Trace metal distributions in sulfide scales of the seawater-dominated Reykjanes geothermal system: Constraints on sub-seafloor hydrothermal mineralizing processes and metal fluxes

Highlights • Predictable trace element enrichments and depletions in the Reykjanes system. • Boiling exerts a major influence on the enrichment of metals. • High concentrations of Au and Ag and Pb indicate accumulation in reservoir fluids. • Three quarters of the metal budget is deposited at depth or in the upflow zone. Abstract Mineral precipitation in the seawater-dominated Reykjanes geothermal system on the Mid-Atlantic Ridge, Iceland is caused by abrupt, artificially induced, pressure and temperature changes as deep high-temperature liquids are drawn from reservoir rocks up through the geothermal wells. Sulfide scales within these wells represent a complete profile of mineral precipitation through a seafloor hydrothermal system, from the deep reservoir to the low-temperature silica-rich surface discharge. Mineral scales have formed under a range of conditions from high pressures and temperatures at depth (>2 km) to boiling conditions in the upflow zone and at the surface. Consistent trace element enrichments, similar to those in black smoker chimneys, are documented: Cu, Zn, Cd, Co, Te, V, Ni, Mo, W, Sn, Fe and S are enriched at higher pressures and temperatures in the deepest scales, Zn and Cu, Bi, Pb, Ag, As, Sb, Ga, Hg, Tl, U, and Th are enriched at lower temperatures and pressures nearer to the surface. A number of elements (e.g., Co, Se, Cd, Zn, Cu, and Au) are deposited in both high- and low-pressure scales, but are hosted by distinctly different minerals. Other trace elements, such as Pb, Ag, and Ga, are strongly partitioned into low-temperature minerals, such as galena (Pb, Ag) and clays (Ga). Boiling and destabilization of metal-bearing aqueous complexes are the dominant control on the deposition of most metals (particularly Au). Other metals (e.g., Cu and Se) may also have been transported in the vapor phase. Very large enrichments of Au, Ag and Pb in the scales (e.g., 948 ppm Au, 23,200 ppm Ag, and 18.8 wt.% Pb) versus average concentrations in black smoker chimneys likely reflect that some elements are preferentially deposited in boiling systems. A mass accumulation of 5.7 t/yr of massive sulfide was calculated for one high-temperature production well, equating to metal fluxes of 1.7 t/yr Zn, 0.3 t/yr Cu, 23 kg/yr Pb, 4.1 kg/yr Ag, and 0.5 kg/yr Au. At least three quarters of the major and trace element load is precipitated within the well before reaching the surface. We suggest that a similar proportion of metals may be deposited below the seafloor in submarine hydrothermal systems where significant boiling has occurred. Mass accumulation estimations over the lifetime of the Reykjanes system may indicate significant enrichment of Zn, Pb, Au, and Ag relative to both modern and ancient mafic-dominated seafloor massive sulfide deposits, and highlights the potential for metal enrichment and accumulation in the deep parts of geothermal systems

A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P= 1.2 × 10−4). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7–2.3 for lung cancer(LC;P= 4.0 × 10−4), chronic obstructive pulmonary disease (COPD;P= 9.3 × 10−4), peripheral artery disease (PAD;P= 0.090) and abdominal aortic aneurysms (AAAs; P= 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49,P= 2.2 × 10−4), COPD (OR = 3.22,P= 2.9 × 10−4), PAD (OR = 3.47,P= 9.2 × 10−3) and AAA (OR = 6.44, P= 6.3 × 10−3). Joint analysis of the four smoking-related diseases reveals significant association (P= 6.8 × 10−5), particularly for early-onset cases (P=2.1 × 10−7). Our results are in agreement with functional studies showing that the human α4β2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation

CA125/MUC16 Is Dispensable for Mouse Development and Reproduction

Cancer antigen 125 (CA125) is a blood biomarker that is routinely used to monitor the progression of human epithelial ovarian cancer (EOC) and is encoded by MUC16, a member of the mucin gene family. The biological function of CA125/MUC16 and its potential role in EOC are poorly understood. Here we report the targeted disruption of the of the Muc16 gene in the mouse. To generate Muc16 knockout mice, 6.0 kb was deleted that included the majority of exon 3 and a portion of intron 3 and replaced with a lacZ reporter cassette. Loss of Muc16 protein expression suggests that Muc16 homozygous mutant mice are null mutants. Muc16 homozygous mutant mice are viable, fertile, and develop normally. Histological analysis shows that Muc16 homozygous mutant tissues are normal. By the age of 1 year, Muc16 homozygous mutant mice appear normal. Downregulation of transcripts from another mucin gene (Muc1) was detected in the Muc16 homozygous mutant uterus. Lack of any prominent abnormal phenotype in these Muc16 knockout mice suggests that CA125/MUC16 is not required for normal development or reproduction. These knockout mice provide a unique platform for future studies to identify the role of CA125/MUC16 in organ homeostasis and ovarian cancer

Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes

Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 x 10(-8)) with GDM, mapping to/near MTNR1B (P = 4.3 x 10(-54)), TCF7L2 (P = 4.0 x 10(-16)), CDKAL1 (P = 1.6 x 10(-4)), CDKN2A-CDKN2B (P = 4.1 x 10(-9)) and HKDC1 (P = 2.9 x 10(-8)). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.Peer reviewe

Dietary fish oil decreases the proportion of classical monocytes in blood in healthy mice but increases their proportion upon induction of inflammation.

Fish oil can have beneficial effects in health and disease. In healthy individuals, reduction of the inflammatory status may be of benefit, whereas in patients with systemic inflammation, such as sepsis, it is important to diminish the immunosuppression that is thought to contribute to poor outcome. The objective of this study was to determine the effects of dietary fish oil on monocytes/macrophages in blood, bone marrow, spleen, and peritoneum and chemokine concentrations in blood and peritoneum in healthy mice and mice with endotoxin-induced inflammation. Mice were fed a Western-type diet without fish oil (C) or with 2.8% fish oil (FO) for 6 wk and then either killed (healthy mice) or injected i.p. with endotoxin (LPS) and killed after 3, 8, 12, 24, or 48 h. Blood, bone marrow, spleen, and peritoneal lavage were collected. Expression of cell surface molecules and chemokine receptors was analyzed by flow cytometry and chemokine concentrations measured by ELISA. Healthy mice in the FO group had lower proportions of classical monocytes in blood than healthy mice in the C group. LPS administration increased the proportion of classical monocytes in blood in mice in the FO group but not in those in the C group. Healthy mice in the FO group had lower serum concentrations of CCL2 than mice in the C group, but in inflamed mice, CCL2 concentrations were higher in the FO group than in the C group. These results indicate that dietary fish oil can attenuate the inflammatory status in homeostasis but intensify the immune response upon inflammation.Icelandic Research Fund University of Icelan

Two circulating neutrophil populations in acute inflammation in mice.

Recent studies indicate that neutrophils are heterogeneous and may have an immunosuppressive role in addition to their well-known phagocytic and bactericidal function. This study examined neutrophil subpopulations in the circulation, peritoneum, spleen and bone marrow from mice at various time points after induction of acute inflammation. MATERIAL, TREATMENT AND METHODS: Female C57BL/6 mice were injected intraperitoneally with lipopolysaccharide (LPS). Blood, peritoneal, spleen and bone marrow cells were collected and counted and expression of surface molecules and chemokine receptors analyzed with flow cytometry. Chemokine and cytokine concentrations in serum and peritoneal fluid were determined by ELISA. Neutrophil numbers in the circulation decreased following administration of LPS but reached similar numbers to those prior to inflammation at 8 h. At that time point, two distinct neutrophil populations were present in the circulation. These two neutrophil populations differed in size, granularity and expression of CD11b and Ly6G. Few neutrophils were recruited into the peritoneum until 24 h after administration of LPS at a time when the neutrophils in the circulation had increased their expression of the chemokine receptor CXCR2. Induction of acute inflammation leads to the appearance of two circulating neutrophil subpopulations, which may differ in their activation state and function.Icelandic Research Fund University of Iceland Research Fun