L'aprofitament ramader a la vall del Madriu-Perafita-Claror (Principat d'Andorra)

The farming exploitation in the Madriu-Perafita-Claror Valley (Principality of Andorra). The Madriu-Perafita-Claror Valley, a natural space located in the Principality of Andorra, has kept a high ecological and landscape value through time. At present, the Valley is considered in the cultural landscape category of the UNESCO World-wide Heritage. A study of the spatial variability of pastures in the Valley conducted from 1994 to 2003 concluded that there was an optimistic future for livestock. This future was mainly explained by new policies in the country, as well as by the new hopes of the tockbreeders. The study also stated that cattle and horse movements within the Valley did not varied over the study period, although entrance and exit points changed. Sheep only fed in the Madriu-Perafita-Claror Valley, but it wouldbe convenient its introduction in other areas where horses and cattle did not pasture. The study concluded that the use of the Valley by the stockbreeders contributed to the development of the vegetation and the landscape, and that the livestock is very important to keep natural and landscape values of the Valley.

Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling

Background: Nolz1 is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE), although its function is still unknown. Results: Here we analyze the role of Nolz1 during LGE development. We show that Nolz1 expression is high in proliferating neural progenitor cells (NPCs) of the LGE subventricular zone. In addition, low levels of Nolz1 are detected in the mantle zone, as well as in the adult striatum. Similarly, Nolz1 is highly expressed in proliferating LGE-derived NPC cultures, but its levels rapidly decrease upon cell differentiation, pointing to a role of Nolz1 in the control of NPC proliferation and/or differentiation. In agreement with this hypothesis, we find that Nolz1 over-expression promotes cell cycle exit of NPCs in neurosphere cultures and negatively regulates proliferation in telencephalic organotypic cultures. Within LGE primary cultures, Nolz1 over-expression promotes the acquisition of a neuronal phenotype, since it increases the number of β-III tubulin (Tuj1)- and microtubule-associated protein (MAP)2-positive neurons, and inhibits astrocyte generation and/or differentiation. Retinoic acid (RA) is one of the most important morphogens involved in striatal neurogenesis, and regulates Nolz1 expression in different systems. Here we show that Nolz1 also responds to this morphogen in E12.5 LGE-derived cell cultures. However, Nolz1 expression is not regulated by RA in E14.5 LGE-derived cell cultures, nor is it affected during LGE development in mouse models that present decreased RA levels. Interestingly, we find that Gsx2, which is necessary for normal RA signaling during LGE development, is also required for Nolz1 expression, which is lost in Gsx2 knockout mice. These findings suggest that Nolz1 might act downstream of Gsx2 to regulate RA-induced neurogenesis. Keeping with this hypothesis, we show that Nolz1 induces the selective expression of the RA receptor (RAR)β without altering RARα or RARγ. In addition, Nozl1 over-expression increases RA signaling since it stimulates the RA response element. This RA signaling is essential for Nolz1-induced neurogenesis, which is impaired in a RA-free environment or in the presence of a RAR inverse agonist. It has been proposed that Drosophila Gsx2 and Nolz1 homologues could cooperate with the transcriptional co-repressors Groucho-TLE to regulate cell proliferation. In agreement with this view, we show that Nolz1 could act in collaboration with TLE-4, as they are expressed at the same time in NPC cultures and during mouse development. Conclusions: Nolz1 promotes RA signaling in the LGE, contributing to the striatal neurogenesis during development.

Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling

Background: Nolz1 is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE), although its function is still unknown. Results: Here we analyze the role of Nolz1 during LGE development. We show that Nolz1 expression is high in proliferating neural progenitor cells (NPCs) of the LGE subventricular zone. In addition, low levels of Nolz1 are detected in the mantle zone, as well as in the adult striatum. Similarly, Nolz1 is highly expressed in proliferating LGE-derived NPC cultures, but its levels rapidly decrease upon cell differentiation, pointing to a role of Nolz1 in the control of NPC proliferation and/or differentiation. In agreement with this hypothesis, we find that Nolz1 over-expression promotes cell cycle exit of NPCs in neurosphere cultures and negatively regulates proliferation in telencephalic organotypic cultures. Within LGE primary cultures, Nolz1 over-expression promotes the acquisition of a neuronal phenotype, since it increases the number of β-III tubulin (Tuj1)- and microtubule-associated protein (MAP)2-positive neurons, and inhibits astrocyte generation and/or differentiation. Retinoic acid (RA) is one of the most important morphogens involved in striatal neurogenesis, and regulates Nolz1 expression in different systems. Here we show that Nolz1 also responds to this morphogen in E12.5 LGE-derived cell cultures. However, Nolz1 expression is not regulated by RA in E14.5 LGE-derived cell cultures, nor is it affected during LGE development in mouse models that present decreased RA levels. Interestingly, we find that Gsx2, which is necessary for normal RA signaling during LGE development, is also required for Nolz1 expression, which is lost in Gsx2 knockout mice. These findings suggest that Nolz1 might act downstream of Gsx2 to regulate RA-induced neurogenesis. Keeping with this hypothesis, we show that Nolz1 induces the selective expression of the RA receptor (RAR)β without altering RARα or RARγ. In addition, Nozl1 over-expression increases RA signaling since it stimulates the RA response element. This RA signaling is essential for Nolz1-induced neurogenesis, which is impaired in a RA-free environment or in the presence of a RAR inverse agonist. It has been proposed that Drosophila Gsx2 and Nolz1 homologues could cooperate with the transcriptional co-repressors Groucho-TLE to regulate cell proliferation. In agreement with this view, we show that Nolz1 could act in collaboration with TLE-4, as they are expressed at the same time in NPC cultures and during mouse development. Conclusions: Nolz1 promotes RA signaling in the LGE, contributing to the striatal neurogenesis during development.

Monotonic continuous-time random walks with drift and stochastic reset events

In this paper we consider a stochastic process that may experience random reset events which suddenly bring the system to the starting value and analyze the relevant statistical magnitudes. We focus our attention on monotonic continuous-time random walks with a constant drift: The process increases between the reset events, either by the effect of the random jumps, or by the action of the deterministic drift. As a result of all these combined factors interesting properties emerge, like the existence (for any drift strength) of a stationary transition probability density function, or the faculty of the model to reproduce power-law-like behavior. General formulas for two extreme statistics, the survival probability, and the mean exit time, are also derived. To corroborate in an independent way the results of the paper, Monte Carlo methods were used. These numerical estimations are in full agreement with the analytical predictions.

Filtration of effluents for microirrigation systems

Clogging, measured through head loss across filters, and the filtration quality of different filters using different effluents were studied. The filters used were: 115, 130, and 200 m disc filters; 98, 115, 130, and 178 m screen filters; and a sand filter filled with a single layer of sand with an effective diameter of 0.65 mm. The filters were used with a meat industry effluent and secondary and tertiary effluents of two wastewater treatment plants. It was observed that clogging depended on the type of effluent. With the meat industry effluent, the poorest quality effluent, disc filters clogged more than the other filter types. When the wastewater treatment plant effluents were used, the disc filters showed less frequent clogging. Several physical and chemical parameters, such as total suspended solids, chemical oxygen demand, turbidity, electrical conductivity, pH, and number of particles, were analyzed in the effluents at the entry and exit points of the filters. In general, filters did not reduce the values of the main clogging parameters to a great degree. It was found that the parameter that explained the clogging, expressed as Boucher’s filterability index, was different depending on the type of effluent and filter. The best quality of filtration was achieved with a sand filter when the meat industry effluent was used. No significant differences were observed between the quality of filtration of disc and screen filters when operating with the secondary and tertiary effluents

Characterizing RecA-Independent Induction of Shiga toxin2-encoding Phages by EDTA Treatment

The bacteriophage life cycle has an important role in Shiga toxin (Stx) expression. The induction of Shiga toxin-encoding phages (Stx phages) increases toxin production as a result of replication of the phage genome, and phage lysis of the host cell also provides a means of Stx toxin to exit the cell. Previous studies suggested that prophage induction might also occur in the absence of SOS response, independently of RecA.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

The republican case for workplace democracy

The republican case for workplace democracy (WD) is presented and defended from two alternative means of ensuring freedom from arbitrary interference in the firmnamely, (a) the right to freely exit the firm and (b) workplace regulation. This paper shows, respectively, that costless exit is neither possible nor desirable in either perfect or imperfect labor markets, and that managerial discretion is both desirable and inevitable due to the incompleteness of employment contracts and labor legislation. The paper then shows that WD is necessary, from a republican standpoint, if workers" interests are to be adequately tracked in the exercise of managerial authority. Three important objections are finally addressed (i) that WD is redundant, (ii) that it is unnecessary provided that litigation and unionism can produce similar outcomes, and (iii) that it falls short of ensuring republican freedom compared to self-employment.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Structure and dynamics of the membrane attaching nitric oxide transporter nitrophorin 7

Nitrophorins represent a unique class of heme proteins that are able to perform the delicate transportation and release of the free-radical gaseous messenger nitric oxide (NO) in a pH-triggered manner. Besides its ability to bind to phospholipid membranes, the N-terminus contains an additional Leu-Pro-Gly stretch, which is a unique sequence trait, and the heme cavity is significantly altered with respect to other nitrophorins. These distinctive features encouraged us to solve the X-ray crystallographic structures of NP7 at low and high pH and bound with different heme ligands (nitric oxide, histamine, imidazole). The overall fold of the lipocalin motif is well preserved in the different X-ray structures and resembles the fold of other nitrophorins. However, a chain-like arrangement in the crystal lattice due to a number of head-to-tail electrostatic stabilizing interactions is found in NP7. Furthermore, the X-ray structures also reveal ligand-dependent changes in the orientation of the heme, as well as in specific interactions between the A-B and G-H loops, which are considered to be relevant for the biological function of nitrophorins. Fast and ultrafast laser triggered ligand rebinding experiments demonstrate the pH-dependent ligand migration within the cavities and the exit route. Finally, the topological distribution of pockets located around the heme as well as from inner cavities present at the rear of the protein provides a distinctive feature in NP7, so that while a loop gated exit mechanism to the solvent has been proposed for most nitrophorins, a more complex mechanism that involves several interconnected gas hosting cavities is proposed for NP7.

"Vinci Cosmetics" Fabricación y comercialización de productos cosméticos

Contexto: La idea principal es la creación de una empresa para la fabricación y comercialización de productos cosméticos de alta gama. A pesar del contexto de crisis económica en el que estamos envueltos estos últimos años y del que no parece que acabamos de salir, el sector de la cosmética está resistiendo la situación de forma envidiable. De la crisis, como dicen los economistas, “se saldrá y se volverá, todo es cíclico” y viendo la fortaleza que éste sector está mostrando unido a la necesidad de que nuestra economía abandone sectores muy deteriorados y sin una previsión positiva de futuro, la cosmética se postula con un futuro prometedor dentro del contexto económico español y europeo. “Vinci Cosmetics” es el nombre inicialmente pensado para que la nueva compañía inicie su andadura. Nombre con tintes latinos de la lejana época del imperio romano como homenaje a la rica herencia histórica de la ciudad del autor del proyecto - Tarragona. La cultura por cuidarse y sentirse bien, muy arraigada en la mentalidad latina y mediterránea, es un factor cultural clave para el desarrollo y futura evolución de esta industria. El slogan de la empresa, “Dieta Mediterránea para tu piel”, clarifica en buena medida la idea a desarrollar y los objetivos pretendidos por la estrategia empresarial. Objetivos: El objetivo esencial del TFC es elaborar un estudio detallado para la creación de una empresa de fabricación y comercialización de productos cosméticos de alta gama que abarque el management y la gestión por procesos de la empresa, la función de marketing, el tipo de operaciones y procesos a realizar, la gestión del factor humano y el presupuesto necesario para cubrir este ambicioso proyecto. En detalle, un completo plan de empresa que marque las directrices de la organización industrial que se pretende crear compuesto a su vez por cinco planes: plan de gerencia, plan de marketing, plan de operaciones, plan de recursos humanos y plan económico – financiero. Procedimientos: El proyecto tiene un alto componente de estudio de mercados y de marketing pero pretende también abarcar el management, los procesos de operación, el factor humano y el aspecto económico y financiero de las inversiones y presupuesto necesario. El estudio inicial centrará su esfuerzo en un análisis del mercado de la península ibérica, y, en función del avance y del progreso esperado por la empresa, la compañía podría extender su campo de acción a Europa aunque no antes de un medio plazo. “Vinci Cosmetics” ha adoptado referenciales de sistemas de gestión integrados en toda la organización. Así tenemos principalmente, por un lado, la norma internacional ISO 9001:2008 y, por otro, el Modelo EFQM de Excelencia en la gestión; ambos plasmados a partir de un enfoque basado en procesos que nos garantiza el control continuo y la gestión excelente. Conclusiones: Tras evaluar la situación actual del mercado de la cosmética, las previsiones futuras de éste y las necesidades que una organización industrial necesita, se puede crear - con plenas garantías de éxito como organización empresarial y desde el punto de vista económico - una empresa de cosméticos de alta gama para cubrir las necesidades de una parte de mercado que lo requiere.