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- Böhm, Johann, et al.
(författare)
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Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.
- 2012
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Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 33:6, s. 949-59
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Tidskriftsartikel (refereegranskat)abstract
- Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.
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| 2. |
- López, A., et al.
(författare)
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Laboratory characterization and astrophysical detection of vibrationally excited states of vinyl cyanide in Orion-KL
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 572
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Tidskriftsartikel (refereegranskat)abstract
- Context. We perform a laboratory characterization in the 18–1893 GHz range and astronomical detection between 80–280 GHz in Orion-KL with IRAM-30 m of CH2CHCN (vinyl cyanide) in its ground and vibrationally excited states. Aims. Our aim is to improve the understanding of rotational spectra of vibrationally excited vinyl cyanide with new laboratory data and analysis. The laboratory results allow searching for these excited state transitions in the Orion-KL line survey. Furthermore, rotational lines of CH2CHCN contribute to the understanding of the physical and chemical properties of the cloud. Methods. Laboratory measurements of CH2CHCN made on several different frequency-modulated spectrometers were combined into a single broadband 50–1900 GHz spectrum and its assignment was confirmed by Stark modulation spectra recorded in the 18–40 GHz region and by ab-initio anharmonic force field calculations. For analyzing the emission lines of vinyl cyanide detected in Orion-KL we used the excitation and radiative transfer code (MADEX) at LTE conditions. Results. Detailed characterization of laboratory spectra of CH2CHCN in nine different excited vibrational states: ?11 = 1, ?15 = 1, 2) ⇔ (?10 = 1,?15 = 1) ⇔ (?11 = 1,?14 = 1), and ?11 = 4 are determined, as well as the detection of transitions in the ?11 = 2and ?11 = 2, ?10 = 1 ⇔ (?11 = 1,?15 = 1), ?11 = 3/?15 = 2/?14 = 1, (?11 = 1,?10 = 1) ⇔ (?11 = 2,?15 = 1), ?9 = 1, (?11 = 1,?15 = The rotational transitions of the ground state of this molecule emerge from four cloud components of hot core nature, which trace the ?11 = 3 states for the first time in Orion-KL and of those in the ?10 = 1 ⇔ (?11 = 1,?15 = 1) dyad of states for the first time in space. physical and chemical conditions of high mass star forming regions in the Orion-KL Nebula. The lowest energy vibrationally excited states of vinyl cyanide, such as ?11 = 1 (at 328.5 K), ?15 = 1 (at 478.6 K), ?11 = 2 (at 657.8 K), the ?10 = 1 ⇔ (?11 = 1,?15 = 1) dyad (at 806.4/809.9 K), and ?11 = 3 (at 987.9 K), are populated under warm and dense conditions, so they probe the hottest parts of the Orion-KL source. The vibrational temperatures derived for the ?11 = 1, ?11 = 2, and ?15 = 1 states are 252 ± 76K, 242 ± 121K, column density of CH2CHCN in the ground state is (3.0 ± 0.9) × 1015 cm−2. We report the detection of methyl isocyanide (CH3NC) and 227 ± 68K, respectively; all of them are close to the mean kinetic temperature of the hot core component (210K). The total for the first time in Orion-KL and a tentative detection of vinyl isocyanide (CH2CHNC). We also give column density ratios between the cyanide and isocyanide isomers, obtaining a N(CH3NC)/N(CH3CN) ratio of 0.002. Conclusions. Laboratory characterization of many previously unassigned vibrationally excited states of vinyl cyanide ranging from microwave to THz frequencies allowed us to detect these molecular species in Orion-KL. Column density, rotational and vibrational temperatures for CH2CHCN in their ground and excited states, and the isotopologues have been constrained by means of a sample of more than 1000 lines in this survey.
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