The wider context of the Lower Jurassic Toarcian oceanic anoxic event in Yorkshire coastal outcrops, UK

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The Toarcian Oceanic Anoxic Event (T-OAE, ∼183 Ma) was characterized by enhanced carbon burial, a prominent negative carbon-isotope excursion (CIE) in marine carbonate and organic matter, and numerous geochemical anomalies. A precursor excursion has also been documented at the Pliensbachian/Toarcian boundary, but its possible causes are less constrained. The T-OAE is intensively studied in the Cleveland Basin, Yorkshire, UK, whose sedimentary deposits have been litho-, bio- and chemostratigraphically characterised. Here, we present new elemental data produced by hand-held X-ray fluorescence analysis to test the expression of redox-sensitive trace metals and detrital elements across the upper Pliensbachian to mid-Toarcian of the Cleveland Basin. Detrital elemental concentrations (Al, Si, Ti, Zr) are used as proxies for siliciclastic grain content and thus, sea-level change, which match previous sequence stratigraphic interpretations from the Cleveland Basin. The timescale of the event is debated, though our new elemental proxies of relative sea level change show evidence for a cyclicity of 350 cm that may be indicative of ∼405 kyr eccentricity cycles in Yorkshire. Trends in total organic carbon and redox-sensitive elements (S, Fe, Mo, As) confirm scenarios of widespread ocean deoxygenation across the T-OAE. The correlation of comparable trends in Mo across the T-OAE in Yorkshire and the Paris Basin suggests a similar oceanic drawdown of this element accompanying widespread anoxia in the two basins. Data from Yorkshire point to a transgressive trend at the time of the Mo drawdown, which contradicts the “basin restriction” model for the euxinic conditions that characterise the CIE interval.The Carlsberg Foundation (project 2011-01-0737 to CK) and the Danish Council for Independent Research-Natural Sciences (project 09-072715 to CK) are acknowledged for contributions to financing this project

Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Recovery from Posttraumatic Stress Symptoms: A Qualitative Study of Attributions in Survivors of War

This study was funded by a grant from the European Commission, contract number INCO-CT-2004-50917

Robust estimation of microbial diversity in theory and in practice

Quantifying diversity is of central importance for the study of structure, function and evolution of microbial communities. The estimation of microbial diversity has received renewed attention with the advent of large-scale metagenomic studies. Here, we consider what the diversity observed in a sample tells us about the diversity of the community being sampled. First, we argue that one cannot reliably estimate the absolute and relative number of microbial species present in a community without making unsupported assumptions about species abundance distributions. The reason for this is that sample data do not contain information about the number of rare species in the tail of species abundance distributions. We illustrate the difficulty in comparing species richness estimates by applying Chao's estimator of species richness to a set of in silico communities: they are ranked incorrectly in the presence of large numbers of rare species. Next, we extend our analysis to a general family of diversity metrics ("Hill diversities"), and construct lower and upper estimates of diversity values consistent with the sample data. The theory generalizes Chao's estimator, which we retrieve as the lower estimate of species richness. We show that Shannon and Simpson diversity can be robustly estimated for the in silico communities. We analyze nine metagenomic data sets from a wide range of environments, and show that our findings are relevant for empirically-sampled communities. Hence, we recommend the use of Shannon and Simpson diversity rather than species richness in efforts to quantify and compare microbial diversity.Comment: To be published in The ISME Journal. Main text: 16 pages, 5 figures. Supplement: 16 pages, 4 figure

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

The Cyclostratigraphy Intercomparison Project (CIP): consistency, merits and pitfalls

Cyclostratigraphy is an important tool for understanding astronomical climate forcing and reading geological time in sedimentary sequences, provided that an imprint of insolation variations caused by Earth’s orbital eccentricity, obliquity and/or precession is preserved (Milankovitch forcing). Numerous stratigraphic and paleoclimate studies have applied cyclostratigraphy, but the robustness of the methodology and its dependence on the investigator have not been systematically evaluated. We developed the Cyclostratigraphy Intercomparison Project (CIP) to assess the robustness of cyclostratigraphic methods using an experimental design of three artificial cyclostratigraphic case studies with known input parameters. Each case study is designed to address specific challenges that are relevant to cyclostratigraphy. Case 1 represents an offshore research vessel environment, as only a drill-core photo and the approximate position of a late Miocene stage boundary are available for analysis. In Case 2, the Pleistocene proxy record displays clear nonlinear cyclical patterns and the interpretation is complicated by the presence of a hiatus. Case 3 represents a Late Devonian proxy record with a low signal-to-noise ratio with no specific theoretical astronomical solution available for this age. Each case was analyzed by a test group of 17-20 participants, with varying experience levels, methodological preferences and dedicated analysis time. During the CIP 2018 meeting in Brussels, Belgium, the ensuing analyses and discussion demonstrated that most participants did not arrive at a perfect solution, which may be partly explained by the limited amount of time spent on the exercises (∼4.5 hours per case). However, in all three cases, the median solution of all submitted analyses accurately approached the correct result and several participants obtained the exact correct answers. Interestingly, systematically better performances were obtained for cases that represented the data type and stratigraphic age that were closest to the individual participants’ experience. This experiment demonstrates that cyclostratigraphy is a powerful tool for deciphering time in sedimentary successions and, importantly, that it is a trainable skill. Finally, we emphasize the importance of an integrated stratigraphic approach and provide flexible guidelines on what good practices in cyclostratigraphy should include. Our case studies provide valuable insight into current common practices in cyclostratigraphy, their potential merits and pitfalls. Our work does not provide a quantitative measure of reliability and uncertainty of cyclostratigraphy, but rather constitutes a starting point for further discussions on how to move the maturing field of cyclostratigraphy forward

Disruption of a GATA4/Ankrd1 Signaling Axis in Cardiomyocytes Leads to Sarcomere Disarray: Implications for Anthracycline Cardiomyopathy

Doxorubicin (Adriamycin) is an effective anti-cancer drug, but its clinical usage is limited by a dose-dependent cardiotoxicity characterized by widespread sarcomere disarray and loss of myofilaments. Cardiac ankyrin repeat protein (CARP, ANKRD1) is a transcriptional regulatory protein that is extremely susceptible to doxorubicin; however, the mechanism(s) of doxorubicin-induced CARP depletion and its specific role in cardiomyocytes have not been completely defined. We report that doxorubicin treatment in cardiomyocytes resulted in inhibition of CARP transcription, depletion of CARP protein levels, inhibition of myofilament gene transcription, and marked sarcomere disarray. Knockdown of CARP with small interfering RNA (siRNA) similarly inhibited myofilament gene transcription and disrupted cardiomyocyte sarcomere structure. Adenoviral overexpression of CARP, however, was unable to rescue the doxorubicin-induced sarcomere disarray phenotype. Doxorubicin also induced depletion of the cardiac transcription factor GATA4 in cardiomyocytes. CARP expression is regulated in part by GATA4, prompting us to examine the relationship between GATA4 and CARP in cardiomyocytes. We show in co-transfection experiments that GATA4 operates upstream of CARP by activating the proximal CARP promoter. GATA4-siRNA knockdown in cardiomyocytes inhibited CARP expression and myofilament gene transcription, and induced extensive sarcomere disarray. Adenoviral overexpression of GATA4 (AdV-GATA4) in cardiomyocytes prior to doxorubicin exposure maintained GATA4 levels, modestly restored CARP levels, and attenuated sarcomere disarray. Interestingly, siRNA-mediated depletion of CARP completely abolished the Adv-GATA4 rescue of the doxorubicin-induced sarcomere phenotype. These data demonstrate co-dependent roles for GATA4 and CARP in regulating sarcomere gene expression and maintaining sarcomeric organization in cardiomyocytes in culture. The data further suggests that concurrent depletion of GATA4 and CARP in cardiomyocytes by doxorubicin contributes in large part to myofibrillar disarray and the overall pathophysiology of anthracycline cardiomyopathy

The evolution of the student as a customer in Australian higher education: a policy perspective

In 2014, the Australian Federal Government attempted to de-regulate higher education fees so as to allow universities to set their own tuition fees. The associated public debate offer critical insights into how the identity of a student as a ‘customer’ of higher education is understood and deployed when developing higher education policy. This paper uses the 2014 Australian higher education reforms as a lens through which to further scholarly research into the student-as-customer metaphor and to see how it is influenced by the perceptions and understandings of policy actors external to the higher education sector. These include politicians, special interest groups, the students and their parents and prospective employers. This study reveals that the public/private nexus—both of funding and benefit— problematizes traditional conceptualisations of students and others as higher education customers. In turn, this restricts the ability or desire of policy actors to describe how the student functions as a customer as a consequence of market reform. This inability compromises the development of effective and sustainable higher education polic

Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults – The GOYA Study

Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ~1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations. Methodology/Principal Findings: From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ~212,000 individuals). We followed up novel (at the time of the study) association signals (