Proyecto de instalación fotovoltaica conectada a red en el Aulario del Campus Universitario “La Yutera” de Palencia

El objeto de este proyecto es hacer más sostenible tanto desde el punto de vista ambiental como económico el Campus” La Yutera” de Palencia para ello se ha propuesto en el presente proyecto una instalación fotovoltaica conectada a red en régimen de autoconsumo, en el edificio Aulario de dicho Campus.Máster en Ingeniería AgronómicaPremio San Isidro otorgado por Colegios Profesionale

Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis

Purified cytolytic T lymphocyte (CTL) proteases granzyme (gzm)A and gzmB with sublytic dose of perforin (perf) initiate distinct proapoptotic pathways. Their physiological relevance in CTL-mediated target cell apoptosis is elusive. Using ex vivo virus-immune CD8+ T cells from mice deficient in perf, gzmA and/or gzmB, and the Fas-resistant EL4.F15 tumor target cell, we show that (a) CTL from gzmA−/− or gzmB−/− mice similarly induced early proapoptotic features, such as phosphatidyl serine (PS) exposure on plasma membrane, ΔΨm loss, and reactive oxygen radical generation, though with distinct kinetics; (b) CTL from gzmA−/− but not from gzmB−/− mice activate caspase 3 and 9; (c) PS exposure induced by CTL from gzmA−/− or gzmB−/− mice is prevented, respectively, by caspase inhibitors or by reactive oxygen scavengers without interfering with target cell death; and (d) all gzm-induced apoptotic features analyzed depend critically on perf. Thus, perf is the principal regulator in CTL-mediated and gzm-facilitated intracellular processes. The ability of gzmA and gzmB to induce multiple independent cell death pathways may be the hosts response to circumvent evasion strategies of pathogens and tumors

Efectos socioeconómicos y ambientales del desarrollo turístico en el valle de Tena

Desde mediados del siglo XX la montaña española y europea se ha visto inmersa en un proceso de transformación. El turismo ha alcanzado un importante grado de desarrollo como actividad económica tras la crisis del denominado sistema tradicional, utilizándose para la revitalización de estas zonas. El valle de Tena no ha sido ajeno a estos cambios, especialmente tras la instalación de las estaciones de esquí alpino de Panticosa en 1971 y Formigal en 1964 que, junto con otras modalidades turísticas, han provocado un cambio de paradigma en la dinámica demográfica, económica, social, urbanística y ambiental de este valle, el cual se ha consolidado como un destino turístico de masas con una economía profundamente tercerizada. En este trabajo se describen el turismo y su desarrollo en zonas de montaña, así como los cambios socioeconómicos derivados de estos procesos de transformación. Para cuantificar estos cambios se analiza el estado actual y la evolución de la dinámica demográfica, la estructura económica, el sector primario, los alojamientos turísticos, la expansión de los núcleos de población y el paisaje. Para contextualizar estos cambios se compara el valle de Tena con otros valles pirenaicos apreciándose una evolución distinta de los parámetros analizados. Los resultados muestran que el desarrollo turístico ha tenido efectos positivos en la evolución demográfica y negativos en el mantenimiento del sector primario, produciéndose a su vez cambios sustanciales en el paisaje.<br /

Transcriptomic Analysis Implicates the p53 Signaling Pathway in the Establishment of HIV-1 Latency in Central Memory CD4 T Cells in an In Vitro Model

The search for an HIV-1 cure has been greatly hindered by the presence of a viral reservoir that persists despite antiretroviral therapy (ART). Studies of HIV-1 latency in vivo are also complicated by the low proportion of latently infected cells in HIV-1 infected individuals. A number of models of HIV-1 latency have been developed to examine the signaling pathways and viral determinants of latency and reactivation. A primary cell model of HIV-1 latency, which incorporates the generation of primary central memory CD4 T cells (TCM), full-length virus infection (HIVNL4-3) and ART to suppress virus replication, was used to investigate the establishment of HIV latency using RNA-Seq. Initially, an investigation of host and viral gene expression in the resting and activated states of this model indicated that the resting condition was reflective of a latent state. Then, a comparison of the host transcriptome between the uninfected and latently infected conditions of this model identified 826 differentially expressed genes, many of which were related to p53 signaling. Inhibition of the transcriptional activity of p53 by pifithrin-α during HIV-1 infection reduced the ability of HIV-1 to be reactivated from its latent state by an unknown mechanism. In conclusion, this model may be used to screen latency reversing agents utilized in shock and kill approaches to cure HIV, to search for cellular markers of latency, and to understand the mechanisms by which HIV-1 establishes latency

Mycobacterium tuberculosis reactivates latent HIV-1 in T cells in vitro

Following proviral integration into the host cell genome and establishment of a latent state, the human immunodeficiency virus type 1 (HIV-1) can reenter a productive life cycle in response to various stimuli. HIV-1 reactivation occurs when transcription factors, such as nuclear factor-κB (NF-κB), nuclear factor of activated T cells (NFAT), and activator protein -1 (AP-1), bind cognate sites within the long terminal repeat (LTR) region of the HIV-1 provirus to promote transcription. Interestingly, pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) can reactivate latent HIV-1 through activation of the transcription factor NF-κB. Some PRRs are expressed on central memory CD4+ T cells (TCM), which in HIV-1 patients constitute the main reservoir of latent HIV-1. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), interacts with PRRs through membrane components. However, the ability of Mtb to reactivate latent HIV-1 has not been extensively studied. Here we show that phosphatidylinositol mannoside 6 (PIM6), a component of the Mtb membrane, in addition to whole bacteria in co-culture, can reactivate HIV-1 in a primary TCM cell model of latency. Using a JLAT model of HIV-1 latency, we found this interaction to be mediated through Toll-like receptor-2 (TLR-2). Thus, we describe a mechanism by which Mtb can exacerbate HIV-1 infection. We hypothesize that chronic Mtb infection can drive HIV-1 reactivation. The phenomenon described here could explain, in part, the poor prognosis that characterizes HIV-1/Mtb co-infection

Downmodulation of CCR7 by HIV-1 Vpu Results in Impaired Migration and Chemotactic Signaling within CD4+ T Cells

SummaryThe chemokine receptor CCR7 plays a crucial role in the homing of central memory and naive T cells to peripheral lymphoid organs. Here, we show that the HIV-1 accessory protein Vpu downregulates CCR7 on the surface of CD4+ T cells. Vpu and CCR7 were found to specifically interact and colocalize within the trans-Golgi network, where CCR7 is retained. Downmodulation of CCR7 did not involve degradation or endocytosis and was strictly dependent on Vpu expression. Stimulation of HIV-1-infected primary CD4+ T cells with the CCR7 ligand CCL19 resulted in reduced mobilization of Ca2+, reduced phosphorylation of Erk1/2, and impaired migration toward CCL19. Specific amino acid residues within the transmembrane domain of Vpu that were previously shown to be critical for BST-2 downmodulation (A14, A18, and W22) were also necessary for CCR7 downregulation. These results suggest that BST-2 and CCR7 may be downregulated via similar mechanisms

Estudio de tamaño y potencia de algunos contrastes de heterocedasticidad

Este trabajo lleva a cabo un análisis de tamaño y potencia de algunos contrastes de heterocedasticidad en el contexto del modelo de regresión lineal. Resulta muy importante que la detección del problema de la heterocedasticidad se realice de manera adecuada, ya que su presencia implica que los estimadores obtenidos dejan de tener propiedades deseables y, adicionalmente, invalida la inferencia habitual sobre los parámetros de los modelos. Por ello se analiza la adecuación de dos contrastes de heterocedasticidad: el contraste específico de Breusch-Pagan y el contraste general de White. El estudio del comportamiento de ambos contrastes se lleva a cabo en términos de tamaño y potencia de los mismos. Para llevar a cabo el análisis, se han diseñado dos experimentos de Monte Carlo en los que se asumen varios supuestos sobre la estructura de la varianza del error, distintos grados de heterocedasticidad y varios tamaños muestrales. A partir de estos experimentos se analiza el tamaño de error tipo I y la potencia calculadas. Se concluye que el contraste de Breusch-Pagan es el más eficaz para detectar la presencia de heterocedasticidad

Long non-coding RNAs and latent HIV : a search for novel targets for latency reversal

The latent cellular reservoir of HIV is recognized as the major barrier to cure from HIV infection. Long non-coding RNAs (lncRNAs) are more tissue and cell type-specific than protein coding genes, and may represent targets of choice for HIV latency reversal. Using two in vitro primary T-cell models, we identified lncRNAs dysregulated in latency. PVT1 and RP11-347C18.3 were up-regulated in common between the two models, and RP11-539L10.2 was down-regulated. The major component of the latent HIV reservoir, memory CD4+ T-cells, had higher expression of these lncRNAs, compared to naive T-cells. Guilt-by-association analysis demonstrated that lncRNAs dysregulated in latency were associated with several cellular pathways implicated in HIV latency establishment and maintenance: proteasome, spliceosome, p53 signaling, and mammalian target of rapamycin (MTOR). PVT1, RP11-347C18.3, and RP11-539L10.2 were down-regulated by latency reversing agents, suberoylanilide hydroxamic acid and Romidepsin, suggesting that modulation of lncRNAs is a possible secondary mechanism of action of these compounds. These results will facilitate prioritization of lncRNAs for evaluation as targets for HIV latency reversal. Importantly, our study provides insights into regulatory function of lncRNA during latent HIV infection