TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Development of a protease-resistant reporter to quantify BCR–ABL activity in intact cells

A peptidase-resistant ABL kinase substrate was developed by identifying protease-susceptible bonds on an ABL substrate peptide and replacing flanking amino acids with non-native amino acids

Separation of peptide fragments of a protein kinase C substrate fused to a β-hairpin by capillary electrophoresis

Synthetic peptides incorporating well-folded β-hairpin peptides possess advantages in a variety of cell biology applications by virtue of increased resistance to proteolytic degradation. In this study, the WKpG β-hairpin peptide fused to a protein kinase C (PKC) substrate was synthesized, and capillary-electrophoretic separation conditions for this peptide and its proteolytic fragments were developed. Fragments of WKpG-PKC were generated by enzymatic treatment with trypsin and Pronase E to produce standards for identification of degradation fragments in a cellular lysate. A simple buffer system of 250 mM H3PO4, pH 1.5 enabled separation of WKpG-PKC and its fragments by capillary electrophoresis in less than 16 min. Using a cellular lysate produced from Ba/F3 cells, the β-hairpin-conjugated substrate and its PKCα-phosphorylated product could be detected and separated from peptidase-generated fragments produced in a cell lysate. The method has potential application for identification and quantification of WKpG-PKC and its fragments in complex biological systems when the peptide is used as a reporter to assay PKC activity

Acoustic cloak based on Bézier scatterers

[EN] Among the different approaches proposed to design acoustic cloaks, the one consisting on the use of an optimum distribution of discrete scatters surrounding the concealing object has been successfully tested. The feasibility of acoustic cloaks mainly depends on the number and shape of the scatterers surrounding the object to be cloaked. This work presents a method allowing the reduction of the number of discrete scatterers by optimizing their external shape, which is here defined by a combination of cubic Bézier curves. Based on scattering cancellation, a two-dimensional directional cloak consisting of just 20 Bézier scatters has been designed, fabricated and experimentally characterized. The method of fundamental solutions has been implemented to calculate the interaction of an incident plane wave with scatterers of arbitrary shape. The acoustic cloak here proposed shows a performance, in terms of averaged visibility, similar to that consisting of 120 scatterers with equal circular cross sections. The operational frequency of the proposed cloak is 5940 Hz with a bandwidth of about 110 Hz.J. Sanchez-Dehesa acknowledges the financial support by the Spanish Ministerio de Economia y Competitividad and the European Union Fondo Europeo para el Desarrollo Regional (FEDER) under Grant with Ref. TEC2014-53088-C3-1-R. Lu Zhimiao acknowledges the financial support from the program of China Scholarships Council (No. 201503170282), Wen Jihong, Cai Li and Lu Zhimiao acknowledge the support by National Natural Science Foundation of China (Grant Nos 51275519 and 11372346)Lu, Z.; Sanchis Martínez, L.; Wen, J.; Cai, L.; Bi, Y.; Sánchez-Dehesa Moreno-Cid, J. (2018). Acoustic cloak based on Bézier scatterers. Scientific Reports. 8. https://doi.org/10.1038/s41598-018-30888-7S8Cummer, S. A. & Schurig, D. One path to acoustic cloaking. New J. Phys. 9(3), 45 (2007).Cai, L.-W. & Sánchez-Dehesa Analysis of Cummer–Schurig acoustic cloaking. J. New J. Phys. 9(12), 450 (2007).Chen, H. & Chan, C. Acoustic cloaking in three dimensions using acoustic metamaterials. Appl. Phys. Lett. 91(18), 183518 (2007).Norris, A. N. Acoustic cloaking theory. Proc. R. Soc. A 464(2097), 2411–2434 (2008).Torrent, D. & Sánchez-Dehesa, J. Acoustic cloaking in two dimensions: a feasible approach. New J. Phys. 10(6), 063015 (2008).Zhang, S., Xia, C. & Fang, N. Broadband acoustic cloak for ultrasound waves. Phys. Rev. Lett. 106, 024301 Jan (2011).Popa, B.-I., Zigoneanu, L. & Cummer, S. A. Experimental acoustic ground cloak in air. Phys. Rev. Lett. 106, 253901 Jun (2011).Zigoneanu, L., Popa, B.-I. & Cummer, S. A. Design and measurements of a broadband two-dimensional acoustic lens. Nat. Mat 13, 352 (2014).Kan, W. et al. Broadband acoustic cloaking within an arbitrary hard cavity. Phys. Rev. Applied 3, 064019 Jun (2015).Scandrett, C. L., Boisvert, J. E. & Howarth, T. R. Acoustic cloaking using layered pentamode materials. J. Acoust. Soc. Am. 127(5), 2856–2864 (2010).Chen, Y. et al. Broadband solid cloak for underwater acoustics. Phys. Rev. B 95, 180104 May (2017).Alù, A. & Engheta, N. Achieving transparency with plasmonic and metamaterial coatings. Phys. Rev. E 72(1), 016623 (2005).Guild, M. D., Alu, A. & Haberman, M. R. Cancellation of acoustic scattering from an elastic sphere. J. Acoust. Soc. Am. 129(3), 1355–1365 (2011).García-Chocano, V. M. et al. Acoustic cloak for airborne sound by inverse design. Appl. Phys. Lett. 99(7), 074102 (2011).Sanchis, L. et al. Three-Dimensional Axisymmetric Cloak Based on the Cancellation of Acoustic Scattering from a Sphere. Phys. Rev. Lett. 110, 124301 Mar (2013).Andkjær, J. & Sigmund, O. Topology optimized for Airborne sound. ASME J. Vib. Acoust. 135(2), 041011 (2013).Guild, M. D. Acoustic Cloaking of Spherical Objects Unsing Thin Elastic Coatings. Univ. of Texas at Austin (2012).Guild, M. D., Haberman, M. R. & Alú, A. Plasmonic-type Acoustic cloak made of a bilaminate shell. Phys. Rev. B 86(10), 104302 (2012).Rohde, C. A. et al. Experimental demonstration of underwater acoustic scattering cancellation. Sci. Rep. 5, 13175 (2015).Popa, B.-I. & Cummer, S. A. Cloaking with optimized homogeneous anisotropic layers. Phys. Rev. A 79, 023806 Feb (2009).Urzhumov, Y., Landy, N., Driscoll, T., Basov, D. & Smith, D. R. Thin low-loss dielectric coatings for freespace cloaking. Opt. Lett. 38(10), 1606–1608 (2013).Andkjaer, J. & Sigmund, O. Topology optimized low-contrast all-dielectric optical cloak. Appl. Phys. Lett. 98(2), 021112 (2011).Climente, A., Torrent, D. & Sánchez-Dehesa, J. Sound focusing by gradient index sonic lenses. Applied Physics Letters 97(10), 104103 (2010).Håkansson, A., Sánchez-Dehesa, J. & Sanchis, L. Acoustic lens design by genetic algorithms Phys. Rev. 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Determination of antioxidant components in rice bran oil extracted by microwave-assisted method

Rice bran oil was extracted by microwave-assisted extraction with isopropanol and hexane using a solvent-to-rice bran ratio of 3:1 (w/w). The experiments were done in triplicate at 40, 60, 80, 100, and 120 °C with a total extraction time of 15 min/sample. The oil components were separated by normal-phase HPLC and quantified with a fluorescence detector. The radical scavenging capability of the oil was tested with DPPH and was expressed as μmol Trolox Equivalent Antioxidant Activity. The increase in total vitamin E with temperature from 40 to 120 °C was 59.63% for isopropanol and 342.01% for hexane. Isopropanol was the best solvent for the extraction of γ-tocopherol and γ-tocotrienol as compared with hexane for both microwave-assisted and conventional solvent extraction. Isopropanol was better for oil yield extraction at high temperatures. Samples extracted with isopropanol at 120 °C had higher antioxidant activity. No differences in oil yield, total vitamin E, and antioxidant activity of oil was noticed between the two methods (microwave-assisted and solvent extractions), at 40 °C. No degradation of α-tocopherol was noticed during the process

Three-dimensional broadband omnidirectional acoustic ground cloak

The control of sound propagation and reflection has always been the goal of engineers involved in the design of acoustic systems. A recent design approach based on coordinate transformations, which is applicable to many physical systems, together with the development of a new class of engineered materials called metamaterials, has opened the road to the unconstrained control of sound. However, the ideal material parameters prescribed by this methodology are complex and challenging to obtain experimentally, even using metamaterial design approaches. Not surprisingly, experimental demonstration of devices obtained using transformation acoustics is difficult, and has been implemented only in two-dimensional configurations. Here, we demonstrate the design and experimental characterization of an almost perfect three-dimensional, broadband, and, most importantly, omnidirectional acoustic device that renders a region of space three wavelengths in diameter invisible to sound

Three-dimensional Ultrathin Planar Lenses by Acoustic Metamaterials

Acoustic lenses find applications in various areas ranging from ultrasound imaging to nondestructive testing. A compact-size and high-efficient planar acoustic lens is crucial to achieving miniaturization and integration, and should have deep implication for the acoustic field. However its realization remains challenging due to the trade-off between high refractive-index and impedance-mismatch. Here we have designed and experimentally realized the first ultrathin planar acoustic lens capable of steering the convergence of acoustic waves in three-dimensional space. A theoretical approach is developed to analytically describe the proposed metamaterial with hybrid labyrinthine units, which reveals the mechanism of coexistence of high refractive index and well-matched impedance. A hyperbolic gradient-index lens design is fabricated and characterized, which can enhance the acoustic energy by 15 dB at the focal point with very high transmission efficiency. Remarkably, the thickness of the lens is only approximately 1/6 of the operating wavelength. The lens can work within a certain frequency band for which the ratio between the bandwidth and the center frequency reaches 0.74. By tailoring the structure of the metamaterials, one can further reduce the thickness of the lens or even realize other acoustic functionalities, opening new opportunity for manipulation of low-frequency sounds with versatile potential