El Principio de Publicidad a la luz de las reformas a la Constitucion Politica y su posible incorporacion a los principios del Estado de Derecho

72 p.La presente memoria tiene por objeto determinar si el Principio de Publicidad de los actos y resoluciones de los órganos del Estado, establecido en el artículo 8º inciso 2º de la Constitución Política de la República, es un componente de los principios del Estado de Derecho consagrados en los artículos 6º, 7º y posiblemente extendiéndose al artículo 8º, en virtud de la reforma constitucional introducida por la Ley Nº 20.050. El método aplicado es el análisis deductivo, para lo cual se efectuó un estudio general de las normativas aplicables y de la doctrina referida a la materia, tanto Chilena como Española. Como resultado de la investigación podemos concluir que el Principio de Publicidad es un elemento integrante del Estado de Derecho, cuya aplicación se hace extensiva a todos los órganos del Estado

Efecto del oxígeno y taninos en la intensidad y estabilidad del color rojo de vinos Carménère

56 p.El vino es uno de los productos agroindustriales que ofrece mayor reconocimiento e ingresos económicos a nuestro país; razón por la cual, la industria vitivinícola se encuentra en una constante búsqueda de mejores técnicas de elaboración que le permitan incrementar su calidad y presencia en el mercado. Dentro de los atributos organolépticos del vino, el color tiene una importancia particular, por cuanto dicho atributo influye sobre otras propiedades sensoriales. Del mismo modo, las características aromáticas y gustativas del producto son muy determinantes a la hora de calificar su calidad, siendo todas estas variables dependientes del tipo de materias primas y las formas de vinificación utilizadas. Dentro de las variables productivas que más influyen sobre la expresión del color en vinos tintos, la acidez, las exposiciones al oxígeno, y el contenido o adiciones de taninos (o madera de roble) son de las más importantes. En relación a la acidez, cuando un vino presenta un menor pH, la intensidad del color aumenta producto de un cambio en el equilibrio químico entre las distintas antocianinas. Por otra parte, el oxígeno es de vital importancia durante el proceso de fermentación alcohólica, permitiendo que las levaduras sinteticen esteroles y ácidos grasos de membrana que les confieren una mayor resistencia al etanol presente en el vino. También, diversos estudios han demostrado que las exposiciones moderadas del vino al oxígeno ayudan a mantener la estabilidad del color en el tiempo y a reducir las sensaciones de astringencia y amargor. Por otra parte, si las exposiciones al oxígeno resultan excesivas, se podría afectar negativamente las características sensoriales del vino y su calidad. Finalmente, las adiciones de taninos, practicadas fundamentalmente en el caso de los vinos tintos buscan mejorar la estabilidad de la materia colorante, y modificar parte de las sensaciones táctiles y gustativas percibidas al beber el vino. Estas adiciones se realizan con taninos que reciben el nombre de taninos condensados porque provienen de las uvas; principalmente de las semillas y las pieles. En cambio, cuando se adiciona madera de roble estos son llamados taninos hidrolizables ya que el vino los extrae de la madera utilizada para el envejecimiento. Esta investigación se compone de dos ensayos que tienen por objetivo general evaluar los efectos de distintas dosis de oxígeno y taninos (o madera de roble) en el color de vinos tintos de la variedad Carménère. Para esto, se utilizaron metodologías espectrofotométricas que permiten medir color y la formación de estructuras poliméricas pigmentadas más estables que las de la fracción monomérica. En el primer ensayo, se evaluó el efecto de dos tratamientos de micro-oxigenación donde se comparó el efecto de un tratamiento convencional de micro-oxigenación versus un tratamiento alternativo basado en aireaciones periódicas del vino. Además de lo anterior, se evaluaron dichos tratamientos con la adición de chips de madera de roble. Para la mayoría de las variables analizadas, el tratamiento de aireación periódica produjo efectos equivalentes a los observados con el tratamiento de micro-oxigenación convencional (ej. una reducción en la concentración de antocianinas libres, y un incremento en los pigmentos poliméricos). Lo anterior sugiere que un buen manejo del tratamiento de aireación discontinua puede ser utilizado como una alternativa a la microoxigenación convencional. En el segundo ensayo se evaluó el efecto de la adición de taninos comerciales en vino tinto en una única dosis, o dividiendo dicha dosis en tres parcialidades. En este caso, los tratamientos con dosis de taninos mayores a las recomendadas por los fabricantes producen reacciones más rápidas y significativas que las observadas siguiendo los protocolos comerciales recomendados. Sin embargo, los resultados del estudio no sugieren un efecto positivo de la parcialización de dosis en la estabilidad del color del vino.Palabras claves: vino, oxígeno, antocianinas, taninos, color, fenoles/ABSTRACT: Wine is one of the main chilean agroindustrial products that offer recognition and significant revenues to our country. Therefore, the wine industry is in a constant search for better processing techniques to improve its quality and presence in different market places. Within the organoleptic attributes of wine, color is particularly important, as it affects other sensory properties the product. Similarly, flavor and taste characteristics are very decisive when evaluating wine quality; all of which dependent on the of raw materials used and the types of winemaking techniques used to produce the wine. Some of the winemaking variables that have a significant influence on the expression of color in red wines, are: acidity, oxygen exposures, and tannin or oak additions. In relation to the an cidity, when a wine has a low pH, their is an increased color intensity due to a change in the chemical equilibrium anthocyanins. Moreover, oxygen has a key role during alcoholic fermentation, allowing yeasts to synthesize sterols and membrane fatty acids that confer increased tolerance to environmental ethanol. Also, several studies have shown that moderate wine exposures to oxygen help maintain color stability over time and reduce the sensation of astringency and bitterness. If oxygen exposures are excessive, it could adversely affect the sensory characteristics of wine and its quality. Finally, additions of tannins, practiced mainly in the case of red wines seek to improve the stability of the coloring matter, and modify part of tactile and gustatory sensations perceived during wine tasting. These additions are made with grape (condensed tannins) or oak tannins (hydrolyzable tannins). This research consists of two trials to assess the effects of different doses of oxygen and tannins (or oak) in the color of red wines of the variety Carmenere. For this, spectrophotometric methods for measuring the formation of color and pigmented polymer structures.In the first trial, the effect of two treatments of micro-oxygenation were tested,comparing the effects of a conventional micro-oxygenation treatment versus an alternative treatment based on periodic aeration. Besides the above, a treatment with the addition of oak chips was evaluated. For most of the variables analyzed, periodic aeration treatment produced effects equivalent to those observed with the treatment of conventional microoxygenation (e.g. a reduction in the concentration of free anthocyanins, and an increase in polymeric pigments). The prior suggests that a good management of periodic aeration treatments can be used as an alternative to conventional micro-oxygenation. In the second experiment, the effects of the addition of commercial tannins in red wine in a single dose was evaluated, or dividing this dose in three installments. In this case, the treatment with tannins at doses higher tan those recommended by the manufacturers produce significant changes, but no clear effect was observed when the total dose was divided in three installments. Keywords: wine, oxygen, anthocyanins, tannins, color, phenol

FAS-dependent cell death in α-synuclein transgenic oligodendrocyte models of multiple system atrophy

Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention

B Cells Participate in Thymic Negative Selection of Murine Auto-reactive CD4+ T Cells

It is well documented that thymic epithelial cells participate in the process of negative selection in the thymus. In recent years it was reported that also dendritic cells enter the thymus and contribute to this process, thus allowing for the depletion of thymocytes that are specific to peripherally expressed self-antigens. Here we report that also B cells may take part in the elimination of auto-reactive thymocytes. Using a unique mouse model we show that B cells induce negative selection of self-reactive thymocytes in a process that leads to the deletion of these cells whereas regulatory T cells are spared. These findings have direct implication in autoimmunity, as expression of a myelin antigen by B cells in the thymus renders the mice resistant to autoimmune inflammation of the CNS

Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-kappaB signaling.

The pathogenesis of chronic lymphocytic leukemia (CLL) has been linked to constitutive NF-kappaB activation but the underlying mechanisms are poorly understood. Here we show that alternative splicing of the negative regulator of NF-kappaB and tumor suppressor gene CYLD regulates the pool of CD5(+) B cells through sustained canonical NF-kappaB signaling. Reinforced canonical NF-kappaB activity leads to the development of B1 cell-associated tumor formation in aging mice by promoting survival and proliferation of CD5(+) B cells, highly reminiscent of human B-CLL. We show that a substantial number of CLL patient samples express sCYLD, strongly implicating a role for it in human B-CLL. We propose that our new CLL-like mouse model represents an appropriate tool for studying ubiquitination-driven canonical NF-kappaB activation in CLL. Thus, inhibition of alternative splicing of this negative regulator is essential for preventing NF-kappaB-driven clonal CD5(+) B-cell expansion and ultimately CLL-like disease

CLIPR-59 regulates TNF-α-induced apoptosis by controlling ubiquitination of RIP1

Tumor necrosis factor-α (TNF-α) has important roles in several immunological events by regulating apoptosis and transcriptional activation of cytokine genes. Intracellular signaling mediated by TNF-receptor-type 1 (TNFR1) is constituted by two sequential protein complexes: Complex-I containing the receptor and Complex-II-containing Caspase-8. Protein modifications, particularly ubiquitination, are associated with the regulation of the formation of these complexes. However, the underlying mechanisms remain poorly defined. Here, we identified CLIP-170-related 59 kDa protein (CLIPR-59) as a novel adaptor protein for TNFR1. Experimental reduction of CLIPR-59 levels prevented induction of apoptosis and activation of caspases in the context of TNF-α signaling. CLIPR-59 binds TNFR1 but dissociates in response to TNF-α stimulation. However, CLIPR-59 is also involved in and needed for the formation of Complex-II. Moreover, CLIPR-59 regulates TNF-α-induced ubiquitination of receptor-interacting protein 1 (RIP1) by its association with CYLD, a de-ubiquitinating enzyme. These findings suggest that CLIPR-59 modulates ubiquitination of RIP1, resulting in the formation of Complex-II and thus promoting Caspase-8 activation to induce apoptosis by TNF-α

Targeted Ablation of Oligodendrocytes Triggers Axonal Damage

Glial dysfunction has been implicated in a number of neurodegenerative diseases. In this study we investigated the consequences of glial and oligodendrocyte ablation on neuronal integrity and survival in Drosophila and adult mice, respectively. Targeted genetic ablation of glia was achieved in the adult Drosophila nervous system using the GAL80-GAL4 system. In mice, oligodendrocytes were depleted by the injection of diphtheria toxin in MOGi-Cre/iDTR double transgenic animals. Acute depletion of oligodendrocytes induced axonal injury, but did not cause neuronal cell death in mice. Ablation of glia in adult flies triggered neuronal apoptosis and resulted in a marked reduction in motor performance and lifespan. Our study shows that the targeted depletion of glia triggers secondary neurotoxicity and underscores the central contribution of glia to neuronal homeostasis. The models used in this study provide valuable systems for the investigation of therapeutic strategies to prevent axonal or neuronal damage

CXCR2 Signaling Protects Oligodendrocytes and Restricts Demyelination in a Mouse Model of Viral-Induced Demyelination

BACKGROUND: The functional role of ELR-positive CXC chemokines during viral-induced demyelination was assessed. Inoculation of the neuroattenuated JHM strain of mouse hepatitis virus (JHMV) into the CNS of susceptible mice results in an acute encephalomyelitis that evolves into a chronic demyelinating disease, modeling white matter pathology observed in the human demyelinating disease Multiple Sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: JHMV infection induced the rapid and sustained expression of transcripts specific for the ELR+ chemokine ligands CXCL1 and CXCL2, as well as their binding receptor CXCR2, which was enriched within the spinal cord during chronic infection. Inhibiting CXCR2 signaling with neutralizing antiserum significantly (p<0.03) delayed clinical recovery. Moreover, CXCR2 neutralization was associated with an increase in the severity of demyelination that was independent of viral recrudescence or modulation of neuroinflammation. Rather, blocking CXCR2 was associated with increased numbers of apoptotic cells primarily within white matter tracts, suggesting that oligodendrocytes were affected. JHMV infection of enriched oligodendrocyte progenitor cell (OPC) cultures revealed that apoptosis was associated with elevated expression of cleaved caspase 3 and muted Bcl-2 expression. Inclusion of CXCL1 within JHMV infected cultures restricted caspase 3 cleavage and increased Bcl-2 expression that was associated with a significant (p<0.001) decrease in apoptosis. CXCR2 deficient oligodendrocytes were refractory to CXCL1 mediated protection from JHMV-induced apoptosis, readily activating caspase 3 and down regulating Bcl-2. CONCLUSION/SIGNIFICANCE: These findings highlight a previously unappreciated role for CXCR2 signaling in protecting oligodendrocyte lineage cells from apoptosis during inflammatory demyelination initiated by viral infection of the CNS

Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis

Autoreactive CD4+ T lymphocytes play a vital role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Since the discovery of T helper 17 cells, there is an ongoing debate whether T helper 1, T helper 17 or both subtypes of T lymphocytes are important for the initiation of autoimmune neuroinflammation. We examined peripheral blood CD4+ cells from patients with active and stable relapsing–remitting multiple sclerosis, and used mice with conditional deletion or over-expression of the transforming growth factor-β inhibitor Smad7, to delineate the role of Smad7 in T cell differentiation and autoimmune neuroinflammation. We found that Smad7 is up-regulated in peripheral CD4+ cells from patients with multiple sclerosis during relapse but not remission, and that expression of Smad7 strongly correlates with T-bet, a transcription factor defining T helper 1 responses. Concordantly, mice with transgenic over-expression of Smad7 in T cells developed an enhanced disease course during experimental autoimmune encephalomyelitis, accompanied by elevated infiltration of inflammatory cells and T helper 1 responses in the central nervous system. On the contrary, mice with a T cell-specific deletion of Smad7 had reduced disease and central nervous system inflammation. Lack of Smad7 in T cells blunted T cell proliferation and T helper 1 responses in the periphery but left T helper 17 responses unaltered. Furthermore, frequencies of regulatory T cells were increased in the central nervous system of mice with a T cell-specific deletion and reduced in mice with a T cell-specific over-expression of Smad7. Downstream effects of transforming growth factor-β on in vitro differentiation of naïve T cells to T helper 1, T helper 17 and regulatory T cell phenotypes were enhanced in T cells lacking Smad7. Finally, Smad7 was induced during T helper 1 differentiation and inhibited during T helper 17 differentiation. Taken together, the level of Smad7 in T cells determines T helper 1 polarization and regulates inflammatory cellular responses. Since a Smad7 deletion in T cells leads to immunosuppression, Smad7 may be a potential new therapeutic target in multiple sclerosis

A20 (Tnfaip3) Deficiency in Myeloid Cells Protects against Influenza A Virus Infection

The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV) produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-κB and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections