22 research outputs found

    Analysis of How Companies Should Prepare to Recruit and Manage Generation Z

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    Enfoque sistémico de las formas de acceso a la tierra en la sociedad prehispánica náhuatl / System approach to the forms of access to land in pre-Hispanic Nahuatl society

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    Se ha asociado constantemente la Propiedad Social de México con la propiedad comunal de las sociedades prehispánicas, sin embargo, existe un conflicto epistemológico en cuanto a la noción de propiedad en los mecanismos reales de acceso a la tierra en estas sociedades. Este trabajo aborda por un lado este conflicto epistemológico de propiedad, y por otro una propuesta de método para comprender problemas planteados vistos como sistema; combinando dos métodos de enfoque de sistemas: el conceptagon y DPSIR. El sistema de acceso a la tierra náhuatl corresponde con uno de no-propiedad basado en la detentación condicionada de la tierra, lo que contribuye parcialmente en la resolución del conflicto epistemológico y por otro lado en la desmitificación de la propiedad comunal de las sociedades prehispánicas.

    Dinámica de los núcleos agrarios en México

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    Este artículo presenta por un lado cómo la ley e instituciones en materia agraria establecen una estructura y funcionamiento para el campo mexicano en su propiedad social, sin embargo, resalta la dinámica que ellos mismos han generado. Donde en la práctica, lo real no corresponde completamente con la legislación, siendo ésta a su vez, un producto de remanentes conceptuales los que hasta hoy, diferencian dos nociones que probablemente no tengan de fondo características suficientes para ser consideradas por la ley de formas distintas

    Bridging the lesion-engineering a permissive substrate for nerve regeneration.

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    Biomaterial-based strategies to restore connectivity after lesion at the spinal cord are focused on bridging the lesion and providing an favourable substrate and a path for axonal re-growth. Following spinal cord injury (SCI) a hostile environment for neuronal cell growth is established by the activation of multiple inhibitory mechanisms that hamper regeneration to occur. Implantable scaffolds can provide mechanical support and physical guidance for axon re-growth and, at the same time, contribute to alleviate the hostile environment by the in situ delivery of therapeutic molecules and/or relevant cells. Basic research on SCI has been contributing with the description of inhibitory mechanisms for regeneration as well as identifying drugs/molecules that can target inhibition. This knowledge is the background for the development of combined strategies with biomaterials. Additionally, scaffold design is significantly evolving. From the early simple hollow conduits, scaffolds with complex architectures that can modulate cell fate are currently being tested. A number of promising pre-clinical studies combining scaffolds, cells, drugs and/or nucleic acids are reported in the open literature. Overall, it is considered that to address the multi-factorial inhibitory environment of a SCI, a multifaceted therapeutic approach is imperative. The progress in the identification of molecules that target inhibition after SCI and its combination with scaffolds and/or cells are described and discussed in this review.This work was financed by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia in the framework of project UID/BIM/04293/2013. L.R.P. thanks FCT for her PhD grant (SFRH/BD/46015 / 2008)

    Selection for Higher Gene Copy Number after Different Types of Plant Gene Duplications

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    The evolutionary origins of the multitude of duplicate genes in the plant genomes are still incompletely understood. To gain an appreciation of the potential selective forces acting on these duplicates, we phylogenetically inferred the set of metabolic gene families from 10 flowering plant (angiosperm) genomes. We then compared the metabolic fluxes for these families, predicted using the Arabidopsis thaliana and Sorghum bicolor metabolic networks, with the families' duplication propensities. For duplications produced by both small scale (small-scale duplications) and genome duplication (whole-genome duplications), there is a significant association between the flux and the tendency to duplicate. Following this global analysis, we made a more fine-scale study of the selective constraints observed on plant sodium and phosphate transporters. We find that the different duplication mechanisms give rise to differing selective constraints. However, the exact nature of this pattern varies between the gene families, and we argue that the duplication mechanism alone does not define a duplicated gene's subsequent evolutionary trajectory. Collectively, our results argue for the interplay of history, function, and selection in shaping the duplicate gene evolution in plants

    Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

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    Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a Kiapp value of 3.8±0.8 µM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC50 value of 100 µM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 Å2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750–1,500 Å2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a Ki value of 760±170 nM using synthesis-based computer-aided molecular design (SBCAMD). This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight into structural modification of known small-molecule BoNTAe inhibitors. It also demonstrates that SBCAMD is capable of improving potency of an inhibitor lead by nearly one order of magnitude, even for BoNTAe as one of the most challenging protein targets. The results are insightful for developing effective small-molecule inhibitors of protein targets with large active sites

    Metabolic and evolutionary costs of herbivory defense: systems biology of glucosinolate synthesis

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    Here, we describe our updated mathematical model of Arabidopsis thaliana Columbia metabolism, which adds the glucosinolates, an important group of secondary metabolites, to the reactions of primary metabolism. In so doing, we also describe the evolutionary origins of the enzymes involved in glucosinolate synthesis. We use this model to address a long-standing question in plant evolutionary biology: whether or not apparently defensive compounds such as glucosinolates are metabolically costly to produce. We use flux balance analysis to estimate the flux through every metabolic reaction in the model both when glucosinolates are synthesized and when they are absent. As a result, we can compare the metabolic costs of cell synthesis with and without these compounds, as well as inferring which reactions have their flux altered by glucosinolate synthesis. We find that glucosinolate production can increase photosynthetic requirements by at least 15% and that this cost is specific to the suite of glucosinolates found in A. thaliana, with other combinations of glucosinolates being even more costly. These observations suggest that glucosinolates have evolved, and indeed likely continue to evolve, for herbivory defense, since only this interpretation explains the maintenance of such costly traits
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