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991.
    
Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disorder and is sometimes associated with frontotemporal dementia. Charcot–Marie–Tooth disease (CMT) is one of the most commonly inherited peripheral neuropathies causing the slow progression of sensory and distal muscle defects. Of note, the severity and progression of CMT symptoms markedly vary. The phenotypic heterogeneity of ALS and CMT suggests the existence of modifiers that determine disease characteristics. Epigenetic regulation of biological functions via gene expression without alterations in the DNA sequence may be an important factor. The methylation of DNA, noncoding RNA, and post-translational modification of histones are the major epigenetic mechanisms. Currently, Drosophila is emerging as a useful ALS and CMT model. In this review, we summarize recent studies linking ALS and CMT to epigenetic regulation with a strong emphasis on approaches using Drosophila models.  相似文献   
992.
    
The process of fracture healing varies depending upon internal and external factors, such as the fracture site, mode of injury, and mechanical environment. This review focuses on site-specific fracture healing, particularly diaphyseal and metaphyseal healing in mouse long bones. Diaphyseal fractures heal by forming the periosteal and medullary callus, whereas metaphyseal fractures heal by forming the medullary callus. Bone healing in ovariectomized mice is accompanied by a decrease in the medullary callus formation both in the diaphysis and metaphysis. Administration of estrogen after fracture significantly recovers the decrease in diaphyseal healing but fails to recover the metaphyseal healing. Thus, the two bones show different osteogenic potentials after fracture in ovariectomized mice. This difference may be attributed to the heterogeneity of the skeletal stem cells (SSCs)/osteoblast progenitors of the two bones. The Hox genes that specify the patterning of the mammalian skeleton during embryogenesis are upregulated during the diaphyseal healing. Hox genes positively regulate the differentiation of osteoblasts from SSCs in vitro. During bone grafting, the SSCs in the donor’s bone express Hox with adaptability in the heterologous bone. These novel functions of the Hox genes are discussed herein with reference to the site-specificity of fracture healing.  相似文献   
993.
    
The infiltration and activation of macrophages as well as lymphocytes within atherosclerotic lesion contribute to the pathogenesis of plaque rupture. We have demonstrated that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens, play a crucial role in atherogenesis. However, it remained unclear whether iNKT cells are also involved in plaque instability. Apolipoprotein E (apoE) knockout mice were fed a standard diet (SD) or a high-fat diet (HFD) for 8 weeks. Moreover, the SD- and the HFD-fed mice were divided into two groups according to the intraperitoneal injection of α-galactosylceramide (αGC) that specifically activates iNKT cells or phosphate-buffered saline alone (PBS). ApoE/Jα18 double knockout mice, which lack iNKT cells, were also fed an SD or HFD. Plaque instability was assessed at the brachiocephalic artery by the histological analysis. In the HFD group, αGC significantly enhanced iNKT cell infiltration and exacerbated atherosclerotic plaque instability, whereas the depletion of iNKT cells attenuated plaque instability compared to PBS-treated mice. Real-time PCR analyses in the aortic tissues showed that αGC administration significantly increased expressional levels of inflammatory genes such as IFN-γ and MMP-2, while the depletion of iNKT cells attenuated these expression levels compared to those in the PBS-treated mice. Our findings suggested that iNKT cells are involved in the exacerbation of plaque instability via the activation of inflammatory cells and upregulation of MMP-2 in the vascular tissues.  相似文献   
994.
    
Discoidin domain receptor 1 (DDR1) inhibitors with a desired pharmacophore were designed using deep generative models (DGMs). DDR1 is a receptor tyrosine kinase activated by matrix collagens and implicated in diseases such as cancer, fibrosis and hypoxia. Herein we describe the synthesis and inhibitory activity of compounds generated from DGMs. Three compounds were found to have sub-micromolar inhibitory activity. The most potent of which, compound 3 (N-(4-chloro-3-((pyridin-3-yloxy)methyl)phenyl)-3-(trifluoromethyl)benzamide), had an IC50 value of 92.5 nM. Furthermore, these compounds were predicted to interact with DDR1, which have a desired pharmacophore derived from a known DDR1 inhibitor. The results of synthesis and experiments indicated that our de novo design strategy is practical for hit identification and scaffold hopping.  相似文献   
995.
Spinel CuFe2O4 has been studied as a precursor for copper catalyst. The spinel CuFe2O4 was effectively formed on the SiO2 by calcination in air at 800 °C with the atomic ratio of Fe/Cu = 2. The spinel CuFe2O4 on the SiO2 was reduced to fine dispersion of Cu and Fe3O4 particles by the H2 reduction at 240 °C. After H2 reduction at 600 °C, sintering of Cu particles over the CuFe2O4/SiO2 (Fe/Cu = 2) was inhibited significantly, while fatal sintering of Cu particles over the Cu/SiO2 (Fe/Cu = 0) occurred. The CuFe2O4/SiO2 catalyst exhibited much higher activity and thermal stability for steam reforming of methanol (SRM), compared with the Cu/SiO2 catalyst. The spinel CuFe2O4 on the SiO2 can be regenerated after an intentional sintering treatment by calcination in air at 800 °C where the activity is also restored completely. Based on these findings, we propose that spinel CuFe2O4 is an effective precursor for a high performance copper catalyst in which the immiscible interaction between Cu and Fe (or Fe oxide) plays an important role in the stabilization of Cu particles.  相似文献   
996.
The additive effects of the novel ethylene-propylene random (EP) copolymers with high isotacticity in propylene sequence on the morphology and mechanical properties of isotactic polypropylene (iPP) were investigated using polarized optical microscopy, transmission electron microscopy, dynamic mechanical analysis and tensile behavior. According to these results, the EP copolymers with a propylene content of more than 84 mol% were miscible with iPP, in which the crystallizable PP sequences in these EP copolymers were incorporated in crystal lattice of iPP and the other portions in the EP chains were excluded to the amorphous phases. Consequently, they act as tie molecules linking between adjacent lamellae, leading to enhancement of yield toughness of iPP. On the other hand, the EP copolymers with a propylene-unit content of less than 77 mol% were incompatible with iPP. The iPP/EP blends showed the phase-separated morphology.  相似文献   
997.
The crystal structure of Zr2Al3C4 was refined by the Rietveld method from conventional X-ray powder diffraction data. The structure was hexagonal (space group P 63 mc , Z =2) with a =0.334680(6) nm, c =2.22394(3) nm, and V =0.215731(6) nm3, being isomorphous with that of U2Al3C4. The final reliability indices were R wp=8.57%, R p=6.06%, and S =1.32. The crystal showed an intergrowth structure with NaCl-type ZrC slabs separated by Al4C3-type Al3C2 layers.  相似文献   
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