2,105 research outputs found

    Temporal Evolution of Island Arc Magmatism and Its Influence on Long-Term Climate: Insights From the Izu Intra-Oceanic Arc

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    Continental arcs have an episodic magmatic activity over long-time periods, which is believed to modulate long-term climate. Island arcs have also the potential to release large amount of CO2 into the atmosphere, but whether they display an episodic magmatic history throughout their lifespan that contributes to the long-term (>10 Ma) climate changes remains an open question. To set additional constraints on the magmatic history of island arcs, here we examine fresh basalts and mineral-hosted melt inclusions from the Izu intra-oceanic arc, shortly after the eruption of boninites (∼45 Ma ago). Using chemical markers, we show that the long-term magmatic activity of the mature Izu arc has been relatively continuous over its lifespan, except during opening of the Shikoku back-arc Basin (∼23–20 Ma). Because slab dehydration and slab melting trigger decarbonation and carbonate dissolution of the subducted plate, we use slab-fluid markers (Ba/Th, Cs/Th, Cs/Ba, Rb/Th, Th/Nb) to examine the variations of slab-derived CO2 captured by the arc magmas. The long-term steadiness in the arc magmatic activity and in the slab-fluid contribution suggests that the CO2 outgassed during mature arc volcanism may have remained relatively homogeneous for the past 40 Ma in Izu. If worldwide mature island arcs also maintain a relatively steady-state magmatic activity over their lifespan, the long-term CO2 outgassed by these arc volcanoes may be rapidly balanced by chemical weathering and tectonic erosion, which rapidly draw down the atmospheric CO2 (within 200–300 kyr). This rapid negative feedback to long-term volcanic degassing permits to sustain a viable atmospheric CO2 for millions of years. The lack of co-variations between the markers of climate changes (δ13O, δ18C) and the long-term averages of the markers of slab fluids further implies that long-term volcanic degassing of CO2 from mature island arcs might play a minor role in the slide into icehouse climatic conditions. This long-term degassing stability may be, instead, a contributor to maintaining a broadly stable climate over long timescales

    Studies of the Antiproliferative Activity of Ruthenium (II) Cyclopentadienyl-Derived Complexes with Nitrogen Coordinated Ligands

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    Four cationic ruthenium(II) complexes with the formula [Ru(η5-C5H5)(PPh3)2]+, with L = 5-phenyl-1H-tetrazole (TzH) 1, imidazole (ImH) 2, benzo[1,2-b;4,3-b′] dithio-phen-2-carbonitrile (Bzt) 3, and [5-(2-thiophen-2-yl)-vinyl]-thiophene-2-carbonitrile] (Tvt) 4 were prepared and characterized in view to evaluate their potentialities as antitumor agents. Studies by Circular Dichroism indicated changes in the secondary structure of ct-DNA. Changes in the tertiary structure of pBR322 plasmid DNA were also observed in gel electrophoresis experiment and the images obtained by atomic force microscopy (AFM) suggest strong interaction with pBR322 plasmid DNA; the observed decreasing of the viscosity with time indicates that the complexes do not intercalate between DNA base pairs. Compounds 1, 2, and 3 showed much higher cytotoxicity than the cisplatin against human leukaemia cancer cells (HL-60 cells)

    NMR-based plant metabolomics protocols: a step-by-step guide.

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    Metabolomics is one of the “omics” sciences that can reveal the metabolic phenotype of organisms. This capability makes it a valuable tool for plant investigation, as plants present a vast chemical diversity. From the analytical point of view, two main techniques are frequently used in metabolomics and are often complementary: Mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. Here, we describe NMR and its applications in plant metabolomics. We start by contextualizing the research field to then explore study design, sample collection, sample preparation, NMR data acquisition, and data analysis, showing the key features for achieving quality and relevant results. Within these topics, the most common databases used for plant metabolites identification and assignments are listed, as these help to shorten the laborious task of metabolomics investigation of natural products. Concerning NMR parameters, we discuss the key pulse sequences, recommend acquisition parameters, and examine the data each sequence can provide. Similarly, we delve into data analysis, highlighting the most commonly used chemometric methods and how to achieve high-quality results. Therefore, this review aims to provide a comprehensive guide for NMR-based metabolomics analysis of plants

    Geodynamic Evolution of a Forearc Rift in the Southernmost Mariana Arc

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    The southernmost Mariana forearc stretched to accommodate opening of the Mariana Trough backarc basin in late Neogene time, erupting basalts now exposed in the SE Mariana Forearc Rift (SEMFR) 3.7 – 2.7 Ma ago. Today, SEMFR is a broad zone of extension that formed on hydrated, forearc lithosphere and overlies the shallow subducting slab (slab depth ≤ 30 – 50 km). It comprises NW-SE trending subparallel deeps, 3 - 16 km wide, that can be traced ≥ ~ 30 km from the trench almost to the backarc spreading center, the Malaguana-Gadao Ridge (MGR). While forearcs are usually underlain by serpentinized harzburgites too cold to melt, SEMFR crust is mostly composed of Pliocene, low-K basaltic to basaltic andesite lavas that are compositionally similar to arc lavas and backarc basin (BAB) lavas, and thus defines a forearc region that recently witnessed abundant igneous activity in the form of seafloor spreading. SEMFR igneous rocks have low Na8, Ti8, and Fe8, consistent with extensive melting, at ~ 23 ± 6.6 km depth and 1239 ± 40oC, by adiabatic decompression of depleted asthenospheric mantle metasomatized by slab-derived fluids. Stretching of pre-existing forearc lithosphere allowed BAB-like mantle to flow along SEMFR and melt, forming new oceanic crust. Melts interacted with preexisting forearc lithosphere during ascent. SEMFR is no longer magmatically active and post-magmatic tectonic activity dominates the rift

    The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome

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    © 2021 Rodríguez-Caballero, Fuentes Herrero, Oliva Ariza, Criado, Alcoceba, Prieto, Pérez Caro, García-Montero, González Díaz, Forconi, Sarmento-Ribeiro, Almeida and Orfao.The HCDR3 sequences of the B-cell receptor (BCR) undergo constraints in length, amino acid use, and charge during maturation of B-cell precursors and after antigen encounter, leading to BCR and antibodies with high affinity to specific antigens. Chronic lymphocytic leukemia consists of an expansion of B-cells with a mixed immature and “antigen-experienced” phenotype, with either a mutated (M-CLL) or unmutated (U-CLL) tumor BCR, associated with distinct patient outcomes. Here, we investigated the hydropathy index of the BCR of 138 CLL patients and its association with the IGHV mutational status and patient outcome. Overall, two clearly distinct subgroups of M-CLL patients emerged, based on a neutral (mean hydropathy index of -0.1) vs. negatively charged BCR (mean hydropathy index of -1.1) with molecular features closer to those of B-cell precursors and peripheral/mature B-cells, respectively. Despite that M-CLL with neutral HCDR3 did not show traits associated with a mature B-cell repertoire, important differences in IGHV gene usage of tumor cells and patient outcome were observed in this subgroup of patients once compared to both U-CLL and M-CLL with negatively charged HCDR3 sequences. Compared to M-CLL with negatively charged HCDR3 sequences, M-CLL with neutral HCDR3 sequences showed predominance of men, more advanced stages of the disease, and a greater frequency of genetic alterations—e.g., del(17p)—together with a higher rate of disease progression and shorter time to therapy (TTT), independently of other prognostic factors. Our data suggest that the hydropathy index of the HCDR3 sequences of CLL cells allows the identification of a subgroup of M-CLL with intermediate prognostic features between U-CLL and the more favorable subgroup of M-CLL with a negatively charged BCR.This work was supported by the following grants: FS/37-2017, from the Fundación Memoria D. Samuel Solórzano, Universidad de Salamanca; FIS PI17/00399-FEDER, from the Fondo de Investigación Sanitaria of Instituto de Salud Carlos III, Madrid, Spain; 0639_IDIAL_NET_3_E, from cooperative network EPINTERREG V A España Portugal (POCTEP); and ECRIN-M3, Accelerator Award Full, Cancer Research UK, Fundación Cientıfíca de la Asociación Española Contra el Cáncer (AECC), Fondazione AIRC per la Ricerca sul Cancro.

    Temporal Evolution of Island Arc Magmatism and Its Influence on Long-Term Climate: Insights From the Izu Intra-Oceanic Arc

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    Continental arcs have an episodic magmatic activity over long-time periods, which is believed to modulate long-term climate. Island arcs have also the potential to release large amount of CO2 into the atmosphere, but whether they display an episodic magmatic history throughout their lifespan that contributes to the long-term (>10 Ma) climate changes remains an open question. To set additional constraints on the magmatic history of island arcs, here we examine fresh basalts and mineral-hosted melt inclusions from the Izu intra-oceanic arc, shortly after the eruption of boninites (∼45 Ma ago). Using chemical markers, we show that the long-term magmatic activity of the mature Izu arc has been relatively continuous over its lifespan, except during opening of the Shikoku back-arc Basin (∼23–20 Ma). Because slab dehydration and slab melting trigger decarbonation and carbonate dissolution of the subducted plate, we use slab-fluid markers (Ba/Th, Cs/Th, Cs/Ba, Rb/Th, Th/Nb) to examine the variations of slab-derived CO2 captured by the arc magmas. The long-term steadiness in the arc magmatic activity and in the slab-fluid contribution suggests that the CO2 outgassed during mature arc volcanism may have remained relatively homogeneous for the past 40 Ma in Izu. If worldwide mature island arcs also maintain a relatively steady-state magmatic activity over their lifespan, the long-term CO2 outgassed by these arc volcanoes may be rapidly balanced by chemical weathering and tectonic erosion, which rapidly draw down the atmospheric CO2 (within 200–300 kyr). This rapid negative feedback to long-term volcanic degassing permits to sustain a viable atmospheric CO2 for millions of years. The lack of co-variations between the markers of climate changes (δ13O, δ18C) and the long-term averages of the markers of slab fluids further implies that long-term volcanic degassing of CO2 from mature island arcs might play a minor role in the slide into icehouse climatic conditions. This long-term degassing stability may be, instead, a contributor to maintaining a broadly stable climate over long timescales

    CD20+ T cells in monoclonal B cell lymphocytosis and chronic lymphocytic leukemia: frequency, phenotype and association with disease progression

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    IntroductionIn monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), the expansion of malignant B cells disrupts the normal homeostasis and interactions between B cells and T cells, leading to immune dysregulation. CD20+ T cells are a subpopulation of T cells that appear to be involved in autoimmune diseases and cancer.MethodsHere, we quantified and phenotypically characterized CD20+ T cells from MBL subjects and CLL patients using flow cytometry and correlated our findings with the B-cell receptor mutational status and other features of the disease. Results and discussionCD20+ T cells were more represented within the CD8+ T cell compartment and they showed a predominant memory Tc1 phenotype. CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vβ 5.1 in CD4+ CD20+ T cells in CLL

    Blockade of mGluR5 in astrocytes derived from human iPSCs modulates astrocytic function and increases phagocytosis

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    TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 (mGluR5). Under neuroinflammatory conditions, mGluR5 activation in astrocytes can be neuroprotective or have the opposite effect. In the current study, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP decreases the secreted levels of pro-inflammatory cytokines (IL-6 and IL-8) following short rTNF-α stimulation, although this effect subsides with time. Additionally, CTEP enhances synaptoneurosome phagocytosis by astrocytes in both non-stimulated and rTNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation augment the expression of the reactivity marker SERPINA3 and reduces the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockade may have beneficial and detrimental effects under inflammatory conditions

    A Review of the Key Demands for a Football Goalkeeper

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    This review evaluates previously published findings relating to the needs of a football goalkeeper during match performance. Whilst there has been much interest in some aspects of goalkeepers training, performance analysis and needs analysis, these have been from closed skill penalty situations or reported as comparisons with outfield players. This paper identifies important demands, assesses the implications for coaching and as a result highlights where the focus for effective future research should be to further enhance the development of goalkeeping performance
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