La gestión de la I+D+i agroalimentaria : un modelo basado en el aprendizaje social

The author has introduced outstanding innovations into the R&D+I management of the Spanish Agri-Food System. Though it is the most difficult sector in the Spanish economy to promote its involvement in research and innovation activities, i.e. because of having the lowest investing activity on the area, its atomisation, the use of ‘low-tech’ technologies and presence of dozens of public technological centres and research organisms; the work carried out confirms that enterprises prospered since they are based on the Social Learning Model, framed in the Evolution Planning Theory developed by Prof. Friedmann. The work includes a review of the academic doctrine on the economical effects of research and technology; an analysis of the Agri-Food R&D+I systems in USA, Holland, France and Spain. Moreover, it is concluded the presence of strong causes concerning the clear inefficiency of the work on this issue in Spain that, according to the author, suggests the presence of ‘erroneous technological routes’, as well as low developed social behaviours, which handicaps our development

On living beings: biological and philosophical aspects.

This is an interdisciplinary work (biology-philosophy) product of reflection on the challenges today presented by a biological vision of the world regarding questions, concepts and notions of cosmology (Philosophy of Nature). Based on and in dialogue with the current state of biological research, this work deals with certain cosmological problems such as that between the living and the inert, the traditional division between the soul or the vital vegetative principle, sensitive or intellective; the problem of individuation and the concept of species, among others; the solution found within classical philosophy in this paper takes into account the latest discoveries findings of modern biology.post-print165 K

The Origin of Man in the Light of Three Fields of Knowledge: Science, Philosophy and Theology.

The reception and development of Darwin’s ideas have displaced mankind from the central place in the Cosmos, becoming no more than another evolved animal. This work offers a criticalscientific critique of the dominant ideas in the field of scientific research and debate into the origins of Man. By means of an interdisciplinary analysis (science, philosophy, and theology) of the scientifically proven facts, it is concluded that specimens classified in the genus Homo constitute a single species whose morphological evolution (hominization) is posterior to its humanization.post-print391 K

Sobre los seres vivos: aspectos biológicos y filosóficos

This is an interdisciplinary work (biology-philosophy) product of reflection on the challenges today presented by a biological vision of the world regarding questions, concepts and notions of cosmology (Philosophy of Nature). Based on and in dialogue with the current state of biological research, this work deals with certain cosmological problems such as that between the living and the inert, the traditional division between the soul or the vital vegetative principle, sensitive or intellective; the problem of individuation and the concept of species, among others; the solution found within classical philosophy in this paper takes into account the latest discoveries findings of modern biology.Este es un trabajo interdisciplinar (biología-filosofía) producto de la reflexión sobre los desafíos que presenta hoy una visión biológica del mundo en torno a cuestiones, conceptos y nociones de cosmología (Filosofía de la Naturaleza). A partir y en diálogo con el estado actual de la investigación biológica, esta obra aborda ciertos problemas cosmológicos como el de lo vivo y lo inerte, la tradicional división entre alma o principio vital vegetativo, sensitivo o intelectivo; el problema de la individuación y el concepto de especie, entre otros; la solución encontrada dentro de la filosofía clásica en este artículo tiene en cuenta los últimos descubrimientos de la biología moderna

Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients.

Schizophrenia pathophysiology implies both abnormal redox control and dysconnectivity of the prefrontal cortex, partly related to oligodendrocyte and myelin impairments. As oligodendrocytes are highly vulnerable to altered redox state, we investigated the interplay between glutathione and myelin. In control subjects, multimodal brain imaging revealed a positive association between medial prefrontal glutathione levels and both white matter integrity and resting-state functional connectivity along the cingulum bundle. In early psychosis patients, only white matter integrity was correlated with glutathione levels. On the other side, in the prefrontal cortex of peripubertal mice with genetically impaired glutathione synthesis, mature oligodendrocyte numbers, as well as myelin markers, were decreased. At the molecular levels, under glutathione-deficit conditions induced by short hairpin RNA targeting the key glutathione synthesis enzyme, oligodendrocyte progenitors showed a decreased proliferation mediated by an upregulation of Fyn kinase activity, reversed by either the antioxidant N-acetylcysteine or Fyn kinase inhibitors. In addition, oligodendrocyte maturation was impaired. Interestingly, the regulation of Fyn mRNA and protein expression was also impaired in fibroblasts of patients deficient in glutathione synthesis. Thus, glutathione and redox regulation have a critical role in myelination processes and white matter maturation in the prefrontal cortex of rodent and human, a mechanism potentially disrupted in schizophrenia

HIV-1 Vpu Blocks Recycling and Biosynthetic Transport of the Intrinsic Immunity Factor CD317/Tetherin To Overcome the Virion Release Restriction

The intrinsic immunity factor CD317 (BST-2/HM1.24/tetherin) imposes a barrier to HIV-1 release at the cell surface that can be overcome by the viral protein Vpu. Expression of Vpu results in a reduction of CD317 surface levels; however, the mechanism of this Vpu activity and its contribution to the virological antagonism are incompletely understood. Here, we characterized the influence of Vpu on major CD317 trafficking pathways using quantitative antibody-based endocytosis and recycling assays as well as a microinjection/microscopy-based kinetic de novo expression approach. We report that HIV-1 Vpu inhibited both the anterograde transport of newly synthesized CD317 and the recycling of CD317 to the cell surface, while the kinetics of CD317 endocytosis remained unaffected. Vpu trapped trafficking CD317 molecules at the trans-Golgi network, where the two molecules colocalized. The subversion of both CD317 transport pathways was dependent on the highly conserved diserine S52/S56 motif of Vpu; however, it did not require recruitment of the diserine motif interactor and substrate adaptor of the SCF-E3 ubiquitin ligase complex, β-TrCP. Treatment of cells with the malaria drug primaquine resulted in a CD317 trafficking defect that mirrored that induced by Vpu. Importantly, primaquine could functionally replace Vpu as a CD317 antagonist and rescue HIV-1 particle release

Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients

Schizophrenia pathophysiology implies both abnormal redox control and dysconnectivity of the prefrontal cortex, partly related to oligodendrocyte and myelin impairments. As oligodendrocytes are highly vulnerable to altered redox state, we investigated the interplay between glutathione and myelin. In control subjects, multimodal brain imaging revealed a positive association between medial prefrontal glutathione levels and both white matter integrity and resting-state functional connectivity along the cingulum bundle. In early psychosis patients, only white matter integrity was correlated with glutathione levels. On the other side, in the prefrontal cortex of peripubertal mice with genetically impaired glutathione synthesis, mature oligodendrocyte numbers, as well as myelin markers, were decreased. At the molecular levels, under glutathione-deficit conditions induced by short hairpin RNA targeting the key glutathione synthesis enzyme, oligodendrocyte progenitors showed a decreased proliferation mediated by an upregulation of Fyn kinase activity, reversed by either the antioxidant N-acetylcysteine or Fyn kinase inhibitors. In addition, oligodendrocyte maturation was impaired. Interestingly, the regulation of Fyn mRNA and protein expression was also impaired in fibroblasts of patients deficient in glutathione synthesis. Thus, glutathione and redox regulation have a critical role in myelination processes and white matter maturation in the prefrontal cortex of rodent and human, a mechanism potentially disrupted in schizophrenia

Phenolic and furanic compounds of Portuguese chestnut and French, American and Portuguese oak wood chips

Botanical species used on aging process must be wisely and judiciously chosen, and for this selection, a basic knowledge of the chemical composition of woods is warranted. Aiming to contribute to extend the knowledge of the chemical composition of several wood species useful for enological purposes, we have focused our studies on Portuguese chestnut and French, American and Portuguese oak chips. The profile of low molecular weight phenolic composition of these chips was achieved, using an optimized extraction method based on pressurized liquid extraction, followed by the quantification of phenolic acids, phenolic aldehydes and furanic derivatives by high-performance liquid chromatography (HPLC-DAD). The identification of those compounds was also confirmed by LC-DAD/ESI-MS. This study allowed the determination of the low molecular phenolic composition of Portuguese chestnut and French, American and Portuguese oak wood. According to our results, the influence of the botanical species seems to be more relevant than the geographic origin of the wood species

HIV-1 Vpu Neutralizes the Antiviral Factor Tetherin/BST-2 by Binding It and Directing Its Beta-TrCP2-Dependent Degradation

Host cells impose a broad range of obstacles to the replication of retroviruses. Tetherin (also known as CD317, BST-2 or HM1.24) impedes viral release by retaining newly budded HIV-1 virions on the surface of cells. HIV-1 Vpu efficiently counteracts this restriction. Here, we show that HIV-1 Vpu induces the depletion of tetherin from cells. We demonstrate that this phenomenon correlates with the ability of Vpu to counteract the antiviral activity of both overexpressed and interferon-induced endogenous tetherin. In addition, we show that Vpu co-immunoprecipitates with tetherin and β-TrCP in a tri-molecular complex. This interaction leads to Vpu-mediated proteasomal degradation of tetherin in a β-TrCP2-dependent manner. Accordingly, in conditions where Vpu-β-TrCP2-tetherin interplay was not operative, including cells stably knocked down for β-TrCP2 expression or cells expressing a dominant negative form of β-TrCP, the ability of Vpu to antagonize the antiviral activity of tetherin was severely impaired. Nevertheless, tetherin degradation did not account for the totality of Vpu-mediated counteraction against the antiviral factor, as binding of Vpu to tetherin was sufficient for a partial relief of the restriction. Finally, we show that the mechanism used by Vpu to induce tetherin depletion implicates the cellular ER-associated degradation (ERAD) pathway, which mediates the dislocation of ER membrane proteins into the cytosol for subsequent proteasomal degradation. In conclusion, we show that Vpu interacts with tetherin to direct its β-TrCP2-dependent proteasomal degradation, thereby alleviating the blockade to the release of infectious virions. Identification of tetherin binding to Vpu provides a potential novel target for the development of drugs aimed at inhibiting HIV-1 replication

Multilayered Mechanism of CD4 Downregulation by HIV-1 Vpu Involving Distinct ER Retention and ERAD Targeting Steps

A key function of the Vpu protein of HIV-1 is the targeting of newly-synthesized CD4 for proteasomal degradation. This function has been proposed to occur by a mechanism that is fundamentally distinct from the cellular ER-associated degradation (ERAD) pathway. However, using a combination of genetic, biochemical and morphological methodologies, we find that CD4 degradation induced by Vpu is dependent on a key component of the ERAD machinery, the VCP-UFD1L-NPL4 complex, as well as on SCFβ-TrCP-dependent ubiquitination of the CD4 cytosolic tail on lysine and serine/threonine residues. When degradation of CD4 is blocked by either inactivation of the VCP-UFD1L-NPL4 complex or prevention of CD4 ubiquitination, Vpu still retains the bulk of CD4 in the ER mainly through transmembrane domain interactions. Addition of a strong ER export signal from the VSV-G protein overrides this retention. Thus, Vpu exerts two distinct activities in the process of downregulating CD4: ER retention followed by targeting to late stages of ERAD. The multiple levels at which Vpu engages these cellular quality control mechanisms underscore the importance of ensuring profound suppression of CD4 to the life cycle of HIV-1