Syn-sedimentary to diagenetic Cu ± Co mineralization in Mesoproterozoic pyritic shale driven by magmatic-hydrothermal activity on the edge of the Great Falls tectonic zone – Black Butte, Helena Embayment, Belt-Purcell Basin, USA: Evidence from sulfide Re-Os isotope geochemistry

The ca. 1,500 to 1,325 Ma Mesoproterozoic Belt-Purcell Basin is an exceptionally preserved archive of Mesoproterozoic Earth and its paleo-environmental conditions. The Belt-Purcell Basin is also host to world-class base metal sediment-hosted mineralization produced in a variety of settings from the rift stage of basin evolution through to the subsequent influence of East Kootenay and Grenvillian orogenies. The mineral potential of this basin has not been fully realized yet. New rhenium-osmium (Re-Os) data presented here for chalcopyrite, pyrite and black shale contribute to refine a robust genetic model for the origin of the Black Butte copper ± cobalt ± silver (Cu ± Co ± Ag) deposit hosted by the ca. >1,475 Ma Newland Formation in the Helena Embayment of the Belt-Purcell Basin in Montana, USA. Chalcopyrite Re-Os data yield an isochron age (1,488 ± 34 Ma, unradiogenic initial 187Os/188 Os composition Osi-chalcopyrite = 0.13 ± 0.11) that overlaps with the geological age of the Newland Formation. Further, the Re-Os data of syn-sedimentary to diagenetic massive pyrite yield evidence of resetting with an isochron age (1,358 ± 42 Ma) coincident with the timing of the East Kootenay Orogeny. The unradiogenic Osi-chalcopyrite at ca. 1,488 Ma (0.13 ± 0.11) argues for derivation of Os from a magmatic source with a 187Os/188 Os isotopic composition inherited from the upper mantle in the Mesoproterozoic (Osmantle 1,475 Ma= 0.12 ± 0.02). The unradiogenic Osi-chalcopyrite also suggests limited contamination from a continental crustal source. This source of Os and our new sulfur isotopic signatures of chalcopyrite [–4.1 to +2.1 ‰ - VCDT] implies a dominantly magmatic source for metals. We integrate our new results and previously published geological and geochemical evidence to conceptualize a genetic model in which Cu and metals were largely contributed by moderate-temperature, reduced magmatic-hydrothermal fluids carrying reduced sulfur species with a magmatic origin and flowing as highly metalliferous fluids within the shale sequence. A subsidiary derivation of metals during thermally forced shale diagenesis is possible. Chalcopyrite mineralization replaced locally massive syn-3 sedimentary to diagenetic pyrite units close to the sediment-water interface, i.e., an ideal locus where magmatic-hydrothermal fluids could cool and the solubility of chalcopyrite would fall. We suggest that Cu mineralization was coeval with the timing of an enhanced thermal gradient in the Helena Embayment triggered until ca. 1,455 Ma by tholeiitic dike swarm that intruded into Archean basement rocks and intersected the NE–SW-trending Great Falls Tectonic Zone

Precise age of Bangiomorpha pubescens dates the origin of eukaryotic photosynthesis

Although the geological record indicates that eukaryotes evolved by 1.9–1.4 Ga, their early evolution is poorly resolved taxonomically and chronologically. The fossil red alga Bangiomorpha pubescens is the only recognized crown-group eukaryote older than ca. 0.8 Ga and marks the earliest known expression of extant forms of multicellularity and eukaryotic photosynthesis. Because it postdates the divergence between the red and green algae and the prior endosymbiotic event that gave rise to the chloroplast, B. pubescens is uniquely important for calibrating eukaryotic evolution. However, molecular clock estimates for the divergence between the red and green algae are highly variable, and some analyses estimate this split to be younger than the widely inferred but poorly constrained first appearance age of 1.2 Ga for B. pubescens. As a result, many molecular clock studies reject this fossil ex post facto. Here we present new Re-Os isotopic ages from sedimentary rocks that stratigraphically bracket the occurrence of B. pubescens in the Bylot Supergroup of Baffin Island and revise its first appearance to 1.047 +0.013/–0.017 Ga. This date is 150 m.y. younger than commonly held interpretations and permits more precise estimates of early eukaryotic evolution. Using cross-calibrated molecular clock analyses with the new fossil age, we calculate that photosynthesis within the Eukarya emerged ca. 1.25 Ga. This date for primary plastid endosymbiosis serves as a benchmark for interpreting the fossil record of early eukaryotes and evaluating their role in the Proterozoic biosphere

Osmium isotopic constraints on sulphide formation in the epithermal environment of magmatic-hydrothermal mineral deposits

In the magmatic-hydrothermal environment, fluids with similar metal concentrations and sources may yield contrasting mineral assemblages in successive stages of sulphide mineralization. These differences are linked to the physico-chemical conditions of the mineralizing fluids (e.g., T, pH, fS2, fO2) acquired during their interaction with country rocks and/or by mixing with groundwater. Here, we integrate petrography and osmium (Os) isotope (187Os/188Os) sulphide geochemistry, and discuss novel constraints on magmatic fluid-rock interaction and magmatic fluid-groundwater mixing that are deemed to govern sulphide deposition in magmatic-hydrothermal systems. We studied pyrite (FeS2) and enargite (Cu3AsS4) from the porphyry-related polymetallic Cerro de Pasco (14.54–14.41 Ma) and Colquijirca (10.83–10.56 Ma) epithermal deposits in the Central Andes, Peru. Sulphide mineralization is genetically associated with Miocene magmatism and includes breccia and replacement bodies of carbonate country rocks, and veins cutting the magmatic and sedimentary country rocks. At both deposits, pyrite is followed by enargite in the paragenesis. Pyrite has a radiogenic initial 187Os/188Os isotopic composition (187Os/188Osi-pyrite or Osi-pyrite = 0.80 to 1.45). Enargite (I) enclosing pyrite or filling in cracks in pyrite also has a radiogenic initial 187Os/188Os isotopic composition (Osi-enargite I = 0.56 to 1.24). Conversely, enargite (II) that formed on irregular surfaces on earlier pyrite has an unradiogenic 187Os/188Os isotopic composition (Osi-enargite II = 0.13 to 0.17). Our data show that the paragenetic evolution from pyrite to enargite records a sharp change in the osmium isotope composition within these sulphides. Pyrite and enargite (I) record radiogenic initial 187Os/188Os isotopic compositions, indicating interaction of magmatic hydrothermal fluids with the sedimentary country rocks. However, the unradiogenic initial 187Os/188Os isotopic composition of enargite (II) suggests that magmatic fluids with a mantle-like 187Os/188Os signature ascended from parental magmatic chambers to the epithermal environment without incorporation of crustal Os via fluid-rock interaction or mixing with groundwater. This difference may be due to the country rocks being altered during previous stages, with the radiogenic crustal Os signature being flushed by earlier magmatic pulses. Our findings imply that ore metals (i.e., Cu, Au) are magma-derived, whereas the Os isotopic composition of pyrite and some enargite in epithermal deposits may capture the signature of the interaction of magmatic fluids with country rock lithologies (e.g., the Eifelian black shale in the study area) and/or groundwater. Thus, the isotopic composition of the siderophile and chalcophile trace element Os in sulphides may act as a tracer of metal source, and degree of wall-rock interaction

Embracing ligands. Synthesis, characterisation and the correlation between 59Co NMR and ligand field parameters of Co(III) complexes with a new class of nitrogen-thioether multidentate ligand

The syntheses of the hexadentate ligands 2,2,10,10-tetra(methyleneamine)-4,8-dithiaundecane (PrN(4)S(2)amp), 2,2,11,11-tetra(methyleneamine)-4,9-dithiadodecane (BuN(4)S(2)amp), and 1,2-bis(4,4-methyleneamine)-2-thiapentyl)benzene (XyN(4)S(2)amp) are reported and the complexes [Co(RN(4)S(2)amp)](3+) (R = Pr, Bu, Xy) characterised by single crystal X-ray study. The low-temperature (11 K) absorption spectra have been measured in Nafion films. From the observed positions of both spin-allowed (1)A(1g) --> T-1(1g) and (1)A(1g) --> T-1(2g) and spin forbidden (1)A(1g) --> T-3(1g) and (1)A(1g) --> T-3(2g) bands, octahedral ligand-field parameters (10D(q), B and C) have been determined. DFT calculations suggest that significant interaction between the d-d and CT excitations occurs for the complexes. The calculations offer an explanation for the observed deviations from linearity of the relationship between Co-59 magnetogyric ratio and beta(DeltaE)(-1) (beta = the nephelauxetic ratio; DeltaE the energy of the (1)A(1g) --> T-1(1g) transition) for a series of amine and mixed amine/thioether donor complexes

Anorthosite formation and emplacement coupled with differential tectonic exhumation of ultrahigh-temperature rocks in a Sveconorwegian continental back-arc setting

The tectonic setting and mechanisms and duration of emplacement of Proterozoic massif-type anorthosites and the significance of typically associated ultrahigh-temperature (UHT) host rocks have been debated for decades. This is particularly true of the Rogaland Anorthosite Province (RAP) in the SW Sveconorwegian Orogen. Earlier studies suggest that the RAP was emplaced over 1–3 Myr around 930 Ma towards the end of orogenesis, resulting in an up to 15–20 km-wide contact metamorphic aureole. However, our structural observations show that the RAP is located in the footwall of a 15 km-wide extensional detachment (Rogaland Extensional Detachment, RED), separating the intrusions and their UHT host rocks from weakly metamorphosed rocks in the hanging wall. U–Pb zircon dating of leucosome in extensional pull-aparts associated with the RED yields ages of 950–935 Ma, consistent with Re–Os molybdenite ages from brittle extensional structures in the hanging-wall block that range between 980 and 930 Ma. A metapelite in the immediate vicinity of the RAP yields a 950 Ma U–Pb age of matrix-hosted monazite, and part of the RAP was intruded by the Storgangen norite dike at ca. 950 Ma, providing a minimum age of emplacement. These ages are consistent with Ar–Ar hornblende and biotite ages that show rapid cooling of the footwall before 930 Ma, but slow cooling of the hanging wall. Field and geochronologic data suggest that the RAP formed and was emplaced over a long period of time, up to 100 Myr, with different emplacement mechanisms reflecting an evolving regional stress regime. The distribution of UHT rocks around the RAP reflects differential extensional exhumation between 980 and 930 Ma, not contact metamorphism. The duration and style of orogenic activity and externally (as opposed to gravitationally) driven extension suggest that the RAP formed in a continental back-arc setting

Precise age of Bangiomorpha pubescens dates the origin of eukaryotic photosynthesis

Although the geological record indicates that eukaryotes evolved by 1.9–1.4 Ga, their early evolution is poorly resolved taxonomically and chronologically. The fossil red alga Bangiomorpha pubescens is the only recognized crown-group eukaryote older than ca. 0.8 Ga and marks the earliest known expression of extant forms of multicellularity and eukaryotic photosynthesis. Because it postdates the divergence between the red and green algae and the prior endosymbiotic event that gave rise to the chloroplast, B. pubescens is uniquely important for calibrating eukaryotic evolution. However, molecular clock estimates for the divergence between the red and green algae are highly variable, and some analyses estimate this split to be younger than the widely inferred but poorly constrained first appearance age of 1.2 Ga for B. pubescens. As a result, many molecular clock studies reject this fossil ex post facto. Here we present new Re-Os isotopic ages from sedimentary rocks that stratigraphically bracket the occurrence of B. pubescens in the Bylot Supergroup of Baffin Island and revise its first appearance to 1.047 +0.013/–0.017 Ga. This date is 150 m.y. younger than commonly held interpretations and permits more precise estimates of early eukaryotic evolution. Using cross-calibrated molecular clock analyses with the new fossil age, we calculate that photosynthesis within the Eukarya emerged ca. 1.25 Ga. This date for primary plastid endosymbiosis serves as a benchmark for interpreting the fossil record of early eukaryotes and evaluating their role in the Proterozoic biosphere

Zebrafish as a model for kidney function and disease

Kidney disease is a global problem with around three million people diagnosed in the UK alone and the incidence is rising. Research is critical to develop better treatments. Animal models can help to better understand the pathophysiology behind the various kidney diseases and to screen for therapeutic compounds, but the use especially of mammalian models should be minimised in the interest of animal welfare. Zebrafish are increasingly used, as they are genetically tractable and have a basic renal anatomy comparable to mammalian kidneys with glomerular filtration and tubular filtration processing. Here, we discuss how zebrafish have advanced the study of nephrology and the mechanisms underlying kidney disease

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

Phenotypic Characterization of <i>EIF2AK4</i> Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 ( BMPR2 ) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene ( EIF2AK4 ) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. Methods: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource–Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of &lt;1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. Results: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (K co ; 33% [interquartile range, 30%–35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23–38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. Conclusions: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low K co and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation. </jats:sec