Examinando por Autor "González, A."

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    Copper-induced increased expression of genes involved in photosynthesis, carotenoid synthesis and C assimilation in the marine alga Ulva compressa
    (NLM (Medline), 2018-11) Rodríguez, F.E.; Laporte, D.; González, A.; Mendez, K.N.; Castro-Nallar, E.; Meneses, C.; Huidobro-Toro, J.P.; Moenne, A.
    BACKGROUND: The marine alga Ulva compressa is the dominant species in coastal areas receiving effluents from copper mines. The alga can accumulate high amounts of copper and possesses a strong antioxidant system. Here, we performed short-term transcriptomic analyses using total RNA of the alga cultivated with 10 μM of copper for 0, 3, 6, 12 and 24 h by RNA-seq. RESULTS: De novo transcriptomes were assembled using the Trinity software, putative proteins were annotated and classified using Blast2GO. Differentially expressed transcripts were identified using edgeR. Transcript levels were compared by paired times 0 vs 3, 0 vs 6, 0 vs 12 and 0 vs 24 h at an FDR < 0.01 and Log2 Fold Change > 2. Up-regulated transcripts encode proteins belonging to photosystem II (PSII), Light Harvesting II Complex (LHCII), PSI and LHCI, proteins involved in assembly and repair of PSII, and assembly and protection of PSI. In addition, transcripts encoding enzymes leading to β-carotene synthesis and enzymes belonging to the Calvin-Benson cycle were also increased. We further analyzed photosynthesis and carotenoid levels in the alga cultivated with 10 μM of copper for 0 to 24 h. Photosynthesis was increased from 3 to 24 h as well as the level of total carotenoids. The increase in transcripts encoding enzymes of the Calvin-Benson cycle suggests that C assimilation may also be increased. CONCLUSIONS: Thus, U. compressa displays a short-term response to copper stress enhancing the expression of genes encoding proteins involved in photosynthesis, enzymes involved carotenoids synthesis, as well as those belonging to the Calvin-Benson cycle, which may result in an increase in C assimilation.
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    Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis
    (Public Library of Science, 2017-06) Pardo, E.; Cárcamo, C.; Martín, R.U.-S.; Ciampi, E.; Segovia-Miranda, F.; Curkovic-Peña, C.; Montecino, F.; Holmes, C.; Tichauer, J.E.; Acuña, E.; Osorio-Barrios, F.; Castro, M.; Cortes, P.; Oyanadel, C.; Valenzuela, D.M.; Pacheco, R.; Naves, R.; Soza, A.; González, A.
    Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-Type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS.
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    Megaparsec-scale structure around the protocluster core SPT2349-56 at z = 4.3
    (Oxford University Press, 2020-05) Hill, R.; Chapman, S.; Scott, D.; Apostolovski, Y.; Aravena, M.; Béthermin, M.; Bradford, C.M.; Canning, R.E.A.; De Breuck, C.; Dong, C.; González, A.; Greve, T.R.; Hayward, C.C.; Hezaveh, Y.; Litke, K.; Malkan, M.; Marrone, D.P.; Phadke, K.; Reuter, C.; Rotermund, K.; Spilker, J.; Vieira, J.D.; Weiß, A.
    We present an extensive ALMA spectroscopic follow-up programme of the $z\, {=}\, 4.3$ structure SPT2349-56, one of the most actively star-forming protocluster cores known, to identify additional members using their [C ii] 158 μm and CO(4-3) lines. In addition to robustly detecting the 14 previously published galaxies in this structure, we identify a further 15 associated galaxies at $z\, {=}\, 4.3$, resolving 55$\, {\pm }\,$5 per cent of the 870 μm flux density at 0.5 arcsec resolution compared to 21 arcsec single-dish data. These galaxies are distributed into a central core containing 23 galaxies extending out to 300 kpc in diameter, and a northern extension, offset from the core by 400 kpc, containing three galaxies. We discovered three additional galaxies in a red Herschel-SPIRE source 1.5 Mpc from the main structure, suggesting the existence of many other sources at the same redshift as SPT2349-56 that are not yet detected in the limited coverage of our data. An analysis of the velocity distribution of the central galaxies indicates that this region may be virialized with a mass of (9$\pm 5)\, {\times }\, 10^{12}$ M⊠, while the two offset galaxy groups are about 30 and 60 per cent less massive and show significant velocity offsets from the central group. We calculate the [C ii] and far-infrared number counts, and find evidence for a break in the [C ii] luminosity function. We estimate the average SFR density within the region of SPT2349-56 containing single-dish emission (a proper diameter of 720 kpc), assuming spherical symmetry, to be roughly 4$\, {\times }\, 10^4$ M⊠yr-1 Mpc-3; this may be an order of magnitude greater than the most extreme examples seen in simulations. © 2020 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society.
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    Molecular basis of ligand dissociation in β-adrenergic receptors
    (Public Library of Science, 2011) González, A.; Perez-Acle, T.; Pardo, L.; Deupi, X.
    The important and diverse biological functions of β-adrenergic receptors (βARs) have promoted the search for compounds to stimulate or inhibit their activity. In this regard, unraveling the molecular basis of ligand binding/unbinding events is essential to understand the pharmacological properties of these G protein-coupled receptors. In this study, we use the steered molecular dynamics simulation method to describe, in atomic detail, the unbinding process of two inverse agonists, which have been recently co-crystallized with β 1 and β 2ARs subtypes, along four different channels. Our results indicate that this type of compounds likely accesses the orthosteric binding site of βARs from the extracellular water environment. Importantly, reconstruction of forces and energies from the simulations of the dissociation process suggests, for the first time, the presence of secondary binding sites located in the extracellular loops 2 and 3 and transmembrane helix 7, where ligands are transiently retained by electrostatic and Van der Waals interactions. Comparison of the residues that form these new transient allosteric binding sites in both βARs subtypes reveals the importance of non-conserved electrostatic interactions as well as conserved aromatic contacts in the early steps of the binding process.