A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms

Crystal chemistry of clinopyroxenes from upper-mantle xenolith series in the Balaton\u2013Bakony volcanic area (Carpathian\u2013Pannonian region, Hungary)

A detailed crystal chemical study of clinopyroxenes (cpx) from a suite of mantle xenoliths of the Balaton\u2013Bakony volcanic highland (Carpathian\u2013Pannonian region (CPR), Hungary) has been undertaken by means of X-ray single-crystal diffraction and electron microprobe. The study aims to evaluate the response of cpx crystal chemistry to textural changes and increasing deformation, and to estimate equilibrium pressure conditions of texturally heterogeneous spinel-peridotite xenolith series. Moreover, our interest also focussed on cpx crystal chemistry of mosaic and poikilitic textured xenoliths. Results demonstrate that cpx from protogranular, porphyroclastic and some equigranular xenoliths define the \u2018\u2018primary\u2019\u2019 compositional trend that reflects structural and textural changes. This cpx-trend also suggests that deformation increase correlates with pressure (and temperature) decrease. Protogranular xenoliths record pressure near to the garnet stability field whereas equigranular xenoliths record lower pressure approaching the plagioclase stability field. Some cpx from equigranular samples show a crystal chemistry similar to that of cpx from poikilitic and mosaic xenoliths which depart from the \u2018\u2018primary\u2019\u2019 trend. This suggests that the latter cpx are likely formed at low pressure near to or within the plagioclase stability field. The inverse relationship between pressure and deformation in the main series can be explained geodynamically by the presence of a mantle diapir beneath the region, which could have caused significant deformation and lithosphere thinning in the centre of the CPR

Petrographic and geochemical investigation of a stone adze made of nephrite from the site Balatonőszöd – Temetői dűlő (Hungary)

The present study reports on results of petrographic and geochemical analyses on a stone adze from the archaeological site Balatonőszöd – Temetői dűlő (Hungary). This is the largest excavated site of the Baden Culture in Hungary (more than 200.000 m2) and has the longest continuous settlement history. In the site, features of the Balaton-Lasinja Culture (Middle Copper Age) and the Boleraz Culture were also found. Altogether 500 stone artefacts were found and registered. The present study reports on the results of the investigation of a unique stone adze made of nephrite, found on the site. The nephrite adze found in Balatonőszöd – Temetői dűlő has proved to be the first find made of nephrite having an established archaeological context in Hungarian prehistory. By applying detailed petrographic, geochemical and petrophysical methods as well as comparing data from technical literature we located the origin of the raw material of the nephrite adze. Its most probable source is the Northern part of the Bohemian Massif, Lower Silesia, a geological site near Jordanów (Poland)

Trace element and C-O-Sr-Nd isotope evidence for subduction-related carbonate-silicate melts in mantle xenoliths (Pannonian Basin, Hungary)

Carbonate globules have been found in amphibole-bearing glass veins of peridotite xenoliths from Szentbékálla (Balaton Highland, Central Hungary). Strong resorption of amphibole suggests multiple fluid-melt infiltration. Textural features of carbonate globules and the surrounding silicate glass indicate a magmatic melt origin for the carbonate and exclude the possibility of significant alteration. The application of the cpx structural barometer for clinopyroxenes formed in the silicate glass indicates high-pressure vein formation. Laser-ablation ICP-MS analyses revealed trace element zoning within the carbonate. Uniform profiles observed for various elements within the carbonate indicate that the zoning is related to non-diffusive mixing during carbonate–silicate interaction rather than to element diffusion. The trace element composition of the centers of the globules (e.g. low Ce/Pb and Nd/Pb ratios) suggests a crustal origin for the carbonate melt. The C, O, and Sr isotope compositions of the calcite globules (13C about ?14‰; 18O about 22‰; 87Sr/86Sr=0.70533) also argue for a crustal origin of the carbonate melt. Trace element and C–O–Sr isotopic compositions of calcite globules suggest that the carbonate melt was derived from subducted material. Injection of the carbonate melt into the peridotite triggered amphibole melting. The carbonate and silicate melts intermingled, but their interaction was confined to the margins of carbonate globules. Preservation of trace element zoning and element diffusion calculations indicate that the vein-hosting peridotite was rapidly brought to the surface after the carbonate melt injection