149 research outputs found

    Gene therapy of Csf2ra deficiency in mouse fetal monocyte precursors restores alveolar macrophage development and function

    Full text link
    Tissue-resident macrophage-based immune therapies have been proposed for various diseases. However, generation of sufficient numbers that possess tissue-specific functions remains a major handicap. Here, we showed that fetal liver monocytes cultured with GM-CSF (CSF2-cFLiMo) rapidly differentiated into a long-lived, homogeneous alveolar macrophage-like population in vitro. CSF2-cFLiMo retained the capacity to develop into bona fide alveolar macrophages upon transfer into Csf2ra-/- neonates and prevented development of alveolar proteinosis and accumulation of apoptotic cells for at least 1 year in vivo. CSF2-cFLiMo more efficiently engrafted empty alveolar macrophage niches in the lung and protected mice from severe pathology induced by respiratory viral infection compared with transplantation of macrophages derived from BM cells cultured with M-CSF (CSF1-cBMM) in the presence or absence of GM-CSF. Harnessing the potential of this approach for gene therapy, we restored a disrupted Csf2ra gene in fetal liver monocytes and demonstrated their capacity to develop into alveolar macrophages in vivo. Altogether, we provide a platform for generation of immature alveolar macrophage-like precursors amenable for genetic manipulation, which will be useful to dissect alveolar macrophage development and function and for pulmonary transplantation therapy

    Comparison of physicochemical properties of commercial UHT-treated plant-based beverages and cow's milk

    Get PDF
    A comparison of consumer-relevant physicochemical and technofunctional properties was performed between plant-based beverages (PBBs) and cow’s milk treated at ultra-high temperatures. The PBBs’ viscosities and pH values were similar to or higher than those in cow’s milk. The PBBs were less white, and their mean particle sizes were usually considerably larger than those of cow’s milk. Foam heights were quite different, from 41.5 mm to 173 mm at room temperature (milk foam height: 134.8 mm) and 50.9 mm to 203.6 mm at 60 °C (milk foam height: 179.3 mm), with a median bubble size radius (root mean square) of 14.0–149.5 μm (milk bubble size: 18 μm) and 31.0–175.5 μm (milk bubble size: 82.8 μm). Our correlation revealed that phytic acid (PA) might affect foam height at 60 °C, the temperature of interest for the consumption of hot beverages. This may be of interest, as PA might be reduced in these beverages for nutritional reasons

    Offshore 1755 CE Lisbon Tsunami deposit in the southern portuguese continental shelf

    Get PDF
    The importance of tsunami hazard assessment is only possible if a complete dataset of events is available, allowing the determination of the recurrence intervals of the tsunamis adapted to local and regional conditions. One possible way to know these intervals is to study the offshore sedimentary record, looking for sediment remobilised and transported by the incoming tsunami waves and generated backwash currents. Even if these deposits are not of easy access (and not so well studied), the tsunami depositional signature has potential to be better preserved than those located onshore.info:eu-repo/semantics/publishedVersio

    The ocean sampling day consortium

    Get PDF
    Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

    Progranulin Gene Variability and Plasma Levels in Bipolar Disorder and Schizophrenia

    Get PDF
    Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n = 271) or BPD (n = 237) as compared with 574 age-, gender- and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls

    MASTL promotes cell contractility and motility through kinase-independent signaling

    Get PDF
    Microtubule-associated serine/threonine-protein kinase-like (MASTL) is a mitosis-accelerating kinase with emerging roles in cancer progression. However, possible cell cycle-independent mechanisms behind its oncogenicity remain ambiguous. Here, we identify MASTL as an activator of cell contractility and MRTF-A/SRF (myocardin-related transcription factor A/serum response factor) signaling. Depletion of MASTL increased cell spreading while reducing contractile actin stress fibers in normal and breast cancer cells and strongly impairing breast cancer cell motility and invasion. Transcriptome and proteome profiling revealed MASTL-regulated genes implicated in cell movement and actomyosin contraction, including Rho guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and MRTF-A target genes tropomyosin 4.2 (TPM4), vinculin (VCL), and nonmuscle myosin IIB (NM-2B, MYH10). Mechanistically, MASTL associated with MRTF-A and increased its nuclear retention and transcriptional activity. Importantly, MASTL kinase activity was not required for regulation of cell spreading or MRTF-A/SRF transcriptional activity. Taken together, we present a previously unknown kinase-independent role for MASTL as a regulator of cell adhesion, contractility, and MRTF-A/SRF activity. [Abstract copyright: © 2020 Taskinen et al.

    Lack of Galectin-3 Drives Response to Paracoccidioides brasiliensis toward a Th2-Biased Immunity

    Get PDF
    There is recent evidence that galectin-3 participates in immunity to infections, mostly by tuning cytokine production. We studied the balance of Th1/Th2 responses to P. brasiliensis experimental infection in the absence of galectin-3. The intermediate resistance to the fungal infection presented by C57BL/6 mice, associated with the development of a mixed type of immunity, was replaced with susceptibility to infection and a Th2-polarized immune response, in galectin-3-deficient (gal3−/−) mice. Such a response was associated with defective inflammatory and delayed type hypersensitivity (DTH) reactions, high IL-4 and GATA-3 expression and low nitric oxide production in the organs of infected animals. Gal3−/− macrophages exhibited higher TLR2 transcript levels and IL-10 production compared to wild-type macrophages after stimulation with P. brasiliensis antigens. We hypothesize that, during an in vivo P. brasiliensis infection, galectin-3 exerts its tuning role on immunity by interfering with the generation of regulatory macrophages, thus hindering the consequent Th2-polarized type of response
    corecore