Accumulation of RNA CUG repeats in myotonic dystrophy type 1 (DM1) patients leads to the induction of a CUG-binding protein, CUGBP1, which increases translation of several proteins that are required for myogenesis. In this paper, we examine the role of overexpression of CUGBP1 in DM1 muscle pathology using transgenic mice that overexpress CUGBP1 in skeletal muscle. Our data demonstrate that the elevation of CUGBP1 in skeletal muscle causes overexpression of MEF2A and p21 to levels that are significantly higher than those in skeletal muscle of wild type animals. A similar induction of these proteins is observed in skeletal muscle of DM1 patients with increased levels of CUGBP1. Immunohistological analysis showed that the skeletal muscle from mice overexpressing CUGBP1 is characterized by a developmental delay, muscular dystrophy, and myofiber-type switch: increase of slow/oxidative fibers and the reduction of fast fibers. Examination of molecular mechanisms by which CUGBP1 up-regulates MEF2A shows that CUGBP1 increases translation of MEF2A via direct interaction with GCN repeats located within MEF2A mRNA. Our data suggest that CUGBP1-mediated overexpression of MEF2A and p21 inhibits myogenesis and contributes to the development of muscle deficiency in DM1 patients. DM11 is a multisystem disease mainly characterized by defects in skeletal muscle with the involvement of many tissues and systems such as cardiac muscle, brain, eye, and endocrine system (1). DM1 is caused by an expansion of CTG trinucleotide repeats within the 3Ј-untranslated region of the myotonin protein kinase gene (2). In DM1 patients, the size of DNA CTG expansion correlates with the severity of the disease. Patients with CTG expansion containing 50 -80 CTG repeats are almost asymptomatic. Individuals bearing the myotonin protein kinase gene with 100 -500 CTG repeats develop a disease in adult life (classical adult form of DM1) that is characterized by a progressive muscle wasting with myotonia. The most severe form of DM1, congenital disease, affects patients before or after birth and is associated with long CTG expansions (up to 2,000 repeats). This form of disease is characterized by a delay or arrest of skeletal muscle development (3). Although there is an overlap in range of repeats between different forms of DM1, there is a clear correlation of repeat number with severity of phenotype and reduction of age of onset.Investigations of molecular alterations in DM1 suggest that the expansion of CTG repeats causes the DM1 pathology through different mechanisms, mediated at both DNA and RNA levels. It has been shown that CTG repeats reduce expression of myotonin protein kinase in cis (4), causing abnormalities in cardiac muscle (5). CTG repeats also affect transcription of genes adjacent to myotonin protein kinase (6), leading to the development of cataracts (7,8). A number of recent studies indicate that other symptoms in DM1 such as myotonia (9, 10), delay of skeletal muscle differentiation (11,12), and a resistance to insulin (13) are mediated ...
Abstract:The rheological behavior of amino-functionalized multi-walled carbon nanotubes (amino-CNTs)/polyacrylonitrile (PAN) concentrated solutions in the dimethyl sulphoxide solvent and the effects of the amino-CNTs on the PAN precursor fibers by wet-spinning method were investigated. The amino-CNT/PAN concentrated solutions prepared by in situ solution polymerization with homogeneous dispersion of amino-CNTs have higher complex viscosity, storage modulus and loss modulus as compared to the control PAN concentrated solutions containing 22% PAN polymer by mass. The composite fibers with amino-CNTs of 1 wt % have lower degree of crystallization, crystal size and crystal region orientation compared to the control PAN precursor fibers. However, the amino-CNT/PAN composite fibers with diameter of about 10.5 µm exhibit higher mechanical properties than the control PAN precursor fibers with diameter of about 8.0 µm. Differential scanning calorimetry analysis demonstrated that the cyclization reaction in composite fibers have broad exothermic temperature range and low exothermic rate. These results indicate that the addition of amino-CNTs into PAN precursor fibers is beneficial to controlling the process of thermal stabilization and obtaining the higher performance of composite fibers.
Amino-functionalized multi-walled carbon nanotube (amino-CNT)/polyacrylonitrile (PAN) microspheres with diameter of about 300-400 nm were prepared by in situ polymerization under aqueous solution. The morphology, crystal structure, and thermal properties of amino-CNTs on a PAN homopolymer were investigated by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectra, X-ray diffraction, and differential scanning calorimetry. The results showed that the amino-CNTs had a significant influence on the morphology of microspheres, and the PAN matrix were grafted onto the surface of amino-CNTs with interfacial bonding between them. The XRD studies showed that the crystal size of amino-CNT/PAN microspheres with lower crystallinity was bigger than in the control PAN homopolymer. The analysis of thermal properties indicated that the amino-CNT/PAN microspheres with lower glass transition temperature had a lower initial temperature and velocity of evolving heat during the exothermic processing as compared with the PAN homopolymer. These results suggested that the incorporation of amino-CNTs into the PAN homopolymer matrix was beneficial for controlling the heat released during the stabilization processing.
The carbon nanotube (CNT)/polyacrylonitrile (PAN) nascent composite fibers were prepared by wet spinning method. The polarized technique was used to characterize the nitrile orientation and the CNTs orientation in the CNT/ PAN nascent composite fibers, and the crystal orientation was also characterized by the azimuthal scan of X-ray diffraction. The results showed that the CNTs had high orientation in the nascent composite fibers after wet spinning, and the nitrile groups of the nascent composite fibers had higher orientation than that of the PAN nascent fibers owing to the interfacial interaction between CNTs and PAN macromolecular chains. Moreover, the CNT/PAN nascent composite fibers had higher parameters of crystal structure and excellent mechanical properties than the PAN nascent fibers. Meanwhile, the addition of CNTs into PAN matrix decreased the intensity of evolved heat in nitrogen atmosphere and made microstructure more compactness than the control PAN nascent fibers.
The composition and structure of polyacrylonitrile (PAN) precursors play an important role during thermal stabilization, which influences the properties of the resulting carbon fibers. In this paper, PAN homopolymer and PAN-itaconic (IA) copolymers with different IA contents were synthesized by aqueous phase precipitation polymerization. The effects of IA content on the structure and thermal properties were studied using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The morphology of PAN polymers showed that the average size of the PAN particles increased with the increase of IA content in the feed. The content of the IA comonomer on the copolymers was quantitatively characterized by the relative absorbance intensity (A1735/A2243) in FTIR spectrum. With the increase of IA content in the feed, PAN-IA copolymers exhibited lower degree of crystallinity and crystal size than the control PAN homopolymer. The results from DSC curves indicated that PAN-IA1.0 copolymers had lower initial exothermic temperature (192.4 °C) and velocity of evolving heat (6.33 J g−1 °C−1) in comparison with PAN homopolymer (Ti = 238.1 °C and ΔH/ΔT = 34.6 J g−1 °C−1) in an air atmosphere. TGA results suggested that PAN-IA1.0 copolymers had higher thermal stability than PAN homopolymer, which can form a ladder structure easier during thermal processing. Therefore, PAN-IA1.0 copolymers would be a suitable candidate for preparing high performance PAN based carbon fibers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.