Lower crustal zircons reveal Neogene metamorphism beneath the Pannonian Basin (Hungary)

Neogene alkaline intraplate volcanic deposits in the Pannonian Basin (Hungary) contain many lower crustal granulite-facies xenoliths. U-Pb ages have been determined for zircons separated from a metasedimentary xenolith, using LA-ICPMS and SHRIMP techniques. The zircons show typical metamorphic characteristics and are not related to the hostmagmatism. The oldest age recorded is late Devonian, probably related to Variscan basement lithologies. Several grains yield Mesozoic dates for their cores, which may correspond to periods of orogenic activity. Most of the zircons show young ages, with some being Palaeocene-Eocene, but the majority being younger than 30Ma. The youngest zircons are Pliocene (5.1-4.2 Ma) and coincide with the age of eruptions of the host alkali basalts. Such young zircons, so close to the eruption age, are unusual in lower crustal xenoliths, and imply that the heat flow in the base of the Pannonian Basin was sufficiently high to keep many of them close to their blocking temperature. This suggests that metamorphism is continuing in the lower crust of the region at the present day

Diamondites: evidence for a distinct tectono-thermal diamond-forming event beneath the Kaapvaal craton

The petrogenesis and relationship of diamondite to well-studied monocrystalline and fibrous diamonds are poorly understood yet would potentially reveal new aspects of how diamond-forming fluids are transported through the lithosphere and equilibrate with surrounding silicates. Of 22 silicate- and oxide-bearing diamondites investigated, most yielded garnet intergrowths (n = 15) with major element geochemistry (i.e. Ca–Cr) classifying these samples as low-Ca websteritic or eclogitic. The garnet REE patterns fit an equilibrium model suggesting the diamond-forming fluid shares an affinity with high-density fluids (HDF) observed in fibrous diamonds, specifically on the join between the saline–carbonate end-members. The δ13C values for the diamonds range from − 5.27 to − 22.48‰ (V-PDB) with δ18O values for websteritic garnets ranging from + 7.6 to + 5.9‰ (V-SMOW). The combined C–O stable isotope data support a model for a hydrothermally altered and organic carbon-bearing subducted crustal source(s) for the diamond- and garnet-forming media. The nitrogen aggregation states of the diamonds require that diamondite-formation event(s) pre-dates fibrous diamond-formation and post-dates most of the gem monocrystalline diamond-formation events at Orapa. The modelled fluid compositions responsible for the precipitation of diamondites match the fluid-poor and fluid-rich (fibrous) monocrystalline diamonds, where all grow from HDFs within the saline-silicic-carbonatitic ternary system. However, while the nature of the parental fluid(s) share a common lithophile element geochemical affinity, the origin(s) of the saline, silicic, and/or carbonatitic components of these HDFs do not always share a common origin. Therefore, it is wholly conceivable that the diamondites are evidence of a distinct and temporally unconstrained tectono-thermal diamond-forming event beneath the Kaapvaal craton

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

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

Magmatic residence times of zoned phenocrysts: introduction and application of the binary element diffusion modelling (BEDM) technique

This paper describes a general technique, binary element diffusion modelling (BEDM), for determining single-crystal residence times in magmas that relies on modelling the diffusion of two or more elements in the crystal. BEDM has the advantage over other diffusion-based models in that it does not need a precisely defined initial compositional profile for the crystal at “zero time”, and instead requires that the concentrations of the two elements are correlated during crystallisation. Any differences subsequently observed between the two elements are caused by intracrystalline diffusion during residence in hot magma. These differences are removed by artificially ageing the slower-diffusing of the two elements, and the amount of time taken to “undo” the difference between the elements is simply related to the crystal residence time (=decoupling time) at high temperatures. The BEDM principle is demonstrated using artificial data and is then applied to literature data for Sr and Ba in a zoned sanidine crystal from the Bishop Tuff (Anderson et al., in J. Petrol 41(3):449–473, 2000). For this crystal, the method gives a residence time estimate of 114 ka at 800°C, which is then compared with estimates from other methods. In theory, the method can be further expanded for use as a geothermometer as well as geochronometer. However, this is not easily possible with the diffusivity data currently available

Estimates of the Temperature and Melting Conditions of the Carpathian‐Pannonian Upper Mantle From Volcanism and Seismology

What drives the formation of basaltic melts beneath intraplate volcanoes not associated with extensive thermal anomalies or lithospheric extension? Detailed constraints on the melting conditions and source region are imperative to resolve this question. Here we model the geochemistry of alkali basalts and mantle nodules brought up by young (12–0.1 Ma) intraplate volcanoes distributed across the Carpathian-Pannonian region and combine the results with geophysical observations. Rare earth element inversion and forward calculation of elemental concentrations show that the basalts require the mantle to have undergone less than 1% melting in the garnet-spinel transition zone, at depths of about 63–72 km. The calculated melt distributions correspond to a mantle potential temperature of ∼1257°C, equivalent to a real temperature of 1290°C at 65 km beneath the Pannonian Basin. The composition, modal mineralogy, and clinopyroxene geochemistry of some of the entrained mantle nodules closely resemble the basalt source, though the latter equilibrated at greater depths. The gravity anomalies and topography of the Basin reveal no large-scale features that can account for the post-extensional volcanism. Instead, the lithospheric thickness and geotherm show that melting occurs because the base of the lithosphere, at ∼50-km depth, is close to or at the solidus temperature over a large part of the Basin. Hence, only a small amount of upwelling is required to produce minor volumes (up to a few cubic kilometers) of melt. We conclude that the Pannonian volcanism originates from upwelling in the asthenosphere just below thinned lithosphere, which is likely to be driven by thermal buoyancy

The expanding genetic overlap between multiple sclerosis and type I diabetes

Familial clustering of autoimmune disease is well recognized and raises the possibility that some susceptibility genes may predispose to autoimmunity in general. In light of this observation, it might be expected that some of the variants of established relevance in one autoimmune disease may also be relevant in other related conditions. On the basis of this hypothesis, we tested seven single nucleotide polymorphisms (SNPs) that are known to be associated with type I diabetes in a large multiple sclerosis data set consisting of 2369 trio families, 5737 cases and 10 296 unrelated controls. Two of these seven SNPs showed evidence of association with multiple sclerosis; that is rs12708716 from the CLEC16A gene (P=1.6 × 10−16) and rs763361 from the CD226 gene (P=5.4 × 10−8). These findings thereby identify two additional multiple sclerosis susceptibility genes and lend support to the notion of autoimmune susceptibility genes