Annexin A2: The Importance of Being Redox Sensitive

Hydrogen peroxide (H2O2) is an important second messenger in cellular signal transduction. H2O2-dependent signalling regulates many cellular processes, such as proliferation, differentiation, migration and apoptosis. Nevertheless, H2O2 is an oxidant and a major contributor to DNA damage, protein oxidation and lipid peroxidation, which can ultimately result in cell death and/or tumourigenesis. For this reason, cells have developed complex antioxidant systems to scavenge ROS. Recently, our laboratory identified the protein, annexin A2, as a novel cellular redox regulatory protein. Annexin A2 possesses a reactive cysteine residue (Cys-8) that is readily oxidized by H2O2 and subsequently reduced by the thioredoxin system, thereby enabling annexin A2 to participate in multiple redox cycles. Thus, a single molecule of annexin A2 can inactivate several molecules of H2O2. In this report, we will review the studies detailing the reactivity of annexin A2 thiols and the importance of these reactive cysteine(s) in regulating annexin A2 structure and function. We will also focus on the recent reports that establish novel functions for annexin A2, namely as a protein reductase and as a cellular redox regulatory protein. We will further discuss the importance of annexin A2 redox regulatory function in disease, with a particular focus on tumour progression.European Union Seventh Framework Programme (FP7) [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Natural Sciences and Engineering Research Council of Canada (NSERC)info:eu-repo/semantics/publishedVersio

Discurso vs. realidades en propuestas innovadoras apoyadas en la web, en la FFHA de la UNSJ : (ampliación)

Se presenta la ampliación del proyecto Discurso vs realidades en propuestas innovadoras apoyadas en la web, en la FFHA de la UNSJ realizado en 2014-2015, para el periodo 2016 -2017, se propone indagar el impacto de la aplicación de un programa de formación para la generación de propuestas innovadoras con recursos en la Web en un grupo de profesores en la FFHA de la UNSJ. Se sugiere repensar ¿los procesos de formación implican un proceso de cambio de actitud en relación a las prácticas didáctico-pedagógicas apoyadas en la Web en la FFHA UNSJ?, ¿generan en su interior procesos de innovación siendo capaces de propiciar la construcción con sentido y significativad de nuevas propuestas didáctico-pedagógicas relacionadas con su saber científico (saber didáctico profesional)? Si están mediados por procesos de sistematización (investigación de, para y en la acción) ¿representan en gran medida la condición sin e qua non de los procesos formativos?.Fil: Carmona, Emilse. Universidad Nacional de San JuanFil: Dipp, Silvia M.. Universidad Nacional de San JuanFil: Olivares Waisman, Laura. Universidad Nacional de San Jua

Toxicomanía juvenil

El campo de la psicopatología infanto-juvenil se extiende desde la temprana infancia hasta la edad adulta. En este marco amplio y polimorfo ubicamos el estudio de la adolescencia. La adolescencia abarca un período de alrededor de diez años en la vida de un individuo; comienza a los 11-12 años con los cambios psicobiológicos de la pubertad y continúa manifestándose, luego que los mismos se han instalado, a través de una problemática y una sintomatología multifacética hasta los veinte años aproximadamente, en que el individuo entra en la adultez. Estas edades son variables desde el punto de vista interindividual, así como intercultural. No es tarea fácil, pues, delimitar lo que se puede considerar normal en este período; es decir, que la palabra “normalidad”, en el sentido de grados de desequilibrio emocional interno, implica una calibración muy sutil y rebasa el límite de las connotaciones que parecen claras al aplicarlas a otras etapas de la existencia individual.Universidad Nacional de La Plat

Sustainability, Globalization, and the Energy Sector Europe in a Global Perspective

International audienceThis paper analyzes the socio-economic effects of energy sustainability challenges raised by oil depletion and climate change at the European and global level. We assess macroeconomic impacts at different time horizons over 2010-2100 and under different visions of the future of globalization . Fragmented capital markets affect the pace and direction of change and induce additional economic losses in the long term. Regionalized good markets have a positive effect in the long term since less intense international trade moderates the effects of fossil fuel constraints. A sustainable energy future will require implementing policies and measures that are able to (i) provide correct incentives for long-term investments by resorting to other signals than current market prices, (ii) incorporate sectoral measures that act complementarily to pricing schemes measures for sectors confronted with biased agents’ behaviors or strong inertias, (iii) foster globalization patterns that are consistent with energy sustainability objectives. The challenge consists in articulating the objectives and the instruments of these different policy and measures triggering the transition towards sustainable future

Tolerance without clonal expansion: Self-antigen-expressing B cells program self-reactive T cells for future deletion

B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T cells became sensitive to Ag-induced cell death. Our results demonstrate that B cells participate in the homeostasis of the immune system by ablation of conventional self-reactive T cells

DNA-PKCS binding to p53 on the p21WAF1/CIP1 promoter blocks transcription resulting in cell death

A key determinant of p53-mediated cell fate following various DNA damage modalities is p21WAF1/CIP1 expression, with elevated p21 expression triggering cell cycle arrest and repressed p21 expression promoting apoptosis. We show that under pro-death DNA damage conditions, the DNA-dependent protein kinase (DNA-PKCS) is recruited to the p21 promoter where it forms a protein complex with p53. The DNA-PKCS-associated p53 displays post-translational modifications that are distinct from those under pro-arrest conditions, ablating p21 transcription and inducing cell death. Inhibition of DNA-PK activity prevents DNA-PKCS binding to p53 on the p21 promoter, restores p21 transcription and significantly reduces cell death. These data demonstrate that DNA-PKCS negatively regulates p21 expression by directly interacting with the p21 transcription machinery via p53, driving the cell towards apoptosis

Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse

Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage

The biochemistry and regulation of S100A10: a multifunctional plasminogen receptor involved in oncogenesis

The plasminogen receptors mediate the production and localization to the cell surface of the broad spectrum proteinase, plasmin. S100A10 is a key regulator of cellular plasmin production and may account for as much as 50% of cellular plasmin generation. In parallel to plasminogen, the plasminogen-binding site on S100A10 is highly conserved from mammals to fish. S100A10 is constitutively expressed in many cells and is also induced by many diverse factors and physiological stimuli including dexamethasone, epidermal growth factor, transforming growth factor-alpha, interferon-gamma, nerve growth factor, keratinocyte growth factor, retinoic acid, and thrombin. Therefore, S100A10 is utilized by cells to regulate plasmin proteolytic activity in response to a wide diversity of physiological stimuli. The expression of the oncogenes, PML-RAR alpha and KRas, also stimulates the levels of S100A10, suggesting a role for S100A10 in pathophysiological processes such as in the oncogenic-mediated increases in plasmin production. The S100A10-null mouse model system has established the critical role that S100A10 plays as a regulator of fibrinolysis and oncogenesis. S100A10 plays two major roles in oncogenesis, first as a regulator of cancer cell invasion and metastasis and secondly as a regulator of the recruitment of tumor-associated cells, such as macrophages, to the tumor site.Canadian Cancer Society Research Institute; Canadian Institutes of Health Research; Foundation for Science and Technology of Portuga