Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder

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Zonation of Merensky-Style platinum-group element mineralization in Turfspruit Thick Reef Facies (Northern Limb of the Bushveld Complex)

The stratigraphy, whole-rock composition, and mineralogy from a thick undisturbed section of the Platreef at depth on Turfspruit in the northern limb of the Bushveld Complex have been examined in detail. This section has much more in common with the Critical zone than with the Platreef structure updip although the high-grade platinum-group element (PGE) reefs, located close to the boundary with the Main zone, are much thicker than any known Merensky reef facies. A key feature that marks the conversion of the Platreefstyle mineralization into the Merensky style is the regular appearance of chromite seams, which become more persistent with decreasing contamination westward and downdip. The similar zonal distribution of platinum-group minerals (PGM) in two consecutive thick PGE reefs correlates with changes in silicate compositions and vertical zonation of PGE concentrations in whole rocks and base metal sulfides. This supports orthomagmatic in situ crystallization of ore minerals during mixing of consecutive magmatic influxes. The typical Merensky-style ore assemblages of predominant Pt sulfides and alloys are developed within ~1-m-thick intervals, which correspond to the highest temperature mixing zones between two magmas, whereas the rest of the reefs host Pt-Pd bismuthotellurides and arsenides. PGE content and tenor, as well as Cu/Pd in major base metal sulfides in the Turfspruit reefs, are within the range of the typical high-grade Merensky values, suggesting the same enrichment process

Trace-element geochemistry of molybdenite from porphyry Cu deposits of the Birgilda-Tomino ore cluster (South Urals, Russia)

Mineralogical, electron microprobe analysis and laser ablation-inductively coupled plasma-mass spectrometry data from molybdenite within two porphyry copper deposits (Kalinovskoe and Birgilda) of the Birgilda-Tomino ore cluster (South Urals) are presented.† The results provide evidence that molybdenites from these two sites have similar trace-element chemistry. Most trace elements (Si, Fe, Co, Cu, Zn, Ag, Sb, Te, Pb, Bi, Au, As and Se) form mineral inclusions within molybdenite. The Re contents in molybdenite vary from 8.7 ppm to 1.13 wt.%. The Re distribution within single molybdenite flakes is always extremely heterogeneous. It is argued that a temperature decrease favours the formation of Re-rich molybdenite. The high Re content of molybdenite observed points to a mantle-derived source.© The Mineralogical Society 2018. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. The attached file is the published version of the article

Changes of KEAP1/NRF2 and IKB/NF-κB Expression Levels Induced by Cell-Free DNA in Different Cell Types

Cell-free DNA (cfDNA) is a circulating DNA of nuclear and mitochondrial origin mainly derived from dying cells. Recent studies have shown that cfDNA is a stress signaling DAMP (damage-associated molecular pattern) molecule. We report here that the expression profiles of cfDNA-induced factors NRF2 and NF-κB are distinct depending on the target cell’s type and the GC-content and oxidation rate of the cfDNA. Stem cells (MSC) have shown higher expression of NRF2 without inflammation in response to cfDNA. In contrast, inflammatory response launched by NF-κB was dominant in differentiated cells HUVEC, MCF7, and fibroblasts, with a possibility of transition to massive apoptosis. In each cell type examined, the response for oxidized cfDNA was more acute with higher peak intensity and faster resolution than that for nonoxidized cfDNA. GC-rich nonoxidized cfDNA evoked a weaker and prolonged response with proinflammatory component (NF-κB) as predominant. The exploration of apoptosis rates after adding cfDNA showed that cfDNA with moderately increased GC-content and lightly oxidized DNA promoted cell survival in a hormetic manner. Novel potential therapeutic approaches are proposed, which depend on the current cfDNA content: either preconditioning with low doses of cfDNA before a planned adverse impact or eliminating (binding, etc.) cfDNA when its content has already become high

Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Human Molecular Genetics. 2011; 20:4076–81. [PubMed: 21791550

ABSTRACT Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association (GWA) study and meta-analysis (totalling 7,946 cases and 19,036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10,260 cases and 23,500 controls). In addition to previously-reported alleles in the major histocompatibility complex (MHC) region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) (OR = 1.09, P = 1.9 x 10 -

Common variants conferring risk of schizophrenia

Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition