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BACKGROUND Mutation in the titin gene(TTN)in left ventricular noncompaction(LVNC)has been reported with a highly heterogeneous prevalence,and the molecular mechanisms underlying the pathogenesis of TTN gene mutation are uncharacte...
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BACKGROUND Mutation in the titin gene(TTN)in left ventricular noncompaction(LVNC)has been reported with a highly heterogeneous prevalence,and the molecular mechanisms underlying the pathogenesis of TTN gene mutation are uncharacteri-zed.In the present study,we identified a novel TTN mutation in a pedigree with LVNC and investigated the potential pathogenic mechanism by functional studies.METHODS The whole-genome sequencing with linkage analysis was performed in a 3-generation family affected by autoso-mal dominant LVNC cardiomyopathy.The clustered regularly interspaced short palindromic repeats associated protein 9(CRISPR/Cas9)technology was used to establish novel truncating mutation in TTN in a rat cardiomyoblast H9C2 cell line in vitro,in which functional studies were carried out and characterized in comparison to its wild-type counterpart.RESULTS A novel truncating mutation TTN p.R2021X was identified as the only plausible disease-causing variant that segreg-ated with disease among the five surviving affected individuals,with an interrogation of the entire genome excluding other po-tential causes.Quantitative reverse transcription-polymerase chain reaction and cellular immunofluorescence supported a haplo-insufficient disease mechanism in titin truncation mutation cardiomyocytes.Further functional studies suggested mitochondrial abnormities in the presence of mutation,including decreased oxygen consumption rate,reduced adenosine triphosphate produc-tion,impaired activity of electron translation chain,and abnormal mitochondrial structure on electron microscopy.Impaired aut-ophagy under electron microscopy accompanied with activation of the Akt-mTORC1 signaling pathway was observed in TTN p.R2021X truncation mutation cardiomyocytes.CONCLUSIONS The TTN p.R2021X mutation has a function in the cause of a highly penetrant familial LVNC.These findings expand the spectrum of titin’s roles in cardiomyopathies and provide novel insight into the molecular basis of titin-truncating variants-associated LVNC.
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Let a moving plane MP over a fixed plane FP occupy four different positions.Eachpair of such positions is associated with a center of rotation called pole so that we have a 6-poleconfiguration.As an illustration of our general met...
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Let a moving plane MP over a fixed plane FP occupy four different positions.Eachpair of such positions is associated with a center of rotation called pole so that we have a 6-poleconfiguration.As an illustration of our general method of mechanical theorem proving and discovering,we discuss in the present paper in some derails certain theorems connected with such a configuration.
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Clearance at turning pair has a strong impact on the kinetic accuracy of linkage, but there is short of a generic model to analyze it so far. Clearance error, input error, and manufacturing tolerance of links are taken into consid...
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Clearance at turning pair has a strong impact on the kinetic accuracy of linkage, but there is short of a generic model to analyze it so far. Clearance error, input error, and manufacturing tolerance of links are taken into consideration as the random variables synthetically. The kinematics and dynamics accuracy analysis models for planar linkages with multiple clearances at joints are built up as well. At last a typical planar linkage is selected for numerical illustration. These models stated in matrix resolve the relativity of output parameter errors of mechanism and therefore are of vital significance for the reliability analysis and synthesis of mechanism with clearances.
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A new type of rapier drive for flexible rapier loom through conjugate cams with five-bar linkage mechanism is raised and analyzed. Two designs suitable for the conversion of 1515-190.5 shuttle looms are given as examples. This mec...
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A new type of rapier drive for flexible rapier loom through conjugate cams with five-bar linkage mechanism is raised and analyzed. Two designs suitable for the conversion of 1515-190.5 shuttle looms are given as examples. This mechanism can be applied to traditional shuttle looms as well as to new flexible rapier loom design.
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Traditionally, the transmission device for cutter adopts gear mechanism combined with planar crank-rocker mechanism. In line with this drawback, this paper presents a practical spatial linkage mechanism. Through three-dimensional ...
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Traditionally, the transmission device for cutter adopts gear mechanism combined with planar crank-rocker mechanism. In line with this drawback, this paper presents a practical spatial linkage mechanism. Through three-dimensional modeling and kinematic analysis, it obtains the equation of motion for output displacement, speed and acceleration. Besides, it gets the kinetic curve through emulation. The emulation results indicate that RCSR mechanism can realize smooth and stable output of cutter, laying a foundation for future dimensional synthesis of the mechanism.
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The design of intermittent-motion linkages using traditional methods iS usually complicated.In this paper,(1)a new method for realizing intermittent motion,using linkages with a slight difference in length between links,is studied...
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The design of intermittent-motion linkages using traditional methods iS usually complicated.In this paper,(1)a new method for realizing intermittent motion,using linkages with a slight difference in length between links,is studied;(2)some new types of intermittent-motion linkages and their software for visual analysis and design are developed;and(3)influences of some design parameters on intermittent.motion characteristics are clarifled.Results confirmed that the theory and the software are useful,making the synthesis of intermittent-motion linkages clear and easy.
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Three types of 4-bar linkages can trace the same coupler curve according to the cognate mechanism law. Based on the investigation of the relationship between dimensions of a linkage and the harmonic component characteristic parame...
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Three types of 4-bar linkages can trace the same coupler curve according to the cognate mechanism law. Based on the investigation of the relationship between dimensions of a linkage and the harmonic component characteristic parameters of the coupler curve of the linkage, it was found that six types of linkages are related to the same coupler curve, and they belong to two groups of cognate mechanisms, in which the coupler curves have the same shape and are symmetric. The relationships among the dimensional types of these six mechanisms are presented. The corresponding examples have also proved these conclusions. This work enriches the cognate mechanism law, and can result in more candidate mechanisms for mechanism dimensional synthesis.
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The construction of China''''s carbon emission trading market has gone through a process from one-way participation in the international carbon market to voluntary emission reduction trading at home, and then to the total carbon e...
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The construction of China''''s carbon emission trading market has gone through a process from one-way participation in the international carbon market to voluntary emission reduction trading at home, and then to the total carbon emission right trading as the main and voluntary emission reduction trading as the auxiliary. The link of regional carbon emission trading system is conducive to reducing the cost of carbon emission reduction, promoting market liquidity, reducing operational risks of carbon market and reducing carbon leakage. The link of inter-provincial carbon market needs to break down administrative barriers and form a consensus on the link elements of carbon emission trading under the unified legal framework. The link of regional carbon emission trading system should be carried out from the aspects of legal mechanism construction, link mode selection and mutual recognition and assimilation of carbon emission trading system.
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