Competition of zinc ion for the [2Fe-2S] cluster binding site in the diabetes drug target protein mitoNEET

Human mitochondrial protein mitoNEET is a novel target of type II diabetes drug pioglitazone, and contains a redox active [2Fe-2S] cluster that is hosted by a unique ligand arrangement of three cysteine and one histidine residues. Here we report that zinc ion can compete for the [2Fe-2S] cluster binding site in human mitoNEET and potentially modulate the physiological function of mitoNEET. When recombinant mitoNEET is expressed in Escherichia coli cells grown in M9 minimal media, purified mitoNEET contains very little or no iron-sulfur clusters. Addition of exogenous iron or zinc ion in the media produces mitoNEET bound with a [2Fe-2S] cluster or zinc, respectively. Mutations of the amino acid residues that hosting the [2Fe-2S] cluster in mitoNEET diminish the zinc binding activity, indicating that zinc ion and the [2Fe-2S] cluster may share the same binding site in mitoNEET. Finally, excess zinc ion effectively inhibits the [2Fe-2S] cluster assembly in mitoNEET in E. coli cells, suggesting that zinc ion may impede the function of mitoNEET by blocking the [2Fe-2S] cluster assembly in the protein. Copyright © Springer Science+Business Media, LLC. 2012

Prevalence of the GJB2 IVS1+1G >A mutation in Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2

<p>Abstract</p> <p>Background</p> <p>Mutations in the GJB2 gene are the most common cause of nonsyndromic recessive hearing loss in China. In about 6% of Chinese patients with severe to profound sensorineural hearing impairment, only monoallelic <it>GJB2 </it>mutations known to be either recessive or of unclear pathogenicity have been identified. This paper reports the prevalence of the <it>GJB2 </it>IVS1+1G>A mutation in a population of Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of <it>GJB2</it>.</p> <p>Methods</p> <p>Two hundred and twelve patients, screened from 7133 cases of nonsyndromic hearing loss in China, with monoallelic mutation (mainly frameshift and nonsense mutation) in the coding region of <it>GJB2 </it>were examined for the <it>GJB2 </it>IVS1+1G>A mutation and mutations in the promoter region of this gene. Two hundred and sixty-two nonsyndromic hearing loss patients without <it>GJB2 </it>mutation and 105 controls with normal hearing were also tested for the <it>GJB2 </it>IVS1+1G>A mutation by sequencing.</p> <p>Results</p> <p>Four patients with monoallelic mutation in the coding region of <it>GJB2 </it>were found carrying the <it>GJB2 </it>IVS1+1G>A mutation on the opposite allele. One patient with the <it>GJB2 </it>c.235delC mutation carried one variant, -3175 C>T, in exon 1 of <it>GJB2</it>. Neither <it>GJB2 </it>IVS1+1G>A mutation nor any variant in exon 1 of <it>GJB2 </it>was found in the 262 nonsyndromic hearing loss patients without <it>GJB2 </it>mutation or in the 105 normal hearing controls.</p> <p>Conclusion</p> <p>Testing for the <it>GJB2 </it>IVS 1+1 G to A mutation explained deafness in 1.89% of Chinese <it>GJB2 </it>monoallelic patients, and it should be included in routine testing of patients with <it>GJB2 </it>monoallelic pathogenic mutation.</p

Study on Bending Creep Performance of GFRP-Reinforced PVC-Based Wood-Plastic Composite Panels

Wood-plastic composites (WPCs) are environment-friendly materials, which have broad application prospects in structures. They cannot be used for bearing structures because of poor mechanical performance and creep deformation. In order to enhance the mechanical behavior and decrease the long-term creep deformation, glass fiber reinforced plastics (GFRP) sheets and rebar reinforcement design methods are proposed. The bending static tests and creep performance tests of WPCs were conducted. The results showed that GFRP sheets and rebars improved the ultimate flexural loading capacity and deformation capacity by 257% and 165%, respectively, decreased the creep deflection effectively, and avoided shear failure. When the load level was very low, the creep deformation of WPC panels unreinforced, or reinforcement developed stably with time, and the damage did not occur within 1100 h. When the load increased to 80% of the ultimate load level, all specimens were damaged in the compression zone, the creep deformation increased quickly and unstably, bending shear failure of the unreinforced specimen occurred after 7 h, shear failure of the GFRP-sheets-reinforced specimen occurred after 1100 h, and the rebar-reinforced specimen failed after 720 h with excessive deflection deformation in the span. The reinforced effect of GFRP sheets is better. The creep strain growth rate of all specimens increased quickly at the first stage and gradually decreased at the second stage and tended to be stable. The creep calculation model was built based on the four-element model, which is simple and efficient and can make scientific and reasonable predictions of the two phases of structural transient creep and deceleration creep

A methodology for cable damage identification based on wave decomposition

© 2018 Elsevier Ltd Vibration-based damage identification has been widely studied in the field of structural health monitoring (SHM) for several decades. It is well known, however, that low-order modal parameters, being among the most frequently used, are not sensitive to local damage. A suitable methodology is therefore needed to extract such damage features from the dynamic response of structures. In the present work, local bending behavior of cables is studied for damage identification. First, the dynamic response of a cable is decomposed into evanescent wave and propagating wave components. It is proven that the contribution of the evanescent wave is spatially concentrated, and is sensitive to local damage. A signal transform is proposed next, which allows the estimation of the wave components from the measured cable response. The reflection coefficient of the evanescent wave (REW), which can be calculated from the estimated wave coefficients, depends only on the characteristics of the local discontinuity, and proves to be a robust indicator for local damage. The feasibility of the proposed methodology is studied by means of a simulated experiment, considering a cable model with two locally damaged parts. The results show that the intensity of REW is significantly higher near the damage locations, allowing damage localization. From the estimated REW near the damage locations, the damage levels can be estimated, showing the potential of this methodology for damage assessment of cable structures.status: publishe

A two-step methodology for cable force identification

status: publishe