Paradoxical Sensitivity to an Integrated Stress Response Blocking Mutation in Vanishing White Matter Cells

The eukaryotic translation initiation factor eIF2B promotes mRNA translation as a guanine nucleotide exchange factor (GEF) for translation initiation factor 2 (eIF2). Endoplasmic reticulum (ER) stress-mediated activation of the kinase PERK and the resultant phosphorylation of eIF2's alpha subunit (eIF2α) attenuates eIF2B GEF activity thereby inducing an integrated stress response (ISR) that defends against protein misfolding in the ER. Mutations in all five subunits of human eIF2B cause an inherited leukoencephalopathy with vanishing white matter (VWM), but the role of the ISR in its pathogenesis remains unclear. Using CRISPR-Cas9 genome editing we introduced the most severe known VWM mutation, EIF2B4$^{A391D}$, into CHO cells. Compared to isogenic wildtype cells, GEF activity of cells with the VWM mutation was impaired and the mutant cells experienced modest enhancement of the ISR. However, despite their enhanced ISR, imposed by the intrinsic defect in eIF2B, disrupting the inhibitory effect of phosphorylated eIF2α on GEF by a contravening EIF2S1/eIF2α$^{S51A}$ mutation that functions upstream of eIF2B, selectively enfeebled both EIF2B4$^{A391D }$ and the related severe VWM EIF2B4$^{R483W}$ cells. The basis for paradoxical dependence of cells with the VWM mutations on an intact eIF2α genotype remains unclear, as both translation rates and survival from stressors that normally activate the ISR were not reproducibly affected by the VWM mutations. Nonetheless, our findings support an additional layer of complexity in the development of VWM, beyond a hyperactive ISR.Supported by grants from the Wellcome Trust (Wellcome 200848/Z/16/Z) and the European Commission (EU FP7 Beta-Bat No: 277713) and, a Wellcome Trust Strategic Award for core facilities to the Cambridge Institute for Medical Research (Wellcome 100140). YS is a Japanese Society for the Promotion of Science Postdoctoral Fellow for Research Abroad. NAW is a Medical Research Council supported PhD student. DR is a Wellcome Trust Principal Research Fellow

Elastic (stress-strain) halo associated to ion-induced nano-tracks in lithium niobate: role of crystal anisotropy

The elastic strain/stress fields (halo) around a compressed amorphous nano-track (core) caused by a single high-energy ion impact on LiNbO3 are calculated. A method is developed to approximately account for the effects of crystal anisotropy of LiNbO3 (symmetry 3m) on the stress fields for tracks oriented along the crystal axes (X, Y or Z). It only considers the zero-order (axial) harmonic contribution to the displacement field in the perpendicular plane and uses effective Poisson moduli for each particular orientation. The anisotropy is relatively small; however, it accounts for some differential features obtained for irradiations along the crystallographic axes X, Y and Z. In particular, the irradiation-induced disorder (including halo) and the associated surface swelling appear to be higher for irradiations along the X- or Y-axis in comparison with those along the Z-axis. Other irradiation effects can be explained by the model, e.g. fracture patterns or the morphology of pores after chemical etching of tracks. Moreover, it offers interesting predictions on the effect of irradiation on lattice parameter

Optimization of nanopores generated by chemical etching of swift-ion irradiated LiNbO3.

The morphology of the nanopores obtained by chemical etching on ion-beam irradiated LiNbO3 has been investigated for a variety of ions (F, Br, Kr, Cu, Pb), energies (up to 2300 MeV), and stopping powers (up to 35 keV/nm) in the electronic energy loss regime. The role of etching time and etching agent on the pore morphology, diameter, depth, and shape has also been studied. The transversal and depth profiles of the pore have been found to be quite sensitive to both, irradiation and etching parameters. Moreover, two etching regimes with different morphologies and etching rates have been identified

Recrystallization of amorphous nano-tracks and uniform layers generated by swift-ion-beam irradiation in lithium niobate.

The thermal annealing of amorphous tracks of nanometer-size diameter generated in lithium niobate (LiNbO3) by Bromine ions at 45 MeV, i.e., in the electronic stopping regime, has been investigated by RBS/C spectrometry in the temperature range from 250°C to 350°C. Relatively low fluences have been used (<1012 cm−2) to produce isolated tracks. However, the possible effect of track overlapping has been investigated by varying the fluence between 3×1011 cm−2 and 1012 cm−2. The annealing process follows a two-step kinetics. In a first stage (I) the track radius decreases linearly with the annealing time. It obeys an Arrhenius-type dependence on annealing temperature with activation energy around 1.5 eV. The second stage (II) operates after the track radius has decreased down to around 2.5 nm and shows a much lower radial velocity. The data for stage I appear consistent with a solid-phase epitaxial process that yields a constant recrystallization rate at the amorphous-crystalline boundary. HRTEM has been used to monitor the existence and the size of the annealed isolated tracks in the second stage. On the other hand, the thermal annealing of homogeneous (buried) amorphous layers has been investigated within the same temperature range, on samples irradiated with Fluorine at 20 MeV and fluences of ∼1014 cm−2. Optical techniques are very suitable for this case and have been used to monitor the recrystallization of the layers. The annealing process induces a displacement of the crystalline-amorphous boundary that is also linear with annealing time, and the recrystallization rates are consistent with those measured for tracks. The comparison of these data with those previously obtained for the heavily damaged (amorphous) layers produced by elastic nuclear collisions is summarily discussed

Analysis and optimization of propagation losses in LiNbO3 optical waveguides produced by swift heavy-ion irradiation

The propagation losses (PL) of lithium niobate optical planar waveguides fabricated by swift heavy-ion irradiation (SHI), an alternative to conventional ion implantation, have been investigated and optimized. For waveguide fabrication, congruently melting LiNbO3 substrates were irradiated with F ions at 20 MeV or 30 MeV and fluences in the range 1013–1014 cm−2. The influence of the temperature and time of post-irradiation annealing treatments has been systematically studied. Optimum propagation losses lower than 0.5 dB/cm have been obtained for both TE and TM modes, after a two-stage annealing treatment at 350 and 375∘C. Possible loss mechanisms are discussed

Isothermal hydrogen absorption process of Pd-capped Mg films traced by ion beam techniques and optical methods

Pd-capped nanocrystalline Mg films were prepared by electron beam evaporation and hydrogenated under isothermal conditions to investigate the hydrogen absorption process via ion beam techniques and in situ optical methods. Films were characterized by different techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM). Rutherford backscattering spectrometry (RBS) and elastic recoil detection analysis (ERDA) provided a detailed compositional depth profile of the films during hydrogenation. Gas-solid reaction kinetics theory applied to ERDA data revealed a H absorption mechanism controlled by H diffusion. This rate-limiting step was also confirmed by XRD measurements. The diffusion coefficient (D) was also determined via RBS and ERDA, with a value of (1.1±0.1)·10−13 cm2/s at 140 ∘C. Results confirm the validity of IBA to monitor the hydrogenation process and to extract the control mechanism of the process. The H kinetic information given by optical methods is strongly influenced by the optical absorption of the magnesium layer, revealing that thinner films are needed to extract further and reliable information from that techniqueTechnical assistance of F. Moreno and financial support by Spanish MICINN through the project PID2021-126098OB-I00/AEI/FEDER10.13039/501100011033 are gratefully acknowledged. We acknowledge the service from the MiNa Laboratory at IMN, and funding from CAM (project S2018/NMT-4291 TEC2SPACE), MINECO (project CSIC13-4E-1794) and EU (FEDER, FSE)

Impact of the Li-loss mechanisms inherent to the physical vapor deposition of LiCoO2 cathode on its electrochemical performance

GPa-resistant conformal LiCoO2 cathodes grown by physical vapor deposition (PVD), with negative chemical expansion coefficients, are promising systems for mechanically stabilizing cathode/solid electrolyte interfaces in solid-state lithium-ion batteries. However, exploiting its potential preliminarily requires that we are able to control the reversibility of Li stoichiometry under PVD conditions, which represents a major challenge since metal Li is lightweight, volatile and has high diffusivity. By combining different chemical and structural analysis techniques, we identify the mechanisms of Li loss by PVD and demonstrate that unlike the electrochemical delithiation of LiCoO2, the crystallization of LiCoO2 admits only a small amount of Li vacancies, so that in a Li-deficient regime, segregated phases of fully stoichiometric LiCoO2 and Li-free Co oxides are formed. From the laterally- and depth-resolved concentrations of the coexisting phases, we can conclude that PVD-grown LiCoO2 is partially stabilized into morphological features with reduced specific surface areas (i.e., large isotropic faceted grains and thick films), resulting in an improvement of its specific electrochemical properties and performanceThis work has been supported by the Spanish Ministry of Science, Innovation and Universities & the State Research Agency MICIU/AEI within the framework of the EU M-ERA.NET Programme (SOLIMEC project/Spanish subprojects PCI2022-132955 and PCI2022-132998), the “Proyectos de Generación de Conocimiento” (NanoCatCom, PID2021–124667OB) and the “María de Maeztu” Programme for Units of Excellence in R&D (CEX2023-001316-M). A.G. acknowledges funding from the Comunidad de Madrid under contract I3-2022-5824 (Programa INVESTIGO 2022). We acknowledge the service from the MiNa Laboratory at IMN, and funding from CM (project S2018/NMT-4291 TEC2SPACE), MINECO (project CSIC13-4E-1794) and EU (FEDER, FSE)

Formation of hollow silver nanoparticles under irradiation with ultrashort laser pulses

9 pags., 5 figs.We have studied the formation of cavities in spherical silver nanoparticles embedded in silica, irradiated with fs laser pulses that produce an intense electronic excitation. Experimentally determined aspect ratio, i.e. the ratio between the cavity and nanoparticle size, for hollow structures formed under different irradiation conditions shows a very good agreement with values obtained by means of atomistic simulations. According to the predictions of the atomistic model, one can produce at will hollow silver nanoparticles with cavities of tailored dimensions, having an accurate control. Hence, laser irradiation can be used to control and design the optical response by tuning the localized surface plasmon resonances of the hollow nanoparticles.This work was partially funded by the regional government of Madrid through the TechnoFusion (III)-CM (S2018/EMT-4437) program, co-financed with Structural Funds (ERDF and ESF) and by the Projects PID2019-105325RB-C32 (Radiafus-5), PID2019-105156GB-I00, PID2021- 123228NB-I00 and PDC2022-133788-I00, funded by the Ministerio de Ciencia e Innovación of Spain. This work has also been partially funded by the Eurofusion consortium (EH150531176). JK was supported by the Beatriz Galindo Program (BEAGAL18/00130) from the Ministerio de Educación y Formación Profesional of Spain. This work was partially funded by Comunidad de Madrid through the Convenio Plurianual with Universidad Politécnica de Madrid in its line of action Apoyo a la realización de proyectos de I + D para investigadores Beatriz Galindo, within the framework of V PRICIT (V Plan Regional de Investigación Científica e Innovación Tecnológica). AP and FJV were supported by FONDECYT grant 3190123. MLC was supported by the research project “Captación de Talento UAM” Ref: #541D300 supervised by the Vice-Chancellor of Research of Universidad Autónoma de Madrid (UAM). The research leading to this result has been supported by the RADIATE project under the Grant Agreement 824096 from the EU Research and Innovation programme HORIZON 2020

Biología floral de 4 clones de granado cultivados en condiciones homogeneas: viabilidad, germinación y conservación del polen

Con el estudio realizado se pretende determinar las causas de la baja fecundación en algunos clones de granado. Los clones estudiados han sido el MA1, MA2, ME18 y MES cultivados en condiciones homogéneas en la colección existente en la Escuela Politécnica Superior de Orihuela (Alicante). El estudio se realizó durante los años 1996 y 1997, Se ha estudiado la viabilidad del polen mediante la técnica de tinción con carmín acético y se ha observado su evolución semanal a lo largo de la floración. Asimismo se ha estudiado este mismo parámetro para el polen conservado a las temperaturas de 5 y 28%C. También se realizó el estudio del potencial germinativo del polen procedente de flores “masculinas” y hermafroditas, en un medio de cultivo a las temperaturas de 15 y 28%C, realizando observaciones a las 48 horas desde la siembra