healthspan--the period of life free from chronic, debilitating diseases. In line with this, the molecular effectors that drive healthspan are even less understood than those responsible for lifespan extension. We recently reported that activation of Alcohol Dehydrogenase 1 (ADH-1) extends lifespan in yeast and C. elegans. In addition, adh-1 is transcriptionally activated in yeast, worms, mice, and humans in response to caloric restriction--an intervention that extends not only lifespan but also healthspan. Therefore, we investigated whether activating adh-1 could also extend healthspan. We demonstrate here that adh-1 activation has broad and robust effects on health, including resistance to age-related obesity, delayed sarcopenia, and attenuated neurodegeneration. Mechanistically, ADH-1-driven healthspan extension is associated with improved proteostasis. These findings position ADH-1 as a promising target for future research aimed at promoting healthy aging.

cell biology↗

bioRxiv2022

Whole-body gene expression atlas of an adult metazoan

Animals are integrated organ systems composed of interacting cells whose structure and function are in turn defined by their active genes. Understanding what distinguishes physiological and disease states therefore requires systemic knowledge of the gene activities that define the distinct cells that make up an animal. Towards this goal, this study reports the first single-cell resolution transcriptional atlas of a fertile multicellular organism: Caenorhabditis elegans. The scRNA-Seq compendium of wild-type young adult C. elegans comprises 159 distinct cell types with 18,033 genes expressed across cell types. Fewer than 300 of these genes are housekeeping genes as evidenced by their consistent expression across cell types and conditions, and by their basic and essential functions; 170 of these housekeeping genes are conserved across phyla. The 362 transcription factors with available ChIP-Seq data are linked to patterns of gene expression of different cell types. To identify potential interactions between cell types, we used the in silico tool cell2cell to predict molecular patterns reflecting both known and uncharacterized intercellular interactions across the C. elegans body. Finally, we present WormSeq (wormseq.org), a web interface that, among other functions, enables users to query gene expression across cell types, identify cell-type specific and potential housekeeping genes, analyze candidate ligand-receptors mediating communication between cells, and study promiscuous and cell-specific transcription factors. The datasets, analyses, and tools presented here will enable the generation of testable hypotheses about the cell and organ-specific function of genes in diverse biological contexts.

genomics↗