Mathematical modelling, analysis and numerical simulation for a general class of gene regulatory networks

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    327 pagesThe research work developed in this thesis is mainly oriented to the mathematical modelling of biological systems, the behaviour of which is inherently stochastic, as it is the case of gene regulatory networks. Their relevance emerges from the fact that all necessary information for life cycle is encoded in the DNA. Consequently, the study of DNA expression, transcription into messenger RNA and translation into proteins, together with their regulation becomes essential to predict cells response to environmental signals. The inherent stochastic nature of gene expression makes these systems to be far away from the classical kinetic limit where the (macroscopic) deterministic methods are valid. In modelling these systems, we need to employ microscopic methods which incorporate the underlying stochastic behaviour. The Chemical Master Equation (CME) remains at the basis for the modelling of these phenomena. However, a closed form solution of the CME is unavailable in general, due to the large number (eventually in nity) of coupled equations. A widespread technique to approximate the CME solution is the Stochastic Simulation Algorithm (SSA), a computationally involved Monte Carlo type method. Although many numerical approximations emerge to reduce the complexity of the CME, we will focus on the Partial Integro-Di erential Equation (PIDE) or Friedman model, which represents a continuous approximation of the CME. For the one dimensional version (self-regulation), the PIDE model has an analytic solution for its steady state. This fact will allow us to characterize the regions in the space of parameters in which the system changes its behaviour (unimodal, bimodal). Also we have carried out an stability analysis by means of entropy methodsMoreover, we obtain a multidimensional version of the Friedman model to handle more complex gene regulatory networks with more than one gene. The mathematical properties of the corresponding equation will be exhaustively analyzed, also with special emphasis on stability of the solution using entropy methods. In addition, we propose two semi-Lagrangian methods for the numerical solution of the multidimensional model. The rst method results very e cient and scalable to higher dimensions, as the numerical results illustrate, although in practice exhibits rst order convergence in time and space. Solutions provided by the proposed method are compared with those obtained by SSA to assess e ciency, accuracy and computational costs. For the second semi-Lagrangian method we develop the theoretical numerical analysis, thus proving second order convergence in time and space. This is clearly illustrated by a numerical example. However, the computational cost of this second approach results much higher, so that the scalability to higher dimensions seems a di cult task. All the numerical techniques have been implemented on a user friendly toolbox (SELANSI) which is detailed in the AppendixMINECO, axudas para contratos predoutoral BES-2013-063112, e axudas á mobilidade predoutoral para a realización de estadías breves noutros centros EEBB-I-16-10540 e EEBB-I-17- 12182. Tamén proxectos AGL2012-29951-C02-01 e MTM 2016-76497-RPeer reviewe

    In vivo 3D analysis of thoracic kinematics: changes in size and shape during breathing and their implications for respiratory function in recent humans and fossil hominins

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    The human ribcage expands and contracts during respiration as a result of the interaction between the morphology of the ribs, the costo-vertebral articulations and respiratory muscles. Variations in these factors are said to produce differences in the kinematics of the upper thorax and the lower thorax, but the extent and nature of any such differences and their functional implications have not yet been quantified. Applying geometric morphometrics we measured 402 three-dimensional (3D) landmarks and semilandmarks of 3D models built from computed tomographic scans of thoraces of 20 healthy adult subjects in maximal forced inspiration (FI) and expiration (FE). We addressed the hypothesis that upper and lower parts of the ribcage differ in kinematics and compared different models of functional compartmentalization. During inspiration the thorax superior to the level of the sixth ribs undergoes antero-posterior expansion that differs significantly from the medio-lateral expansion characteristic of the thorax below this level. This supports previous suggestions for dividing the thorax into a pulmonary and diaphragmatic part. While both compartments differed significantly in mean size and shape during FE and FI the size changes in the lower compartment were significantly larger. Additionally, for the same degree of kinematic shape change, the pulmonary thorax changes less in size than the diaphragmatic thorax. Therefore, variations in the form and function of the diaphragmatic thorax will have a strong impact on respiratory function. This has important implications for interpreting differences in thorax shape in terms of respiratory functional differences within and among recent humans and fossil hominins. Anat Rec, 300:255–264, 2017. © 2016 Wiley Periodicals, Inc.Grant sponsor: Spanish Ministry of Economy and Competitiveness; Grant numbers: CGL2012-37279, CGL2015-63648-P; MINECO; Grant sponsor: Ministry of Health, Spain (Fondo de Investigacióon Sanitaria);Peer Reviewe

    Acquisition of Uropygial Gland Microbiome by Hoopoe Nestlings

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    Mutualistic symbioses between animals and bacteria depend on acquisition of appropriate symbionts while avoiding exploitation by non-beneficial microbes. The mode of acquisition of symbionts would determine, not only the probability of encountering but also evolutionary outcomes of mutualistic counterparts. The microbiome inhabiting the uropygial gland of the European hoopoe (Upupa epops) includes a variety of bacterial strains, some of them providing antimicrobial benefits. Here, the mode of acquisition and stability of this microbiome is analyzed by means of Automated rRNA Intergenic Spacer Analysis and two different experiments. The first experiment impeded mothers’ access to their glands, thus avoiding direct transmission of microorganisms from female to offspring secretions. The second experiment explored the stability of the microbiomes by inoculating glands with secretions from alien nests. The first experiment provoked a reduction in similarity of microbiomes of mother and nestlings. Interestingly, some bacterial strains were more often detected when females had not access to their glands, suggesting antagonistic effects among bacteria from different sources. The second experiment caused an increase in richness of the microbiome of receivers in terms of prevalence of Operational Taxonomic Units (OTUs) that reduced differences in microbiomes of donors and receivers. That occurred because OTUs that were present in donors but not in receivers incorporated to the microbiome of the latter, which provoked that cross-inoculated nestlings got similar final microbiomes that included the most prevalent OTUs. The results are therefore consistent with a central role of vertical transmission in bacterial acquisition by nestling hoopoes and support the idea that the typical composition of the hoopoe gland microbiome is reached by the incorporation of some bacteria during the nestling period. This scenario suggests the existence of a coevolved core microbiome composed by a mix of specialized vertically transmitted strains and facultative symbionts able to coexist with them. The implications of this mixed mode of transmission for the evolution of the mutualism are discussedSupport by funding was provided by Spanish Ministerio de Ciencia e Innovación, European funds (FEDER) (CGL2009-14006, CGL2010-19233-C03-01, CGL2010-19233-C03-03, CGL2013-48193-C3-1-P, CGL2013-48193-C3-2-P) and Junta de Andalucía (P09-RNM4557). AM-G had a predoctoral grant from the Junta de Andalucía (P09-RNM-4557).Peer reviewe

    The Drosophila endoderm as a model for the role of GATA factors in EMT and migration

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    Trabajo presentado en la Drosophila as a model in cancer, Barcelona BioMed Conference, celebrada en Barcelona, España, del 15 al 17 de junio de 2015Peer Reviewe

    La vaca y la gallina: hambre, violencia sexual e indigenismo en la literatura andina

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    El hambre fue uno de los grandes motivos que recorrieron la literatura indigenista latinoamericana durante el siglo pasado. El hambre como síntesis del oprobio contra pueblos enteros, como consecuencia palpable y vulgar de la aplicación de sistemas de explotación económicos y políticos que vampirizaron las entrañas medioambientales y humanas de lo que José Martí denominó en 1891 Nuestra América.Peer reviewe

    The small mammals (Eulipotyphla, Chiroptera, Rodentia and Lagomorpha) from the Late Pleistocene site of the cave of El Castillo (Cantabria, Spain).

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    [ES] El material de micromamíferos del yacimiento del Pleistoceno Superior de la cueva de El Castillo, objeto de estudio detallado en este trabajo, proviene de los niveles auriñacienses 18b y 18c (datados en 40.000-45.000 BP), nivel 19, y niveles musterienses 20b, 20c, 20d, 20e (datados en 41.000-49.000 BP), 21a y 21b. La asociación de micromamíferos es la siguiente: Erinaceus europaeus, Crocidura russula, Sorex coronatus, Sorex minutus, Neomys fodiens, Talpa europaea, Galemys pyrenaicus, cf. Miniopterus schreibersii, Chiroptera indet., Pliomys lenki, Microtus arvalis - Microtus agrestis, Microtus lusitanicus, Microtus oeconomus, Chionomys nivalis, Arvicola terrestris, Apodemus sylvaticus - Apodemus flavicollis y Lepus sp. La mayoría de estas especies están presen¬tes en la fauna actual de Cantabria, excepto Pliomys lenki que se extinguió en el último tercio del Pleistoceno Superior, y Microtus oeconomus, que persistió en la península ibérica durante el Holoceno bien avanzado hasta su desaparición en tiempos históricos, y que actualmente está en regiones euroasiáticas más septentrionales. Hay una gran continuidad de la gran mayoría de los taxones en todos los niveles. La fauna en su conjunto parece indicar un medio predominantemente abierto, por lo general de praderas húmedas (y en mucha menor medida praderas secas) con una buena cobertura vegetal a nivel del suelo, en el que habría también algunas zonas arboladas o boscosas, y algún curso de agua. Los indicadores termófilos son escasos y poco abundantes, lo que podría indicar que el clima podría ser algo menos templado que en otros periodos del Pleistoceno Superior y quizás también que actualmente en la zona.[EN] The micromammals remains from the Late Pleistocene site of the cave of El Castillo studied here in detail, came from the Aurignacian levels 18b and 18c (dated in 40.000-45.000 BP), level 19, and the Musterian levels 20b, 20c, 20d, 20e (dated in 41.000-49.000 BP), 21a and 21b. The micromammal association is the following: Erinaceus europaeus, Crocidura russula, Sorex coronatus, Sorex minutus, Neomys fodiens, Talpa europaea, Galemys pyrenaicus, cf. Miniopterus schreibersii, Chiroptera indet., Pliomys lenki, Microtus arvalis - Microtus agrestis, Microtus lusitanicus, Microtus oeconomus, Chionomys nivalis, Arvicola terrestris, Apodemus sylvaticus - Apodemus flavicollis and Lepus sp. Most of these species are in the present fauna of Cantabria, except Pliomys lenki that got extinct in the last third of the Upper Pleistocene, and Microtus oeconomus that disappeared from the Iberian Peninsula during the Holocene, in historical times, and is nowadays present in northern Euroasiatic regions. There is a great continuity of most of the taxa in all the levels. The faunal association seems to indicate a mainly open environment, in general with wet meadows (and few dry meadows), with good vegetation cover in the soil, with perhaps also some tree-covered areas, and some watercourses. The thermophiles indicators are very scarce, which could indicate that the climate could be a lesser temperate than other Upper Pleistocene periods and the present-day climate in the area.Peer reviewe

    Data on litter quality of host grass plants with and without fungal endophytes

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    4 páginas.Certain Pooideae species form persistent symbiosis with fungal endophytes of Epichloë genus. Although endophytes are known to impact the ecology and evolution of host species, their effects on parameters related with quality of plant biomass has been elusive. This article provides information about parameters related with the quality of plant litter biomass of two important grass species (Schedonorus phoenix and Schedonorus pratensis) affected by the symbiosis with fungal endophytes (Epichloë coenophiala and Epichloë uncinata, respectively). Four population origins of S. phoenix and one of S. pratensis were included. Mineral, biochemical and structural parameters were obtained from three samples per factors combination [species (and population origin)×endophyte]. This data can be potentially used in other studies which, by means of ‘data reanalyzing’ or meta-analysis, attempt to find generalizations about endophyte effects on host plant litter biomass. The present data is associated with the research article “Role of foliar fungal endophytes on litter decomposition among species and population origins” (Gundel et al., In preparation)Peer reviewe

    Sources and distribution of yttrium and rare earth elements in surface sediments from Tagus estuary, Portugal

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    9 pages, 5 figuresThe distribution and sources of yttrium and rare-earth elements (YREE) in surface sediments were studied on 78 samples collected in the Tagus estuary (SW Portugal, SW Europe). Yttrium and total REE contents ranged from 2.4 to 32 mg·kg− 1 and 18 to 210 mg·kg− 1, respectively, and exhibited significant correlations with sediment grain-size, Al, Fe, Mg and Mn, suggesting a preferential association to fine-grained material (e.g. aluminosilicates but also Al hydroxides and Fe oxyhydroxides). The PAAS (Post-Archean Australian Shale) normalized patterns display three distinct YREE fractionation pattern groups along the Tagus estuary: a first group, characterized by medium to coarse-grained material, a depleted and almost flat PAAS-normalized pattern, with a positive anomaly of Eu, representing one of the lithogenic components; a second group, characterized mainly by fine-grained sediment, with higher shale-normalized ratios and an enrichment of LREE relative to HREE, associated with waste water treatment plant (WWTP) outfalls, located in the northern margin; and, a third group, of fine-grained material, marked by a significant enrichment of Y, a depletion of Ce and an enrichment of HREE over LREE, located near an inactive chemical-industrial complex (e.g. pyrite roast plant, chemical and phosphorous fertilizer industries), in the southern margin. The data allow the quantification of the YREE contents and its spatial distribution in the surface sediments of the Tagus estuary, identifying the main potential sources and confirming the use of rare earth elements as tracers of anthropogenic activities in highly hydrodynamic estuariesThis work was financially supported by the Portuguese Science and Technology Foundation through the REEUSE Project (FCT/PTDC/QEQ-EPR/1249/2014). An award from the COST Action TD 1407 supported the costs for the presentation of this study at the Workshop on Environmental Concentrations, Cycling and Modelling of Technology Critical Elements, held at the Weizmann Institute of Sciences, in Rehovot, IsraelPeer reviewe

    Genetic Redundancies Enhance Information Transfer in Noisy Regulatory Circuits

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    This work has been supported by BFU2015-66894-P (MINECO/FEDER) and GV/2016/079 (GVA) Grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe
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