Geology and geochronology of the Two-Thirty prospect, Northparkes district, NSW

The Northparkes district, central New South Wales, hosts several economic Cu–Au deposits associated with discrete, thin, porphyry intrusive complexes emplaced in the Late Ordovician during formation of the Macquarie Arc. The recently discovered Two-Thirty Cu–Au–(Mo) prospect is a mineralised magmatic–hydrothermal breccia complex that is hosted by the moderately east-dipping Goonumbla Volcanic Complex on the western limb of the Milpose Syncline ∼15 km south of the Northparkes porphyry district. Generation of the magmatic–hydrothermal breccia complex is interpreted to be related to the 448.0 ± 4.4 Ma emplacement of the Two-Thirty porphyry. However, Re–Os dating of molybdenite from the breccia complex indicates a potential for a ca 440 Ma mineralising event that has similar timing to economic porphyry mineralisation in the Northparkes district. The discovery of the Two-Thirty prospect has important implications for exploration in the Northparkes district and the broader Macquarie Arc. Two-Thirty is only the second known occurrence of magmatic-hydrothermal breccia-hosted mineralisation discovered within the Macquarie Arc, with the other being Cadia Quarry. Mineralisation at Two-Thirty is potentially older than the Northparkes and Cadia deposits, and younger than the epithermal and calc-alkaline deposits at Cowal, Marsden and Ridgeway.KEY POINTS: The Two-Thirty is a polyphase magmatic–hydrothermal breccia complex that hosts Cu–Au (Mo). The Two-Thirty is the first significant breccia-hosted mineralisation found in the Northparkes district. U–Pb zircon crystallisation ages of the causative intrusion at Two-Thirty pre-date mineralisation at Northparkes. Re–Os dates of molybdenite from the Two-Thirty breccia complex are coeval with syn-mineralisation at Northparkes, supporting the model of periodic release of melts and fluids from underlying magma chambers during the formation of porphyry mineralisation in the Northparkes district.This research is funded by Australian Research Council sponsors of the Lachlan ARC Linkage Project ‘LP160100483’ CMOC-Northparkes, Rio Tinto, Evolution Mining, IMEx Consulting, Heron Resources, Sandfire Resources NL, New South Resources, AngloGold Ashanti, Alkane Resources, Geoscience Australia, The University of Tasmania, Australian National University, University of Melbourne, CCFS, Curtin University, the New South Wales, Tasmanian and Victorian state governments

Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown

Epithelial cells that line the gut secrete complex glycoproteins that form a mucus layer to protect the gut wall from enteric pathogens. Here, the authors provide a comprehensive characterisation of endo-acting glycoside hydrolases expressed by mucin-degrading members of the microbiome that are able to cleave the O-glycan chains of a range of different animal and human mucins

Identification of Tuberculosis Susceptibility Genes with Human Macrophage Gene Expression Profiles

Although host genetics influences susceptibility to tuberculosis (TB), few genes determining disease outcome have been identified. We hypothesized that macrophages from individuals with different clinical manifestations of Mycobacterium tuberculosis (Mtb) infection would have distinct gene expression profiles and that polymorphisms in these genes may also be associated with susceptibility to TB. We measured gene expression levels of >38,500 genes from ex vivo Mtb-stimulated macrophages in 12 subjects with 3 clinical phenotypes: latent, pulmonary, and meningeal TB (n = 4 per group). After identifying differentially expressed genes, we confirmed these results in 34 additional subjects by real-time PCR. We also used a case-control study design to examine whether polymorphisms in differentially regulated genes were associated with susceptibility to these different clinical forms of TB. We compared gene expression profiles in Mtb-stimulated and unstimulated macrophages and identified 1,608 and 199 genes that were differentially expressed by >2- and >5-fold, respectively. In an independent sample set of 34 individuals and a subset of highly regulated genes, 90% of the microarray results were confirmed by RT-PCR, including expression levels of CCL1, which distinguished the 3 clinical groups. Furthermore, 6 single nucleotide polymorphisms (SNPs) in CCL1 were found to be associated with TB in a case-control genetic association study with 273 TB cases and 188 controls. To our knowledge, this is the first identification of CCL1 as a gene involved in host susceptibility to TB and the first study to combine microarray and DNA polymorphism studies to identify genes associated with TB susceptibility. These results suggest that genome-wide studies can provide an unbiased method to identify critical macrophage response genes that are associated with different clinical outcomes and that variation in innate immune response genes regulate susceptibility to TB

Considering methodological options for reviews of theory: illustrated by a review of theories linking income and health

Background: Review of theory is an area of growing methodological advancement. Theoretical reviews are particularly useful where the literature is complex, multi-discipline, or contested. It has been suggested that adopting methods from systematic reviews may help address these challenges. However, the methodological approaches to reviews of theory, including the degree to which systematic review methods can be incorporated, have received little discussion in the literature. We recently employed systematic review methods in a review of theories about the causal relationship between income and health. Methods: This article discusses some of the methodological issues we considered in developing the review and offers lessons learnt from our experiences. It examines the stages of a systematic review in relation to how they could be adapted for a review of theory. The issues arising and the approaches taken in the review of theories in income and health are considered, drawing on the approaches of other reviews of theory. Results: Different approaches to searching were required, including electronic and manual searches, and electronic citation tracking to follow the development of theories. Determining inclusion criteria was an iterative process to ensure that inclusion criteria were specific enough to make the review practical and focused, but not so narrow that key literature was excluded. Involving subject specialists was valuable in the literature searches to ensure principal papers were identified and during the inductive approaches used in synthesis of theories to provide detailed understanding of how theories related to another. Reviews of theory are likely to involve iterations and inductive processes throughout, and some of the concepts and techniques that have been developed for qualitative evidence synthesis can be usefully translated to theoretical reviews of this kind. Conclusions: It may be useful at the outset of a review of theory to consider whether the key aim of the review is to scope out theories relating to a particular issue; to conduct in-depth analysis of key theoretical works with the aim of developing new, overarching theories and interpretations; or to combine both these processes in the review. This can help decide the most appropriate methodological approach to take at particular stages of the review

Analysis of the transcriptional activity of endogenous NFAT5 in primary cells using transgenic NFAT-luciferase reporter mice

<p>Abstract</p> <p>Background</p> <p>The transcription factor NFAT5/TonEBP regulates the response of mammalian cells to hypertonicity. However, little is known about the physiopathologic tonicity thresholds that trigger its transcriptional activity in primary cells. Wilkins et al. recently developed a transgenic mouse carrying a luciferase reporter (9xNFAT-Luc) driven by a cluster of NFAT sites, that was activated by calcineurin-dependent NFATc proteins. Since the NFAT site of this reporter was very similar to an optimal NFAT5 site, we tested whether this reporter could detect the activation of NFAT5 in transgenic cells.</p> <p>Results</p> <p>The 9xNFAT-Luc reporter was activated by hypertonicity in an NFAT5-dependent manner in different types of non-transformed transgenic cells: lymphocytes, macrophages and fibroblasts. Activation of this reporter by the phorbol ester PMA plus ionomycin was independent of NFAT5 and mediated by NFATc proteins. Transcriptional activation of NFAT5 in T lymphocytes was detected at hypertonic conditions of 360–380 mOsm/kg (isotonic conditions being 300 mOsm/kg) and strongly induced at 400 mOsm/kg. Such levels have been recorded in plasma in patients with osmoregulatory disorders and in mice deficient in aquaporins and vasopressin receptor. The hypertonicity threshold required to activate NFAT5 was higher in bone marrow-derived macrophages (430 mOsm/kg) and embryonic fibroblasts (480 mOsm/kg). Activation of the 9xNFAT-Luc reporter by hypertonicity in lymphocytes was insensitive to the ERK inhibitor PD98059, partially inhibited by the PI3-kinase inhibitor wortmannin (0.5 μM) and the PKA inhibitor H89, and substantially downregulated by p38 inhibitors (SB203580 and SB202190) and by inhibition of PI3-kinase-related kinases with 25 μM LY294002. Sensitivity of the reporter to FK506 varied among cell types and was greater in primary T cells than in fibroblasts and macrophages.</p> <p>Conclusion</p> <p>Our results indicate that NFAT5 is a sensitive responder to pathologic increases in extracellular tonicity in T lymphocytes. Activation of NFAT5 by hypertonicity in lymphocytes was mediated by a combination of signaling pathways that differed from those required in other cell types. We propose that the 9xNFAT-Luc transgenic mouse model might be useful to study the physiopathological regulation of both NFAT5 and NFATc factors in primary cells.</p

Hubble Space Telescope spectra of the Type Ia supernova SN 2011fe: a tail of low-density, high-velocity material with Z < Z⊙

Hubble Space Telescope spectroscopic observations of the nearby Type Ia supernova (SN Ia) SN 2011fe, taken on 10 epochs from −13.1 to +40.8 d relative to B-band maximum light, and spanning the far-ultraviolet (UV) to the near-infrared (IR) are presented. This spectroscopic coverage makes SN 2011fe the best-studied local SN Ia to date. SN 2011fe is a typical moderately luminous SN Ia with no evidence for dust extinction. Its near-UV spectral properties are representative of a larger sample of local events (Maguire et al.). The near-UV to optical spectra of SN 2011fe are modelled with a Monte Carlo radiative transfer code using the technique of ‘abundance tomography’, constraining the density structure and the abundance stratification in the SN ejecta. SN 2011fe was a relatively weak explosion, with moderate Fe-group yields. The density structures of the classical model W7 and of a delayed detonation model were tested. Both have shortcomings. An ad hoc density distribution was developed which yields improved fits and is characterized by a high-velocity tail, which is absent in W7. However, this tail contains less mass than delayed detonation models. This improved model has a lower energy than one-dimensional explosion models matching typical SNe Ia (e.g. W7, WDD1; Iwamoto et al.). The derived Fe abundance in the outermost layer is consistent with the metallicity at the SN explosion site in M101 (∼0.5 Z⊙). The spectroscopic rise-time (∼19 d) is significantly longer than that measured from the early optical light curve, implying a ‘dark phase’ of ∼1 d. A longer rise-time has significant implications when deducing the properties of the white dwarf and binary system from the early photometric behaviour

Early impacts of the COVID-19 pandemic on mental health care and on people with mental health conditions: framework synthesis of international experiences and responses

PURPOSE: The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these. METHODS: We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach. RESULTS: We found 872 eligible sources from 28 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future. CONCLUSION: Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research

Expression profiling during arabidopsis/downy mildew interaction reveals a highly-expressed effector that attenuates responses to salicylic acid

Plants have evolved strong innate immunity mechanisms, but successful pathogens evade or suppress plant immunity via effectors delivered into the plant cell. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on Arabidopsis thaliana, and a genome sequence is available for isolate Emoy2. Here, we exploit the availability of genome sequences for Hpa and Arabidopsis to measure gene-expression changes in both Hpa and Arabidopsis simultaneously during infection. Using a high-throughput cDNA tag sequencing method, we reveal expression patterns of Hpa predicted effectors and Arabidopsis genes in compatible and incompatible interactions, and promoter elements associated with Hpa genes expressed during infection. By resequencing Hpa isolate Waco9, we found it evades Arabidopsis resistance gene RPP1 through deletion of the cognate recognized effector ATR1. Arabidopsis salicylic acid (SA)-responsive genes including PR1 were activated not only at early time points in the incompatible interaction but also at late time points in the compatible interaction. By histochemical analysis, we found that Hpa suppresses SA-inducible PR1 expression, specifically in the haustoriated cells into which host-translocated effectors are delivered, but not in non-haustoriated adjacent cells. Finally, we found a highly-expressed Hpa effector candidate that suppresses responsiveness to SA. As this approach can be easily applied to host-pathogen interactions for which both host and pathogen genome sequences are available, this work opens the door towards transcriptome studies in infection biology that should help unravel pathogen infection strategies and the mechanisms by which host defense responses are overcome