Diversity, variability and persistence elements for a non-equilibrium theory of eco-evolutionary dynamics

Natural ecosystems persist in variable environments by virtue of a suite of traits that span from the individual to the community, and from the ecological to the evolutionary scenarios. How these internal characteristics operate to allow living beings to cope with the uncertainty present in their environments is the subject matter of quantitative theoretical ecology. Under the framework of structural realism, the present dissertation project has advocated for the strategy of mathematical modeling as a strategy of abstraction. The goal is to explore if a range of natural ecosystems display the features of complex systems, and evaluate whether these features provide insights into how they persist in their current environments, and how might they cope with changing environments in the future. A suite of inverse, linear and non-linear dynamical mathematical models, including non-equilibrium catastrophe models, and structured demographic approaches is applied to five case studies of natural systems fluctuating in the long-term in diverse scenarios: phytoplankton in the global ocean, a mixotrophic plankton food web in a marine coastal environment, a wintering waterfowl community in a major Mediterranean biodiversity hot-spot, a breeding colony of a keystone avian scavenger in a mountainous environment and the shorebird community inhabiting the coast of UK. In all case studies, there is strong evidence that ecosystems are able to closely track their common environment through several strategies. For example, in global phytoplankton communities, a latitudinal gradient in the positive impact of functional diversity on community stability counteracts the increasing environmental variability with latitude. Mixotrophy, by linking several feeding strategies in a food web, internally drives community dynamics to the edge of instability while maximizing network complexity. In contrast, an externally generated major perturbation, operating through planetary climatic disruptions, induce an abrupt regime shift between alternative stable states in the wintering waterfowl community. Overall, the natural systems studied are shown to posses features of complex systems: connectivity, autonomy, emergence, non-equilibrium, non-linearity, self-organization and coevolution. In rapidly changing environments, these features are hypothesized to allow natural system to robustly respond to stress and disturbances to a large extent. At the same time, future scenarios will be probably characterized by conditions never experienced before by the studied systems. How will they respond to them, is an open question. Based on the results of this dissertation, future research directions in theoretical quantitative ecology will likely benefit from non-autonomous dynamical system approaches, where model parameters are a function of time, and from the deeper exploration of global attractors and the non-equilibriumness of dynamical systems

Applied diagnostics in liver cancer. Efficient combinations of sorafenib with targeted inhibitors blocking AKT/mTOR

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There is increasing interest in developing specific markers to serve as predictors of response to sorafenib and to guide targeted therapy. Using a sequencing platform designed to study somatic mutations in a selection of 112 genes (HepatoExome), we aimed to characterize lesions from HCC patients and cell lines, and to use the data to study the biological and mechanistic effects of case-specific targeted therapies used alone or in combination with sorafenib. We characterized 331 HCC cases in silico and 32 paired samples obtained prospectively from primary tumors of HCC patients. Each case was analyzed in a time compatible with the requirements of the clinic (within 15 days). In 53% of the discovery cohort cases, we detected unique mutational signatures, with up to 34% of them carrying mutated genes with the potential to guide therapy. In a panel of HCC cell lines, each characterized by a specific mutational signature, sorafenib elicited heterogeneous mechanistic and biological responses, whereas targeted therapy provoked the robust inhibition of cell proliferation and DNA synthesis along with the blockage of AKT/mTOR signaling. The combination of sorafenib with targeted therapies exhibited synergistic anti-HCC biological activity concomitantly with highly effective inhibition of MAPK and AKT/mTOR signaling. Thus, somatic mutations may lead to identify case-specific mechanisms of disease in HCC lesions arising from multiple etiologies. Moreover, targeted therapies guided by molecular characterization, used alone or in combination with sorafenib, can effectively block important HCC disease mechanisms.FUNDING: Grants from ISCIII, co-financed by the European Union (FEDER) (PI16/00156), Ramón and Cajal research program from MINECO (RYC-2013-14097) and FUNDACIÓN LUCHAMOS POR LA VIDA to JPV. Grants from ISCIII (RD06/0020/0107-RD012/0036/0060) to MAP. Grant from ISCIII (Ref. PIE15/00079) to JC & JPV. NGD is a recipient of a UC-IDIVAL pre-doctoral fellow. I.V. was also supported by the Ramón and Cajal research program

CALYPSO 2019 Cruise Report: field campaign in the Mediterranean

This cruise aimed to identify transport pathways from the surface into the interior ocean during the late winter in the Alborán sea between the Strait of Gibraltar (5°40’W) and the prime meridian. Theory and previous observations indicated that these pathways likely originated at strong fronts, such as the one that separates salty Mediterranean water and the fresher water in owing from the Atlantic. Our goal was to map such pathways and quantify their transport. Since the outcropping isopycnals at the front extend to the deepest depths during the late winter, we planned the cruise at the end of the Spring, prior to the onset of thermal stratification of the surface mixed layer.Funding was provided by the Office of Naval Research under Contract No. N000141613130

Reproduction of Spatio-Temporal Patterns of Major Mediterranean Phytoplankton Groups from Remote Sensing OC-CCI Data

During the last two decades, several satellite algorithms have been proposed to retrieve information about phytoplankton groups using ocean color data. One of these algorithms, the so-called PHYSAT-Med, was developed specifically for the Mediterranean Sea due to the optical peculiarities of this basin. The method allows the detection from ocean color images of the dominant Mediterranean phytoplankton groups, namely nanoeukaryotes, Prochlorococcus, Synechococcus, diatoms, coccolithophorids, and Phaeocystis-like phytoplankton. Here, we present a new version of PHYSAT-Med applied to the Ocean Colour—Climate Change Initiative (OC-CCI) database. The OC-CCI database consists of a multi-sensor, global ocean-color product that merges observations from four different sensors. This retuned version presents improvements with respect to the previous version, as it increases the temporal range (since 1998), decreases the cloud cover, improves the bias correction and a validation exercise was performed in the NW Mediterranean Sea. In particular, the PHYSAT-Med version has been used here to analyse the annual cycles of the major phytoplankton groups in the Mediterranean Sea. Wavelet analyses were used to explore the spatial variability in dominance both in the time and frequency domains in several Mediterranean sub-regions, such as the Alboran Sea, Ligurian Sea, Northern Adriatic Sea, and Levantine basin. Results extended the interpretation of previously detected patterns, indicating the dominance of Synechococcus-like vs. prochlorophytes throughout the year at the basin level, and the predominance of nanoeukaryotes during the winter months. The method successfully reproduced the diatom blooms normally detected in the basin during the spring season (March to April), especially in the Adriatic Sea. According to our results, the PHYSAT-Med OC-CCI algorithm represents a useful tool for the spatio-temporal monitoring of dominant phytoplankton groups in Mediterranean surface waters. The successful applications of other regional ocean color algorithms to the OC-CCI database will give rise to extended time series of phytoplankton functional types, with promising applications to the study of long-term oceanographic trends in a global change context.This work was financially supported by the Junta de Andalucía Projects PR11-RNM-7722, PIE 201530I012 and the National Project CTM2014-58181-R.Peer reviewe

Experiencias de Educación Vial en Asturias : premiadas por la D.G.T. en el Concurso Nacional de 2007

'Un viaje a la fantasía' del CP de Lada y el proyecto 'Puntos grises' del IES de Candás merecieron dos primeros premios, al tiempo que 'Trompita y la Educación Vial' del CP Begoña de Gijón y la experiencia 'Una calle para todos' del CP El Parque de Blimea, se hicieron acreedores a dos de los segundos premios otorgadosSe presenta un compendio de las cuatro experiencias de Educación Vial que resultaron premiadas por la DGT. en el Concurso Nacional correspondiente a 2007. 'Una calle para todos' del CP El Parque, de Blimea, es un proyecto que surge y se desarrolla en la etapa de Educación Infantil cuyo objetivo esencial es que todos los participantes consigan ser un poco más conscientes de los riesgos que corremos y hacemos correr a otros en la calle y mediante este programa de educación vial contribuir a eliminarlos. 'Un viaje a la fantasía' del CP de Lada (Langreo) se desarrolla en los tres ciclos de Educación Primaria y tiene como objetivo general ayudar a los alumnos a que adquieran un concepto 'moral' que sea el embrión, a partir del cual, desarrollen una ética circulatoria. El proyecto 'Puntos grises' del IES de Candás, es un proyecto concreto sobre la seguridad vial en el municipio de Carreño (Avilés) dirigido fundamentalmente al alumnado de Educación Secundaria, que pretende contribuir a mejorar la seguridad vial del entorno de los alumnos. 'Trompita y la Educación Vial' del CP Begoña, de Gijón, nace con la pretensión de superar el tratamiento de la Educación Vial en la etapa de Educación Infantil en el centro, introduciendo elementos que lo hagan más práctico, más motivador y mucho más real en cuanto a temporalidad y al uso de los materiales.AsturiasUniversidad de Oviedo. Facultad de Ciencias de la Educación; Calle Aniceto Sela s. n.; 33005 Oviedo; +34985103215; +34985103214;ES

Synergism between ALK and PIM inhibition in ALCL.

<p>(A) ALK expression was explored by Western blot in 4 PTCL cell lines. (B) IC₅₀ values were measured upon 72 h treatment with the ALKi Crizotinib: ALK+ ALCL cell lines were around 10 times as sensitive to the ALKi as the ALK− cells. (C) Cells were treated for 24 h with IC₅₀ of ALKi and pan-PIMi, alone and combined. The combination of ALKi + PIMi was highly synergistic (Combination Index, CI<1) and strongly enhanced apoptosis in ALK+ ALCL cell lines after 24 h, while this combination was antagonistic in ALK− PTCL cell lines (CI>1) (*, p<0.05 in comparison with DMSO). Data represent Annexin V+/PI− and Annexin V+/PI+ cells in each treatment. Black columns highlight the combined treatment.</p

Comparison between the compound ETP-39010 and other pan-PIMi.

<p>(A) Selectivity profile showing the IC₅₀ values of each of the compounds for the kinase activity of the indicated enzymes. (B) Percentage of inhibition of a panel of unrelated kinases by ETP-39010 and ETP-47551. A similar profile was found for ETP-47551, ETP-47652 and ETP-46638 compounds. (C) Sensitivity of PTCL cell lines to all pan-PIMi. (D) The newly developed pan-PIMi ETP-47551 reduced cell viability in all studied PTCL cell lines (IC₅₀ values calculated after 72 h of treatment are shown). (E) The pan-PIMi ETP-47551 strongly induced apoptosis in a time-dependent manner in all studied PTCL cell lines (*, p<0.05, from comparison with DMSO-treated cells). The percentage of non-viable cells was calculated as Annexin V+/7AAD− plus Annexin V+/7AAD+ cells in the PIMi-treated condition minus the DMSO-treated control. (F) The combination of ALKi + ETP-39010 was highly synergistic only in ALK+ ALCL cell lines, as was (G) the combination of ALKi + ETP-47551 (Combination Index, CI, <1 indicates synergism between the two drugs; CI ≈1 indicates an additive effect; CI>1 indicates antagonism).</p

PIM kinases as potential therapeutic targets in PTCL.

<p>(A) Gene expression profiling of tumoral samples from 38 human PTCL patients compared with 6 reactive lymph nodes (LN) by microarrays revealed a significantly increased expression of <i>PIM1</i> and <i>PIM2</i> genes (FDR<0.05), but not <i>PIM3</i>. The heatmap is shown in the upper panel, and the relative quantification (Log₂ ratio) comparing PIM expression in PTCL <i>versus</i> LN is shown in the lower panel. (B) GSEA ranked all significantly altered genes between PTCL and LN according to its correlation with <i>PIM1</i> or <i>PIM2</i> expression and displayed them in the red-to-blue bar. Each gene belonging to every pathway was interrogated whether it appeared positively (in the red region of the bar) or negatively (in the blue side) correlated. Using this approach GSEA identified a positive and significant correlation between <i>PIM1</i> and <i>PIM2</i> expression and Jak/STAT, NF-κB and IL-2 signaling pathways in the PTCL molecular signature (FDR<0.25). (C) PIM family genes mRNA level was measured by RT-qPCR in eight PTCL cell lines and (D) primary tumoral T cells from 5 Sézary Syndrome patients (SS #1–5), and compared with normal T cells isolated from 3 healthy donors (Control #1–3). The relative RNA amount of PIM has been calculated as a relative quantification, as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112148#s2" target="_blank">Methods</a> section (RQ = 2^−ΔCt), normalized with non-tumoral cells: RQ in PTCL/RQ in healthy #3. In both settings, <i>PIM1</i>, and especially <i>PIM2</i>, but not <i>PIM3</i> expression was found to be increased in PTCL. (E) PIM kinase protein basal levels in PTCL cell lines measured by Western blot. PIM1 and PIM2 isoforms are also shown. (F) Distribution of PIM2 protein in a series of tumoral samples from 136 PTCL patients measured by immunohistochemistry. Negative, weakly positive and strongly positive samples were defined by the presence of <5%, 5–20% and >20% positive cells. (G) Distribution of PIM2 protein in the most common PTCL subtypes measured by immunohistochemistry.</p