THE FATE OF SMECTITE IN KOH SOLUTIONS

International audienceThe aim of the present study was to investigate the detailed evolution of the SAz-1 smectite in 1 M KOH at 80°C at a solid/liquid ratio of 1/80. AFM observations indicated no change in crystal size or shape. XRD measurements at 40% relative humidity revealed changes in expandability of the smectite. The 001 reflection profile of smectite was modelled using the trial-and-error approach of Sakharov et al., 1999b. The results indicate that with increasing run time the number of non expandable layers with zero or one water layer increases and that the coherent scattering domain size of the smectite decreases. Infrared spectroscopy of the reacted smectite suggests that there is no change from the initial clay products. The dehydroxylation temperature showed a slight decrease from 619° to 605°C. STA measurements demonstrated that the cis-vacant character of the octahedral sheet remained nearly unchanged throughout the experiment. Determination of the average layer charge showed a continuous increase from 0.32 to 0.42 eq/Si (Si/Al)4O10 whereas the layer charge distribution indicated the appearance of high charged smectite layers with a charge of ~ 0.6 eq/Si (Si/Al)4O10 and the disappearance of the low charged layers. XPS and SEM measurements indicate an increase of the aluminium in the smectite samples. Isotope data support the theory of a internal diffusion mechanism by gradual changes in δ 18O values. From these data it appears that KOH solutions provoke a mineralogical change in the 2:1 layer of the smectite minerals which increases the layer charge by increasing the Al content. This mineralogical change does not involve dissolution/crystallization processes and then must show solid state transformation of the clays at 80°C

The discovery of ash dieback in the UK: the making of a focusing event

Why did the identification of ‘Ash Dieback’ (Chalara Fraxinea) in 2012 in the UK catch the national media, public and political zeitgeist, and lead to policy changes, in a way that no other contemporary tree pest or pathogen outbreak has?The identification of Ash Dieback in the UK is conceptualised as a successful ‘focusing event’ and the ways in which it was socially constructed by the media, stakeholders and the government are analysed. National newspaper coverage contributed to the way that the disease was understood and was significant in driving the political response. Ash Dieback’s focal power derived from the perceived scale and nature of its impact; the initial attribution of blame on government; the ‘war-like’ response from the government; and Ash’s status as a threatened ‘native’ tree. The Ash Dieback focusing event has increased the salience of plant health issues amongst policymakers, the public and conservation organisations in the UK

CHD7 Mutational Analysis and Clinical Considerations for Auditory Rehabilitation in Deaf Patients with CHARGE Syndrome

BACKGROUND: Otologic manifestations are one of the most consistent findings of CHARGE syndrome found in more than 90%. Since genetic analysis of the CHD7 gene has rarely been performed in previous reports dealing with ear abnormalities, the genotypic spectrum of CHD7 mutations was analyzed in deaf patients with CHARGE syndrome, and the clinical considerations concerning auditory rehabilitation were investigated. METHODS: Nine Korean patients with CHARGE syndrome showing profound hearing loss and semicircular canal aplasia were included. All 38 exons of CHD7 were analyzed by direct sequencing. For splice site variations, in silico and exon-trapping analyses were performed to verify the pathogenicity of nucleotide variations. Clinical features and the outcome of auditory rehabilitation were also analyzed. RESULTS: Eight of 9 patients revealed alterations of the CHD7 gene including 3 frameshift, 2 nonsense, 2 splice site, and 1 missense mutations. Five of 9 patients were clinically diagnosed as atypical CHARGE syndrome but demonstrated various mutations of the CHD7 gene. One familial case showed intra-familial variability. Radiologic findings suggesting cochleovestibular nerve deficiency were identified in most of the patients. Of the 8 patients who underwent cochlear implantation, 5 patients demonstrated favorable outcome. Larger diameter of the cochleovestibular nerve on imaging and absence of severe mental retardation were factors related to better outcome after cochlear implantation rather than the type of CHD7 mutations. Auditory brainstem implantation was performed in two patients who did not benefit from cochlear implantation. CONCLUSIONS: Genetic analysis of the CHD7 gene should be performed in cases with semicircular canal aplasia even when other typical features of CHARGE syndrome are absent. For auditory rehabilitation in CHARGE syndrome, cochlear implantation should be strongly recommended in selected cases with favorable prognostic factors. Auditory brainstem implantation may be a viable option in patients with CHARGE syndrome who have failed to benefit from cochlear implantation

GANDALF - Graphical Astrophysics code for N-body Dynamics And Lagrangian Fluids

GANDALF is a new hydrodynamics and N-body dynamics code designed for investigating planet formation, star formation and star cluster problems. GANDALF is written in C++, parallelised with both OpenMP and MPI and contains a python library for analysis and visualisation. The code has been written with a fully object-oriented approach to easily allow user-defined implementations of physics modules or other algorithms. The code currently contains implementations of Smoothed Particle Hydrodynamics, Meshless Finite-Volume and collisional N-body schemes, but can easily be adapted to include additional particle schemes. We present in this paper the details of its implementation, results from the test suite, serial and parallel performance results and discuss the planned future development. The code is freely available as an open source project on the code-hosting website github at https://github.com/gandalfcode/gandalf and is available under the GPLv2 license.This research was supported by the DFG cluster of excellence "Origin and Structure of the Universe", DFG Projects 841797-4, 841798-2 (DAH, GPR), the DISCSIM project, grant agreement 341137 funded by the European Research Council under ERC-2013-ADG (GPR, RAB). Some development of the code and simulations have been carried out on the computing facilities of the Computational centre for Particle and Astrophysics (C2PAP) and on the DiRAC Data Analytic system at the University of Cambridge, operated by the University of Cambridge High Performance Computing Service on behalf of the STFC DiRAC HPC Facility (www.dirac.ac.uk); the equipment was funded by BIS National E-infrastructure capital grant (ST/K001590/1), STFC capital grants ST/H008861/1 and ST/H00887X/1, and STFC DiRAC Operations grant ST/K00333X/1

Characterization of FUS Mutations in Amyotrophic Lateral Sclerosis Using RNA-Seq

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in severe muscle weakness and eventual death by respiratory failure. Although little is known about its pathogenesis, mutations in fused in sarcoma/translated in liposarcoma (FUS) are causative for familial ALS. FUS is a multifunctional protein that is involved in many aspects of RNA processing. To elucidate the role of FUS in ALS, we overexpressed wild-type and two mutant forms of FUS in HEK-293T cells, as well as knocked-down FUS expression. This was followed by RNA-Seq to identify genes which displayed differential expression or altered splicing patterns. Pathway analysis revealed that overexpression of wild-type FUS regulates ribosomal genes, whereas knock-down of FUS additionally affects expression of spliceosome related genes. Furthermore, cells expressing mutant FUS displayed global transcription patterns more similar to cells overexpressing wild-type FUS than to the knock-down condition. This observation suggests that FUS mutants do not contribute to the pathogenesis of ALS through a loss-of-function. Finally, our results demonstrate that the R521G and R522G mutations display differences in their influence on transcription and splicing. Taken together, these results provide additional insights into the function of FUS and how mutations contribute to the development of ALS.ALS Foundation NetherlandsAdessium FoundationSeventh Framework Programme (European Commission) (grant number 259867)Thierry Latran FoundationNational Institutes of Health (U.S.) (NIH/NINDS grant R01NS073873)National Institute of Neurological Disorders and Stroke (U.S.) (NIH/NINDS grant numbers 1R01NS065847

Knockdown of the Drosophila Fused in Sarcoma (FUS) Homologue Causes Deficient Locomotive Behavior and Shortening of Motoneuron Terminal Branches

Mutations in the fused in sarcoma/translated in liposarcoma gene (FUS/TLS, FUS) have been identified in sporadic and familial forms of amyotrophic lateral sclerosis (ALS). FUS is an RNA-binding protein that is normally localized in the nucleus, but is mislocalized to the cytoplasm in ALS, and comprises cytoplasmic inclusions in ALS-affected areas. However, it is still unknown whether the neurodegeneration that occurs in ALS is caused by the loss of FUS nuclear function, or by the gain of toxic function due to cytoplasmic FUS aggregation. Cabeza (Caz) is a Drosophila orthologue of human FUS. Here, we generated Drosophila models with Caz knockdown, and investigated their phenotypes. In wild-type Drosophila, Caz was strongly expressed in the central nervous system of larvae and adults. Caz did not colocalize with a presynaptic marker, suggesting that Caz physiologically functions in neuronal cell bodies and/or their axons. Fly models with neuron-specific Caz knockdown exhibited reduced climbing ability in adulthood and anatomical defects in presynaptic terminals of motoneurons in third instar larvae. Our results demonstrated that decreased expression of Drosophila Caz is sufficient to cause degeneration of motoneurons and locomotive disability in the absence of abnormal cytoplasmic Caz aggregates, suggesting that the pathogenic mechanism underlying FUS-related ALS should be ascribed more to the loss of physiological FUS functions in the nucleus than to the toxicity of cytoplasmic FUS aggregates. Since the Caz-knockdown Drosophila model we presented recapitulates key features of human ALS, it would be a suitable animal model for the screening of genes and chemicals that might modify the pathogenic processes that lead to the degeneration of motoneurons in ALS

FUS and TARDBP but Not SOD1 Interact in Genetic Models of Amyotrophic Lateral Sclerosis

Mutations in the SOD1 and TARDBP genes have been commonly identified in Amyotrophic Lateral Sclerosis (ALS). Recently, mutations in the Fused in sarcoma gene (FUS) were identified in familial (FALS) ALS cases and sporadic (SALS) patients. Similarly to TDP-43 (coded by TARDBP gene), FUS is an RNA binding protein. Using the zebrafish (Danio rerio), we examined the consequences of expressing human wild-type (WT) FUS and three ALS–related mutations, as well as their interactions with TARDBP and SOD1. Knockdown of zebrafish Fus yielded a motor phenotype that could be rescued upon co-expression of wild-type human FUS. In contrast, the two most frequent ALS–related FUS mutations, R521H and R521C, unlike S57Δ, failed to rescue the knockdown phenotype, indicating loss of function. The R521H mutation caused a toxic gain of function when expressed alone, similar to the phenotype observed upon knockdown of zebrafish Fus. This phenotype was not aggravated by co-expression of both mutant human TARDBP (G348C) and FUS (R521H) or by knockdown of both zebrafish Tardbp and Fus, consistent with a common pathogenic mechanism. We also observed that WT FUS rescued the Tardbp knockdown phenotype, but not vice versa, suggesting that TARDBP acts upstream of FUS in this pathway. In addition we observed that WT SOD1 failed to rescue the phenotype observed upon overexpression of mutant TARDBP or FUS or upon knockdown of Tardbp or Fus; similarly, WT TARDBP or FUS also failed to rescue the phenotype induced by mutant SOD1 (G93A). Finally, overexpression of mutant SOD1 exacerbated the motor phenotype caused by overexpression of mutant FUS. Together our results indicate that TARDBP and FUS act in a pathogenic pathway that is independent of SOD1