54 research outputs found

    IFNα-mediated remodeling of endothelial cells in the bone marrow niche

    Get PDF
    In the bone marrow, endothelial cells are a major component of the hematopoietic stem cell vascular niche and are a first line of defense against inflammatory stress and infection. The primary response of an organism to infection involves the synthesis of immune-modulatory cytokines, including interferon alpha. In the bone marrow, interferon alpha induces rapid cell cycle entry of hematopoietic stem cells in vivo. However, the effect of interferon alpha on bone marrow endothelial cells has not been described. Here, we demonstrate that acute interferon alpha treatment leads to rapid stimulation of bone marrow endothelial cells in vivo, resulting in increased bone marrow vascularity and vascular leakage. We find that activation of bone marrow endothelial cells involves the expression of key inflammatory and endothelial cell-stimulatory markers. This interferon alpha-mediated activation of bone marrow endothelial cells is dependent in part on vascular endothelial growth factor signaling in bone marrow hematopoietic cell types, including hematopoietic stem cells. Thus, this implies a role for hematopoietic stem cells in remodeling of the bone marrow niche in vivo following inflammatory stress. These data increase our current understanding of the relationship between hematopoietic stem cells and the bone marrow niche under inflammatory stress and also clarify the response of bone marrow niche endothelial cells to acute interferon alpha treatment in vivo

    TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration

    Get PDF
    Mechanoelectrical transduction is a cellular signalling pathway where physical stimuli are converted into electro-chemical signals by mechanically activated ion channels. We describe here the presence of mechanically activated currents in melanoma cells that are dependent on TMEM87a, which we have renamed Elkin1. Heterologous expression of this protein in PIEZO1-deficient cells, that exhibit no baseline mechanosensitivity, is sufficient to reconstitute mechanically activated currents. Melanoma cells lacking functional Elkin1 exhibit defective mechanoelectrical transduction, decreased motility and increased dissociation from organotypic spheroids. By analysing cell adhesion properties, we demonstrate that Elkin1 deletion is associated with increased cell-substrate adhesion and decreased homotypic cell-cell adhesion strength. We therefore conclude that Elkin1 supports a PIEZO1-independent mechanoelectrical transduction pathway and modulates cellular adhesions and regulates melanoma cell migration and cell-cell interactions

    Observations of the Sun using LOFAR Baldy station

    Get PDF
    We report first results of solar spectroscopic observations carried out with the Baldy LOFAR (LOw-Frequency ARray) station, Poland from October 2016 to July 2017. During this time, we observed different types of radio emission: type I and type III radio bursts. Our observations show that the station is fully operational and it is capable to work efficiently in the single station mode for solar observations. Furthermore, in this paper we will briefly describe the observational technique and instrument capabilities and show some examples of first observations. (C) 2018 COSPAR. Published by Elsevier Ltd. All rights reserved.Peer reviewe

    Absolute positions of 6.7-GHz methanol masers

    Full text link
    The ATCA, MERLIN and VLA interferometers were used to measure the absolute positions of 35 6.7 GHz methanol masers to subarcsecond or higher accuracy. Our measurements represent essential preparatory data for Very Long Baseline Interferometry, which can provide accurate parallax and proper motion determinations of the star-forming regions harboring the masers. Our data also allow associations to be established with infrared sources at different wavelengths. Our findings support the view that the 6.7 GHz masers are associated with the earliest phases of high-mass star formation.Comment: A&A accepted 29 pages, 6 figures, 5 table

    A complex proinflammatory cascade mediates the activation of HSCs upon LPS exposure in vivo

    Get PDF
    Infections are a key source of stress to the hematopoietic system. While infections consume short-lived innate immune cells, their recovery depends on quiescent hematopoietic stem cells (HSCs) with long-term self-renewal capacity. Both chronic inflammatory stress and bacterial infections compromise competitive HSC capacity and cause bone marrow failure. However, our understanding of how HSCs act during acute and contained infections remains incomplete. Here, we used advanced chimeric and genetic mouse models in combination with pharmacological interventions to dissect the complex nature of the acute systemic response of HSCs to lipopolysaccharide (LPS), a well-established model for inducing inflammatory stress. Acute LPS challenge transiently induced proliferation of quiescent HSCs in vivo. This response was not only mediated via direct LPS-TLR4 conjugation on HSCs, but also involved indirect TLR4 signaling in CD115+ monocytic cells, inducing a complex pro-inflammatory cytokine cascade in the bone marrow. Downstream of LPS-TLR4 signaling, the combined action of pro-inflammatory cytokines such as IFNα, IFNγ, TNFα, IL-1α, IL-1β and many others is required to mediate full HSC activation in vivo. Together, our study reveals detailed mechanistic insights into the interplay of proinflammatory cytokine-induced molecular pathways and cell types that jointly orchestrate the complex process of emergency hematopoiesis and HSC activation upon LPS exposure in vivo

    Interferometric imaging of the type IIIb and U radio bursts observed with LOFAR on 22 August 2017

    Get PDF
    Context. The Sun is the source of different types of radio bursts that are associated with solar flares, for example. Among the most frequently observed phenomena are type III solar bursts. Their radio images at low frequencies (below 100 MHz) are relatively poorly studied due to the limitations of legacy radio telescopes.Aims. We study the general characteristics of types IIIb and U with stria structure solar radio bursts in the frequency range of 20-80 MHz, in particular the source size and evolution in different altitudes, as well as the velocity and energy of electron beams responsible for their generation.Methods. In this work types IIIb and U with stria structure radio bursts are analyzed using data from the LOFAR telescope including dynamic spectra and imaging observations, as well as data taken in the X-ray range (GOES and RHESSI satellites) and in the extreme ultraviolet (SDO satellite).Results. In this study we determined the source size limited by the actual shape of the contour at particular frequencies of type IIIb and U solar bursts in a relatively wide frequency band from 20 to 80 MHz. Two of the bursts seem to appear at roughly the same place in the studied active region and their source sizes are similar. It is different in the case of another burst, which seems to be related to another part of the magnetic field structure in this active region. The velocities of the electron beams responsible for the generation of the three bursts studied here were also found to be different.Peer reviewe

    Marine malacofauna from vistulian deposits of the lower Vistula river

    No full text

    FEM Based Improvement of CAD for Non-Conventional Railway Track

    No full text
    This paper shows a new method for numerical modelling of railway track in Autodesk Symulation Multiphisics software. The model of non-conventional railway foundation type of LONGASF is analysed. The improvement of modelling process of railway track considered as a structure consisting of separately modelled components is presented as the main novelty of the paper. The created model aims to improve design capabilities associated with change of individual material properties and, consequently, the change of railway track structure. This model allows an analysis of many railway tracks, depending on their material solutions. The obtain results are analysed in order to formulate the guidelines for design of this type of railway track
    corecore