Publications by authors named "J K Hurley"

Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE).

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In previous work, we found that short sleep caused sensitivity to oxidative stress; here we set out to characterize the physiological state of a diverse group of chronically short-sleeping mutants during hyperoxia as an acute oxidative stress. Using RNA-sequencing analysis, we found that short-sleeping mutants had a normal transcriptional oxidative stress response relative to controls. In both short-sleeping mutants and controls, hyperoxia led to downregulation of glycolytic genes and upregulation of genes involved in fatty acid metabolism, reminiscent of metabolic shifts during sleep.

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Mechanistic target of rapamycin complex 1 (mTORC1), which consists of mTOR, Raptor, and mLST8, receives signaling inputs from growth factor signals and nutrients. These signals are mediated by the Rheb and Rag small GTPases, respectively, which activate mTORC1 on the cytosolic face of the lysosome membrane. We biochemically reconstituted the activation of mTORC1 on membranes by physiological submicromolar concentrations of Rheb, Rags, and Ragulator.

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Article Synopsis
  • The text discusses the critical research questions regarding the impact of antibiotics on the microbiome and the subsequent risk of bloodstream infections in ICU patients.
  • It proposes using structural equation modeling (SEM) as a tool to examine complex causal relationships among factors like antibiotic exposure and infection outcomes, particularly focusing on unobservable mediators within the microbiome.
  • The use of SEM allows researchers to compare different theoretical models and identify harmful mediators, such as colonization and concurrency, that contribute to increased infection risk.
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Objective: To estimate the herd effects of anti-microbial-based decontamination (ABD) interventions on bloodstream infections (BSIs) among groups of intensive care unit (ICU) patients in relation to group mean length of stay (LOS). To deduce which of three competing hypotheses of ABD effect mediation best accounts for the observed effects.

Design: Arms-based meta-regression of ICU-acquired BSI incidence against group mean LOS for control and interventions arms of ABD and non-ABD controlled trials each versus that in arms of observational studies.

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