Pax3/7BP Is a Pax7- and Pax3-Binding Protein that Regulates the Proliferation of Muscle Precursor Cells by an Epigenetic Mechanism

SummaryIn mouse skeletal muscles, Pax7 uniquely marks muscle satellite cells and plays some important yet unknown functions at the perinatal stage. To elucidate its in vivo functions, we initiated a yeast two-hybrid screening to look for Pax7-interacting proteins and identified a previously uncharacterized Pax7- and Pax3-binding protein (Pax3/7BP). Pax3/7BP is a ubiquitously expressed nuclear protein, enriched in Pax7+ muscle precursor cells (MPCs), and serves as an indispensable adaptor for Pax7 to recruit the histone 3 lysine 4 (H3K4) methyltransferase (HMT) complex by bridging Pax7 and Wdr5. Knockdown of Pax3/7BP abolished the Pax3/7-associated H3K4 HMT activity and inhibited the proliferation of Pax7+ MPCs from young mice both in culture and in vivo. Id3 and Cdc20 were direct target genes of Pax7 and Pax3/7BP involved in the proliferation of Pax7+ MPCs. Collectively, our work establishes Pax3/7BP as an essential adaptor linking Pax3/7 with the H3K4 HMT to regulate the proliferation of MPCs

Identification and validation of a gap junction protein related signature for predicting the prognosis of renal clear cell carcinoma

BackgroundGap junction proteins (GJPs) are a class of channel proteins that are closely related to cell communication and tumor development. The objective of this study was to screen out GJPs related prognostic signatures (GRPS) associated with clear cell renal cell carcinoma (ccRCC).Materials and MethodsGJPs microarray data for ccRCC patients were obtained from The Gene Expression Omnibus (GEO) database, along with RNA sequencing data for tumor and paired normal tissues from The Cancer Genome Atlas (TCGA) database. In the TCGA database, least absolute shrinkage and selection Operator (LASSO) and Cox regression models were used to identify GJPs with independent prognostic effects as GRPS in ccRCC patients. According to the GRPS expression and regression coefficient from the multivariate Cox regression model, the risk score (RS) of each ccRCC patient was calculated, to construct the RS prognostic model to predict survival. Overall survival (OS) and progression-free survival (PFS) analyses; gene pan-cancer analysis; single gene survival analysis; gene joint effect analysis; functional enrichment analysis; tumor microenvironment (TME) analysis; tumor mutational burden (TMB) analysis; and drug sensitivity analysis were used to explore the biological function, mechanism of action and clinical significance of GRPS in ccRCC. Further verification of the genetic signature was performed with data from the GEO database. Finally, the cytofunctional experiments were used to verify the biological significance of GRPS associated GJPs in ccRCC cell lines.ResultsGJA5 and GJB1, which are GRPS markers of ccRCC patients, were identified through LASSO and Cox regression models. Low expression of GJA5 and GJB1 is associated with poor patient prognosis. Patients with high-RS had significantly shorter OS and PFS than patients with low-RS (p< 0.001). The risk of death for individuals with high-RS was 1.695 times greater than that for those with low-RS (HR = 1.695, 95%CI= 1.439-1.996, p< 0.001). Receiver Operating Characteristic (ROC) curve showed the great predictive power of the RS prognostic model for the survival rate of patients. The area under curve (AUC) values for predicting 1-year, 3-year and 5-year survival rates were 0.740, 0.781 and 0.771, respectively. The clinical column chart was also reliable for predicting the survival rate of patients, with AUC values of 0.859, 0.846 and 0.796 for predicting 1-year, 3-year and 5-year survival, respectively. The GRPS was associated with immune cell infiltration, the TME, the TMB, and sensitivity to chemotherapy drugs. Further in vitro experiments showed that knockdown of GJA5 or GJB1 could promote the proliferation, migration and epithelial-mesenchymal transition (EMT) and inhibit apoptosis of ccRCC cells.ConclusionGJA5 and GJB1 could be potential biological markers for predicting survival in patients with ccRCC

The many dimensions of competitive balance and the attendance of major league baseball

This research proposed a set of measures of Competitive Balance which aims to address three dimensions of Competitive Balance: Closeness, Dominance and Consistency. Longitudinal MLB data is used for empirical evaluation purpose. The matched pair of teams is used as the basic research object in this study, and the growth model is applied to analyze the relationship between game attendances and the proposed measures of Competitive Balance. Research confirmed that Competitive Balance is multidimensional, and not every dimension of Competitive Balance is correlated with game attendance. Fans prefer changes, and they are not attracted by consecutive wins or losses. Rather fans are more like to go to games that can potentially affect teams??? standings in their divisions or league. Fans show no specific preferences to upset games

An Experimental Study on the Precision Abrasive Machining Process of Hard and Brittle Materials with Ultraviolet-Resin Bond Diamond Abrasive Tools

Ultraviolet-curable resin was introduced as a bonding agent into the fabrication process of precision abrasive machining tools in this study, aiming to deliver a rapid, flexible, economical, and environment-friendly additive manufacturing process to replace the hot press and sintering process with thermal-curable resin. A laboratory manufacturing process was established to develop an ultraviolet-curable resin bond diamond lapping plate, the machining performance of which on the ceramic workpiece was examined through a series of comparative experiments with slurry-based iron plate lapping. The machined surface roughness and weight loss of the workpieces were periodically recorded to evaluate the surface finish quality and the material removal rate. The promising results in terms of a 12% improvement in surface roughness and 25% reduction in material removal rate were obtained from the ultraviolet-curable resin plate-involved lapping process. A summarized hypothesis was drawn to describe the dynamically-balanced state of the hybrid precision abrasive machining process integrated both the two-body and three-body abrasion mode

miR-324-5p inhibits gallbladder carcinoma cell metastatic behaviours by downregulation of transforming growth factor beta 2 expression

AbstractIncreasing studies have demonstrated that microRNAs (miRNAs) are associated with the metastasis of gallbladder carcinoma (GBC). Recently, miR-324-5p has been reported to be a tumour-suppressive miRNA in many types of malignant cancer. However, the biological function and molecular mechanism of miR-324-5p in GBC still remain largely unknown. Here, we found that miR-324-5p expression was notably down-regulated in both GBC tissues and cells compared with that in normal controls. Downregulated miR-324-5p expression was negatively associated with the status of local invasion and lymph node metastasis and predicted a poor prognosis in GBC patients. Further functional assays revealed that restoration of miR-324-5p significantly suppressed GBC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and impeded the metastasis of GBC cells in vivo. Moreover, RNA immunoprecipitation (RIP) and dual-luciferase reporter assay confirmed that the transforming growth factor beta 2 (TGFB2) was a direct target gene of miR-324-5p in GBC cells. Mechanically, small interfering RNA (siRNA)-mediated knockdown of TGFB2 partially phenocopied the inhibitory effects of miR-324-5p overexpression on GBC cell metastatic phenotypes. In summary, our findings demonstrated that miR-324-5p targets TGFB2 expression to inhibit GBC cell metastatic behaviors, and implying miR-324-5p as a potential biomarker for diagnostic and therapeutic strategies in GBC

Growth Variations of Tree Saplings in Relation to Species Diversity and Functional Traits in a Tree Diversity Pot Experiment

Despite the accumulating evidence of the beneficial effects of diverse mixed species forests on ecosystem functioning and services, foresters in subtropical forest cultivation in China still prefer easily managed monocultures, which is also due to the complexity of mixed forests and the unknown underlying mechanisms related to relationships between biodiversity and forest growth. In a designed pot experiment, we selected two early-successional tree species (Pinus massoniana Lamb., Liquidambar formosana Hance.) and two late-successional tree species (Schima superba Champ., Elaeocarpus decipiens Hemsl.) and planted four saplings in one pot with regard to tree species diversity (monoculture, two species and four species mixtures), each combination replicated four times. In this three-year duration experiment, the effect of tree species diversity, tree identity, and functional traits on sapling growth (tree height, ground diameter, crown projection area), were analyzed. The results showed that the increments of ground diameter and crown projection area increased with tree species richness, whereas the mean tree height increment showed the opposite effect. This growth variation was species specific and related to functional traits (early or late succession), as the increments of the early successional tree species (P. massoniana Lamb. and L. formosana Hance.) had a positive correlation with tree species richness, while the late successional tree species (E. decipiens Hemsl. and S. superba Champ.) showed negative effects. In addition, our study provided evidence for the allometric differences between mixtures and monocultures, which have an important reference value on mixed-species forests