The alpine Swiss-French airborne gravity survey

In February 1998, a regional-scale, airborne gravity survey was carried out over the French Occidental Alps within the framework of the GéoFrance 3-D research program.The survey consisted of 18 NS and 16 EW oriented lines with a spacing of 10 and 20 km respectively, covering the whole of the Western French Alps (total area: 50 000 km2; total distance of lines flown: 10 000 km). The equipment was mounted in a medium-size aircraft (DeHavilland Twin Otter) flowing at a constant altitude of 5100 m a.s.l, and at a mean ground speed of about 280 km h−1. Gravity was measured using a LaCoste & Romberg relative, air/sea gravimeter (type SA) mounted on a laser gyro stabilized platform. Data from 5 GPS antennae located on fuselage and wings and 7 ground-based GPS reference stations were used to determine position and aircraft induced accelerations.The gravimeter passband was derived by comparing the vertical accelerations provided by the gravimeter with those estimated from the GPS positions. This comparison showed that the gravimeter is not sensitive to very short wavelength aircraft accelerations, and therefore a simplified formulation for computing airborne gravity measurements was developed. The intermediate and short wavelength, non-gravitational accelerations were eliminated by means of digital, exponential low-pass filters (cut-off wavelength: 16 km). An important issue in airborne gravimetry is the reliability of the airborne gravity surveys when compared to ground surveys. In our studied area, the differences between the airborne-acquired Bouguer anomaly and the ground upward-continued Bouguer anomaly of the Alps shows a good agreement: the rms of these differences is equal to 7.68 mGal for a spatial resolution of 8 km. However, in some areas with rugged topography, the amplitudes of those differences have a striking correlation with the topography. We then argue that the choice of an appropriate density (reduction by a factor of 10 per cent) for computing the ground topographic corrections over the highest mountains, results in significantly reducing the differences between airborne and ground upward-continued Bouguer anomalies, which shows that some of the misfit stems from errors in the ground dat

CNApp, a tool for the quantification of copy number alterations and integrative analysis revealing clinical implications.

Somatic copy number alterations (CNAs) are a hallmark of cancer, but their role in tumorigenesis and clinical relevance remain largely unclear. Here, we developed CNApp, a web-based tool that allows a comprehensive exploration of CNAs by using purity-corrected segmented data from multiple genomic platforms. CNApp generates genome-wide profiles, computes CNA scores for broad, focal and global CNA burdens, and uses machine learning-based predictions to classify samples. We applied CNApp to the TCGA pan-cancer dataset of 10,635 genomes showing that CNAs classify cancer types according to their tissue-of-origin, and that each cancer type shows specific ranges of broad and focal CNA scores. Moreover, CNApp reproduces recurrent CNAs in hepatocellular carcinoma and predicts colon cancer molecular subtypes and microsatellite instability based on broad CNA scores and discrete genomic imbalances. In summary, CNApp facilitates CNA-driven research by providing a unique framework to identify relevant clinical implications. CNApp is hosted at https://tools.idibaps.org/CNApp/

Hermeneutics and Nature

This paper contributes to the on-going research into the ways in which the humanities transformed the natural sciences in the late Eighteenth and early Nineteenth Centuries. By investigating the relationship between hermeneutics -- as developed by Herder -- and natural history, it shows how the methods used for the study of literary and artistic works played a crucial role in the emergence of key natural-scientific fields, including geography and ecology

Tetanus toxin Hc fragment induces the formation of ceramide platforms and protects neuronal cells against oxidative stress

Tetanus toxin (TeTx) is the protein, synthesized by the anaerobic bacteria Clostridium tetani, which causes tetanus disease. TeTx gains entry into target cells by means of its interaction with lipid rafts, which are membrane domains enriched in sphingomyelin and cholesterol. However, the exact mechanism of host membrane binding remains to be fully established. In the present study we used the recombinant carboxyl terminal fragment from TeTx (Hc-TeTx), the domain responsible for target neuron binding, showing that Hc-TeTx induces a moderate but rapid and sustained increase in the ceramide/sphingomyelin ratio in primary cultures of cerebellar granule neurons and in NGF-differentiated PC12 cells, as well as induces the formation of ceramide platforms in the plasma membrane. The mentioned increase is due to the promotion of neutral sphingomyelinase activity and not to the de novo synthesis, since GW4869, a specific neutral sphingomyelinase inhibitor, prevents neutral sphingomyelinase activity increase and formation of ceramide platforms. Moreover, neutral sphingomyelinase inhibition with GW4869 prevents Hc-TeTx-triggered signaling (Akt phosphorylation), as well as the protective effect of Hc-TeTx on PC12 cells subjected to oxidative stress, while siRNA directed against nSM2 prevents protection by Hc-TeTx of NSC-34 cells against oxidative insult. Finally, neutral sphingomyelinase activity seems not to be related with the internalization of Hc-TeTx into PC12 cells. Thus, the presented data shed light on the mechanisms triggered by TeTx after membrane binding, which could be related with the events leading to the neuroprotective action exerted by the Hc-TeTx fragment

Identification of Rhoptry Trafficking Determinants and Evidence for a Novel Sorting Mechanism in the Malaria Parasite Plasmodium falciparum

The rhoptry of the malaria parasite Plasmodium falciparum is an unusual secretory organelle that is thought to be related to secretory lysosomes in higher eukaryotes. Rhoptries contain an extensive collection of proteins that participate in host cell invasion and in the formation of the parasitophorous vacuole, but little is known about sorting signals required for rhoptry protein targeting. Using green fluorescent protein chimeras and in vitro pull-down assays, we performed an analysis of the signals required for trafficking of the rhoptry protein RAP1. We provide evidence that RAP1 is escorted to the rhoptry via an interaction with the glycosylphosphatidyl inositol-anchored rhoptry protein RAMA. Once within the rhoptry, RAP1 contains distinct signals for localisation within a sub-compartment of the organelle and subsequent transfer to the parasitophorous vacuole after invasion. This is the first detailed description of rhoptry trafficking signals in Plasmodium

Chronic Intranasal Treatment with an Anti-Aβ30-42 scFv Antibody Ameliorates Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease

Amyloid-beta peptide (Aβ)-directed active and passive immunization therapeutic strategies reduce brain levels of Aβ, decrease the severity of beta-amyloid plaque pathology and reverse cognitive deficits in mouse models of Alzheimer's disease (AD). As an alternative approach to passive immunization with full IgG molecules, single-chain variable fragment (scFv) antibodies can modulate or neutralize Aβ-related neurotoxicity and inhibit its aggregation in vitro. In this study, we characterized a scFv derived from a full IgG antibody raised against the C-terminus of Aβ, and studied its passage into the brains of APP transgenic mice, as well as its potential to reduce Aβ-related pathology. We found that the scFv entered the brain after intranasal application, and that it bound to beta-amyloid plaques in the cortex and hippocampus of APP transgenic mice. Moreover, the scFv inhibited Aβ fibril formation and Aβ-mediated neurotoxicity in vitro. In a preventative therapeutic approach chronic intranasal treatment with scFv reduced congophilic amyloid angiopathy (CAA) and beta-amyloid plaque numbers in the cortex of APPswe/PS1dE9 mice. This reduction of CAA and plaque pathology was associated with a redistribution of brain Aβ from the insoluble fraction to the soluble peptide pool. Due to their lack of the effector domain of full IgG, scFv may represent an alternative tool for the treatment of Aβ-related pathology without triggering Fc-mediated effector functions. Additionally, our observations support the possibility that Aβ-directed immunotherapy can reduce Aβ deposition in brain vessels in transgenic mice

Synthesis and characterisation of the vibrational and electrical properties of antiferromagnetic 6L-Ba2CoTeO6 ceramics

Optimal processing conditions for fabrication of dense single-phase 6L-Ba2CoTeO6 ceramics via the solid-state reaction method were determined. These ceramics possess a room-temperature crystal structure described by the centrosymmetric P[3 with combining macron]m1 space group. Polarized Raman spectroscopy enabled the observation of all the 25 predicted Raman modes and assignment of their symmetries. On cooling, BCTO ceramics exhibit two antiferromagnetic transitions at 3 K and 12.5 K, in broad agreement with a recent single-crystal study [P. Chanlert, N. Kurita, H. Tanaka, D. Goto, A. Matsuo and K. Kindo, Phys. Rev. B: Condens. Matter Mater. Phys., 2016, 93, 094420]. Low temperature Fourier-transform infrared reflectivity analyses suggest the antiferromagnetic phase transitions to be driven by small distortions of the CoO6 octahedra, lowering locally their C3v symmetry. This causes splitting of the associated vibrational modes, but without a long-range structural change. AC impedance spectroscopy revealed BCTO ceramics to be leaky insulators with an activation energy for conduction of ∼0.15−0.25 eV, which suggests electron hopping between mixed oxidation states of Co

Response to metal stress of Nicotiana langsdorffii plants wild-type and transgenic for the rat glucocorticoid receptor gene

Recently our findings have shown that the integration of the gene coding for the rat gluco-corticoid receptor (GR receptor) in Nicotiana langsdorffii plants induced morphophysiological effects in transgenic plants through the modification of their hormonal pattern. Phytohormones play a key role in plant responses to many different biotic and abiotic stresses since a modified hormonal profile up-regulates the activation of secondary metabolites involved in the response to stress. In this work transgenic GR plants and isogenic wild type genotypes were exposed to metal stress by treating them with 30 ppm cadmium(II) or 50 ppm chromium(VI). Hormonal patterns along with changes in key response related metabolites were then monitored and compared. Heavy metal up-take was found to be lower in the GR plants. The transgenic plants exhibited higher values of S-abscisic acid (S-ABA) and 3-indole acetic acid (IAA), salicylic acid and total polyphenols, chlorogenic acid and antiradical activity, compared to the untransformed wild type plants. Both Cd and Cr treatments led to an increase in hormone concentrations and secondary metabolites only in wild type plants. Analysis of the results suggests that the stress responses due to changes in the plant's hormonal system may derive from the interaction between the GR receptor and phytosteroids, which are known to play a key role in plant physiology and development. (C) 2013 Elsevier GmbH. All rights reserved