Fosssalinas1522

The beta subunit of F1Fo-ATP synthase (ATP5B) has been demonstrated to play an essential role in tumor progression and metastasis. However, there has been no comprehensive pan-cancer multi-omics analysis of ATP5B, while the clinical relevance of ATP5B and its potential mechanism in regulating breast cancer are still poorly understood. In this study, we demonstrated that ATP5B has a higher frequency of amplification than deletion in most cancer types, and the copy number variation (CNV) of ATP5B was significantly positively correlated with its mRNA expression level. DNA methylation analysis across pan-cancer also revealed a strong correlation between ATP5B expression and epigenetic changes. We identified 6 significant methylation sites involved in the regulation of ATP5B expression. Tissue microarrays (TMA) from 129 breast cancer samples, integrated with multiple additional breast cancer dataset, were used to evaluate the ATP5B expression and its correlation with prognosis. Higher levels of ATP5B expression were consistently associated with a worse OS in all datasets, and Cox regression analysis suggested that ATP5B expression was an independent prognostic factor. Gene enrichment analysis indicated that the gene signatures of DNA damage recognition, the E-cadherin nascent pathway and the PLK1 pathway were enriched in ATP5B-high patients. Moreover, somatic mutation analysis showed that a significant different mutation frequency of CDH1 and ADAMTSL3 could be observed between the ATP5B-high and ATP5B-low groups. In conclusion, this study reveals novel significance regarding the genetic characteristics and clinical value of ATP5B highlighted in predicting the outcome of breast cancer patients.Aegilops tauschii is the diploid progenitor of the D subgenome of hexaploid wheat (Triticum aestivum L.). Here, the phenotypic data of kernel length (KL), kernel width (KW), kernel volume (KV), kernel surface area (KSA), kernel width to length ratio (KWL), and hundred-kernel weight (HKW) for 223 A. tauschii accessions were gathered across three continuous years. Based on population structure analysis, 223 A. tauschii were divided into two subpopulations, namely T-group (mainly included A. tauschii ssp. tauschii accessions) and S-group (mainly included A. tauschii ssp. strangulata). Classifications based on cluster analysis were highly consistent with the population structure results. Meanwhile, the extent of linkage disequilibrium decay distance (r 2 = 0.5) was about 110 kb and 290 kb for T-group and S-group, respectively. Furthermore, a genome-wide association analysis was performed on these kernel traits using 6,723 single nucleotide polymorphism (SNP) markers. Sixty-six significant markers, distributed on all seven chromosomes, were identified using a mixed linear model explaining 4.82-13.36% of the phenotypic variations. Among them, 15, 28, 22, 14, 21, and 13 SNPs were identified for KL, KW, KV, KSA, KWL, and HKW, respectively. Moreover, six candidate genes that may control kernel traits were identified (AET2Gv20774800, AET4Gv20799000, AET5Gv20005900, AET5Gv20084100, AET7Gv20644900, and AET5Gv21111700). The transfer of beneficial genes from A. tauschii to wheat using marker-assisted selection will broaden the wheat D subgenome improve the efficiency of breeding.The pandemic of Coronavirus disease 2019 (COVID-19) has posed an enormous threat to human health. According to observational studies, abnormal liver and kidney functions and blood cell traits were associated with severe COVID-19, yet the causal risk factors for COVID-19 severity and the underlying mechanism remained elusive. We performed Mendelian randomization analyses to assess the potential causal role of eight liver function biomarkers, one kidney function biomarker, and 14 hematological traits on COVID-19 severity using genetic association summary statistics from Europeans. Our findings showed that albumin, direct bilirubin, white blood cell count, neutrophil count, lymphocyte count, and mean corpuscular hemoglobin are casually associated with the risk of severe COVID-19. Notably, lymphocyte count and mean corpuscular hemoglobin had an independent effect on severe COVID-19 risk. These causal evidences provide insights into directions for the risk stratification of individuals with abnormal liver function or blood cell indices and motivate more studies to unveil the roles of these abnormalities in COVID-19 pathogenesis.Background Chronic kidney disease (CKD) in childhood and adolescence occurs with a median incidence of 9 per million of the age-related population. Over 70% of CKD cases under the age of 25 years can be attributed to a hereditary kidney disease. Among these are hereditary podocytopathies, ciliopathies and (monogenic) congenital anomalies of the kidney and urinary tract (CAKUT). These disease entities can present with a vast variety of extrarenal manifestations. So far, skeletal anomalies (SA) have been infrequently described as extrarenal manifestation in these entities. The aim of this study was to retrospectively investigate a cohort of individuals with hereditary podocytopathies, ciliopathies or CAKUT, in which molecular genetic testing had been performed, for the extrarenal manifestation of SA. Material and Methods A cohort of 65 unrelated individuals with a clinically presumed hereditary podocytopathy (focal segmental glomerulosclerosis, steroid resistant nephrotic syndrome), ciliopathy (nephronophthisis, Bardet-Biedl syndrome, autosomal recessive/dominant polycystic kidney disease), or CAKUT was screened for SA. Data was acquired using a standardized questionnaire and medical reports. 57/65 (88%) of the index cases were analyzed using exome sequencing (ES). Results 8/65 (12%) index individuals presented with a hereditary podocytopathy, ciliopathy, or CAKUT and an additional skeletal phenotype. selleck In 5/8 families (63%), pathogenic variants in known disease-associated genes (1x BBS1, 1x MAFB, 2x PBX1, 1x SIX2) could be identified. Conclusions This study highlights the genetic heterogeneity and clinical variability of hereditary nephropathies in respect of skeletal anomalies as extrarenal manifestation.