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

Critical current density: Measurements vs. reality

Different experimental techniques are employed to evaluate the critical current density (Jc), namely transport current measurements and two different magnetisation measurements forming quasi-equilibrium and dynamic critical states. Our technique-dependent results for superconducting YBa 2Cu3O7 (YBCO) film and MgB2 bulk samples show an extremely high sensitivity of Jc and associated interpretations, such as irreversibility fields and Kramer plots, which lose meaning without a universal approach. We propose such approach for YBCO films based on their unique pinning features. This approach allows us to accurately recalculate the magnetic-field-dependent Jc obtained by any technique into the Jc behaviour, which would have been measured by any other method without performing the corresponding experiments. We also discovered low-frequency-dependent phenomena, governing flux dynamics, but contradicting the considered ones in the literature. The understanding of these phenomena, relevant to applications with moving superconductors, can clarify their dramatic impact on the electric-field criterion through flux diffusivity and corresponding measurements. © Copyright EPLA, 2013

Short-term shrinkage stress in deck concrete of rail-cum-road truss bridge

Rail-cum-road truss bridges are rapidly developing, and frequent cracking in freshly poured concrete is of great concern. For the performance of such a load-bearing deck, it is necessary to understand its stress status due to short-term shrinkage. In this study, a newly constructed railway-cum-highway truss bridge in Guangdong Province was used to analyze the stress distribution in the concrete deck under short-term shrinkage. In-situ tests were performed to measure the shrinkage of one deck panel and two companion specimens shortly after the concrete pouring. It was found that the free shrinkage of companion specimens at 42 days was 140–150 microstrains, which was significantly higher than that indicated by current codes or standards. An exponential form of shrinkage development curve was proposed based on shrinkage test results. The measured shrinkage of the deck panel varied with locations, with a relatively large concrete shrinkage between grillages, reaching 45–55 microstrains at the end of the shrinkage test. The resulting mechanical strain due to restraints, taken as the difference in measured strains between the deck panel and companion specimen, was consistent with numerical simulation results, demonstrating the validity of the analysis method adopted. Under short-term shrinkage, the secondary tensile stress of 1.5–3.5 MPa was present in the deck above the main trusses and cross beams, triggering potential cracking. The stress is primarily attributed to the external restraint from connecting steel members, whose degree of restraint dramatically exceeds that of internal restraint from reinforcement. Although creep tends to reduce such shrinkage stress slightly, the effect of short-term shrinkage requires significant attention

Size-Dependent Cytotoxicity of Nanocarbon Blacks

In this study, we investigated the toxic effects of nanocarbon blacks (NCBs) with different sizes to mouse macrophage RAW264.7 cells. MTT and fluorescence-based LIVE assays demonstrated that NCBs uptake caused a size and dose-dependent growth inhibition to the cells. Optical microscopy observations and 99mTc radionuclide labeling techniques were used to investigate the cellular uptake of NCBs with different sizes qualitatively and quantitatively, respectively. Results showed that the cellular uptake amounts of NCBs increased with their increasing size. Large quantities of internal NCBs induced oxidative stress and nuclear damage in cells; these effects may be the critical factors involved in the cytotoxicity of NCBs. The implications associated with these findings are discussed

A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-Like Properties and Invasion in Human Bladder Cancer

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 blockade have been identified to target immune checkpoints to treat human cancers with durable clinical benefit. Several studies reveal that the response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells. However, the mechanistic pathways that regulate PD-L1 protein expression are not understood. Here, we reported that PD-L1 protein is regulated by ATG7-autophagy with an ATG7-initiated positive feedback loop in bladder cancer (BC). Mechanistic studies revealed that ATG7 overexpression elevates PD-L1 protein level mainly through promoting autophagy-mediated degradation of FOXO3a, thereby inhibiting its initiated miR-145 transcription. The lower expression of miR-145 increases pd-l1 mRNA stability due to the reduction of its direct binding to 3′-UTR of pd-l1 mRNA, in turn leading to increasing in pd-l1 mRNA stability and expression, and finally enhancing stem-like property and invasion of BC cells. Notably, overexpression of PD-L1 in ATG7 knockdown cells can reverse the defect of autophagy activation, FOXO3A degradation, and miR-145 transcription attenuation. Collectively, our results revealed a positive feedback loop to promoting PD-L1 expression in human BC cells. Our study uncovers a novel molecular mechanism for regulating pd-l1 mRNA stability and expression via ATG7/autophagy/FOXO3A/miR-145 axis and reveals the potential for using combination treatment with autophagy inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human BCs

Experimental protocol designed to employ Nd:YAG laser surgery for anterior chamber glaucoma detection via UBM

Angle closure glaucoma leads to fluid deposition in eye, and intraocular pressure occurs that damage the optic nerve, causes blindness and vision loss. Anterior chamber (AC) evaluation is imperative for determining the risk of angle-closure. Previously, techniques were dependent on either Pentacam–Scheimpflug that interprets poor visual information, anterior segment optical coherence tomography is injurious to intercede opaque optical structures. Therefore, in this paper, an experimental protocol is designed for detailed disease analysis based on IBM SPSS statistics via ultrasound biomicroscopy which is superior in evaluating deep structures; first, the affected parameter for AC is analysed, and afterwards the direction that needs laser surgery is explored. Experiments are conducted on large-scale clinical studies from an affiliated hospital in Shanghai, China. The dataset comprised 600 AC images in five directions of 60 subjects. The mean with standard deviation for anterior open distance is 0.15879 ± 0.096779 mm, 0.15863 ± 0.081435 mm, and anterior chamber angle is 18.749 ± 08.0315 ∘ , 18.741 ± 08.3889 ∘ for left and right eye respectively. It is found that anterior chamber angle in the downside of the AC is wider than the upside. However, this decision is partly based on the narrowest part of the angle to widen the depth of the direction and eliminate pupil block

STAT3 Regulates Self-Renewal of Adult Muscle Satellite Cells during Injury-Induced Muscle Regeneration

Recent studies have shown that STAT3 negatively regulates the proliferation of muscle satellite cells (MuSCs) and injury-induced muscle regeneration. These studies have been largely based on STAT3 inhibitors, which may produce off-target effects and are not cell type-specific in vivo. Here, we examine the role of STAT3 in MuSCs using two different mouse models: a MuSC-specific Stat3 knockout line and a Stat3 (MuSC-specific)/dystrophin (Dmd) double knockout (dKO) line. Stat3−/− MuSCs from both mutant lines were defective in proliferation. Moreover, in both mutant strains, the MuSC pool shrank, and regeneration was compromised after injury, with defects more pronounced in dKO mice along with severe muscle inflammation and fibrosis. We analyzed the transcriptomes of MuSCs from dKO and Dmd−/− control mice and identified multiple STAT3 target genes, including Pax7. Collectively, our work reveals a critical role of STAT3 in adult MuSCs that regulates their self-renewal during injury-induced muscle regeneration

W: Circulating adipocyte fatty acid-binding protein levels are independently associated with heart failure. Clin Sci 2013

Abstract A-FABP (adipocyte fatty acid-binding protein), one of the most abundant proteins in adipocytes, plays a key role in obesity-related insulin resistance, inflammation and atherosclerosis in animals. In the present study, we sought to investigate the association of A-FABP with HF (heart failure) in Chinese subjects. Serum A-FABP levels were measured in 252 HF patients and 261 age-, gender-and BMI (body mass index)-matched non-HF subjects. Echocardiography was performed on each patient. The severity of HF was determined by the NYHA (New York Heart Association) classification system. After adjustments for age, gender and BMI, serum A-FABP concentrations in patients with HF were significantly higher than in non-HF patients [11.17 (6.63-19.93) ng/ml compared with 5.67 (3.20-8.87) ng/ml; P < 0.001] and significantly progressed with the NYHA class (P < 0.001). In addition, NT-proBNP (N-terminal pro-brain natriuretic peptide) was independently and positively correlated with A-FABP (standardized β = 0.340, P < 0.001) after adjusting for confounding factors. Each echocardiographic parameter, especially LVEF (left ventricular ejection fraction), was independently associated with A-FABP (all P < 0.05). Multivariate logistic regression analysis demonstrated that A-FABP concentration was an independent risk factor for HF [odds ratio, 6.93 (95 % confidence interval, 2.49-19.30); P < 0.001]. Our results demonstrate that A-FABP is closely associated with HF, and raise the possibility that increased A-FABP may be causally related to the pathogenesis of heart dysfunction in humans