Suchergebnisse

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 13-12-2018 ; Dendritic cells (DCs) are the most specialized antigen presenting cells (APCs), being a key link between innate and acquired immunity. A previous study in our group identified a cell subset that expresses CD8α and major histocompatibility complex II (MHC II) on the cell membrane in rainbow trout skin (Oncorhynchus mykiss) (CD8+ DCs). These CD8+ cells shown phenotypical and functional characteristics of cross-presenting DCs such us expression of CD8, CD103, CD141, Batf3, and others. In this work, we report the identification of homologue populations in rainbow trout gills and intestine. Consequently, we have carried out a broad phenotypic and functional characterization of these new populations that includes the confirmation of novel capacities for DCs in teleost. Interestingly, phenotypic and functional differences were found between the three populations suggesting that the location of DCs strongly shape their mature stage and their immune capacities. Despite the differences found among these populations, some common characteristics were identified in all subset such as the expression of cross presenting markers and regulatory B cell cytokines belonging to the tumor necrosis factor (TNF) superfamily of ligands such us B cell activating factor (BAFF) a proliferation-inducing ligand (APRIL) and BAFF and APRIL like molecule (BALM). These members of the TNF superfamily are produced mainly by innate cells like DCs and play and important role in activation and differentiation of B cells. For this reason, we have studied how these cytokines and their potential receptors are regulated throughout an inflammation model. To carry this out, we have studied the response of the peritoneal cavity to an intraperitoneal injection (i.p) with viral hemorrhagic septicemia virus (VHSV), given that previous studies had described that this inflammatory process is mainly mediated by IgM+ B cells. We first performed a transcriptional analysis in total leukocytes from peritoneum, observing an up regulation of the BAFF and BAFF receptor (BAFF-R) mRNA levels after the (i.p) of VHSV. On the other hand, when we analyzed the regulation of these genes in sorted IgM+ B cells, we observed increases in the levels of transcription of BAFF, APRIL, BALM and their receptors. These results reveal that these cytokines as well as their receptors play a key role in peritoneal inflammation processes mediated by IgM+ B cells. Finally, having demonstrated that fish DCs also produce APRIL, we studied the functionality of this cytokine on IgM+ B cells, using in this case splenic B cells. We have compared the effects produced by APRIL on IgM+ B cells to those previously reported for BAFF, to increase our knowledge on the relation between these phylogenetically close cytokines. In the current work, we have demonstrated that APRIL induces an exclusive proliferation of IgM+ B cells, increases the number of IgM secreting cells and also increases the levels on MHC II on the surface of these cells as well as their antigen processing capacity. The results of this study increase our knowledge concerning the crosstalk between innate and adaptive immune responses and on how B cells are regulated by innate cells such as DCs. This knowledge will be essential for the rational design of vaccines, one of the most important goals of aquaculture at the moment ; The work presented in this thesis has been founded by the following projects: AGL2014-53061-R and AGL2014-54556-JIN from the Spanish Ministry of Economy and Competitiveness (MINECO); by the European Commission under the Seventh Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH); and by the European Research Council (ERC) Starting Grant 2011 (TEBLYM 280469) and ERC Consolidator Grant 2016 (TEMUBLYM 725061). Irene Soleto has been founded by a BES-2015-072193 scholarship from MINECO

Horizontal gene transfer drives the rapid evolution of bacterial populations. Classical processes that promote the lateral flow of genetic information are conserved throughout the prokaryotic world. However, some species have nonconserved transfer mechanisms that are not well known. This is the case for the ancient extreme thermophile Thermus thermophilus. In this work, we show that T. thermophilus strains are capable of exchanging large DNA fragments by a novel mechanism that requires cell-tocell contacts and employs components of the natural transformation machinery. This process facilitates the bidirectional transfer of virtually any DNA locus but favors by 10-fold loci found in the megaplasmid over those in the chromosome. In contrast to naked DNA acquisition by transformation, the system does not activate the recently described DNA-DNA interference mechanism mediated by the prokaryotic Argonaute protein, thus allowing the organism to distinguish between DNA transferred from a mate and exogenous DNA acquired from unknown hosts. This Argonaute-mediated discrimination may be tentatively viewed as a strategy for safe sharing of potentially "useful" traits by the components of a given population of Thermus spp. without increasing the genome sizes of its individuals ; This work has been supported by grant BIO2013-44963-R from the Spanish Ministry of Economy and Competence and FP7-PEOPLE-2012-IAPP grant 324439 from the European Union to J. Berenguer and by grant AV9/6-1 from the Deutsche Forschungsgemeinschaft to B. Averhoff. An institutional grant from the Fundación Ramón Areces to CBMSO and financial support to the Spanish National Network for Extremophilic Microorganisms (BIO2011-12879-E) are also acknowledged. An FPI fellowship for A. Blesa from the Ministry of Education is acknowledged. C. E. César thanks the Ministry of Science and Innovation for a Juan de la Cierva contract

Viking missions reported adverse conditions for life in Mars surface. High hydrogen signal obtained by Mars orbiters has increased the interest in subsurface prospection as putative protected Mars environment with life potential. Permafrost has attracted considerable interest from an astrobiological point of view due to the recently reported results from the Mars exploration rovers. Considerable studies have been developed on extreme ecosystems and permafrost in particular, to evaluate the possibility of life on Mars and to test specific automated life detection instruments for space missions. The biodiversity of permafrost located on the Bering Land Bridge National Preserve has been studied as an example of subsurface protected niche of astrobiological interest. Different conventional (enrichment and isolation) and molecular ecology techniques (cloning, fluorescence "in situ" probe hybridization, FISH) have been used for isolation and bacterial identification ; The expedition to Imuruk Lake was supported by Centro de Astrobiología-INTA (Spain). The laboratory experimental procedures were supported by Grant AYA 2010–20213 "Desarrollo de Tecnología para la identificación de vida de forma automática" from the Spanish Government

Mycolicibacterium hassiacum is the most thermophilic of all the mycobacteria. A partial sequence based on Illumina technology of around 5 Mbp was published in 2012. Here, we report the 5,269,097-bp complete genome sequence assembled into a single circular chromosome ; This work was supported by grants RTC2014-14391-1 and BIO2016-77031-R from the Spanish Ministry of Economy and Competitiveness and grant 685474 from the H2020 research and innovation program of the European Union. An institutional grant from Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa (CBMSO) is acknowledged

La biología de sistemas y la biología sintética pueden ser consideradas como ejemplos de tecnociencias emergentes. Están esencialmente marcadas por promesas de futuro y por visiones, por una cierta lógica y uso de términos, por determinadas formas de organización social, por la integración en un régimen específico de fomento e innovación, así como por una matriz característica de orientaciones para la praxis de investigación. Esta constitución específica de la biología de sistemas y de la biología sintética tiene, por su parte, consecuencias fundamentales para la práctica científica, su análisis y su gobierno.

The Dallol geothermal area in the northern part of the Danakil Depression (up to 124–155 meter below sea level) is deemed one of the most extreme environments on Earth. The area is notable for being part of the Afar Depression, an incipient seafloor-spreading center located at the triple junction, between Nubian, Somali and Arabian plates, and for hosting environments at the very edge of natural physical-chemical extremities. The northern part of the Danakil Depression is dominated by the Assale salt plain (an accumulation of marine evaporite deposits) and hosts the Dallol volcano. Here, the interaction between the evaporitic deposit and the volcanisms have created the unique Dallol hot springs, which are highly acidic (pH ~ 0) and saline (saturation) with maximum temperatures ranging between 90 and 109 °C. Here we report for the first time evidence of life existing with these hot springs using a combination of morphological and molecular analyses. Ultra-small structures are shown to be entombed within mineral deposits, which are identified as members of the Order Nanohaloarchaea. The results from this study suggest the microorganisms can survive, and potential live, within this extreme environment, which has implications for understanding the limits of habitability on Earth and on (early) Mars ; Europlanet 2020 RI received funding from the European Union's Horizon 2020 research and innovation program under Grant Agreement No 654208

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología. Fecha de lectura: 30-06-2017 ; Esta tesis tiene embargado el acceso al texto completo hasta el 30-12-2018 ; The thesis was supported by the Spanish Government (Projects MICIN CGL2010-15675 and MINECO CTM2013-45775-C2-2-R) and the Dirección General de Universidades e Investigación de la Comunidad de Madrid, Research Network (Comunidad de Madrid S-2009/AMB/1511)

There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate– activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double- strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism ; This work was supported by grants from Ministerio de Economía y Competitividad (BFU2011-28958 to A. Aranda and SAF2009-11150 to A. Pascual), from the Instituto de Salud Carlos III (RD012/0036/0030 to A. Aranda; and PI 07/0167 and PI 10/0703 to R. Garesse), from the Comunidad de Madrid (S2011/BMD-2328 TIRONET to A. Aranda), and European Union grant project CRESCENDO (FP6-018652 to A. Aranda and L.M. Sachs).

This is the peer reviewed version of the following article: Functional Ecology 29.4 (2015): 579-588, which has been published in final form at http://dx.doi.org/10.1111/1365-2435.12366. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving ; Ecologists use approaches based on plant functional traits to tackle several fundamental and applied questions. Although a perfect characterization of functional trait structure requires the measurement of all the individuals in communities, this is prohibitively resource-consuming. Consequently, the general practice is to average the trait values of a reduced number of individuals per species. However, there are different alternatives regarding the number, identity and spatial location of the individuals chosen to calculate species-averaged trait values. In this study, we compared different strategies for sampling functional traits, using community-weighted mean trait values (CWM) and the Rao index of functional diversity (FD). We intensively sampled the functional trait structure along a topographical gradient in a Mediterranean grassland, obtaining accurate estimations of the 'real' values of these indices (CWMI and FDI) for three traits (height, leaf area and specific leaf area). We simulated three different sampling strategies differing in the spatial location of the individuals used to estimate species-mean trait: (i) average of the whole gradient (GLO), (ii) average of the sampling unit in which the abundances of species maximize (MAX) and (iii) average of a reduced number of individuals per species and sampling unit (LOC). For each strategy, we simulated different sampling intensities (number of individuals sampled). For each trait, we examined the ability of each strategy and sampling intensity to accurately estimate CWMI and FDI, as well as their ability to detect changes in functional trait structure along the topographical gradient. LOC outperformed the other strategies in terms of accuracy and bias, and was much more efficient to describe changes along the gradient, regardless of the traits and indicators considered. Furthermore, LOC was the only strategy that improved consistently as sampling intensity increased, especially at low levels of intensity. Our results indicate that the impact of considering intraspecific variability in trait values can be greater than commonly assumed. Strategies that neglect this source of variability can result in inaccurate or biased estimations of the functional trait structure of plant communities. Most importantly, we show that intraspecific variability can be taken into consideration without any increases in the total number of individuals measured ; Financial support was received from the Spanish Ministry of Science (Project CGL2011-24871), the Madrid Regional Government (Project REMEDINAL3), and the Spanish Ministry of Education (FPU AP2012-2849 for CR). CPC was supported by a Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme (TANDEM; project id. 626392)

Arsenic toxicity has been studied for a long time due to its effects in humans. Although epidemiological studies have demonstrated multiple effects in human physiology, there are many open questions about the cellular targets and the mechanisms of response to arsenic. Using the fission yeast Schizosaccharomyces pombe as model system, we have been able to demonstrate a strong activation of the MAPK Spc1/Sty1 in response to arsenate. This activation is dependent on Wis1 activation and Pyp2 phosphatase inactivation. Using arsenic speciation analysis we have also demonstrated the previously unknown capacity of S. pombe cells to reduce As (V) to As (III). Genetic analysis of several fission yeast mutants point towards the cell cycle phosphatase Cdc25 as a possible candidate to carry out this arsenate reductase activity. We propose that arsenate reduction and intracellular accumulation of arsenite are the key mechanisms of arsenate tolerance in fission yeast ; This work has been supported by Projects CTQ2008-01031/BQU from Spanish Science and Innovation Ministry. JS was supported by Madrid government and AMMG by Spanish Ministry of Science and Innovation. This research was supported by grants awarded to MARG by the Spanish Science and Innovation Ministry (BFU2006/01767 and BFU2009/09116)

En este artículo se defiende la necesidad de que el actor de la ciencia, el científico, disponga de suficiente formación filosófica como para analizar críticamente el alcance de su propia actividad especializada, análisis que debiera empezar por entender qué es eso a lo que llamamos ciencia. Se ejemplifica la necesidad de tal formación recurriendo a la biología sintética. Se muestran los peligros que se corren de la derivación hacia campos no científicos si el científico está imbuido de una ciencia fáustica orientada a la obtención del producto –el ente biológico sintético– disminuyendo veladamente el interés por estudiar el mismo desde la óptica de la ciencia prometeica, aquella que se aproxima progresivamente a la comprensión de los entes vivos.

RESUMENEl intento de sentar las bases para convertir la biología en objeto de ingeniería es hoy una prioridad en la agenda de investigación científica. La bio-ingeniería permitiría fabricar y obtener lo que queramos a partir de la materia viviente, abriendo nuevos potenciales de expansión para la incipiente bioeconomía. El presente artículo aspira a discutir los retos éticos, filosóficos y políticos de la biología sintética, atendiendo tanto a su comprensión implícita de la vida como a sus posibles consecuencias para la relación entre ciencia, bioeconomía y sociedad.PALABRAS CLAVEÉTICA DE LA BIOLOGÍA SINTÉTICA; BIOINGENIERÍA; VIDA; TECNO-CIENCIA Y SOCIEDADABSTRACTThe attempt to render biology a matter of engineering has been settled as one of the priorities in the scientific research agenda. Bio-engineering is supposed to allow us to manufacture and obtain anything we wish from living material, opening new expansion potentials for the emerging bioeconomy. This papers aims at discussing the ethical, philosophical and political challenges of synthetic biology, focusing both on its implicit understanding of the living as well as on its possible consequences for the relations between science, bioeconomy and society.KEYWORDSETHICS OF SYNTHETIC BIOLOGY; BIO-ENGINEERING; LIFE; TECHNO-SCIENCE AND SOCIETY

Aims. Chagas disease pathology is dependent on the infecting T. cruzi strain. However, the relationship between the extent and type of myocarditis caused by different T. cruzi strains in the acute and chronic phases of infection has not been studied in detail. To address this, we infected mice with three genetically distant T. cruzi strains as well as infected in vitro different cell types. Methods and Results. Parasitemia was detected in mice infected with the Y and VFRA strains, but not with the Sc43 strain; however, only the Y strain was lethal. When infected with VFRA, mice showed higher inflammation and parasitism in the heart than with Sc43 strain. Y and VFRA caused homogeneous pancarditis with inflammatory infiltrates along the epicardium, whereas Sc43 caused inflammation preferentially in the auricles in association with intracellular parasite localization. We observed intramyocardic perivasculitis in mice infected with the VFRA and Y strains, but not with Sc43, during the acute phase, which suggests that endothelial cells may be involved in heart colonization by these more virulent strains. In in vitro infection assays, the Y strain had the highest parasite-cell ratio in epithelial, macrophage and endothelial cell lines, but Y and VFRA strains were higher than Sc43 in cardiomyocytes. Conclusions. This study supports parasite variability as a cause for the diverse cardiac outcomes observed in Chagas disease, and suggests that endothelial cells could be involved in heart infection during the acute phase. ; This work was partially supported by grants from "Fondo de Investigaciones Sanitarias" (PS09/00538 and PI12/00289); "Ministerio de Ciencia e Innovación" (SAF2010-18733); The European Union (ChagasEpiNet); "Comunidad de Madrid" S2010/BMD-2332; RED RECAVA RD06/0014/1013;RED RICET RD12/0018/004 and an institutional grant from "Fundación Ramon Areces"