In situ thermochemical sulfate reduction during ore formation at the Itxaspe Zn-(Pb) MVT occurrence (Basque-Cantabrian basin, Northern Spain)

International audienceOrganic matter is thought to play a role in the genesis of many Mississippi Valley-type (MVT) deposits, acting as a reducing agent during thermochemical sulfate reduction (TSR). Although TSR is an extremely slow reaction at low temperatures (<100ºC), under favorable conditions it may supply the necessary reduced sulfur during ore formation. To test this hypothesis, the Itxaspe Zn-(Pb) MVT occurrence in the Basque-Cantabrian basin (Northern Spain) was studied. Sphalerite, the main ore phase, is generally found disseminated in Urgonian (Lower Cretaceous) carbonates, and in close relationship with solid bitumen. The bitumen source rock was very likely deposited in a marine marginal setting. Differences in composition of the bitumen samples are attributed to a fractionation during hydrocarbon expulsion and/or migration. The fluids involved in ore deposition were low temperature (Th ~130ºC), Na-Ca-Cl-(K-Mg)-type brines (salinities ~12.5 equiv. mass % NaCl). The origin of brine solutes (including sulfate) is related to the dissolution of Mesozoic evaporite units, although the contribution of evaporated seawater brines cannot be ruled out. The temperatures of ore deposition, the close relationship between the bitumen and ore phases, the presence of aromatic sulfur-bearing compounds and the 34S of sulfides and sulfates are consistent with an in situ TSR during ore formation in the Itxaspe Zn-(Pb) occurrence. Therefore, at least for small mineralizations like Itxaspe, our conclusion is that the necessary reduced sulfur can be supplied by TSR during ore genesis at the site of metal deposition

Applications of Solid Freeform Fabrication at the Naval Research Laboratory

Solid Freeform Fabrication (SFF) and related techniques are used at the Naval Research Laboratory (NRL) for a variety of materials related investigations. Research and applications conducted over the past few years are described including: Helisys Laminated Object Manufacturing System (LOMS) fabrication of: ceramic piezoelectric actuators, tooling for multifunctional materials, and anatomical prototypes for surgical visualization; fabrication of mesoscale electronic and sensor components using a laser forward transfer direct write technique; and visualization of complex, 3-D microstructures using a Stratasys Fused-Deposition Modeler. The paper closes with a brief overview of future SFF related work at the NRL.Support for this work from DARPA, Office of Naval Research, and the Naval Research Laboratory Core Research Program is gratefully acknowledged.Mechanical Engineerin

R-Gada: a fast and flexible pipeline for copy number analysis in association studies

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies (GWAS) using Copy Number Variation (CNV) are becoming a central focus of genetic research. CNVs have successfully provided target genome regions for some disease conditions where simple genetic variation (i.e., SNPs) has previously failed to provide a clear association.</p> <p>Results</p> <p>Here we present a new R package, that integrates: (i) data import from most common formats of Affymetrix, Illumina and aCGH arrays; (ii) a fast and accurate segmentation algorithm to call CNVs based on Genome Alteration Detection Analysis (GADA); and (iii) functions for displaying and exporting the Copy Number calls, identification of recurrent CNVs, multivariate analysis of population structure, and tools for performing association studies. Using a large dataset containing 270 HapMap individuals (Affymetrix Human SNP Array 6.0 Sample Dataset) we demonstrate a flexible pipeline implemented with the package. It requires less than one minute per sample (3 million probe arrays) on a single core computer, and provides a flexible parallelization for very large datasets. Case-control data were generated from the HapMap dataset to demonstrate a GWAS analysis.</p> <p>Conclusions</p> <p>The package provides the tools for creating a complete integrated pipeline from data normalization to statistical association. It can effciently handle a massive volume of data consisting of millions of genetic markers and hundreds or thousands of samples with very accurate results.</p

On the relationship between subjective and objective measures of virtual reality experiences : a case study of a serious game

In this paper we present a Virtual Reality game related to Cultural Heritage. We contribute with an analysis of subjective measures taken from questionnaires filled by users after the VR experience, and objective measures taken from logs during the VR game. Specifically, we were interested on study data globally and in groups of user behaviour. Analysing data globally we see a high value of users’ subjective perceptions. Nevertheless, we found differences of subjective measures when splitting the Novice group. Specifically, the subjective perception of Strugglers is considerably lower than the rest of groups, and this difference is significant. Then, we propose strategies to provide a better experience to Strugglers. We also found correlations between objective and subjective data when they were analysed globally (i.e. without using groups), but these measures did not correlate when they were analysed using behaviour groups

Genetic and Transcriptional Analysis of Human Host Response to Healthy Gut Microbiota

Many studies have demonstrated the importance of the gut microbiota in healthy and disease states. However, establishing the causality of host-microbiota interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiota for human cells and to shed light on the molecular mechanisms underlying host-gut microbiota interactions. In primary human colonic epithelial cells, we identified over 6,000 genes whose expression changed at various time points following coculturing with the gut microbiota of a healthy individual. Among the differentially expressed genes we found a 1.8-fold enrichment of genes associated with diseases that have been previously linked to the microbiome, such as obesity and colorectal cancer. In addition, our experimental system allowed us to identify 87 host single nucleotide polymorphisms (SNPs) that show allele-specific expression in 69 genes. Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is conditional on the exposure to the microbiota. Of these 12 genes, 8 have been associated with diseases linked to the gut microbiota, specifically colorectal cancer, obesity, and type 2 diabetes. Our study demonstrates a scalable approach to study host-gut microbiota interactions and can be used to identify putative mechanisms for the interplay between host genetics and the microbiota in health and disease

Cellular Prion Protein Mediates alpha-Synuclein Uptake, Localization, and Toxicity In Vitro and In Vivo

Background The cellular prion protein (PrPC) is a membrane-bound, multifunctional protein mainly expressed in neuronal tissues. Recent studies indicate that the native trafficking of PrPC can be misused to internalize misfolded amyloid beta and α-synuclein (aSyn) oligomers. Objectives We define PrPC's role in internalizing misfolded aSyn in α-synucleinopathies and identify further involved proteins. Methods We performed comprehensive behavioral studies on four transgenic mouse models (ThySyn and ThySynPrP00, TgM83 and TgMPrP00) at different ages. We developed PrPC-(over)-expressing cell models (cell line and primary cortical neurons), used confocal laser microscopy to perform colocalization studies, applied mass spectrometry to identify interactomes, and determined disassociation constants using surface plasmon resonance (SPR) spectroscopy. Results Behavioral deficits (memory, anxiety, locomotion, etc.), reduced lifespans, and higher oligomeric aSyn levels were observed in PrPC-expressing mice (ThySyn and TgM83), but not in homologous Prnp ablated mice (ThySynPrP00 and TgMPrP00). PrPC colocalized with and facilitated aSyn (oligomeric and monomeric) internalization in our cell-based models. Glimepiride treatment of PrPC-overexpressing cells reduced aSyn internalization in a dose-dependent manner. SPR analysis showed that the binding affinity of PrPC to monomeric aSyn was lower than to oligomeric aSyn. Mass spectrometry-based proteomic studies identified clathrin in the immunoprecipitates of PrPC and aSyn. SPR was used to show that clathrin binds to recombinant PrP, but not aSyn. Experimental disruption of clathrin-coated vesicles significantly decreased aSyn internalization. Conclusion PrPC's native trafficking can be misused to internalize misfolded aSyn through a clathrin-based mechanism, which may facilitate the spreading of pathological aSyn. Disruption of aSyn-PrPC binding is, therefore, an appealing therapeutic target in α-synucleinopathies. <br

VASAO: visible all sky adaptive optics: a new adaptive optics concept for CFHT

International audienceVASAO is an ambitious project that explores new conceptual direction in the field of astronomical adaptive optics. In the era of 8 meter and larger telescopes, and their instrument costs and telescope time pressure, there is a natural niche for such ground-breaking conceptual development in the 4 meter class telescope. The aim of VASAO is to provide diffraction limited imaging in the visible with 100% sky coverage; the challenge (but potential rewards) arises from the simultaneity of these requirements. To this end, CFHT is conducting a feasibility study based on the polychromatic guide star concept (Foy et al., 1995 [4]) coupled with a high order curvature AO system, presented in this paper. A number of experiments have been started (or carried out) to study the challenges and limits of the techniques involved in an operational setting; these include the FlyEyes detector, and a polychromatic tip-tilt test on natural stars. Because such a project straddles such a fine line between facility instrument and experimental facility, careful thought has to be given to the balance between modes of operations and potential astrophysical targets

A fast and accurate method to detect allelic genomic imbalances underlying mosaic rearrangements using SNP array data

<p>Abstract</p> <p>Background</p> <p>Mosaicism for copy number and copy neutral chromosomal rearrangements has been recently identified as a relatively common source of genetic variation in the normal population. However its prevalence is poorly defined since it has been only studied systematically in one large-scale study and by using non optimal <it>ad-hoc </it>SNP array data analysis tools, uncovering rather large alterations (> 1 Mb) and affecting a high proportion of cells. Here we propose a novel methodology, Mosaic Alteration Detection-MAD, by providing a software tool that is effective for capturing previously described alterations as wells as new variants that are smaller in size and/or affecting a low percentage of cells.</p> <p>Results</p> <p>The developed method identified all previously known mosaic abnormalities reported in SNP array data obtained from controls, bladder cancer and HapMap individuals. In addition MAD tool was able to detect new mosaic variants not reported before that were smaller in size and with lower percentage of cells affected. The performance of the tool was analysed by studying simulated data for different scenarios. Our method showed high sensitivity and specificity for all assessed scenarios.</p> <p>Conclusions</p> <p>The tool presented here has the ability to identify mosaic abnormalities with high sensitivity and specificity. Our results confirm the lack of sensitivity of former methods by identifying new mosaic variants not reported in previously utilised datasets. Our work suggests that the prevalence of mosaic alterations could be higher than initially thought. The use of appropriate SNP array data analysis methods would help in defining the human genome mosaic map.</p

Computational Reconstruction of Multidomain Proteins Using Atomic Force Microscopy Data

SummaryClassical structural biology techniques face a great challenge to determine the structure at the atomic level of large and flexible macromolecules. We present a novel methodology that combines high-resolution AFM topographic images with atomic coordinates of proteins to assemble very large macromolecules or particles. Our method uses a two-step protocol: atomic coordinates of individual domains are docked beneath the molecular surface of the large macromolecule, and then each domain is assembled using a combinatorial search. The protocol was validated on three test cases: a simulated system of antibody structures; and two experimentally based test cases: Tobacco mosaic virus, a rod-shaped virus; and Aquaporin Z, a bacterial membrane protein. We have shown that AFM-intermediate resolution topography and partial surface data are useful constraints for building macromolecular assemblies. The protocol is applicable to multicomponent structures connected in the polypeptide chain or as disjoint molecules. The approach effectively increases the resolution of AFM beyond topographical information down to atomic-detail structures