Micro-crystalline inclusions analysis by PIXE and RBS

A characteristic feature of the nuclear microprobe using a 3 MeV proton beam is the long range of particles (around 70 \mu m in light matrices). The PIXE method, with EDS analysis and using the multilayer approach for treating the X-ray spectrum allows the chemistry of an intra-crystalline inclusion to be measured, provided the inclusion roof and thickness at the impact point of the beam (Z and e, respectively) are known (the depth of the inclusion floor is Z + e). The parameter Z of an inclusion in a mineral can be measured with a precision of around 1 \mu m using a motorized microscope. However, this value may significantly depart from Z if the analyzed inclusion has a complex shape. The parameter e can hardly be measured optically. By using combined RBS and PIXE measurements, it is possible to obtain the geometrical information needed for quantitative elemental analysis. This paper will present measurements on synthetic samples to investigate the advantages of the technique, and also on natural solid and fluid inclusions in quartz. The influence of the geometrical parameters will be discussed with regard to the concentration determination by PIXE. In particular, accuracy of monazite micro-inclusion dating by coupled PIXE-RBS will be presented

Pour en finir avec le Bronze final ? Les haches à douille de type armoricain en France

A discussion about socket armorican bronze axes datation. They are from Ha D period (VII th & VIt h century B.C.)Révision de la datation des haches à douille de type armoricain, au seul Hallstatt D (VIIe-VIe s; av. J.-C.

The abundances and distributions of molluscs in the southern Iberian Peninsula: A comparison of marine and terrestrial systems

Molluscs are the second most diverse of all animal phyla, and occur in many habitat types. They are, therefore, a particularly good phylum with which to compare and contrast differences between ecosystems. Mollusc data from a number of sites along the southern coast of the Iberian Peninsula are analysed to study patterns of diversity and distribution using a range of multivariate techniques. Within each site, data are presented from three locations -fully terrestrial, rocky intertidal and soft bottom benthic (10 m and 20 m depths)- all in close proximity. The species are then classified in relation to morphology and size, and analysed at supraspecific levels to elucidate underlying patterns. The observed patterns are briefly discussed, with particular reference to the differential scope and importance of controlling factors in each ecosystem, such as dispersal processes. The results from the systems are compared and discussed in the context of ecological and evolutionary constraints in Mollusca.Los moluscos constituyen el segundo filo animal más diverso y se encuentran en muchos tipos de hábitat, por lo que son idóneos para establecer comparaciones entre distintos ecosistemas. Se han analizado los datos de los moluscos obtenidos en una serie de emplazamientos que cubrían el sur de la península Ibérica para determinar, empleando distintas técnicas multivariantes, los patrones de diversidad y distribución de estos organismos. Los datos se tomaron de ejemplares capturados en lugares del medio terrestre próximos a la línea de costa, de la franja intermareal rocosa y de sedimentos de fondos marinos situados a 10 y 20 m de profundidad. Las especies fueron clasificadas atendiendo a la morfología y el tamaño, y se analizaron a nivel supraespecífico para elucidar los patrones generales, que se discuten aquí, brevemente, con especial énfasis en las diferencias según la importancia de los factores que controlan cada ecosistema, como, por ejemplo, los procesos de dispersión. Los resultados de los distintos sistemas se comparan y discuten en el contexto de las tendencias ecológicas y evolutivas de los moluscos.Instituto Español de Oceanografí

Scanning mutagenesis of omega-atracotoxin-Hv1a reveals a spatially restricted epitope that confers selective activity against insect calcium channels

We constructed a complete panel of alanine mutants of the insect-specific calcium channel blocker omega-atracotoxin-Hv1a. Lethality assays using these mutant toxins identified three spatially contiguous residues, Pro(10), Asn(27), and Arg(35), that are critical for insecticidal activity against flies (Musca domestica) and crickets (Acheta domestica). Competitive binding assays using radiolabeled omega-atracotoxin-Hv1a and neuronal membranes prepared from the heads of American cockroaches (Periplaneta americana) confirmed the importance of these three residues for binding of the toxin to target calcium channels presumably expressed in the insect membranes. At concentrations up to 10 muM, omega-atracotoxin-Hv1a had no effect on heterologously expressed rat Ca(v)2.1, Ca(v)2.2, and Ca(v)1.2 calcium channels, consistent with the previously reported insect selectivity of the toxin. 30 muM omega-atracotoxin-Hv1a inhibited rat Ca-v currents by 10-34%, depending on the channel subtype, and this low level of inhibition was essentially unchanged when Asn(27) and Arg(35), which appears to be critical for interaction of the toxin with insect Ca-v channels, were both mutated to alanine. We propose that the spatially contiguous epitope formed by Pro(10), Asn(27), and Arg(35) confers specific binding to insect Ca-v channels and is largely responsible for the remarkable phyletic selectivity of omega-atracotoxin-Hv1a. This epitope provides a structural template for rational design of chemical insecticides that selectively target insect Ca-v channels

Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions

Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS) provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance

ICAM-2 Expression Mediates a Membrane-Actin Link, Confers a Nonmetastatic Phenotype and Reflects Favorable Tumor Stage or Histology in Neuroblastoma

The actin cytoskeleton is a primary determinant of tumor cell motility and metastatic potential. Motility and metastasis are thought to be regulated, in large part, by the interaction of membrane proteins with cytoplasmic linker proteins and of these linker proteins, in turn, with actin. However, complete membrane-to-actin linkages have been difficult to identify. We used co-immunoprecipitation and competitive peptide assays to show that intercellular adhesion molecule-2 (ICAM-2)/α-actinin/actin may comprise such a linkage in neuroblastoma cells. ICAM-2 expression limited the motility of these cells and redistributed actin fibers in vitro, and suppressed development of disseminated tumors in an in vivo model of metastatic neuroblastoma. Consistent with these observations, immunohistochemical analysis demonstrated ICAM-2 expression in primary neuroblastoma tumors exhibiting features that are associated with limited metastatic disease and more favorable clinical outcome. In neuroblastoma cell lines, ICAM-2 expression did not affect AKT activation, tumorigenic potential or chemosensitivity, as has been reported for some types of transfected cells. The observed ICAM-2-mediated suppression of metastatic phenotype is a novel function for this protein, and the interaction of ICAM-2/α-actinin/actin represents the first complete membrane-linker protein-actin linkage to impact tumor cell motility in vitro and metastatic potential in an in vivo model. Current work focuses on identifying specific protein domains critical to the regulation of neuroblastoma cell motility and metastasis and on determining if these domains represent exploitable therapeutic targets

HAMLET Binding to α-Actinin Facilitates Tumor Cell Detachment

Cell adhesion is tightly regulated by specific molecular interactions and detachment from the extracellular matrix modifies proliferation and survival. HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a protein-lipid complex with tumoricidal activity that also triggers tumor cell detachment in vitro and in vivo, suggesting that molecular interactions defining detachment are perturbed in cancer cells. To identify such interactions, cell membrane extracts were used in Far-western blots and HAMLET was shown to bind α-actinins; major F-actin cross-linking proteins and focal adhesion constituents. Synthetic peptide mapping revealed that HAMLET binds to the N-terminal actin-binding domain as well as the integrin-binding domain of α-actinin-4. By co-immunoprecipitation of extracts from HAMLET-treated cancer cells, an interaction with α-actinin-1 and -4 was observed. Inhibition of α-actinin-1 and α-actinin-4 expression by siRNA transfection increased detachment, while α-actinin-4-GFP over-expression significantly delayed rounding up and detachment of tumor cells in response to HAMLET. In response to HAMLET, adherent tumor cells rounded up and detached, suggesting a loss of the actin cytoskeletal organization. These changes were accompanied by a reduction in β1 integrin staining and a decrease in FAK and ERK1/2 phosphorylation, consistent with a disruption of integrin-dependent cell adhesion signaling. Detachment per se did not increase cell death during the 22 hour experimental period, regardless of α-actinin-4 and α-actinin-1 expression levels but adherent cells with low α-actinin levels showed increased death in response to HAMLET. The results suggest that the interaction between HAMLET and α-actinins promotes tumor cell detachment. As α-actinins also associate with signaling molecules, cytoplasmic domains of transmembrane receptors and ion channels, additional α-actinin-dependent mechanisms are discussed

The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the \u27venom-ome\u27 and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 \u27venom-ome-specific toxins\u27 (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery

Central sites. Atlantis Massif: Serpentinisation and life

International Ocean Discovery Program (IODP) Expedition 357 successfully cored an east–west transect across the southern wall of Atlantis Massif on the western flank of the Mid-Atlantic Ridge (MAR) to study the links between serpentinization processes and microbial activity in the shallow subsurface of highly altered ultramafic and mafic sequences that have been uplifted to the seafloor along a major detachment fault zone. The primary goals of this expedition were to (1) examine the role of serpentinization in driving hydrothermal systems, sustaining microbial communities, and sequestering carbon; (2) characterize the tectonomagmatic processes that lead to lithospheric heterogeneities and detachment faulting; and (3) assess how abiotic and biotic processes change with variations in rock type and progressive exposure on the seafloor. To accomplish these objectives, we developed a coring and sampling strategy centered on the use of seabed drills—the first time that such systems have been used in the scientific ocean drilling programs. This technology was chosen in the hope of achieving high recovery of the carbonate cap sequences and intact contact and deformation relationships. The expedition plans also included several engineering developments to assess geochemical parameters during drilling; sample bottom water before, during, and after drilling; supply synthetic tracers during drilling for contamination assessment; acquire in situ electrical resistivity and magnetic susceptibility measurements for assessing fractures, fluid flow, and extent of serpentinization; and seal boreholes to provide opportunities for future experiments. Seventeen holes were drilled at nine sites across Atlantis Massif, with two sites on the eastern end of the southern wall (Sites M0068 and M0075), three sites in the central section of the southern wall north of the Lost City hydrothermal field (Sites M0069, M0072, and M0076), two sites on the western end (Sites M0071 and M0073), and two sites north of the southern wall in the direction of the central dome of the massif and Integrated Ocean Drilling Program Site U1309 (Sites M0070 and M0074). Use of seabed drills enabled collection of more than 57 m of core, with borehole penetration ranging from 1.30 to 16.44 meters below seafloor and core recoveries as high as 74.76% of total penetration. This high level of recovery of shallow mantle sequences is unprecedented in the history of ocean drilling. The cores recovered along the southern wall of Atlantis Massif have highly heterogeneous lithologies, types of alteration, and degrees of deformation. The ultramafic rocks are dominated by harzburgites with intervals of dunite and minor pyroxenite veins, as well as gabbroic rocks occurring as melt impregnations and veins, all of which provide information about early magmatic processes and the magmatic evolution in the southernmost portion of Atlantis Massif. Dolerite dikes and basaltic rocks represent the latest stage of magmatic activity. Overall, the ultramafic rocks recovered during Expedition 357 reveal a high degree of serpentinization, as well as metasomatic talc-amphibole-chlorite overprinting and local rodingitization. Metasomatism postdates an early phase of serpentinization but predates late-stage intrusion and alteration of dolerite dikes and the extrusion of basalt. The intensity of alteration is generally lower in the gabbroic and doleritic rocks. Chilled margins in dolerite intruded into talc-amphibole-chlorite schists are observed at the most eastern Site M0075. Deformation in Expedition 357 cores is variable and dominated by brecciation and formation of localized shear zones; the degree of carbonate veining was lower than anticipated. All types of variably altered and deformed ultramafic and mafic rocks occur as components in sedimentary breccias and as fault scarp rubble. The sedimentary cap rocks include basaltic breccias with a carbonate sand matrix and/or fossiliferous carbonate. Fresh glass on basaltic components was observed in some of the breccias. The expedition also successfully applied new technologies, namely (1) extensively using an in situ sensor package and water sampling system on the seabed drills for evaluating real-time dissolved oxygen and methane, pH, oxidation-reduction potential (ORP), temperature, and conductivity during drilling; (2) deploying a borehole plug system for sealing seabed drill boreholes at four sites to allow access for future sampling; and (3) proving that tracers can be delivered into drilling fluids when using seabed drills. The rock drill sensor packages and water sampling enabled detection of elevated dissolved methane and hydrogen concentrations during and/or after drilling, with “hot spots” of hydrogen observed over Sites M0068–M0072 and methane over Sites M0070–M0072. Shipboard determination of contamination tracer delivery confirmed appropriate sample handling procedures for microbiological and geochemical analyses, which will aid all subsequent microbiological investigations that are part of the science party sampling plans and will verify this new tracer delivery technology for seabed drill rigs. Shipboard investigation of biomass density in select samples revealed relatively low and variable cell densities, and enrichment experiments set up shipboard reveal growth. Thus, we anticipate achieving many of the deep biosphere–related objectives of the expedition through continued scientific investigation in the coming years. Finally, although not an objective of the expedition, we were serendipitously able to generate a high-resolution (20 m per pixel) multibeam bathymetry map across the entire Atlantis Massif and the nearby fracture zone, MAR, and eastern conjugate, taking advantage of weather and operational downtime. This will assist science party members in evaluating and interpreting tectonic and mass-wasting processes at Atlantis Massif