Ecologia, manejo e utilização da Virola surinamensis Rol.(Warb.).

bitstream/item/63285/1/Oriental-Doc74.pd

Along strike preorogenic thickness variation and onlapping geometries control on thrust wedge evolution: insight from sandbox analogue modelling

Abstract: Thickness variation of sedimentary sequences is largely viewed as a controlling factor on the evolution of orogenic wedges; among the different structural and stratigraphic features generating thickness variation, we focused our analysis on the onlapping geometries, using laboratory sandbox experiments. The aim was trying to describe how a common sedimentary configuration could influence thrusts geometry and mode of accretion. Model results showed that onlapping geometries in pretectonic sediments cause a great complexity, dominated by curvilinear thrusts, back thrust and out-ofsequence thrusts. They also influence mode of accretion, generating diachronous thrusting along strike, reactivation and under-thrusting alternating to simple piggy-back sequence. Our modeling results are compared with natural examples from the Apennines, the southern Pyrenees, the Pindos (Greece) and the West Spitsbergen (Greenland) fold and thrust belts, among many others, where strain localization and diachronic thrusting affecting thrust propagation in correspondence to complex geometries both in the pre-orogenic stratigraphy and in the upper crust

New boundary conditions for simulating the filling stage of the injection molding process

Purpose The purpose of this paper is to develop new boundary conditions for simulating the injection molding process of polymer melts. Design/methodology/approach The boundary conditions are derived and implemented to simulate real-life air vents (used to allow the air escape from the mold). The simulations are performed in the computational libraryOpenFOAM (R) by considering two different fluid models, namely, Newtonian and generalized Newtonian (Bird-Carreau model). Findings A detailed study on the accuracy of the solverinterFoamfor simulating the filling stage is presented, by considering simple geometries and adaptive mesh refinement. The verified code is then used to study the three-dimensional filling of a more complex geometry. Originality/value The results obtained showed that the numerical method is stable and allows one to model the filling process, simulating the real injection molding process.This work is funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT (Portuguese Foundation for Science and Technology) under the projects UID-B/05256/2020, UID-P/05256/2020 and MOLDPRO-Aproximacoes multi-escala para moldacao por injecao de materiais plasticos (POCI-01-0145-FEDER-016665).The research of L.L. Ferras was partially financed by the Portuguese Funds through FCT within the Projects UID-B/00013/2020, UID-P/00013/2020 and the scholarship SFRH/BPD/100353/2014.The authors would like to acknowledge the Minho University Cluster (NORTE-07-0162-FEDER-000086) for providing the HPC resources that contributed to the research results reported within this paper

MicroRNA-24 regulates vascularity after myocardial infarction

BACKGROUND: Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood. METHODS AND RESULTS: Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2-associated death promoter) and Sirtuin1 were identified by transcriptome, protein arrays, and chromatin immunoprecipitation analyses. Overexpression of miR-24 or silencing of its targets significantly impaired angiogenesis in zebrafish embryos. Blocking of endothelial miR-24 limited myocardial infarct size of mice via prevention of endothelial apoptosis and enhancement of vascularity, which led to preserved cardiac function and survival. CONCLUSIONS: Our findings indicate that miR-24 acts as a critical regulator of endothelial cell apoptosis and angiogenesis and is suitable for therapeutic intervention in the setting of ischemic heart disease. [KEYWORDS: Animals, Apoptosis/drug effects, Arterioles/pathology, Capillaries/pathology, Cell Hypoxia, Cells, Cultured/drug effects/metabolism, Collagen, Drug Combinations, Drug Evaluation, Preclinical, Endothelial Cells/ metabolism/pathology, GATA2 Transcription Factor/biosynthesis/genetics, Gene Expression Profiling, Heart Failure/etiology, Heme Oxygenase-1/biosynthesis/genetics, Laminin, Male, Mice, Mice, Inbred C57BL, MicroRNAs/antagonists & inhibitors/genetics/ physiology, Myocardial Infarc

GW0742, a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice.

Peroxisome Proliferator-Activated Receptor β/δ belongs to a family of ligand-activated transcription factors. Recent data have clarified its metabolic roles and enhanced the potential role of this receptor as a pharmacological target. Moreover, although its role in acute inflammation remains unclear, being the nuclear receptor PPAR β/δ widely expressed in many tissues, including the vascular endothelium, we assume that the infiltration of PMNs into tissues, a prominent feature in inflammation, may also be related to PPAR β/δ. Mice subjected to intratracheal instillation of bleomycin (BLEO, 1 mg/kg), a glycopeptide produced by the bacterium Streptomyces verticillus, develop lung inflammation and injury characterized by a significant neutrophil infiltration and tissue oedema. Therefore, the aim of this study is to investigate the effects of GW0742, a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Our data showed that GW0742-treatment (0.3 mg/Kg, 10% DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of: 1) cytokine production; 2) leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity; 3) IκBα degradation and NF-κB nuclear translocation; 4) ERK phosphorylation; 5) stress oxidative by NO formation due to iNOS expression; 6) nitrotyrosine and PAR localization; 7) the degree of apoptosis, evaluated by Bax and Bcl2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO-instillation in mice

CD100 Effects in Macrophages and Its Roles in Atherosclerosis

CD100 or Sema4D is a protein from the semaphorin family with important roles in the vascular, nervous and immune systems. It may be found as a membrane bound dimer or as a soluble molecule originated by proteolytic cleavage. Produced by the majority of hematopoietic cells including B and T lymphocytes, natural killer and myeloid cells, as well as endothelial cells, CD100 exerts its actions by binding to different receptors depending on the cell type and on the organism. Cell-to-cell adhesion, angiogenesis, phagocytosis, T cell priming, and antibody production are examples of the many functions of this molecule. Of note, high CD100 serum levels has been found in inflammatory as well as in infectious diseases, but the roles of the protein in the pathogenesis of these diseases has still to be clarified. Macrophages are highly heterogeneous cells present in almost all tissues, which may change their functions in response to microenvironmental conditions. They are key players in the innate and adaptive immune responses and have decisive roles in sterile conditions but also in several diseases such as atherosclerosis, autoimmunity, tumorigenesis, and antitumor responses, among others. Although it is known that macrophages express CD100 and its receptors, few studies have focused on the role of this semaphorin in this cell type or in macrophage-associated diseases. The aim of this review is to critically revise the available data about CD100 and atherosclerosis, with special emphasis on its roles in macrophages and monocytes. We will also describe the few available data on treatments with anti-CD100 antibodies in different diseases. We hope that this review stimulates future studies on the effects of such an important molecule in a cell type with decisive roles in inflammatory diseases such as atherosclerosis

ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment

Mechanisms underlying the resistance of acute lymphoblastic leukemia (ALL) blasts to L-asparaginase are still incompletely known. Here we demonstrate that human primary bone marrow mesenchymal stromal cells (MSCs) successfully adapt to L-asparaginase and markedly protect leukemic blasts from the enzyme-dependent cytotoxicity through an amino acid tradeoff. ALL blasts synthesize and secrete glutamine, thus increasing extracellular glutamine availability for stromal cells. In turn, MSCs use glutamine, either synthesized through glutamine synthetase (GS) or imported, to produce asparagine, which is then extruded to sustain asparagine-auxotroph leukemic cells. GS inhibition prevents mesenchymal cells adaptation to L-asparaginase, lowers glutamine secretion by ALL blasts, and markedly hinders the protection exerted by MSCs on leukemic cells. The pro-survival amino acid exchange is hindered by the inhibition or silencing of the asparagine efflux transporter SNAT5, which is induced in mesenchymal cells by ALL blasts. Consistently, primary MSCs from ALL patients express higher levels of SNAT5 (P <.05), secrete more asparagine (P <.05), and protect leukemic blasts (P <.05) better than MSCs isolated from healthy donors. In conclusion, ALL blasts arrange a pro-leukemic amino acid trade-off with bone marrow mesenchymal cells, which depends on GS and SNAT5 and promotes leukemic cell survival during L-asparaginase treatment

Synergism in the antibacterial action of ternary mixtures involving silver nanoparticles, chitosan and antibiotics

The investigations of the antibacterial actions, observed in ternary associations involving silver nanoparticles (AgNPs), chitosan and the antibiotics azithromycin (AZ), levofloxacin (LE) or tetracycline (TE), against Gram-negative and Gram-positive bacterial strains, were performed by in vitro antimicrobial susceptibility testing and checkerboard assays. The pH impact in the culture medium was carefully discarded, but preserving the best conditions for solubilizing chitosan. The synergistic antibacterial effects were observed in the most combinations of AgNPs, chitosan and antibiotic, leading to a reduction from 37 to 97% in the minimum inhibitory concentration of the drugs. The mechanisms for the enhanced antimicrobial effects were proposed based on the investigations of the adsorptions of the drugs on the silver surfaces through surface-enhanced Raman scattering (SERS) spectroscopy.