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Deviations from additivity in APOE4-mediated late-onset Alzheimer’s disease risk across races and ethnicitiesNARA Subscribed
APOE ’s ε4 haplotype ( APOE4 ) is late onset Alzheimer’s disease’s (LOAD) strongest genetic risk factor. Therefore, accurately modeling APOE4 ’s effect is critical to understanding LOAD. This is especially important as APOE4 odds ratios (OR) vary across racial and ethnic (R/E) groups. We analyzed the APOE4 -LOAD association in 3,196 East Asian, 31,105 non-Hispanic White (White), 1,646 Hispanic and Latino (Hispanic), and 6,068...
Aim Energy availability is often assumed to be a primary driver of variation in biodiversity across large‐scale environmental gradients such as elevation, but support for the role of energetic constraints is far from universal. Here, we assume that these variations in energy–richness relationships might arise from the degree of match between the scale of the response of organisms to energy (response scale) and the scale of the...
Multi‐Model Ensembles in Ecosystem Modeling: Challenges and Best Practices for Decision‐MakingNARA Subscribed
Ecosystem models are increasingly central to the decision‐making for environmental policy, conservation planning, and climate‐related investments. Yet, the growing reliance on Multi‐Model Ensembles (MMEs) of ecosystem models by practitioners and policymakers, sometimes under tight timelines and imperfect information, has frequently outpaced the scientific rigor required to ensure ensemble reliability. Here, MMEs refer to appro...
AI-designed crop populations for sustainable intensificationNARA Subscribed
Interpretable deep learning reveals spatiotemporal MRI features of brain aging that align with neurodegenerationNARA Subscribed
Cortical thinning and atrophy are hallmarks of brain aging that have been characterized using magnetic resonance imaging (MRI). Brain aging involves many neuroanatomic features whose effects on brain structure remain unexplored. To address this challenge, we trained interpretable deep neural networks (DNNs) to estimate brain age (BA) from T 1 -weighted ( T 1 w) MRI. By identifying MRI features unapparent to humans, DNNs can fi...
Small Molecules to Elevate Rab7-GTPase Activity and Lower Cholesterol Accumulation in Niemann-Pick Type C DiseaseNARA Subscribed
Purpose Niemann-Pick type C (NPC) disease caused by mutations in cholesterol transporters NPC1 or NPC2 is characterized by cholesterol accumulation in late endosomes/lysosomes (LE/Lys). The activation of alternative cholesterol export routes that can bypass NPC1/2 deficiency could provide therapeutic opportunities. We previously demonstrated that gene depletion of the Rab7-GTPase activating protein (GAP) TBC1D15, which hydroly...
The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)™ trial was a randomized, 2-year controlled trial of caloric restriction (CR) versus an ad libitum (AL) control condition in nonobese humans. We performed exploratory analyses of muscle mitochondrial DNA (mtDNA) integrity, one element of mitochondrial quality. Our aims were to assess the feasibility of this approach, explore associations to...
Clumped isotopes tracing methane cycle and budget: a reviewNARA Subscribed
Acupuncture is used worldwide to treat migraine, but its scientific mechanism remains unclear. Here, we report a 1 H NMR metabolomics study involving 40 migraine patients and 10 healthy individuals randomly receiving acupuncture or sham acupuncture, followed by machine learning techniques and functional analysis. We found that acupuncture at acupoints particularly enhanced anaerobic glycolysis and modified mitochondrial functi...