In the central nervous system (CNS), oligodendrocyte maturation and axonal myelination occur on a predictable schedule, but the underlying timing mechanisms are largely unknown. In the present study, we demonstrate that Nkx2.2 homeodomain transcription factor is a key regulator for the timing of oligodendrocyte differentiation during development. Whereas induced expression of Nkx2.2 in early oligodendrocyte precursor cells (OPCs) causes precocious differentiation of oligodendrocytes, conditional ablation of Nkx2.2 temporally delays oligodendrocyte maturation. Moreover, Nkx2.2 can directly bind to the promoter of platelet-derived growth factor receptor alpha (Pdgfra) and repress its gene expression. Genetic ablation of Pdgfra mimics the effect of Nkx2.2 overexpression in accelerating OPC differentiation in the developing spinal cord. Together, our findings strongly suggest that Nkx2.2 functions as a major 'switch' to turn off Pdgfra signaling in OPCs and initiate the intrinsic program for oligodendrocyte differentiation. KEY WORDS: Spinal cord, Tet-on, Transcription factor, Mouse INTRODUCTIONA requisite component of nervous system development is the achievement of proper axonal myelination for rapid and accurate transmission of electric activities. In the central nervous system (CNS), myelin sheaths are elaborated by oligodendrocytes (OLs), and the myelination process is preceded by molecular and morphological differentiation of oligodendrocyte precursor cells (OPCs). It was observed that OPCs differentiate on a predictable schedule both in vivo and in vitro, but the molecular pathways that control the timing of OPC differentiation have not been clearly defined.It has been recently shown that multiple classes of transcription factors are involved in the regulation of the OL differentiation process. They include the negative differentiation regulators Id2, Id4 and Hes5 (Kondo and Raff, 2000; Liu et al., 2006;Wang et al., 2001), and positive regulators such as Olig1 (Lu et al., 2002), Mrf (Myrf -Mouse Genome Informatics) (Emery, 2010), Mash-1 (Ascl1 -Mouse Genome Informatics) (Sugimori et al., 2008), Sip1 (Gemin2 -Mouse Genome Informatics) (Weng et al., 2012), Nkx2.2 (Qi et al., 2001 and Sox10 (Soula et al., 2001). Among these transcription factors, Nkx2.2 (Nkx2-2 -Mouse Genome Informatics) is uniquely positioned as a candidate regulator for the timing of OL differentiation. In the developing mouse spinal cord, Nkx2.2 expression is upregulated in OPCs immediately before their differentiation but rapidly downregulated after OPC differentiation (Fu et al., 2002;Soula et al., 2001;Xu et al., 2000;Zhou et al., 2001). Thus, Nkx2.2 expression in differentiating OPCs correlates seamlessly with the onset of OL differentiation. Functional analyses revealed that Nkx2.2 plays an essential role in the terminal differentiation of OLs (Qi et al., 2001;Zhou et al., 2001). However, because of the neonatal lethality of Nkx2.2 mutants, it has remained unknown whether Nkx2.2 is absolutely required for OPC maturation or simp...
Thermal barrier coatings (TBCs) can effectively protect the alloy substrate of hot components in aeroengines or land-based gas turbines by the thermal insulation and corrosion/erosion resistance of the ceramic top coat. However, the continuous pursuit of a higher operating temperature leads to degradation, delamination, and premature failure of the top coat. Both new ceramic materials and new coating structures must be developed to meet the demand for future advanced TBC systems. In this paper, the latest progress of some new ceramic materials is first reviewed. Then, a comprehensive spalling mechanism of the ceramic top coat is summarized to understand the dependence of lifetime on various factors such as oxidation scale growth, ceramic sintering, erosion, and calcium-magnesium-aluminium-silicate (CMAS) molten salt corrosion. Finally, new structural design methods for high-performance TBCs are discussed from the perspectives of lamellar, columnar, and nanostructure inclusions. The latest developments of ceramic top coat will be presented in terms of material selection, structural design, and failure mechanism, and the comprehensive guidance will be provided for the development of next-generation advanced TBCs with higher temperature resistance, better thermal insulation, and longer lifetime.
In modern internet of things (IoT), visual analysis and predictions are often performed by deep learning models. Salient object detection (SOD) is a fundamental pre-processing for these applications. Executing SOD on the fog devices is a challenging task due to the diversity of data and fog devices. To adopt convolutional neural networks (CNN) on fog-cloud infrastructures for SOD-based applications, we introduce a semisupervised adversarial learning method in this paper. The proposed model, named as SaliencyGAN, is empowered by a novel concatenated-GAN framework with partially shared parameters. The backbone CNN can be chosen flexibly based on the specific devices and applications. In the meanwhile, our method uses both the labelled and unlabelled data from different problem domains for training. Using multiple popular benchmark datasets, we compared state-of-the-art baseline methods to our SaliencyGAN obtained with 10% to 100% labelled training data. SaliencyGAN gained performance comparable to the supervised baselines when the percentage of labelled data reached 30%, and outperformed the weakly supervised and unsupervised baselines. Furthermore, our ablation study shows that SaliencyGAN were more more robust to the common "mode missing" (or "mode collapse") issue compared to the selected popular GAN models. The visualized ablation results proved that SaliencyGAN learned a better estimation of data distributions. To the best of our knowledge, this is the first IoT-oriented semi-supervised SOD method.
Axonal myelination is an essential process for normal functioning of vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. It was observed that the differentiation occurs on a predictable schedule both in culture and during development. However, the timing mechanisms for oligodendrocyte differentiation during normal development have not been fully uncovered. Recent studies have identified a large number of regulatory factors including the cell-intrinsic factors and extracellular signals that could control the timing of oligodendrocyte differentiation. Here we provide a mechanistic and critical review on the timing control of oligodendrocyte differentiation.
Human papillomavirus infection plays a key role in the development of cervical cancer. To establish a foundation for HPV-based screening and vaccination programs, we investigated the HPV prevalence and genotypic distributions in Chinese women from Zhejiang Province. Between 2011 and 2015, a total of 961,029 samples from 2021 clinical hospitals were tested HPV genotype by a PCR-based hybridization gene chip assay, and 443,890 samples were evaluated cervical cytology by liquid-based cytology analysis. Our results showed that the positive rate for HPV was 20.54%, which ranged from 28.72% to 17.81% and varied by year of recruitment. Age-specific prevalence showed a “two-peak” pattern, with the ≤20-year-old group presenting the highest HPV infection rate, followed by 61–70-year-old group. Overall, the most prevalent genotypes were HPV16, 52 and 58. Additionally, the odds ratios for the prevalence of the HR-HPV, LR-HPV and HPV-negative groups with abnormal cytology were 12.56, 3.21 and 0.06, respectively. Among genotypes, HPV 16 has been found to have the highest OR, followed by HPV58, 18, 52. Here, we present data regarding the prevalence and type distribution of HPV infection, which can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs.
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