CAPS-1 and CAPS-2 are essential synaptic vesicle priming proteins

SummaryBefore transmitter-filled synaptic vesicles can fuse with the plasma membrane upon stimulation they have to be primed to fusion competence. The regulation of this priming process controls the strength and plasticity of synaptic transmission between neurons, which in turn determines many complex brain functions. We show that CAPS-1 and CAPS-2 are essential components of the synaptic vesicle priming machinery. CAPS-deficient neurons contain no or very few fusion competent synaptic vesicles, which causes a selective impairment of fast phasic transmitter release. Increases in the intracellular Ca2+ levels can transiently revert this defect. Our findings demonstrate that CAPS proteins generate and maintain a highly fusion competent synaptic vesicle pool that supports phasic Ca2+ triggered release of transmitters

Stress corrosion cracking in Al-Zn-Mg-Cu aluminum alloys in saline environments

Copyright 2013 ASM International. This paper was published in Metallurgical and Materials Transactions A, 44A(3), 1230 - 1253, and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.Stress corrosion cracking of Al-Zn-Mg-Cu (AA7xxx) aluminum alloys exposed to saline environments at temperatures ranging from 293 K to 353 K (20 °C to 80 °C) has been reviewed with particular attention to the influences of alloy composition and temper, and bulk and local environmental conditions. Stress corrosion crack (SCC) growth rates at room temperature for peak- and over-aged tempers in saline environments are minimized for Al-Zn-Mg-Cu alloys containing less than ~8 wt pct Zn when Zn/Mg ratios are ranging from 2 to 3, excess magnesium levels are less than 1 wt pct, and copper content is either less than ~0.2 wt pct or ranging from 1.3 to 2 wt pct. A minimum chloride ion concentration of ~0.01 M is required for crack growth rates to exceed those in distilled water, which insures that the local solution pH in crack-tip regions can be maintained at less than 4. Crack growth rates in saline solution without other additions gradually increase with bulk chloride ion concentrations up to around 0.6 M NaCl, whereas in solutions with sufficiently low dichromate (or chromate), inhibitor additions are insensitive to the bulk chloride concentration and are typically at least double those observed without the additions. DCB specimens, fatigue pre-cracked in air before immersion in a saline environment, show an initial period with no detectible crack growth, followed by crack growth at the distilled water rate, and then transition to a higher crack growth rate typical of region 2 crack growth in the saline environment. Time spent in each stage depends on the type of pre-crack (“pop-in” vs fatigue), applied stress intensity factor, alloy chemistry, bulk environment, and, if applied, the external polarization. Apparent activation energies (E a) for SCC growth in Al-Zn-Mg-Cu alloys exposed to 0.6 M NaCl over the temperatures ranging from 293 K to 353 K (20 °C to 80 °C) for under-, peak-, and over-aged low-copper-containing alloys (~0.8 wt pct), they are typically ranging from 20 to 40 kJ/mol for under- and peak-aged alloys, and based on limited data, around 85 kJ/mol for over-aged tempers. This means that crack propagation in saline environments is most likely to occur by a hydrogen-related process for low-copper-containing Al-Zn-Mg-Cu alloys in under-, peak- and over-aged tempers, and for high-copper alloys in under- and peak-aged tempers. For over-aged high-copper-containing alloys, cracking is most probably under anodic dissolution control. Future stress corrosion studies should focus on understanding the factors that control crack initiation, and insuring that the next generation of higher performance Al-Zn-Mg-Cu alloys has similar longer crack initiation times and crack propagation rates to those of the incumbent alloys in an over-aged condition where crack rates are less than 1 mm/month at a high stress intensity factor

Evidence for reduced collectivity around the neutron mid-shell in the stable even-mass Sn isotopes from new lifetime measurements

Precise measurements of the lifetimes of the first excited 2+ states in the stable even-A Sn isotopes 112-124Sn have been performed using the Doppler shift attenuation technique. For the isotopes 112Sn, 114Sn and 116Sn the E2 transition strengths deduced from the measured lifetimes are in disagreement with the previously reported values and indicate a shallow minimum at N=66. The observed deviation from a maximum at mid-shell is attributed to the obstructive effect of the s1/2 neutron orbital in generating collectivity when near the Fermi level. © 2010 Elsevier B.V.Financial support from the Spanish Ministerio de Ciencia e Innovaci on under contracts FPA2007-66069, FPA2009-13377-C02-01 and FPA2009-13377-C02-02, the Spanish Consolider-Ingenio 2010 Programme CPAN (CSD2007-00042) and the Australian Re- search Council Discovery Scheme, grant no. DP0773273Peer Reviewe

From scrap metal to highly efficient electrodes: harnessing the nanotextured surface of swarf for effective utilisation of Pt and Co for hydrogen production

Hydrogen is considered to be the key element to achieving climate neutrality, leading to a massive demand for electrocatalysts. This work explores the transformation of metal waste into active and stable electrode materials for water splitting by modifying the surface through atomic deposition of platinum (Pt) and cobalt (Co). Our study finds that with the addition of only 28 μg cm−2 of Pt and 30 μg cm−2 of Co to metal waste, high-performance electrolysis can be achieved. We investigated discarded stainless-steel (SST), titanium (Ti), and nickel (Ni) alloys and found that they had nanotextured surfaces, consisting of 10–50 nm wide grooves, which offered an excellent platform for effective bonding of Pt or Co atoms. We demonstrate a strong synergistic relationship between the metal of the swarf surface and the metal of catalytically active centers, such that only some combinations lead to effective electrocatalysts. Furthermore, we discovered that the surface density of atomically deposited Pt or Co has a profound impact on the nanoscale morphology of the active centers, providing a mechanism for the optimization of electrocatalytic characteristics. For instance, the optimal Pt loading (28 μg cm−2) on Ti swarf yields 5–20 nm Pt nanoparticles within the grooves with exceptional hydrogen evolution reaction (HER) activity. Similarly, the optimal surface density of Co (30 μg cm−2) on Ni swarf generates ∼100 nm interlinked flakes of Co(OH)2 with outstanding oxygen evolution reaction (OER) performance. Combining these best electrodes in a full-cell electrolyser resulted in a current density of 40 mA cm−2 at 1.6 V vs. RHE and the rates of H2 and O2 production of 22.09 and 10.75 mmol min−1, respectively, with 100% faradaic efficiency with no decrease in activity in 24 hours. This study opens the door to more sustainable electrode fabrication and effective hydrogen production in alkaline water electrolysis

Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells

Glioblastoma is the most common malignant brain tumor in adults. The currently available treatments offer only a palliative survival advantage and the need for effective treatments remains an urgent priority. Activation of the p53 growth suppression/apoptotic pathway is one of the promising strategies in targeting glioma cells. We show that the quinoline derivative chloroquine activates the p53 pathway and suppresses growth of glioma cells in vitro and in vivo in an orthotopic (U87MG) human glioblastoma mouse model. Induction of apoptosis is one of the mechanisms underlying the effects of chloroquine on suppressing glioma cell growth and viability. siRNA-mediated downregulation of p53 in wild-type but not mutant p53 glioblastoma cells substantially impaired chloroquine-induced apoptosis. In addition to its p53-activating effects, chloroquine may also inhibit glioma cell growth via p53-independent mechanisms. Our results clarify the mechanistic basis underlying the antineoplastic effect of chloroquine and reveal its therapeutic potential as an adjunct to glioma chemotherapy

Diffusion on networked systems is a question of time or structure

Network science investigates the architecture of complex systems to understand their functional and dynamical properties. Structural patterns such as communities shape diffusive processes on networks. However, these results hold under the strong assumption that networks are static entities where temporal aspects can be neglected. Here we propose a generalized formalism for linear dynamics on complex networks, able to incorporate statistical properties of the timings at which events occur. We show that the diffusion dynamics is affected by the network community structure and by the temporal properties of waiting times between events. We identify the main mechanism—network structure, burstiness or fat tails of waiting times—determining the relaxation times of stochastic processes on temporal networks, in the absence of temporal–structure correlations. We identify situations when fine-scale structure can be discarded from the description of the dynamics or, conversely, when a fully detailed model is required due to temporal heterogeneities

Abel Symposia

Discrete Morse theory has recently lead to new developments in the theory of random geometric complexes. This article surveys the methods and results obtained with this new approach, and discusses some of its shortcomings. It uses simulations to illustrate the results and to form conjectures, getting numerical estimates for combinatorial, topological, and geometric properties of weighted and unweighted Delaunay mosaics, their dual Voronoi tessellations, and the Alpha and Wrap complexes contained in the mosaics