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84 ± 5.38 degrees in the PHOMS group and 3.71 ± 4.41 degrees in the control group. SE and ONH tilt angle were significantly associated with PHOMS according to both univariable [odds ratio (OR) 1.59; p less then 0.001 and OR 1.35; p less then 0.001, respectively] and multivariable (OR 1.71; p = 0.001 and OR 1.29; p = 0.001, respectively) logistic regression analyses. There was a significant correlation between SE and ONH tilt (r = -0.46; p less then 0.001). In conclusion, PHOMS is associated with myopic shift in children, and optic disc tilt may be a mediator between myopia and PHOMS.ROBO2 gene disruption causes vesicoureteric reflux (VUR) amongst other congenital anomalies. Several VUR patient cohorts have been screened for variants in the ubiquitously expressed transcript, ROBO2b, but, apart from low levels in a few adult tissues, ROBO2a expression is confined to the embryo, and might be more relevant to VUR, a developmental disorder. ROBO2a has an alternative promoter and two alternative exons which replace the first exon of ROBO2b. We screened probands from 251 Irish VUR families for DNA variants in these. The CpG island of ROBO2a, which includes the non-coding first exon, was found to contain a run of six variants abolishing/creating CpG dinucleotides, including a novel variant, present in the VUR cases in one family, that was not present in 592 healthy Irish controls. In three of these positions, the CpG was created by the non-reference allele, and the reference allele was not the nucleotide that would result from spontaneous deamination of methylcytosine to thymine, suggesting that there might have been selection for variability in number of CpGs in this island. https://www.selleckchem.com/products/sbc-115076.html This is in marked contrast to the CpG island at the start of ROBO2b, which only contained a single variant that abolishes a CpG.Blueberries are a rich source of polyphenols, widely studied for the prevention or attenuation of metabolic diseases. However, the health contribution and mechanisms of action of polyphenols depend on their type and structure. Here, we evaluated the effects of a wild blueberry polyphenolic extract (WBE) (Vaccinium angustifolium Aiton) on cardiometabolic parameters, gut microbiota composition and gut epithelium histology of high-fat high-sucrose (HFHS) diet-induced obese mice and determined which constitutive polyphenolic fractions (BPF) was responsible for the observed effects. To do so, the whole extract was separated in three fractions, F1) Anthocyanins and phenolic acids, F2) oligomeric proanthocyanidins (PACs), phenolic acids and flavonols (PACs degree of polymerization DP 4) and supplied at their respective concentration in the whole extract. After 8 weeks, WBE reduced OGTT AUC by 18.3% compared to the HFHS treated rodents and the F3 fraction contributed the most to this effect. The anthocyanin rich F1 fraction did not reproduce this response. WBE and the BPF restored the colonic mucus layer. Particularly, the polymeric PACs-rich F3 fraction increased the mucin-secreting goblet cells number. WBE caused a significant 2-fold higher proportion of Adlercreutzia equolifaciens whereas oligomeric PACs-rich F2 fraction increased by 2.5-fold the proportion of Akkermansia muciniphila. This study reveals the key role of WBE PACs in modulating the gut microbiota and restoring colonic epithelial mucus layer, providing a suitable ecological niche for mucosa-associated symbiotic bacteria, which may be crucial in triggering health effects of blueberry polyphenols.Activation of the inflammasome is involved in the progression of retinal degenerative diseases, in particular, in the pathogenesis of Age-Related Macular Degeneration (AMD), with NLRP3 activation the focus of many investigations. In this study, we used genetic and pharmacological approaches to explore the role of the inflammasome in a mouse model of retinal degeneration. We identify that Casp1/11-/- mice have better-preserved retinal function, reduced inflammation and increased photoreceptor survivability. While Nlrp3-/- mice display some level of preservation of retinal function compared to controls, pharmacological inhibition of NLRP3 did not protect against photoreceptor cell death. Further, Aim2-/-, Nlrc4-/-, Asc-/-, and Casp11-/- mice show no substantial retinal protection. We propose that CASP-1-associated photoreceptor cell death occurs largely independently of NLRP3 and other established inflammasome sensor proteins, or that inhibition of a single sensor is not sufficient to repress the inflammatory cascade. Therapeutic targeting of CASP-1 may offer a more promising avenue to delay the progression of retinal degenerations.Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. A large proportion of genetic cause remains unexplained, especially in idiopathic DCM. We performed target next-generation sequencing of 102 genes which were known causes or candidate genes for cardiomyopathies and channelpathies in 118 prospectively recruited Han Chinese patients with idiopathic DCM. 41 of the 118 patients carried 40 pathogenic or likely pathogenic variants, providing a molecular diagnosis in 34.7% of patients. 32 of these variants were novel. TTN truncating variants were predominant, with a frequency of 31.0%, followed by variants of LMNA (14.3%), RBM20 (4.8%), and NEXN (4.8%). These 4 genes accounted for over half variants identified. No significant difference in clinical characteristics or rates of reaching the composite end point (cardiac transplantation and death from cardiac causes) between pathogenic or likely pathogenic variant carriers and noncarriers (hazard ratio 1.11, 95% CI 0.41 to 3.00), or between patients with TTN truncating variants or without (hazard ratio 0.49, 95% CI 0.36 to 6.10). In our prospective study, we first determined the overall genetic profiles and genotype-phenotype correlations in Han Chinese idiopathic DCM patients, which could provide insight for genetic diagnosis of DCM in this population.Understanding the geodynamic and Earth surface processes at the origin of post-collisional surface uplift in mountain ranges requires reconstruction of paleo-elevation. Here, we focus on the topographic evolution of the Cerdanya Basin in the eastern Pyrenees formed by post-orogenic extension during the Late Miocene. Stable isotope (δ18O) analyses of small rodent teeth and biogenic carbonates show the basin uplifted by 500 m since 6.5 Ma. These new paleoaltitudes constraints when combined with the regional geology and geophysical data reveal the anomalously high topography of the region is the result of density changes in the sublithospheric mantle associated with crustal thinning and then opening of Gulf of Lion during the Chattian-early Burdigalian.
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