PI3K/Akt cooperates with oncogenic Notch by inducing nitric oxide-dependent inflammation Villegas, Santiago Nahuel; Gombos, Rita; García López, Lucia; Gutiérrez Pérez, Irene; García Castillo, Jesús; Vallejo, Diana Marcela; Da Ros, Vanina Gabriela; Ballesta Illán, Esther; Mihály, József; Dominguez, Maria The PI3K/Akt signaling pathway, Notch, and other oncogenes cooperate in the induction of aggressive cancers. Elucidating how the PI3K/Akt pathway facilitates tumorigenesis by other oncogenes may offer opportunities to develop drugs with fewer side effects than those currently available. Here, using an unbiased in vivo chemical genetic screen in Drosophila, we identified compounds that inhibit the activity of proinflammatory enzymes nitric oxide synthase (NOS) and lipoxygenase (LOX) as selective suppressors of Notch-PI3K/Akt cooperative oncogenesis. Tumor silencing of NOS and LOX signaling mirrored the antitumor effect of the hit compounds, demonstrating their participation in Notch-PI3K/Akt-induced tumorigenesis. Oncogenic PI3K/Akt signaling triggered inflammation and immunosuppression via aberrant NOS expression. Accordingly, activated Notch tumorigenesis was fueled by hampering the immune response or by NOS overexpression to mimic a protumorigenic environment. Our lead compound, the LOX inhibitor BW B70C, also selectively killed human leukemic cells by dampening the NOTCH1-PI3K/AKT-eNOS axis.

Overexpression of 11β-hydroxysteroid dehydrogenase 1 in visceral adipose tissue and underexpression of endothelial nitric oxide synthase in the adrenal cortex of dogs with hyperadrenocorticism Miceli, Diego Daniel; Abiuso, Adriana María Belén; Vidal, Patricia Noemi; Gallelli, Maria Florencia; Pignataro, Omar Pedro; Castillo, Victor Alejandro 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) is an enzyme that activates cortisone into cortisol in tissues. Alterations in this enzyme are related to the development of metabolic syndrome, obesity and hyperadrenocorticism (HAC). Endothelial nitric oxide synthase (eNOS) produces nitric oxide and is related to the regulation of adrenal steroidogenesis. The aim of the study was to evaluate 11β-HSD1 and eNOS expression in dogs with HAC. Visceral adipose tissue samples were taken to evaluate 11β-HSD1 expression by immunohistochemistry and western blotting. In parallel, adrenal gland samples were collected to evaluate eNOS expression by immunohistochemistry. 11β-HSD1 expression was significantly higher in the adipocytes of dogs with HAC than in those of the control dogs. eNOS expression in the adrenal cortex (zona fasciculata) was significantly lower in the dogs with HAC than in the control dogs. 11β-HSD1 overexpression and eNOS underexpression could play a role in the maintenance of hypercortisolism in dogs with HAC.

Direct analysis of benzo[a]pyrene metabolites with strong overlapping in both the spectral and lifetime domains Alfarhani, Bassam; Al-Tameemi, Maha; Goicoechea, Hector Casimiro; Barbosa, Fernando Jr.; Campiglia, Andres D. The ultimate goal of the present study is to develop screening methodology for the urine analysis of metabolites of polycyclic aromatic hydrocarbons. The investigated approach is based on surface matrix fluorescence spectroscopy, where octadecyl silica membranes serve the dual purpose of metabolite extraction and solid substrate for fluorescence measurements. One of the main challenges faced by this approach is the interference of concomitants in the sample matrix. The present study focuses on three metabolites with strong spectral and lifetime overlapping, namely benzo[a]pyrene-trans-9,10-dihydrodiol, benzo[a]pyrene-r-7,t-8,c-9-tetrahydrotriol and benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol. As an attempt to improve spectral and lifetime resolution, time-resolved excitation emission matrices are recorded at 77 K with the aid of a cryogenic fiber optic probe and laser-based instrumentation. In comparison to conventional spectrofluorimeters, the use of laser-based instrumentation improves the limits of detection by approximately two-orders of magnitude. The fiber optic probe facilitates the collection of time-resolved excitation emission matrices for the detection of the three metabolites at the pg mL− 1 concentration level. Their accurate determination in urine samples of unknwon composition is only possible with the aid of unfolded-partial least squares/residual tri-linearization. This algorithm demonstrated to be well-equipped to handle strong overlapping in both the spectral and time domains.

Pesca con cebo activo por Ardea alba (Pelecaniformes: Ardeidae) en Argentina Sovrano, Lorena Vanesa; Beltzer, Adolfo Hector El comportamiento de pesca con cebo activo ha sido registrado en especies de la familia Ardeidae. Para la Garza Blanca (Ardea alba) sólo existe un registro previo en la literatura. Mediante este aporte se documenta el registro de pesca con cebo activo por la Garza Blanca observado en un Parque urbano de Argentina.

Óxido nítrico y factores relacionados a oxidación e inflamación como posibles biomarcadores de insuficiencia cardíaca; Nitric oxide and related factors linked to oxidation and inflammation as possible biomarkers of heart failure Bonafede, Roberto Jorge; Manucha, Walter Ariel Fernando Como enfermedad cardiovascular prevalente, la insuficiencia cardíaca es una de las principales causas de morbimortalidad prematura. Por ello, existe un especial interés sobre el estudio de marcadores eficientes asociados al riesgo y/o predicción de eventos cardiovasculares. En consecuencia se proponen a múltiples candidatos, pero sobresalen especialmente aquellos implicados en procesos oxidativos e inflamatorios propios de la enfermedad cardiovascular como el anión superóxido, óxido nítrico y peroxinitrito. En este sentido, existe una falta de conocimiento sobre las potenciales utilidades de estos sistemas como biomarcadores. La presente revisión procura contribuir a la mayor comprensión de estos sistemas para una mejor caracterización de pacientes. Por otra parte, un profundo conocimiento de estos complejos sistemas también permitiría proponer nuevas líneas de investigación para el desarrollo de inéditas herramientas terapéuticas como una auspiciosa frontera para el abordaje de esta patología.; As a prevalent cardiovascular disease, heart failure is one of the leading causes of morbidity and premature mortality. Therefore, there is a special interest in the study of efficient markers associated with risk and / or prediction of cardiovascular events. Multiple candidates are proposed, especially those involved in oxidative and inflammatory processes typical of cardiovascular disease, such as superoxide anion, nitric oxide, and peroxynitrite. There is a lack of knowledge on the potential usefulness of these systems as biomarkers. This review aims to contribute to a better understanding of these systems, as well as an improved patient profile. Furthermore, a deep knowledge of these complex systems would also allow proposing new lines of research for the development of new therapeutic tools as a promising start for new approaches to this disease.

Hydrogen sulfide increases production of NADPH oxidase-dependent hydrogen peroxide and phospholipase D-derived phosphatidic acid in guard cell signaling Scuffi, Denise; Nietzel, Thomas; Di Fino, Luciano Martin; Meyer, Andreas J.; Lamattina, Lorenzo; Schwarzlände, Markus; Laxalt, Ana Maria; Garcia-Mata, Carlos Hydrogen sulfide (H2S) is an important gaseous signaling molecule in plants that participates in stress responses and development. L-Cys desulfhydrase 1, one of the enzymatic sources of H2S in plants, participates in abscisic acid-induced stomatal closure. We combined pharmacological and genetic approaches to elucidate the involvement of H2S in stomatal closure and the interplay between H2S and other second messengers of the guard cell signaling network, such as hydrogen peroxide (H2O2) and phospholipase D (PLD)-derived phosphatidic acid in Arabidopsis (Arabidopsis thaliana). Both NADPH oxidase isoforms, respiratory burst oxidase homolog (RBOH)D and RBOHF, were required for H2S-induced stomatal closure. In vivo imaging using the cytosolic ratiometric fluorescent biosensor roGFP2-Orp1 revealed that H2S stimulates H2O2 production in Arabidopsis guard cells. Additionally, we observed an interplay between H2S and PLD activity in the regulation of reactive oxygen species production and stomatal movement. The PLDα1 and PLDδ isoforms were required for H2S-induced stomatal closure, and most of the H2S-dependent H2O2 production required the activity of PLDα1. Finally, we showed that H2S induced increases in the PLDδ-derived phosphatidic acid levels in guard cells. Our results revealed the involvement of H2S in the signaling network that controls stomatal closure, and suggest that H2S regulates NADPH oxidase and PLD activity in guard cells.

Efecto de la concentración y la aplicación de MTMO sobre acero electrocincado Seré, Pablo Ricardo; Egli, Walter Alfredo; Elsner, Cecilia Ines; Di Sarli, Alejandro Ramón; Deya, Marta Cecilia Los pretratamientos superficiales a base de silanos son una de las alternativas más convenientes para reemplazara los cromatos como protectores temporarios de sustratos metálicos expuestos a la acción de ambientesagresivos. El mecanismo de protección contra la corrosión, en el caso de los silanos es por efecto barrera, loque hace que características como porosidad, espesor y homogeneidad de la película tengan una marcadainfluencia sobre su eficacia[1, 2]. En el presente trabajo se estudió la capacidad protectora contra la corrosióndel mercaptopropiltrimetoxisilano (MTMO) sobre chapas de acero electrocincado, analizando la influenciade su concentración durante la aplicación y de la cantidad de capas aplicadas. Como pretratamiento, lasmuestras fueron desengrasadas por ultrasonido sumergiéndolas en tolueno durante 2 min a 40 ºC. La superficiede las muestras fue activada sumergiéndolas en una solución de NaOH al 10% p/v y aplicando una densidadde corriente catódica de 0,12 A/cm2, la temperatura se controló a 40 ºC. La solución de MTMO se preparóañadiendo 2 ó 4% v/v de MTMO a una solución de agua destilada/metanol (3:2 v/v, de pH 4 ajustado conácido acético) [3], y se hidrolizó durante 60 min; a algunas muestras se les aplicó una y a otras dos capas deMTMO. Posteriormente se curaron a 80 ºC durante 10 min. La porosidad se evaluó por voltametría cíclica [4]y por reacción al sulfato de cobre, la morfología y espesor mediante SEM-EDS, y el comportamiento frente ala corrosión mediante la obtención de curvas de polarización, espectrometría de impedancia electroquímica yexponiendo las muestras en cámara de humedad y temperatura controladas. De los resultados obtenidos puedeinferirse que la capacidad protectora aportada por dos capas de MTMO es mayor que la debida a un aumentode su concentración. Además, estas variables de proceso afectan tanto la morfología como el espesorde la película.

The comings and goings of sheep and pottery in the coastal desert of Namaqualand, South Africa Dewar, Genevieve; Marsh, Erik Johnson This paper evaluates chronological trends in the presence and absence of domestic animal bone (sheep, goat, and cattle) and pottery in Namaqualand, the proposed gateway to the rest of South Africa for early herders or hunter-gatherers with sheep and ceramics. We update date calibrations with local ΔR corrections and mixtures of recent calibration curves and include five previously unpublished dates. We use histograms of calibrated medians, sorted in 100-year bins, to assess sustained regional patterns with dates associated with domestic animal bone and pottery (n = 73). While too small to be useful as a population proxy, the current set of dates does reveal three pulses of occupation separated by two clear gaps, which we evaluate with a Bayesian model of three sequential phases. The model's boundaries are used as estimates of the dates of Early (AD 80–210), Middle (AD 490–790), and Late (AD 1180–1690) occupational phases separated by two substantial lapses of 280 and 380 years, respectively. The alternating phases of presence and absence are suggestively correlated with climate shifts, leading to a discussion of the idea that effective moisture was a crucial factor in choosing whether to occupy Namaqualand. The set of archaeological dates has greater temporal and spatial resolution than many regional climate data, so we suggest that these trends may more accurately reflect the variable conditions specific to Namaqualand, at least until they are refined by future climate research.

Los erizos del oro en la poesía de Arturo Carrera y los encuentros con los agujeros de la historia Rasic, María Eugenia En el siguiente trabajo intentaremos poner a prueba una lectura archifilológica de la obra del poeta argentino Arturo Carrera, más precisamente, de los comienzos de su escritura. Dicha lectura nos enfrentará al menos con dos inquietudes. La primera, de qué manera es posible ver aparecer la potencia del archivo en su obra poética. La segunda, qué tradiciones y qué dimensiones se activan en la obra desde esa perspectiva, tomando como punto de partida el mapa cosmológico Momento de Simetría (1973), Oro (1975) y Mi padre (1985), más allá de sus filiaciones barrocas. Entre ambas cuestiones veremos si es posible configurar un método de lectura para el armado de un recorrido histórico particular que opere con los destellos temporales o erizos dorados que la poesía deja a la vista, para volver a ser activados en otro tiempo y lugar de obra.; In the following paper we will test an archifilological reading of the work of the Argentine poet Arturo Carrera, more precisely, of the beginnings of his writing. This reading will confront us with at least two concerns. First, in what way it is possible to see the power of file appear in his poetic work. The second, what traditions and what dimensions are activated in the work from that perspective, taking as starting point the cosmological map Momento de simetría (1973), Oro (1975) and Mi padre (1985), beyond its baroque filiations. Both questions will help us see if it is possible to configure a reading method for the assembly of a particular historical tour that operates with the temporary flashes or golden urchins that the poetry leaves in sight, to be activated again in another time and place of work.

Galectins in intestinal inflammation: Galectin-1 expression delineates response to treatment in celiac disease patients Sundblad, Victoria; Quintar, Amado Alfredo; Morosi, Luciano Gastón; Niveloni, Sonia I.; Cabanne, Ana; Smecuol, Edgardo; Mauriño, Eduardo; Mariño, Karina Valeria; Bai, Julio C.; Maldonado, Cristina Alicia; Rabinovich, Gabriel Adrián Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn´s disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings.

Mudflat Use and Predation on Male Southwestern Atlantic Fiddler Crabs (Uca uruguayensis) by Gull-billed Terns (Gelochelidon nilotica) Ribeiro, Pablo Damián; Navarro, Diego; Jaureguy, Luciano M.; Iribarne, Oscar Osvaldo Gull-billed Terns (Gelochelidon nilotica) comprise a group of cosmopolitan subspecies that make use of a wide range of aquatic ecosystems and have a broad dietary spectrum. This study documents the use of a southwestern Atlantic mudflat in Argentina and depredation of the southwestern Atlantic fiddler crab (Uca uruguayensis) by Gull-billed Terns. Gull-billed Terns preyed exclusively on male fiddler crabs. This may have been due to the observed presence of Gull-billed Terns mainly between 2 and 3 hr after low tide, when more than 80% of fiddler crabs active on the surface were males. Gull-billed Terns spent 66.9% of the time flying over and feeding on fiddler crabs. Gull-billed Terns landed without feeding 9.3% of the time. Gull-billed Terns succeeded in capturing prey in 29.8% of cases. Food capture rate of Gull-billed Terns was 68.9 items/hr, which is higher than rates reported for the species feeding on fiddler crabs in Mauritania and Guinea Bissau.

New Neotropical species of Downeshelea Wirth and Grogan and redescription of D. multilineata (Lutz) (Diptera: Ceratopogonidae) Santarém, Maria Clara Alves; Borkent, Art; Spinelli, Gustavo Ricardo; Felippe Bauer, Maria Luiza Seven new species of Downeshelea Wirth and Grogan 1988–D. casimirensis, D. costaricensis, D. eclectica, D. jarina, D. litorale, D. marambaia and D. moravia–are described and illustrated based on male and female specimens from Central and South America. The new species are compared with their similar congener D. multilineata (Lutz). A redescription of D. multilineata is presented and its neotype designated. These eight species were included in the multilineata species group, and a diagnosis and identification key are presented for each.

Effects of lysozyme on the activity of ionic of fluoroquinolone species Pérez, Hugo Alejandro; Bustos, Ana Yanina; Taranto, Maria Pia; Frías, María de los Ángeles; Ledesma, Ana Estela Fluoroquinolones (FQs) constitute an important class of biologically active broad-spectrum antibacterial drugs that are which are in contact with many biological fluids under different acidity conditions. We studied the reactivity of ciprofloxacin (Cpx) and levofloxacin (Lev) and their interaction with lysozyme (Lyz) at different pH values, using UV-visible absorption, fluorescence, infrared spectroscopies supported by DFT calculation and docking. In addition, by antimicrobial assays, the biological consequences of the interaction were evaluated. DFT calculation predicted that the FQ cationic species present at acid pH have lower stabilization energies, with an electric charge rearrangement because of their interactions with solvent molecules. NBO and frontier orbital calculations evidenced the role of two charged centers, NH 2 + and COO − , for interactions by electronic delocalization effects. Both FQs bind to Lyz via a static quenching with a higher interaction in neutral medium. The interaction induces a structural rearrangement in β-sheet content while in basic pH a protective effect against the denaturation of Lyz was inferred. The analysis of thermodynamic parameters and docking showed that hydrophobic, electrostatic forces and hydrogen bond are the responsible of Cpx-Lyz and Lev-Lyz associations. Antimicrobial assays evidenced an antagonist effect of Lyz in acid medium while in neutral medium the FQs’ activities were not modified by Lyz.

A new Pliosaurus species (Sauropterygia, Plesiosauria) from the Upper Jurassic of Patagonia: New insights on the Tithonian morphological disparity of mandibular symphyseal morphology O'gorman, Jose Patricio; Brandoni, Zulma Nelida; Spalletti, Luis Antonio Most species of the genus Pliosaurus Owen, 1842 come from the Northern Hemisphere, however, a growing number of new specimens are now available from the Southern Hemisphere. Here, a new species of Pliosaurus is described, the second for the genus from the Southern Hemisphere, collected from the upper Tithonian (Jurassic) levels of the Vaca Muerta Formation, Neuquén Province, Patagonia. Pliosaurus almanzaensis new species is characterized by two autapomophies: the angular participating in the mandibular symphysis and the occipital condyle without a notochordal pit or several, irregularly arranged grooves. Additionally, P. almanzaensis n. sp. can be differentiated from other Pliosaurus species by the following characters: trihedral teeth, nine or more symphyseal alveoli, 15-17 post-symphyseal alveoli, and the parasphenoid without a ventral keel. Pliosaurus almanzaensis n. sp. shows that Pliosaurus species with nine or more symphyseal alveoli persisted until the late Tithonian, contrary to previous assumptions that only species with six symphyseal alveoli were present.

Does the Morphology of the Forelimb Flexor Muscles Differ Between Lizards Using Different Habitats? Lowie, Aurélien; Herrel, Anthony; Abdala, Virginia Sara Luz; Manzano, Adriana Silvina; Fabre, Anne Claire Lizards are an interesting group to study how habitat use impacts the morphology of the forelimb because they occupy a great diversity of ecological niches. In this study, we specifically investigated whether habitat use impacts the morphology of the forelimb flexor muscles in lizards. To do so, we performed dissections and quantified the physiological cross sectional area (PCSA), the fiber length, and the mass of four flexor muscles in 21 different species of lizards. Our results show that only the PCSA of the m. flexor carpi radialis is different among lizards with different ecologies (arboreal versus non-arboreal). This difference disappeared, however, when taking phylogeny into account. Arboreal species have a higher m. flexor carpi radialis cross sectional area likely allowing them to flex the wrist more forcefully which may allow them climb and hold on to branches better. In contrast, other muscles are not different between arboreal and non-arboreal species. Further studies focusing on additional anatomical features of the lizard forelimb as well as studies documenting how lizards use the arboreal niche are needed to fully understand how an arboreal life style may constrain limb morphology in lizards. Anat Rec, 301:424–433, 2018.

New brachyrostran remains (Theropoda, Abelisauridae) from La Invernada fossil site (Bajo de la Carpa Formation, Upper Cretaceous), northern Patagonia, Argentina Méndez, Ariel Hernán; Filippi, Leonardo S.; Gianechini, Federico Abel; Juárez Valieri, Rubén D. Several remains of an abelisaurid theropod including a nearly complete sacral complex articulated with both ilia, the distal boot of the pubes, the furcula, teeth, and fragments of transverse processes of caudal vertebrae was discovered in the La Invernada fossil site, northern Patagonia from the Bajo de la Carpa Formation (Santonian). The sacrum exhibit features typical of abelisauroids as narrowing of the middle sacral centra, fused neural spines forming a continuous sheet and ventral bow of the sacrum, in lateral view. The furcula represents de first mention of this bone for a South American abelisaurid. The morphology observed in the transverse processes with distal end projected forward and sagittal ridge on the ventral surface allows its taxonomic assignment to the clade Brachyrostra.

The silence of the layers: Archaeological site visibility in the Pleistocene-Holocene transition at the Ebro Basin Alday, Alfonso; Domingo, Rafael; Sebastián, María; Soto, Adriana; Aranbarri, Josu; González Sampériz, Penélope; Sampietro Vattuone, Maria Marta; Utrilla, Pilar; Montes, Lourdes; Peña Monné, José Luis The Ebro Basin constitutes one of the most representative territories in SW Europe for the study of prehistoric societies during the Pleistocene-Holocene transition. The correlation of palaeoenvironmental and geomorphological proxies obtained from sedimentary records with chronologically well-constrained reference archaeological sites has allowed defining this time frame precisely, such that three main pilot areas haven been broadly depicted: the Alavese region, the Pre-Pyrenees and the Bajo Aragón. Overall, the human imprint in the Ebro Basin was rare during the Upper Palaeolithic, but more visible from the Upper Magdalenian (14500–13500 cal BP) to Neolithic times (up to 5500 cal BP). Local environmental resources were continuously managed by the prehistoric communities in the different areas of study. In fact, the Ebro Basin acted during those millennia as a whole, developing the same cultural trends, industrial techniques and settlement patterns in parallel throughout the territory. However, some gaps exist in the 14C frequency curve (SCDPD curve). This is partially related to prehistoric sites in particular lithologies and geological structures that could have partly been lost by erosional processes, especially during the Early Holocene. In addition, this gap also parallels the reconstructed climate trend for the Pre-Pyrenean and the Bajo Aragón areas, which are defined by high frequencies of xerophilous flora until ca. 9500 cal BP, suggesting that continental climate features could have hampered the presence of well-established human communities in inland regions. The interdisciplinary research (archaeology, geomorphology and palaeoclimatology) discussed in this paper offers clues to understand the existence of fills and gaps in the archaeological record of the Ebro Basin, and can be applied in other territories with similar geographic and climate patterns.

B cells producing type i IFN modulate macrophage polarization in tuberculosis Bénard, Alan; Sakwa, Imme; Schierloh, Luis Pablo; Colom, André; Mercier, Ingrid; Tailleux, Ludovic; Jouneau, Luc; Boudinot, Pierre; Al Saati, Talal; Lang, Roland; Rehwinkel, Jan; Loxton, Andre G.; Kaufmann, Stefan H. E.; Anton Leberre, Veronique; O'Garra, Anne; Sasiain, María del Carmen; Gicquel, Brigitte; Fillatreau, Simon; Neyrolles, Olivier; Hudrisier, Denis In addition to their well-known function as antibody-producing cells, B lymphocytes can markedly influence the course of infectious or noninfectious diseases via antibody-independent mechanisms. In tuberculosis (TB), B cells accumulate in lungs, yet their functional contribution to the host response remains poorly understoo

Narrativas del cine ambiental en Buenos Aires: ¿Discursos expertos o enfoques alternativos?; Narratives of the environmental films in Buenos Aires: Expert’s speeches or alternative approaches? Fernandez Bouzo, Maria Soledad El presente artículo analiza y compara las principales narrativas que los distintos dispositivos institucionales de cine ambiental ponen en circulación en Buenos Aires a través de sus películas documentales. Las preguntas clave son: ¿qué tipo de narrativas y enfoques del ambientalismo movilizan tales dispositivos?, ¿a través de qué argumentos lo hacen?, ¿predominan en ellos discursos expertos que confían en la potencialidad de ciertos cambios culturales y/o en las innovaciones científico-tecnológicas dentro de las economías capitalistas globales?, ¿o más bien encontramos enfoques alternativos que cuestionan las bases mismas del capitalismo en la actualidad? Con el fin de contestar los interrogantes, llevamos adelante un análisis sociológico en dos niveles: uno de orden institucional, orientado a caracterizar las redes de actores que se conforman alrededor de los dispositivos de cine ambiental, y otro nivel de carácter narrativo, cuyo objetivo es rastrear los distintos enfoques y discursos sobre la cuestión ambiental.; This article analyzes and compares the main narratives circulated by different environmental film institutional devices in Buenos Aires through their documentary films. The key questions are: What type of narratives and approaches of environmentalism mobilize such devices? Which arguments are used? Are they dominated by expert’s speeches which rely on the potential of certain cultural changes and/or science and technology innovations within global capitalist economies? Or rather are they alternative approaches questioning the very foundations of capitalism today? In order to answer those questions, we conducted a sociological analysis on two levels: an institutional one, aimed at characterizing the networks of actors that are formed around the environmental film devices, and a narrative one, the purpose of which is to track the main speeches and approaches on the environmental issue.

Residuos dinámicamente importantes en la diversidad conformacional de proteínas Saldaño, Tadeo Enrique Las propiedades de flexibilidad y dinámica de las proteínas han sido desde hace tiempo asociadas a sus funciones biológicas. Estas propiedades han sido originalmente usadas para explicar la heterogeneidad de las propiedades de unión de la seroalbúmina bovina por Kurush en 1950 y su descripción formal fue incluida en el clásico modelo de Monod-Wyman-Changeux de regulación alostérica, también conocido como modelo de pre-equilibrio. Actualmente está bien establecido que la forma funcional de una proteína, normalmente conocida como el estado nativo, no es única. El concepto de “embudo” propuesto por Wolynes et al. en 1995 ha sido utilizado para explicar los canales de plegamiento de las proteínas considerando un “fondo de potencial rugoso” representando al conjunto de isómeros conformacionales. El grado de la diversidad conformacional de una proteína puede entonces relacionarse con la extensión de la “rugosidad del fondo del embudo”. La distribución de los confórmeros en este potencial ha sido previamente asociada al plegamiento, la historia evolutiva, y la presencia de ciertas mutaciones. Actualmente, los conceptos antes mencionados han derivado en la noción de la preexistencia de poblaciones de confórmeros en equilibrio dinámico (dinamismo) sobre la superficie de energía potencial de una proteína. Este equilibrio dinámico soporta la hipótesis de la unión del ligando a una conformación específica de mayor afinidad y ofrece una visión central que permite explicar la función biológica. La dinámica vibracional intramolecular asociada a cada conformación garantiza las transiciones conformacionales que, debido a su importancia, podrían estar asociadas con rasgos conservados evolutivamente. El análisis de modos normales, basado en un modelo de “grano grueso” de la proteína, puede proporcionar la información necesaria para explorar estas características. En la primer parte de la tesis presentamos un nuevo procedimiento para identificar residuos en posiciones clave para el mantenimiento de la diversidad conformacional asociada a la unión al ligando. El método se aplicó a un conjunto de 188 pares de estructuras de proteínas, cristalizadas con y sin ligando. En primer lugar, se seleccionaron los modos normales implicados en el cambio conformacional de acuerdo con las distorsiones estructurales introducidas por unión al ligando. El subespacio definido por estos modos se utilizó para analizar el efecto de mutaciones puntuales en la conservación de la diversidad conformacional de la proteína. Definimos las posiciones cuyas mutaciones alteran en mayor medida estos subespacios como posiciones claves, es decir, son residuos dinámicamente importantes que median el cambio conformacional de unión al ligando. Encontramos una correlación negativa entre la conservación evolutiva de los residuos de una proteína y el impacto de sus mutaciones sobre los subespacios de modos normales asociados a la unión del ligando. Estas posiciones se muestran conservadas evolutivamente, en su mayoría son residuos con baja exposición al solvente, alifáticos y localizados en estructuras regulares de la proteína como hoja-β y hélice-α . Durante la segunda etapa del doctorado, combinamos la información obtenida de métodos basados en propiedades estructurales y dinámicas de proteínas con información relacionada con redes de interacciones de residuos. La representación de la estructura proteica como red facilita la búsqueda de determinantes topológicos, que pueden estar relacionados con residuos funcionalmente importantes. Cada estructura proteica de nuestro set de estudio se representó como una red de contacto de residuos y se realizó un análisis exhaustivo de las propiedades de la red. Se analizaron tres parámetros topológicos de redes, Grado, Centralidad de Intermediación y Proximidad Central. Particularmente los últimos dos se han previamente utilizado en diversos trabajos para identificar residuos funcionales ya que la Centralidad de Intermediación refleja el control que ejerce un nodo sobre las interacciones de otros nodos en la red y la Proximidad Central se asocia a cuan rápido se propaga la información desde un nodo dado a otros nodos alcanzables en la red. Estudiamos la correlación de estos parámetros topológicos de redes con nuestro parámetro para definir mutaciones que alteran en mayor medida el subespacio de modos normales asociado a la unión al ligando. Además, analizamos la correlación entre la conservación evolutiva y el área de accesibilidad al solvente, con estos parámetros topológicos. Encontramos una buena correlación entre los efectos de las mutaciones en los subespacios de modos normales asociados a la unión del ligando y los parámetros topológicos de redes. Estos parámetros han sido utilizados para predecir con éxito sitios activos o sitios funcionales en varias proteínas. Esto apoya nuestro método para detectar residuos dinámicamente importantes que median el cambio conformacional de unión al ligando. Determinamos que los residuos dinámicamente relevantes tienden a estar interconectados, por lo que es posible definir redes de residuos que modulan dinámicamente los cambios conformacionales. Como etapa final de la tesis, exploramos las posiciones claves que sustentan la estabilidad dinámica de la estructura homotetramérica de la Transtiretina Humana. El estado nativo de la Transtiretina presenta dos sitios de unión a la hormona tiroxina, que son generados por la interfaz dímero-dímero, mediante interacciones débiles. La disociación de la estructura tetramérica es el primer paso del proceso de formación de fibrillas de amiloide. Un gran número de mutaciones puntuales por desestabilizar la estructura cuaternaria del tetrámero muestran efectos pro-amiloidogénicos. Basándonos en el análisis de modos normales y su respuesta a las perturbaciones locales hemos identificado las posiciones cuyas mutaciones alteran en mayor medida la dinámica de equilibrio del tetrámero de Transtiretina. Encontramos que estas posiciones están localizadas principalmente en las hojas-β E y F, del monómero de Transtiretina y el loop entre estas estructuras secundarias. Determinamos que la interfase monómero-monómero es una de las regiones más vulnerables, ya que mutaciones en residuos de esta región conducen a cambios significativos en la dinámica de equilibrio del tetrámero y, por lo tanto, favorece la disociación de la estructura. Además, hemos encontrado que las mutaciones en los residuos localizados en la interfaz dímero-dímero y/o en el sitio de unión a la hormona tiroxina desestabilizan al tetrámero más que el promedio. La unión de la tiroxina estabiliza la estructura tetramérica estableciendo interacciones con los residuos en la interfaz dímero-dímero. Debido a esto se han propuesto varios compuestos como drogas en la terapia de la amiloidosis por Transtiretina, siendo clave la afinidad por el sitio unión del tetrámero, y por tanto, la contribución a la integridad de la estructura. Comparamos varios compuestos de acuerdo a su efecto sobre las vibraciones asociadas a la unión del ligando. Discutimos y analizamos nuestra comparación de drogas en términos de parámetros y mediciones asociadas a las afinidades de unión al ligando y la estabilización del estado nativo del tetrámero de Transtiretina. A pesar de la presencia en el tetrámero de dos sitios de unión idénticos, la unión de la tiroxina en solución se caracteriza por una fuerte cooperatividad negativa. La flexibilidad estructural del tetrámero, simulada mediante el análisis de modos normales, expuso patrones vibratorios asimétricos en ambos dímeros. Las fluctuaciones térmicas revelan diferencias en el tamaño y la flexibilidad de las cavidades de unión de los ligandos en la interfaz dímero-dímero. Es decir, pequeñas diferencias estructurales entre los dímeros, o monómeros pueden conducir a diferencias funcionales significativas en la dinámica del tetrámero de Transtiretina.