Platinum-group element geochemistry of the Paraná flood basalts – modelling metallogenesis in rifting continental plume environments

This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this recordThe 135 Ma Paraná-Etendeka Large Igneous Province (PELIP) is one of the largest areas of continental flood basalt (CFB) volcanism in the world and is widely agreed to be a product of intracontinental melts related to thermal anomalies from the Tristan mantle plume. The province rifted during the break-up of Gondwana, as the plume transitioned into an oceanic geodynamic environment. This study reports analyses of plume-derived basalts from the Brazilian side of the PELIP (the Serra Geral Group) to investigate major, trace and platinum-group element (PGE) abundances in an evolving plume-rift metallogenic setting, with the aim of contextualising metallogenic controls alongside existing magmatic interpretations of the region. The chalcophile geochemistry of these basalts defines three distinct metallogenic groupings that fit with three modern multi-element magma classifications for Serra Geral lavas. In this scheme, Type 4 lavas have a distinctive PGE-poor signature, Type 1 (Central-Northern) lavas are enriched in Pd, Au and Cu, and Type 1 (Southern) lavas are enriched in Ru and Rh. Our trace element melt modelling indicates that the compositional variations result from changes in the melting regime between the garnet and spinel stability fields, in response to the thinning and ‘unlidding’ of the rifting continent above. This process imposes progressively shallower melting depths and higher degrees of partial melting. Accordingly, Type 4 magmas formed from small degree melts, reducing the likelihood of sulfide exhaustion/chalcophile acquisition at source. Type 1 (Central-Northern) magmas incorporated components of the sub-continental lithospheric mantle (SCLM)-derived in higher-degree partial melts; the SCLM was heterogeneously enriched via metasomatism prior to plume melting, and this produced enrichment in volatile metals (Pd, Cu, and Au) in these magmas. In contrast, the Ru-Rh enrichment in Type 1 (Southern) lavas is attributed to increased spinel-group mineral and sulphide incorporation from the mantle into higher degree partial melts close to the continental rift zone. Our models confirm the importance of contributions from SCLM melts in precious metal mineral systems within CFB provinces, and reinforce the role of heterogeneous metasomatic enrichment underneath cratons in boosting intracontinental prospectivity with respect to ore deposits.University of Exete

Modelling the potential non-breeding distribution of Spoon-billed Sandpiper Calidris pygmaea

SummaryThe Spoon-billed Sandpiper Calidris pygmaea is a ‘Critically Endangered’ migratory shorebird. The species faces an array of threats in its non-breeding range, making conservation intervention essential. However, conservation efforts are reliant on identifying the species’ key stopover and wintering sites. Using Maximum Entropy models, we predicted Spoon-billed Sandpiper distribution across the non-breeding range, using data from recent field surveys and satellite tracking. Model outputs suggest only a limited number of stopover sites are suitable for migrating birds, with sites in the Yellow Sea and on the Jiangsu coast in China highlighted as particularly important. All the previously known core wintering sites were identified by the model including the Ganges-Brahmaputra Delta, Nan Thar Island and the Gulf of Mottama. In addition, the model highlighted sites subsequently found to be occupied, and pinpointed potential new sites meriting investigation, notably on Borneo and Sulawesi, and in parts of India and the Philippines. A comparison between the areas identified as most likely to be occupied and protected areas showed that very few locations are covered by conservation designations. Known sites must be managed for conservation as a priority, and potential new sites should be surveyed as soon as is feasible to assess occupancy status. Site protection should take place in concert with conservation interventions including habitat management, discouraging hunting, and fostering alternative livelihoods.Field surveys in Russian non-breeding grounds were supported by RSPB, MHS and NABU. Field surveys in Gulf of Mottama partly supported by BBC Wildlife Fund. Satellite tagging data collection partly supported by The Biodiversity Investigation, Observation and Assessment Program (2019 - 2023) of the Ministry of Ecology and Environment of China, RSPB and a private donor. Bangladesh Spoon-billed Sandpiper Conservation Project’s fieldwork in Meghna Estuary (2015 - 2016) supported by RSPB. Data collection by EL partly supported by Basic research program (budgetary funds), projects number АААА-А19-119022190168-8 and АААА-А19-119021990093-8). PT supported by Moscow State University Grant for Leading Scientific Schools "Depository of the Living Systems" in the MSU Development Program framework. TBL was funded by the Natural Environment Research Council UK, and the IAPETUS Doctoral Training Partnership

A Bayesian Partition Method for Detecting Pleiotropic and Epistatic eQTL Modules

Studies of the relationship between DNA variation and gene expression variation, often referred to as “expression quantitative trait loci (eQTL) mapping”, have been conducted in many species and resulted in many significant findings. Because of the large number of genes and genetic markers in such analyses, it is extremely challenging to discover how a small number of eQTLs interact with each other to affect mRNA expression levels for a set of co-regulated genes. We present a Bayesian method to facilitate the task, in which co-expressed genes mapped to a common set of markers are treated as a module characterized by latent indicator variables. A Markov chain Monte Carlo algorithm is designed to search simultaneously for the module genes and their linked markers. We show by simulations that this method is more powerful for detecting true eQTLs and their target genes than traditional QTL mapping methods. We applied the procedure to a data set consisting of gene expression and genotypes for 112 segregants of S. cerevisiae. Our method identified modules containing genes mapped to previously reported eQTL hot spots, and dissected these large eQTL hot spots into several modules corresponding to possibly different biological functions or primary and secondary responses to regulatory perturbations. In addition, we identified nine modules associated with pairs of eQTLs, of which two have been previously reported. We demonstrated that one of the novel modules containing many daughter-cell expressed genes is regulated by AMN1 and BPH1. In conclusion, the Bayesian partition method which simultaneously considers all traits and all markers is more powerful for detecting both pleiotropic and epistatic effects based on both simulated and empirical data

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria.

The clinical effects of alkaptonuria (AKU) are delayed and ageing influences disease progression. Morbidity of AKU is secondary to high circulating homogentisic acid (HGA) and ochronosis. It is not known whether HGA is produced by or processed in the kidney in AKU. Data from AKU patients from four studies were merged to form a single AKU group. A control group of non-AKU subjects was generated by merging data from two non-AKU studies. Data were used to derive renal clearance and fractional excretion (FE) ratios for creatinine, HGA, phenylalanine (PHE) and tyrosine (TYR) using standard calculations, for comparison between the AKU and the control groups. There were 225 AKU patients in the AKU group and 52 in the non-AKU control group. Circulating HGA increased with age (P < 0.001), and was significantly associated with decreased HGA clearance (CLHGA ) (P < 0.001) and FEHGA (P < 0.001). CLHGA and FEHGA were increased beyond the theoretical maximum renal plasma flow, confirming renal production and emphasising the greater contribution of net tubular secretion than glomerular filtration to renal elimination of HGA. The kidneys are crucial to elimination of HGA. Elimination of HGA is impaired with age resulting in worsening disease over time. The kidney is an important site for production of HGA. Tubular secretion of HGA contributes more to elimination of HGA in AKU than glomerular filtration

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

Massive stars as thermonuclear reactors and their explosions following core collapse

Nuclear reactions transform atomic nuclei inside stars. This is the process of stellar nucleosynthesis. The basic concepts of determining nuclear reaction rates inside stars are reviewed. How stars manage to burn their fuel so slowly most of the time are also considered. Stellar thermonuclear reactions involving protons in hydrostatic burning are discussed first. Then I discuss triple alpha reactions in the helium burning stage. Carbon and oxygen survive in red giant stars because of the nuclear structure of oxygen and neon. Further nuclear burning of carbon, neon, oxygen and silicon in quiescent conditions are discussed next. In the subsequent core-collapse phase, neutronization due to electron capture from the top of the Fermi sea in a degenerate core takes place. The expected signal of neutrinos from a nearby supernova is calculated. The supernova often explodes inside a dense circumstellar medium, which is established due to the progenitor star losing its outermost envelope in a stellar wind or mass transfer in a binary system. The nature of the circumstellar medium and the ejecta of the supernova and their dynamics are revealed by observations in the optical, IR, radio, and X-ray bands, and I discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure

Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses

Background: Mutations in the Otopetrin 1 gene (Otop1) in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP) family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence-and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH) subtype 1G (Ush1g), both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. Results: We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF), a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq) data in mouse and human embryonic stem (ES) cells combined with detection of CTCF-binding motifs. Conclusions: The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s) of Ush1g and Otop in developmental pathways

From Classical Genetics to Quantitative Genetics to Systems Biology: Modeling Epistasis

Gene expression data has been used in lieu of phenotype in both classical and quantitative genetic settings. These two disciplines have separate approaches to measuring and interpreting epistasis, which is the interaction between alleles at different loci. We propose a framework for estimating and interpreting epistasis from a classical experiment that combines the strengths of each approach. A regression analysis step accommodates the quantitative nature of expression measurements by estimating the effect of gene deletions plus any interaction. Effects are selected by significance such that a reduced model describes each expression trait. We show how the resulting models correspond to specific hierarchical relationships between two regulator genes and a target gene. These relationships are the basic units of genetic pathways and genomic system diagrams. Our approach can be extended to analyze data from a variety of experiments, multiple loci, and multiple environments