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Improving reproducibility of differentially expressed genes in single-cell transcriptomic studies of neurodegenerative diseases through meta-analysis

3 months 4 weeks ago
False positive claims of differentially expressed genes (DEGs) in scRNA-seq studies are of substantial concern. We found that DEGs from individual Parkinson's (PD), Huntington's (HD), and COVID-19 datasets had moderate predictive power for case-control status of other datasets, but DEGs from Alzheimer's (AD) and Schizophrenia (SCZ) datasets had poor predictive power. We developed a non-parametric meta-analysis method, SumRank, based on reproducibility of relative differential expression ranks...
Nathan Nakatsuka

The Influence of CG sites on dynamic DNA sequence mutagenesis in the genomic evolution of mammalian lifespan

3 months 4 weeks ago
Previous work showed that natural selection has acted to minimize the genomic frequencies of representative dynamic DNA sequences capable of forming G-quadruplex, Triplex, hairpin, and i-motif structures in long-lived mammals, thus diminishing the mutagenic potential of their genomes. This report extends findings with single sequences to broadly distributed G3-4N1-7G3-4N1-7G3-4N1-7G3-4 dynamic sequence motifs and identifies a second, previously unknown, pool of dynamic DNA sequences that escape...
Steven S Smith

Modeling the genomic architecture of adiposity and anthropometrics across the lifespan

3 months 4 weeks ago
Obesity-related conditions are among the leading causes of preventable death and are increasing in prevalence worldwide. Body size and composition are complex traits that are challenging to characterize due to environmental and genetic influences, longitudinal variation, heterogeneity between sexes, and differing health risks based on adipose distribution. Here, we construct a 4-factor genomic structural equation model using 18 measures, unveiling shared and distinct genetic architectures...
Christopher H Arehart

Impaired capillary-venous drainage contributes to gliosis and demyelination in mouse white matter during aging

3 months 4 weeks ago
The progressive loss of cerebral white matter during aging contributes to cognitive decline, but whether reduced blood flow is a cause or a consequence remains debatable. Using deep multi-photon imaging in mice, we examined microvascular networks perfusing myelinated tissues in cortical layer 6 and the corpus callosum. We identified sparse, wide-reaching venules, termed principal cortical venules, which exclusively drain deep tissues and resemble the vasculature at the human cortex and U-fiber...
Stefan Stamenkovic

Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons

3 months 4 weeks ago
Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by reexpression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral reexpression of ISL1 and LHX3 selectively in postnatal motor...
Emily R Lowry

Effects of cannabidiol to circadian period, sleep, life span, close-proximity rhythm, egg reproduction and motor function in Drosophila melanogaster

3 months 4 weeks ago
Cannabidiol (CBD), a non-psychoactive cannabinoid, has been studied for its various health-promoting effects recently. This study investigates the effects of dietary CBD to the circadian clock of Drosophila melanogaster as a model animal and its many physiological effect to flies. We showed that CBD extended the period of locomotor activity in a dose-dependent manner, suggesting its influence on the circadian clock. Additionally, CBD improved sleep quality and extended lifespan under starvation...
Haruhisa Kawasaki