130 research outputs found

    The senescent secretome drives PLVAP expression in cultured human hepatic endothelia to promote monocyte transmigration

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    Liver sinusoidal endothelial cells (LSEC) undergo significant phenotypic change in chronic liver disease (CLD), and yet the factors that drive this process and the impact on their function as a vascular barrier and gatekeeper for immune cell recruitment are poorly understood. Plasmalemma-vesicle-associated protein (PLVAP) has been characterized as a marker of LSEC in CLD; notably we found that PLVAP upregulation strongly correlated with markers of tissue senescence. Furthermore, exposure of human LSEC to the senescence-associated secretory phenotype (SASP) led to a significant upregulation of PLVAP. Flow-based assays demonstrated that SASP-driven leukocyte recruitment was characterized by paracellular transmigration of monocytes while the majority of lymphocytes migrated transcellularly. Knockdown studies confirmed that PLVAP selectively supported monocyte transmigration mediated through PLVAP's impact on LSEC permeability by regulating phospho-VE-cadherin expression and endothelial gap formation. PLVAP may therefore represent an endothelial target that selectively shapes the senescence-mediated immune microenvironment in liver disease. [Abstract copyright: © 2023 The Author(s).

    Psychological responses to the proximity of climate change

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    A frequent suggestion to increase individuals’ willingness to take action on climate change and to support relevant policies is to highlight its proximal consequences. However, previous studies that have tested this proximising approach have not revealed the expected positive effects on individual action and support for addressing climate change. We present three lines of psychological reasoning that provide compelling arguments as to why highlighting proximal impacts of climate change might not be as effective a way to increase individual mitigation and adaptation efforts as is often assumed. Our contextualisation of the proximising approach within established psychological research suggests that, depending on the particular theoretical perspective one takes to this issue, and on specific individual characteristics suggested by these perspectives, proximising can bring about the intended positive effects, can have no (visible) effect, or can even backfire. Thus, the effects of proximising are much more complex than is commonly assumed. Revealing this complexity contributes to a refined theoretical understanding of the role psychological distance plays in the context of climate change and opens up further avenues for future research and for interventions

    Kelvin-Helmholtz instability in the presence of variable viscosity for mudflow resuspension in estuaries

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    The temporal stability of a parallel shear flow of miscible fluid layers of dif- ferent density and viscosity is investigated through a linear stability analysis and direct numerical simulations. The geometry and rheology of this Newto- nian fluid mixing can be viewed as a simplified model of the behavior of mud- flow at the bottom of estuaries for suspension studies. In this study, focus is on the stability and transition to turbulence of an initially laminar configuration. A parametric analysis is performed by varying the values of three control pa- rameters, namely the viscosity ratio, the Richardson and Reynolds numbers, in the case of initially identical thickness of the velocity, density and viscosity profiles. The range of parameters has been chosen so as to mimic a wide variety of real configurations. This study shows that the Kelvin-Helmholtz instability is controlled by the local Reynolds and Richardson numbers of the inflection point. In addition, at moderate Reynolds number, viscosity strat- ification has a strong influence on the onset of instability, the latter being enhanced at high viscosity ratio, while at high Reynolds number, the influ- ence is less pronounced. In all cases, we show that the thickness of the mixing layer (and thus resuspension) is increased by high viscosity stratification, in particular during the non-linear development of the instability and especially pairing processes. This study suggests that mud viscosity has to be taken into account for resuspension parameterizations because of its impact on the inflec- tion point Reynolds number and the viscosity ratio, which are key parameters for shear instabilities

    A critical appraisal of appendage disparity and homology in fishes

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    Fishes are both extremely diverse and morphologically disparate. Part of this disparity can be observed in the numerous possible fin configurations that may differ in terms of the number of fins as well as fin shapes, sizes and relative positions on the body. Here, we thoroughly review the major patterns of disparity in fin configurations for each major group of fishes and discuss how median and paired fin homologies have been interpreted over time. When taking into account the entire span of fish diversity, including both extant and fossil taxa, the disparity in fin morphologies greatly complicates inferring homologies for individual fins. Given the phylogenetic scope of this review, structural and topological criteria appear to be the most useful indicators of fin identity. We further suggest that it may be advantageous to consider some of these fin homologies as nested within the larger framework of homologous fin‐forming morphogenetic fields. We also discuss scenarios of appendage evolution and suggest that modularity may have played a key role in appendage disparification. Fin modules re‐expressed within the boundaries of fin‐forming fields could explain how some fins may have evolved numerous times independently in separate lineages (e.g., adipose fin), or how new fins may have evolved over time (e.g., anterior and posterior dorsal fins, pectoral and pelvic fins). We favour an evolutionary scenario whereby median appendages appeared from a unique field of competence first positioned throughout the dorsal and ventral midlines, which was then redeployed laterally leading to paired appendages.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151971/1/faf12402_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151971/2/faf12402.pd

    A New Mechanistic Scenario for the Origin and Evolution of Vertebrate Cartilage

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    The appearance of cellular cartilage was a defining event in vertebrate evolution because it made possible the physical expansion of the vertebrate “new head”. Despite its central role in vertebrate evolution, the origin of cellular cartilage has been difficult to understand. This is largely due to a lack of informative evolutionary intermediates linking vertebrate cellular cartilage to the acellular cartilage of invertebrate chordates. The basal jawless vertebrate, lamprey, has long been considered key to understanding the evolution of vertebrate cartilage. However, histological analyses of the lamprey head skeleton suggest it is composed of modern cellular cartilage and a putatively unrelated connective tissue called mucocartilage, with no obvious transitional tissue. Here we take a molecular approach to better understand the evolutionary relationships between lamprey cellular cartilage, gnathostome cellular cartilage, and lamprey mucocartilage. We find that despite overt histological similarity, lamprey and gnathostome cellular cartilage utilize divergent gene regulatory networks (GRNs). While the gnathostome cellular cartilage GRN broadly incorporates Runx, Barx, and Alx transcription factors, lamprey cellular cartilage does not express Runx or Barx, and only deploys Alx genes in certain regions. Furthermore, we find that lamprey mucocartilage, despite its distinctive mesenchymal morphology, deploys every component of the gnathostome cartilage GRN, albeit in different domains. Based on these findings, and previous work, we propose a stepwise model for the evolution of vertebrate cellular cartilage in which the appearance of a generic neural crest-derived skeletal tissue was followed by a phase of skeletal tissue diversification in early agnathans. In the gnathostome lineage, a single type of rigid cellular cartilage became dominant, replacing other skeletal tissues and evolving via gene cooption to become the definitive cellular cartilage of modern jawed vertebrates

    STAGES IN THE ORIGIN OF VERTEBRATES: ANALYSIS BY MEANS OF SCENARIOS

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    Vertebrates lack an epidermal nerve plexus. This feature is common to many invertebrates from which vertebrates differ by an extensive set of shared-derived characters (synapomorphies) derived from the neural crest and epidermal neurogenic placodes. Hence, the hypothesis that the developmental precursor of the epidermal nerve plexus may be homologous to the neural crest and epidermal neurogenic placodes. This account attempts to generate a nested set of scenarios for the prevertebrate-vertebrate transition, associating a presumed sequence of behavioural and environmental changes with the observed phenotypic ones. Toward this end, it integrates morphological, developmental, functional (physiological/behavioural) and some ecological data, as many phenotypic shifts apparently involved associated transitions in several aspects of the animals. The scenarios deal with the origin of embryonic and adult tissues and such major organs as the notochord, the CNS, gills and kidneys and propose a sequence of associated changes. Alternative scenarios are stated as the evidence often remains insufficient for decision. The analysis points to gaps in comprehension of the biology of the animals and therefore suggests further research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72629/1/j.1469-185X.1989.tb00471.x.pd
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