Sheppard Craven (effecttiger4)

Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP-SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P less then 3.5 × 10-9) and 3145 (P less then 1 × 10-5) SNP-SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene-gene interactions were KLK3-COL4A1COL4A2, KLK3-CDH13, and KLK3-TGFBR3. see more Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP-SNP interactions were supported by gene expression and protein-protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.Modifications of the myocardial architecture can cause abnormal electrical activity of the heart. Fibro-fatty infiltrations have been implicated in various cardiac pathologies associated with arrhythmias and sudden cardiac death, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Here, we report the development of an MRI protocol to observe these modifications at 9.4 T. Two fixed ex vivo human hearts, one healthy and one ARVC, were imaged with an Iterative decomposition with echo asymmetry and least-square estimations (IDEAL) and a magnetization transfer (MT) 3D sequences. The resulting fat fraction and MT ratio (MTR) were analyzed and compared to histological analysis of the three regions ("ARVC triangle") primarily involved in ARVC structural remodeling. In the ARVC heart, high fat content was observed in the "ARVC triangle" and the superimposition of the MTR and fat fraction allowed the identification of fibrotic regions in areas without the presence of fat. The healthy heart exhibited twice less fat than the ARVC heart (31.9%, 28.7% and 1.3% of fat in the same regions, respectively). Localization of fat and fibrosis were confirmed by means of histology. This non-destructive approach allows the investigation of structural remodeling in human pathologies where fibrosis and/or fatty tissue infiltrations are expected to occur.The stability of nanoparticles and their supports are critical, but poorly understood, parameters for applications of such systems in liquid environments. Here we develop an approach to systematically investigate the stability of aerosol-generated nanoparticles after exposure to commonly used solvents using a combination of identical location-SEM and density/size analysis. We demonstrate that the choice of solvent needs to be carefully matched with both the particle and support materials. We show that thermal annealing significantly increases the adhesion of the particles and expands the scope of applications in aqueous media and for biological applications. The results clarify combinations of inorganic nanoparticles on oxide and semiconductor supports with solvents and environmental conditions that give sufficient stability. Combined, the presented methods should be of value in investigating the stability of nanoparticle systems after exposure to solvent and can be used for future developments of high-performing supported aerosol-generated nanoparticles for solvent-based applications.APOE genotypes are associated with ischemic heart disease (IHD), several other cardiovascular diseases and dementia. Previous stud