Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Wedge versus core biopsy at time zero: which provides better predictive value for delayed graft function with the Remuzzi histological scoring system?

Background: Histopathological features on time-zero renal biopsies correlate with graft outcome after renal transplantation. With increasing numbers of marginal donors, assessment of pre-implantation graft quality is essential. The clinician's choice of wedge or core biopsy is performed without evidence of efficacy or safety. This study aims to compare the information derived from wedge biopsy versus core biopsy. Methods: Prospective evaluation of 37 wedge biopsies and 30 core biopsies was performed. Histopathological data were collected on number of glomeruli and arterioles observed, and Remuzzi scoring for glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriolar narrowing was performed. Clinical data on delayed graft function (DGF) were also collated. Sensitivity, specificity, and positive and negative predictive values for DGF were compared. Results: Patient demographics between the two cohorts were comparable. No complications of biopsies occurred; 81% of wedge biopsies versus 50% of core biopsies had >10 glomeruli (P = .01), whereas 32% of wedge biopsies and 57% of core biopsies had >2 arterioles (P = .02). Wedge biopsies were more likely to identify pathology with more glomerulosclerosis, tubular atrophy (P < .01), and interstitial fibrosis (P < .01). There was a non-significant trend toward high Remuzzi scores in wedge biopsy (22% versus 7% with Remuzzi ≥4; P = .12). The sensitivity and positive predictive value of Remuzzi ≥4 for predicting DGF was better on wedge biopsy (45.5% versus 0%; P < .01 and 62.5% versus 0%; P < .01, respectively). Conclusions: Wedge biopsies were safe and superior to core biopsies for identifying clinically significant histopathological findings on pre-implantation renal biopsy. We believe that the wedge biopsy is the method of choice for time-zero biopsies

Plasma metabolome alteration in dairy cows with left displaced abomasum before and after surgical correction

Left displaced abomasum (LDA) leads to substantial changes in the metabolism of dairy cows. Surgical correction of LDA can rapidly improve the health of cows; however, changes in metabolism following surgery are rarely described. To investigate the changes of plasma metabolome in cows with LDA before and after surgical correction, blood samples were collected from 10 healthy postpartum cows and 10 cows with LDA on the day of diagnosis, then again from the LDA cows 14 d after surgery. Serum nonesterified fatty acid, β-hydroxybutyric acid, cortisol and histamine concentration, and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities were evaluated, and the metabolic profile in plasma was analyzed using ultra-high-performance liquid chromatography time-of-flight mass spectrometry. The results demonstrated that cows with LDA experienced severe negative energy balance and oxidative stress, which can be improved by surgical correction. The metabolic profile was analyzed using multidimensional and univariate statistical analyses, and different metabolites were identified. In total, 102 metabolites differed between cows with LDA and healthy cows. After surgical correction, 65 metabolites changed in cows with LDA, compared with these cows during the LDA event. Following surgical correction, AA levels tended to increase, and lipid levels tended to decrease in cows with LDA. Pathway analysis indicated marked changes in linoleic acid metabolism, Arg biosynthesis, and Gly, Ser, and Thr metabolism in cows at the onset of LDA and following surgical correction. Surgical treatment reversed the changes in AA and lipid metabolism in cows with LDA

Optimisation of ultrasonic-assisted hot-water extraction conditions of soluble dietary fibre from Lentinula edodes and analysis of its hypolipidaemic and anti-inflammatory properties in STZ-induced diabetic mice

Soluble dietary fibre (SDF) is well recognised for its remarkable effectiveness in promoting human health. This study utilised response surface methodology to evaluate the optimal conditions required to extract SDF (U-SDF) from Lentinula edodes via the ultrasonic-assisted hot-water method, and evaluated the hypolipidemic effects and anti-inflammatory effects of U-SDF. The optimal extraction conditions for U-SDF were ultrasonic power of 182 W, extraction time of 2 h, extraction temperature of 81 °C, and solid-liquid ratio of 1:24 (g mL −1 ). Under these conditions, the extraction rate of U-SDF reached 8.08%. U-SDF treatment significantly improved liver and kidney indices in diabetic mice, markedly reduced the levels of plasma triglycerides (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and significantly increased the level of high-density lipoprotein-cholesterol (HDL-C) in a dose-dependent manner. U-SDF also improved adipose tissue injury in diabetic mice, significantly decreased the levels of cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α), and alleviated inflammation of the abdominal aorta. In conclusion, U-SDF from L. edodes is an excellent source of dietary fibres, which exhibit good hypolipidemic and anti-inflammatory activities, suggesting potential applications as a functional additive in diverse food products