106 research outputs found

    Quantitative stratigraphic analysis in a source-to-sink numerical framework

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    The sedimentary architecture at continental margins reflects the interplay between the rate of change of accommodation creation (δA) and the rate of change of sediment supply (δS). Stratigraphic interpretation increasingly focuses on understanding the link between deposition patterns and changes in δA=δS, with an attempt to reconstruct the contributing factors. Here, we use the landscape modelling code pyBadlands to (1) investigate the development of stratigraphic sequences in a source-to-sink context; (2) assess the respective performance of two well-established stratigraphic interpretation techniques: the trajectory analysis method and the accommodation succession method; and (3) propose quantitative stratigraphic interpretations based on those two techniques. In contrast to most stratigraphic forward models (SFMs), pyBadlands provides self-consistent sediment supply to basin margins as it simulates erosion, sediment transport and deposition in a source-to-sink context. We present a generic case of landscape evolution that takes into account periodic sea level variations and passive margin thermal subsidence over 30 million years, under uniform rainfall. A set of post-processing tools are provided to analyse the predicted stratigraphic architecture. We first reconstruct the temporal evolution of the depositional cycles and identify key stratigraphic surfaces based on observations of stratal geometries and facies relationships, which we use for comparison to stratigraphic interpretations. We then apply both the trajectory analysis and the accommodation succession methods to manually map key stratigraphic surfaces and define sequence units on the final model output. Finally, we calculate shoreline and shelf-edge trajectories, the temporal evolution of changes in relative sea level (proxy for δA) and sedimentation rate (proxy for δS) at the shoreline, and automatically produce stratigraphic interpretations. Our results suggest that the analysis of the presented model is more robust with the accommodation succession method than with the trajectory analysis method. Stratigraphic analysis based on manually extracted shoreline and shelf-edge trajectory requires calibrations of time-dependent processes such as thermal subsidence or additional constraints from stratal terminations to obtain reliable interpretations. The 3-D stratigraphic analysis of the presented model reveals small lateral variations of sequence formations. Our work provides an efficient and flexible quantitative sequence stratigraphic framework to evaluate the main drivers (climate, sea level and tectonics) controlling sedimentary architectures and investigate their respective roles in sedimentary basin development. © Author(s) 2019.Acknowledgements. Xuesong Ding, Tristan Salles and Patrice Rey were supported by Australian Research Council grant IH130200012 (Basin GENESIS Hub), and Nicolas Flament was supported by Australian Research Council grant DE160101020. Ding acknowledges supports from the International Association for Mathematical Geosciences (IAMG) grant. This research was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government. We thank Zoltan Sylvester and Jack Neal for their constructive comments on this paper. We also thank Kyle Straub, Cornel Olariu and Jack Neal for their valuable comments on an earlier version of the manuscript. Australian Research Council (grant nos. IH130200012 and DE160101020)

    The Chlamydia effector TarP mimics the mammalian leucine-aspartic acid motif of paxillin to subvert the focal adhesion kinase during invasion

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    Host cell signal transduction pathways are often targets of bacterial pathogens, especially during the process of invasion when robust actin remodeling is required. We demonstrate that the host cell focal adhesion kinase (FAK) was necessary for the invasion by the obligate intracellular pathogen Chlamydia caviae. Bacterial adhesion triggered the transient recruitment of FAK to the plasma membrane to mediate a Cdc42- and Arp2/3-dependent actin assembly. FAK recruitment was via binding to a domain within the virulence factor TarP that mimicked the LD2 motif of the FAK binding partner paxillin. Importantly, bacterial two-hybrid and quantitative imaging assays revealed a similar level of interaction between paxillin-LD2 and TarP-LD. The conserved leucine residues within the L(D/E)XLLXXL motif were essential to the recruitment of FAK, Cdc42, p34Arc, and actin to the plasma membrane. In the absence of FAK, TarP-LD-mediated F-actin assembly was reduced, highlighting the functional relevance of this interaction. Together, the data indicate that a prokaryotic version of the paxillin LD2 domain targets the FAK signaling pathway, with TarP representing the first example of an LD-containing Type III virulence effector

    Population Structure of Staphylococcus aureus from Remote African Babongo Pygmies

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    Staphylococcus aureus is a bacterium that colonizes humans worldwide. The anterior nares are its main ecological niche. Carriers of S. aureus are at a higher risk of developing invasive infections. Few reports indicated a different clonal structure and profile of virulence factors in S. aureus isolates from Sub-Saharan Africa. As there are no data about isolates from remote indigenous African populations, we conducted a cross-sectional survey of S. aureus nasal carriage in Gabonese Babongo Pygmies. The isolates were characterized regarding their susceptibility to antibiotic agents, possession of virulence factors and clonal lineage. While similar carriage rates were found in populations of industrialized countries, isolates that encode the genes for the Panton-Valentine leukocidin (PVL) were clearly more prevalent than in European countries. Of interest, many methicillin-susceptible S. aureus isolates from Babongo Pygmies showed the same genetic background as pandemic methicillin-resistant S. aureus (MRSA) clones. We advocate a surveillance of S. aureus in neglected African populations to control the development of resistance to antibiotic drugs with particular respect to MRSA and to assess the impact of the high prevalence of PVL-positive isolates

    Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

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    RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Quantitative stratigraphic analysis in a source-to-sink numerical framework

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    The sedimentary architecture at continental margins reflects the interplay between the rate of change of accommodation creation (δA) and the rate of change of sediment supply (δS). Stratigraphic interpretation increasingly focuses on understanding the link between deposition patterns and changes in δA=δS, with an attempt to reconstruct the contributing factors. Here, we use the landscape modelling code pyBadlands to (1) investigate the development of stratigraphic sequences in a source-to-sink context; (2) assess the respective performance of two well-established stratigraphic interpretation techniques: the trajectory analysis method and the accommodation succession method; and (3) propose quantitative stratigraphic interpretations based on those two techniques. In contrast to most stratigraphic forward models (SFMs), pyBadlands provides self-consistent sediment supply to basin margins as it simulates erosion, sediment transport and deposition in a source-to-sink context. We present a generic case of landscape evolution that takes into account periodic sea level variations and passive margin thermal subsidence over 30 million years, under uniform rainfall. A set of post-processing tools are provided to analyse the predicted stratigraphic architecture. We first reconstruct the temporal evolution of the depositional cycles and identify key stratigraphic surfaces based on observations of stratal geometries and facies relationships, which we use for comparison to stratigraphic interpretations. We then apply both the trajectory analysis and the accommodation succession methods to manually map key stratigraphic surfaces and define sequence units on the final model output. Finally, we calculate shoreline and shelf-edge trajectories, the temporal evolution of changes in relative sea level (proxy for δA) and sedimentation rate (proxy for δS) at the shoreline, and automatically produce stratigraphic interpretations. Our results suggest that the analysis of the presented model is more robust with the accommodation succession method than with the trajectory analysis method. Stratigraphic analysis based on manually extracted shoreline and shelf-edge trajectory requires calibrations of time-dependent processes such as thermal subsidence or additional constraints from stratal terminations to obtain reliable interpretations. The 3-D stratigraphic analysis of the presented model reveals small lateral variations of sequence formations. Our work provides an efficient and flexible quantitative sequence stratigraphic framework to evaluate the main drivers (climate, sea level and tectonics) controlling sedimentary architectures and investigate their respective roles in sedimentary basin development

    Drainage and Sedimentary Responses to Dynamic Topography

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    Dynamic topography due to mantle flow contributes to shaping Earth\u27s evolving landscapes by affecting sediment routing, which has rarely been explored in source-to-sink contexts. Here we design a generic model to investigate the impact of dynamic topography on both landscape evolution and stratigraphic formations. An imposed wave of dynamic topography propagates laterally under a fixed continent, exerting transient surface uplift and subsidence. We find that a migrating dynamic topography can induce significant drainage reorganizations and affect sediment routing from source to sink. Variations in sediment supply driven by the lateral migrating dynamic topography contribute to the formation of diachronous unconformities along the margin. The predicted sediment flux histories are then put into perspective with the Cretaceous sedimentary records along the Southern African margins. Finally, we demonstrate that correlating offshore depositional hiatuses and unconformities has the potential to constrain the spatiotemporal evolution of past dynamic topography events

    Vinculin Interacts with the Chlamydia Effector TarP Via a Tripartite Vinculin Binding Domain to Mediate Actin Recruitment and Assembly at the Plasma Membrane

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    The mammalian protein vinculin is often a target of bacterial pathogens to subvert locally host cell actin dynamics. In Chlamydia infection, vinculin has been implicated in RNA interference screens, but the molecular basis for vinculin requirement has not been characterized. In this report, we show that vinculin was involved in the actin recruitment and F-actin assembly at the plasma membrane to facilitate invasion. Vinculin was recruited to the plasma membrane via its interaction with a specific tripartite motif within TarP that resembles the vinculin-binding domain (VBD) found in the Shigella invasion factor IpaA. The TarP-mediated plasma membrane recruitment of vinculin resulted in the localized recruitment of actin. In vitro pulldown assays for protein-protein interaction and imaging-based evaluation of recruitment to the plasma membrane demonstrated the essential role of the vinculin-binding site 1 (VBS1), and the dispensability of VBS2 and VBS3. As further support for the functionality of VBD-vinculin interaction, VBD-mediated actin recruitment required vinculin. Interestingly, while both vinculin and the focal adhesion kinase (FAK) colocalized at the sites of adhesion, the recruitment of one was independent of the other; and the actin recruitment function of the VBD/vinculin signaling axis was independent of the LD/FAK pathway
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