Disruption of ER-mitochondria tethering and signalling in C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia

Hexanucleotide repeat expansions in C9orf72 are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The mechanisms by which the expansions cause disease are not properly understood but a favoured route involves its translation into dipeptide repeat (DPR) polypeptides, some of which are neurotoxic. However, the precise targets for mutant C9orf72 and DPR toxicity are not fully clear, and damage to several neuronal functions has been described. Many of these functions are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. ER-mitochondria signalling requires close physical contacts between the two organelles that are mediated by the VAPB-PTPIP51 ‘tethering’ proteins. Here, we show that ER-mitochondria signalling and the VAPB-PTPIP51 tethers are disrupted in neurons derived from induced pluripotent stem (iPS) cells from patients carrying ALS/FTD pathogenic C9orf72 expansions and in affected neurons in mutant C9orf72 transgenic mice. In these mice, disruption of the VAPB-PTPIP51 tethers occurs prior to disease onset suggesting that it contributes to the pathogenic process. We also show that neurotoxic DPRs disrupt the VAPB-PTPIP51 interaction and ER-mitochondria contacts and that this may involve activation of glycogen synthase kinases-3β (GSK3β), a known negative regulator of VAPB-PTPIP51 binding. Finally, we show that these DPRs disrupt delivery of Ca2+ from ER stores to mitochondria, which is a primary function of the VAPB-PTPIP51 tethers. This delivery regulates a number of key neuronal functions that are damaged in ALS/FTD including bioenergetics, autophagy and synaptic function. Our findings reveal a new molecular target for mutant C9orf72-mediated toxicity

Analysis of plasma enhanced pulsed laser deposition of transition metal oxide thin films using medium energy ion scattering

In this study, plasma-enhanced pulsed laser deposition (PE-PLD), which is a novel variant of pulsed laser deposition that combines laser ablation of metal targets with an electrically-produced oxygen plasma background, has been used for the fabrication of ZnO and Cu2O thin films. Samples prepared using the PE-PLD process, with the aim of generating desirable properties for a range of electrical and optical applications, have been analysed using medium energy ion scattering. Using a 100 keV He+ ion beam, high resolution depth profiling of the films was performed with an analysis of the stoichiometry and interface abruptness of these novel materials. It was found that the PE-PLD process can create stoichiometric thin films, the uniformity of which can be controlled by varying the power of the inductively coupled plasma. This technique showed a high deposition rate of ∼0.1 nm s−1

Investigation of the structure of tungsten oxide films obtained by chemical vapor deposition

Thin amorphous and polycrystalline tungsten oxide films have been prepared by Chemical Vapor Deposition (CVD) from metallorganic precursor − tungsten hexacarbonyl − at atmospheric pressure. The dependence of the composition and the structure of tungsten oxide films on the technological conditions has been investigated by XPS, XRD, DTA-TGA and Raman spectroscopy. As a result it has been established that: at high values of the flow-rates of the reaction gases amorphous films of very low density have been obtained; in the XPS spectra of the understoichiometric WO3−y (0 < y < 0.3) films besides W6+, also W5+ and W4+ states have been observed. First to observe in the Raman spectra of amorphous CVD-WO3 films is the band at ~ 950 cm−1, characteristic for terminal W6+ = O bonds in result of the presence of structural water. The existence of structural water in the amorphous material has been established by thermal analyze, also

Vapor growth of electrochromic thin films of transition metal oxides

Mixed oxide films of transition metals gain considerable much attention due to their interesting optoelectronic properties. The low temperature chemical vapor growth processing of thin films of mixed W and Mo oxides is presented. The investigation is related to optimization of films structure and the related optoelectronic properties in dependence on the chemical vapor deposition (CVD) process parameters. Their electrochromic behavior and photoelectrode properties were studied

Plasma assisted deposition of thin carbon films from methane and the influence of the plasma parameters and additional gases

Aschentrup A, Szekeres A, Gesheva K, Hamelmann F, Heinzmann U, Brechling A. Plasma assisted deposition of thin carbon films from methane and the influence of the plasma parameters and additional gases. Vacuum 76. 2004;76(2-3):139-142

Optical and electrochromic characterization of multilayered mixed metal oxide thin films

Hamelmann F, Gesheva K, Ivanova T, Szekeres A, Abrashev M, Heinzmann U. Optical and electrochromic characterization of multilayered mixed metal oxide thin films. JOURNAL OF OPTOELECTRONICS AND ADVANCED MATERIALS. 2005;7(1):393-396.The paper presents results on the preparation and study of the structure, optical and electrochromic properties of sol-gel derived thin films Of WO3, MoO3, and mixed films on based upon these. The films were deposited in a simplified sol-gel process. Raman spectra results showed that WO3 and the mixed films were predominantly amorphous, while crystallization of the MoO3 films was detected. All films showed an electrochromic effect. Color efficiencies were in the range 58 to 100 cm(2)/mC for a wavelength of 550 nm, reaching a value of 130 cm(2)/mC for the WO3 film. The results confirm that the simple sol-gel process which has been developed is promising for low cost applications in electrochromic smart windows

Electrochromic mixed films based On WO3 and MoO3, obtained by an APCVD method

Ivanova T, Gesheva KA, Kalitzova M, Hamelmann F, Lükermann F, Heinzmann U. Electrochromic mixed films based On WO3 and MoO3, obtained by an APCVD method. JOURNAL OF OPTOELECTRONICS AND ADVANCED MATERIALS. 2009;11(10):1513-1516.Electrochromism is a reversible effect, for which the transmittance (colour) modulation is induced by an applied external voltage. By changing the polarity, the film returns to its initial state. The low temperature chemical vapour growth processing of thin films of mixed W and Mo oxides is presented. The investigation is related to optimization of the film structure and the related optoelectronic properties as a function of the CVD process parameters. The morphology of the films is determined by SEM microscopy and EDX analysis reveals their compositions. The vibrational properties of the films are investigated by FTIR and Raman spectroscopy. Electrochromic behavior was examined by cyclic voltammetric experiments, performed in a standard three-electrode arrangement. From the cyclic voltammetry data, the optical modulation and colour efficiency (CE) values were estimated. The estimated CE values for a wavelength of 550 nm (the maximum of the solar energy spectrum) are one of the best reported in the literature

Thin molybdenum oxide films produced by molybdenum pentacarbonyl 1-methylbutylisonitrile with plasma-assisted chemical vapor deposition

Hamelmann F, Brechling A, Aschentrup A, et al. Thin molybdenum oxide films produced by molybdenum pentacarbonyl 1-methylbutylisonitrile with plasma-assisted chemical vapor deposition. THIN SOLID FILMS. 2004;446(2):167-171.Molybdenum oxide thin films were prepared by plasma-enhanced chemical vapor deposition of molybdenum pentacarbonyl 1-methylbutylisonitrile. This precursor is an interesting alternative for the commonly used molybdenum hexacarbonyl, because the substance is liquid at room temperature, offers sufficient volatility and stability to air and water. The film growth was monitored in situ by a soft X-ray reflectivity measurement. The films were deposited with different plasma gases (hydrogen and oxygen) under different conditions and analysed by Auger electron spectroscopy, X-ray diffraction and spectral ellipsometry. (C) 2003 Elsevier B.V All rights reserved