Variaciones del humor y el terror en Su turno (1976), de Alberto Laiseca

Este escrito se ocupa de los vínculos entre el terror y el humor en la primera novela de Alberto Laiseca: Su turno, publicada por primera vez en 1976.Previo al análisis de la novela, deslindo qué se entiende por “terror” y qué por “humor”. La hipótesis central consiste en que esta novela oscila entre el terror y el humor mediante el uso de la hipérbole. A pesar de que algunas escenas y tópicos parecen remitir a la violencia estatal y paraestatal de los primeros años 70, Su turno dista de ser una narración de carácter realista o siquiera de denuncia

A DESOBEDIÊNCIA CIVIL COMO PARTICIPAÇÃO COMUNITÁRIA À EFETIVAÇÃO DO PLURALISMO JURÍDICO

O presente artigo empreende uma visão crítica sobre a efetivação do Estado de Direito nos países periféricos, como o Brasil, e dos princípios programáticos contidos em sua Constituição, enfocando uma nova atuação de atores que devem desempenhar um papel fundamental na concretização da justiça social por meio da promoção aos direitos humanos. Procuramos superar uma visão técnico-formal-legalista empreendida ao sistema jurídico nacional por meio da negação de suas características cultivadas por uma visão conservadora e dominante, que mantém o sistema social refém da manutenção ao status quo, da marginalização, exploração e opressão de grande parte da sociedade, excluídas da condição de cidadãos

A DESOBEDIÊNCIA CIVIL COMO PARTICIPAÇÃO COMUNITÁRIA À EFETIVAÇÃO DO PLURALISMO JURÍDICO

O presente artigo empreende uma visão crítica sobre a efetivação do Estado de Direito nos países periféricos, como o Brasil, e dos princípios programáticos contidos em sua Constituição, enfocando uma nova atuação de atores que devem desempenhar um papel fundamental na concretização da justiça social por meio da promoção aos direitos humanos. Procuramos superar uma visão técnico-formal-legalista empreendida ao sistema jurídico nacional por meio da negação de suas características cultivadas por uma visão conservadora e dominante, que mantém o sistema social refém da manutenção ao status quo, da marginalização, exploração e opressão de grande parte da sociedade, excluídas da condição de cidadãos

SHMT1 and SHMT2 Are Functionally Redundant in Nuclear De novo Thymidylate Biosynthesis

The three enzymes that constitute the de novo thymidylate synthesis pathway in mammals, cytoplasmic serine hydroxymethyltransferase (SHMT1), thymidylate synthase (TYMS) and dihydrofolate reductase (DHFR) undergo sumoylation and nuclear import during S-phase. In this study, we demonstrate that purified intact mouse liver nuclei convert dUMP to dTMP in the presence of NADPH and serine. Neither nuclear extracts nor intact nuclei exposed to aminomethylphosphonate, a SHMT inhibitor, exhibit thymidylate synthesis activity. Nuclei isolated from Shmt1−/− mouse livers retained 25% of thymidylate synthesis activity exhibited by nuclei isolated from wild type mice. This residual activity was due to the presence of a cytoplasmic/nuclear isozyme of SHMT encoded by Shmt2. Shmt2 is shown to encode two transcripts, one which encodes a protein that localizes exclusively to the mitochondria (SHMT2), and a second transcript that lacks exon 1 and encodes a protein that localizes to the cytoplasm and nucleus during S-phase (SHMT2α). The ability of Shmt2 to encode a cytoplasmic isozyme of SHMT may account for the viability of Shmt1−/− mice and provide redundancy that permitted the expansion of the human SHMT1 L474F polymorphism that impairs SHMT1 sumoylation and nuclear translocation

Protein Tyrosine Phosphatases, TC-PTP, SHP1, and SHP2, Cooperate in Rapid Dephosphorylation of Stat3 in Keratinocytes Following UVB Irradiation

Stat3 is initially dephosphorylated in murine keratinocytes in response to UVB irradiation. Treatment with Na3VO4 desensitized keratinocytes to UVB-induced apoptosis with the recovery of phosphorylated Stat3 protein levels, implying that a protein tyrosine phosphatase (PTP) is involved in this mechanism. In the current work, we report that three PTPs including TC45 (the nuclear form of TC-PTP), SHP1, and SHP2 are involved in this rapid dephosphorylation of Stat3 in keratinocytes induced by UVB irradiation. Dephosphorylation of Stat3 was increased rapidly after UVB irradiation of cultured keratinocytes. Knockdown of TC-PTP, SHP1, or SHP2 using RNAi showed that these PTPs are likely responsible for most of the rapid Stat3 dephosphorylation observed following UVB irradiation. The level of phosphorylated Stat3 was significantly higher in keratinocytes transfected with TC-PTP, SHP1, or SHP2 siRNA in the presence or absence of UVB compared with keratinocytes transfected with control siRNA. TC45 was mainly localized in the cytoplasm of keratinocytes and translocated from cytoplasm to nucleus upon UVB irradiation. Stat3 dephosphorylation was associated with nuclear translocation of TC45. Further studies revealed that knockdown of all three phosphatases, using RNAi, prevented the rapid dephosphorylation of Stat3 following UVB irradiation. In mouse epidermis, the level of phosphorylated Stat3 was initially decreased, followed by a significant increase at later time points after UVB exposure. The levels of Stat3 target genes, such as cyclin D1 and c-Myc, followed the changes in activated Stat3 in response to UVB irradiation. Collectively, these results suggest that three phosphatases, TC45, SHP1, and SHP2, are primarily responsible for UVB-mediated Stat3 dephosphorylation and may serve as part of an initial protective mechanism against UV skin carcinogenesis

Microglial activation decreases retention of the protease inhibitor saquinavir: implications for HIV treatment

Background Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide. Methods To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent microglia exposed to the prototypical inflammatory mediator lipopolysaccharide (LPS). Results [3H]-Saquinavir accumulation by microglia was rapid, and was increased up to two-fold in the presence of the specific P-glycoprotein inhibitor, PSC833. After six or 24 hours of exposure to 10 ng/ml LPS, saquinavir accumulation was decreased by up to 45%. LPS did not directly inhibit saquinavir transport, and did not affect P-glycoprotein protein expression. LPS exposure did not alter RNA and/or protein expression of other transporters including multidrug resistance-associated protein 1 and several solute carrier uptake transporters. Conclusions The decrease in saquinavir accumulation in microglia following treatment with LPS is likely multi-factorial, since drug accumulation was attenuated by inhibitors of NF-κβ and the MEK1/2 pathway in the microglia cell line HAPI, and in primary microglia cultures from toll-like receptor 4 deficient mice. These data provide new pharmacological insights into why microglia act as a difficult-to-treat viral sanctuary site

Un nuevo Notungulado Hipsodonte (Hegetotheriidae, Pachyrukhinae) del Mioceno tardío de la Cordillera Oriental, provincia de Salta, Noroeste de Argentina

Late Miocene fluvial strata of the Palo Pintado Formation are broadly exposed to the northwest of the town of Angastaco, Salta province, Northwest of Argentina. These strata accumulated in the extensional Angastaco Basin. Recent field work at the Palo Pintado Formation (late Miocene), Valle Calchaquí, Salta province, Argentina has provided fossil remains that greatly increased the knowledge of the faunal assemblage of this site. A number of notoungulates and rodents were collected. A partial left jaw was collected at Quebrada Peñas Blancas along the west bank of the Río Calchaquí. Morphological and morphometric comparisons permit referral of this specimen to a new species of hegetotheriid notoungulate Paedotherium kakai sp. nov. It represents the first report of Paedotherium for the Eastern Cordillera and one of the few well-documented occurrences of this genus outside of middle-high latitudes Argentina. The widespread geographic range of Paedotherium, combined with its restricted temporal range, suggest it may be one of the most useful biostratigraphic indicator taxa for Neogene faunas. Paedotherium kakai would have been a mixed feeder that lived in gallery forests, feeding close to water bodies of a system river and lagoons, in food plains developed under humid and subtropical climate.Los estratos fluviales asignados al Mioceno tardío de la Formación Palo Pintado están ampliamente expuestos al noroeste de la localidad Angastaco, provincia de Salta, noroeste de Argentina. Estos estratos fueron acumulados en la Cuenca de Angastaco. Recientes trabajos de campo en la Formación Palo Pintado (Mioceno tardío), Valle Calchaquí, provincia de Salta, Argentina ha provisto restos fósiles que han incrementado el conocimiento de la asociación faunística de ese sitio. Un número discreto de especímenes (notoungulados y roedores) fueron colectados. Una porción de cuerpo mandibular izquierdo fue colectado en la localidad Quebrada Peñas Blancas a lo largo del margen oeste del río Calchaquí. Comparaciones morfológicas permiten referir a este espécimen a una nueva especie de notoungulado hegetotérido, Paedotherium kakai sp. nov. Esta nueva especie representa el primer registro de Paedotherium para la Cordillera Oriental y una de las pocas bien documentadas ocurrencias de este género fuera de las latitudes medias y altas de Argentina. El amplio rango de registro geográfico de Paedotherium, combinado con su restringido rango temporal sugiere que este género puede considerarse como un buen indicador bioestratigráfico para las faunas del Neógeno. Paedotherium kakai puede ser considerado un ‘mixed feeder’ que vivió en bosques, en galerías, alimentándose en las proximidades de los cuerpos de agua de un río, lagunas o en planicies de inundación bajo un clima húmedo y subtropical.Facultad de Ciencias Naturales y Muse

Un nuevo Notungulado Hipsodonte (Hegetotheriidae, Pachyrukhinae) del Mioceno tardío de la Cordillera Oriental, provincia de Salta, Noroeste de Argentina

Late Miocene fluvial strata of the Palo Pintado Formation are broadly exposed to the northwest of the town of Angastaco, Salta province, Northwest of Argentina. These strata accumulated in the extensional Angastaco Basin. Recent field work at the Palo Pintado Formation (late Miocene), Valle Calchaquí, Salta province, Argentina has provided fossil remains that greatly increased the knowledge of the faunal assemblage of this site. A number of notoungulates and rodents were collected. A partial left jaw was collected at Quebrada Peñas Blancas along the west bank of the Río Calchaquí. Morphological and morphometric comparisons permit referral of this specimen to a new species of hegetotheriid notoungulate Paedotherium kakai sp. nov. It represents the first report of Paedotherium for the Eastern Cordillera and one of the few well-documented occurrences of this genus outside of middle-high latitudes Argentina. The widespread geographic range of Paedotherium, combined with its restricted temporal range, suggest it may be one of the most useful biostratigraphic indicator taxa for Neogene faunas. Paedotherium kakai would have been a mixed feeder that lived in gallery forests, feeding close to water bodies of a system river and lagoons, in food plains developed under humid and subtropical climate.Los estratos fluviales asignados al Mioceno tardío de la Formación Palo Pintado están ampliamente expuestos al noroeste de la localidad Angastaco, provincia de Salta, noroeste de Argentina. Estos estratos fueron acumulados en la Cuenca de Angastaco. Recientes trabajos de campo en la Formación Palo Pintado (Mioceno tardío), Valle Calchaquí, provincia de Salta, Argentina ha provisto restos fósiles que han incrementado el conocimiento de la asociación faunística de ese sitio. Un número discreto de especímenes (notoungulados y roedores) fueron colectados. Una porción de cuerpo mandibular izquierdo fue colectado en la localidad Quebrada Peñas Blancas a lo largo del margen oeste del río Calchaquí. Comparaciones morfológicas permiten referir a este espécimen a una nueva especie de notoungulado hegetotérido, Paedotherium kakai sp. nov. Esta nueva especie representa el primer registro de Paedotherium para la Cordillera Oriental y una de las pocas bien documentadas ocurrencias de este género fuera de las latitudes medias y altas de Argentina. El amplio rango de registro geográfico de Paedotherium, combinado con su restringido rango temporal sugiere que este género puede considerarse como un buen indicador bioestratigráfico para las faunas del Neógeno. Paedotherium kakai puede ser considerado un ‘mixed feeder’ que vivió en bosques, en galerías, alimentándose en las proximidades de los cuerpos de agua de un río, lagunas o en planicies de inundación bajo un clima húmedo y subtropical.Facultad de Ciencias Naturales y Muse

First record of Toxodontidae (Mammalia, Notoungulata) from the late Miocene - Early Pliocene of the southern central Andes, NW Argentina

A new species of toxodontid notoungulate, Xotodon maimarensis n. sp., is described from the Maimará Formation (late Miocene - early Pliocene), Jujuy Province, northwestern Argentina. This is the first record of a toxodontid from the Eastern Cordillera. The specimen is housed at the Museo de Geología, Mineralogía y Paleontología, Instituto de Geología y Minería de la Universidad Nacional de Jujuy. It consists of an incomplete mandible preserving the right mandibular ramus with part of the dental series, partially preserved symphysis with all the incisors, and a small portion of the left ramus without teeth. The following characters distinguish it as a new taxon: symphysis long and narrow with slight divergence of its lateral borders; strong procumbence of lower incisors and deeply implanted i3; chin angle lower than in X. major and X. cristatus and bulging labial keel limiting strong lateral concavities. Comparative analysis in the context of the recently revised Neogene Toxodontidae indicates that the Maimará specimen shares mandibular features and dental characters with Xotodon and Mixotoxodon, differing from the latter by the more upraised symphysis. The phylogenetic position of Xotodon maimarensis n. sp. supports the taxonomic interpretation of the studied specimen as a new species of Xotodon. This new Toxodontidae increases the knowledge of the diversity and radiation of this group of notoungulates in northwest Argentina.Facultad de Ciencias Naturales y Muse

Lipoic Acid Attenuates Inflammation via cAMP and Protein Kinase A Signaling

Abnormal regulation of the inflammatory response is an important component of diseases such as diabetes, Alzheimer's disease and multiple sclerosis (MS). Lipoic acid (LA) has been shown to have antioxidant and anti-inflammatory properties and is being pursued as a therapy for these diseases. We first reported that LA stimulates cAMP production via activation of G-protein coupled receptors and adenylyl cyclases. LA also suppressed NK cell activation and cytotoxicity. In this study we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are mediated by the cAMP/PKA signaling cascade. Additionally, we show that LA oral administration elevates cAMP levels in MS subjects.We determined the effects of LA on IL-6, IL-17 and IL-10 secretion using ELISAs. Treatment with 50 µg/ml and 100 µg/ml LA significantly reduced IL-6 levels by 19 and 34%, respectively, in T cell enriched PBMCs. IL-17 levels were also reduced by 35 and 50%, respectively. Though not significant, LA appeared to have a biphasic effect on IL-10 production. Thymidine incorporation studies showed LA inhibited T cell proliferation by 90%. T-cell activation was reduced by 50% as measured by IL-2 secretion. Western blot analysis showed that LA treatment increased phosphorylation of Lck, a downstream effector of protein kinase A. Pretreatment with a peptide inhibitor of PKA, PKI, blocked LA inhibition of IL-2 and IFN gamma production, indicating that PKA mediates these responses. Oral administration of 1200 mg LA to MS subjects resulted in increased cAMP levels in PBMCs four hours after ingestion. Average cAMP levels in 20 subjects were 43% higher than baseline.Oral administration of LA in vivo resulted in significant increases in cAMP concentration. The anti-inflammatory effects of LA are mediated in part by the cAMP/PKA signaling cascade. These novel findings enhance our understanding of the mechanisms of action of LA