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Huber Dillard posted an update 6 months ago
We conclude with best practices for the implementation of these additions to realize conservation and agricultural benefits.Ppara-null and PPARA-humanized mice are refractory to hepatocarcinogenesis caused by the peroxisome proliferator-activated receptor-α (PPARα) agonist Wy-14,643. However, the duration of these earlier studies was limited to approximately one year of treatment, and the ligand used has higher affinity for the mouse PPARα compared to the human PPARα. Thus, the present study examined the effect of long-term administration of a potent, high affinity human PPARα agonist (GW7647) on hepatocarcinogenesis in wild-type, Ppara-null, or PPARA-humanized mice. In wild-type mice, GW7647 caused hepatic expression of known PPARα target genes, hepatomegaly, hepatic MYC expression, hepatic cytotoxicity, and a high incidence of hepatocarcinogenesis. By contrast, these effects were essentially absent in Ppara-null mice or diminished in PPARA-humanized mice, although hepatocarcinogenesis was observed in both genotypes. Fungal inhibitor Enhanced fatty change (steatosis) was also observed in both Ppara-null and PPARA-humanized mice independent of GW7se these mice.
To evaluate how change in menopausal status related to spectral analysis and polysomnographic measures of sleep characteristics.
The Study of Women’s Health Across the Nation (SWAN) Ancillary Sleep Study evaluated sleep characteristics of 159 women who were initially pre- or early perimenopausal and repeated the assessment about 3 ½ years later when 38 were pre- or early perimenopausal, 31 late perimenopausal, and 90 postmenopausal. Participants underwent in-home ambulatory polysomnography for 2 to 3 nights. Average EEG power in the delta and beta frequency bands was calculated during NREM and REM sleep, and sleep duration, wake after sleep onset (WASO), and apnea hypopnea index (AHI) were based on visually-scored sleep.
The women who transitioned to postmenopause had increased beta NREM EEG power at the second assessment, compared to women who remained pre-or early premenopausal; no other sleep measures varied by change in menopausal status. In multivariate models the associations remained; statistical controls for self-reported hot flashes did not explain findings. In secondary analysis, NREM beta power at the second assessment was greater among women who transitioned into the postmenopause after adjustments for initial NREM beta power.
Sleep duration and WASO did not vary by menopause transition group across assessments. Consistent with prior cross-sectional analysis, elevated beta EEG power in NREM sleep was apparent among women who transitioned to postmenopause, suggesting that independent of self-reported hot flashes, the menopausal transition is associated with physiological hyperarousal during sleep.
Sleep duration and WASO did not vary by menopause transition group across assessments. Consistent with prior cross-sectional analysis, elevated beta EEG power in NREM sleep was apparent among women who transitioned to postmenopause, suggesting that independent of self-reported hot flashes, the menopausal transition is associated with physiological hyperarousal during sleep.The nucleotide composition of the genome is a balance between origin and fixation rates of different mutations. For example, it is well-known that transitions occur more frequently than transversions, particularly at CpG sites. Differences in fixation rates of mutation types are less explored. Specifically, recombination-associated GC-biased gene conversion (gBGC) may differentially impact GC-changing mutations, due to differences in their genomic distributions and efficiency of mismatch repair mechanisms. Given that recombination evolves rapidly across species, we explore gBGC of different mutation types across human populations and great ape species. We report a stronger correlation between segregating GC frequency and recombination for transitions than for transversions. Notably, CpG transitions are most strongly affected by gBGC in humans and chimpanzees. We show that the overall strength of gBGC is generally correlated with effective population sizes in humans, with some notable exceptions, such as a stronger effect of gBGC on non-CpG transitions in populations of European descent. Furthermore, species of the Gorilla and Pongo genus have a greatly reduced gBGC effect on CpG sites. We also study the dependence of gBGC dynamics on flanking nucleotides and show that some mutation types evolve in opposition to the gBGC expectation, likely due to hypermutability of specific nucleotide contexts. Our results highlight the importance of different gBGC dynamics experienced by GC-changing mutations and their impact on nucleotide composition evolution.
Many high-throughput screening studies have been carried out in cancer cell lines to identify therapeutic agents and targets. Existing consistency assessment studies only examined two datasets at a time, with conclusions based on a subset of carefully selected features rather than considering global consistency of all the data. However, poor concordance can still be observed for a large part of the data even when selected features are highly consistent.
In this study we assembled nine compound screening datasets and three functional genomics datasets. We derived direct measures of consistency as well as indirect measures of consistency based on association between functional data and copy number-adjusted gene expression data. These results have been integrated into a web application – the Functional Data Consistency Explorer (FDCE), to allow users to make queries and generate interactive visualizations so that functional data consistency can be assessed for individual features of interest.
The FDCE web tool and we have developed and the functional data consistency measures we have generated are available at https//lccl.shinyapps.io/FDCE/.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
The interaction between exercise and nutritional supplementation is unclear among older adults at risk of sarcopenia.
We aimed to examine if β-hydroxy-β-methylbutyrate (HMB) supplementation enhances the effects of exercise on muscle mass, strength, and physical performance and observe potential residual effects in older women with low muscle mass.
This 12-wk, randomized, double-blind, placebo-controlled, 2×2 factorial design (exercise-only, HMB-only, both, and none) trial included 156 women aged 65-79 y with skeletal muscle index <5.7 kg/m2, and was followed by a 12-wk observational period. Resistance training twice weekly or education programs every 2 wk and calcium-HMB (1500 mg) or placebo supplements daily were provided. The primary outcome was the change in muscle mass from baseline to postintervention. Secondary outcomes included changes in muscle strength and physical performance.
In total, 149 and 144 participants completed the assessment at weeks 12 and 24, respectively. ANOVAs based on the intention-to-treat principle showed no significant interactions between exercise and HMB on any primary outcomes.
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