CONICET Digital

Lyapunov exponents and poles in a non Hermitian dynamics

Lyapunov exponents and poles in a non Hermitian dynamics Gomez, Ignacio Sebastián By means of expressing volumes in phase space in terms of traces of quantum operators, a relationship between the poles of the scattering matrix and the Lyapunov exponents in a non Hermitian quantum dynamics, is presented. We illustrate the formalism by characterizing the behavior of the Gamow model whose dissipative decay time, measured by its decoherence time, is found to be inversely proportional to the Lyapunov exponents of the unstable periodic orbits. The results are in agreement with those obtained by means of the semiclassical periodic–orbit approach in quantum resonances theory but using a simpler mathematics.

Anisotropic BV–L2 regularization of linear inverse ill-posed problems

Anisotropic BV–L2 regularization of linear inverse ill-posed problems Mazzieri, Gisela Luciana; Temperini, Karina Guadalupe; Spies, Ruben Daniel During the last two decades several generalizations of the traditional Tikhonov-Phillips regularization method for solving inverse ill-posed problems have been proposed. Many of these variants consist essentially of modifications on the penalizing term, which force certain features in the obtained regularized solution ([11,18]). If it is known that the regularity of the exact solution is inhomogeneous it is often desirable the use of mixed, spatially adaptive methods ([7,12]). These methods are also highly suitable when the preservation of edges is an important issue, since they allow for the inclusion of anisotropic penalizers for border detection ([20]). In this work we propose the use of a penalizer resulting from the convex spatially-adaptive combination of a classic L2penalizer and an anisotropic bounded variation seminorm. Results on existence and uniqueness of minimizers of the corresponding Tikhonov-Phillips functional are presented. Results on the stability of those minimizers with respect to perturbations in the data, in the regularization parameter and in the operator are also established. Applications to image restoration problems are shown.

Mancha angular del poroto: avances en su investigacion en la EEAOC

Mancha angular del poroto: avances en su investigacion en la EEAOC; Angular leaf spot of common bean: advances on its research at the EEAOC Mamani Gonzales, Silvana Yacqueline; Vizgarra, Oscar N.; Espeche, Clara M.; Mendez, Diego Eduardo; Ploper, Leonardo Daniel La mancha angular del poroto causada por el hongo Pseudocercospora griseola afecta el rendimiento y la calidad de la semilla. En Argentina esta enfermedad fue convirtiéndose gradualmente en una limitante del cultivo, por lo que sumanejo es un aspecto importante a tener en cuenta en la producción de poroto. En el presente trabajo se describen brevemente los resultados de las actividades llevadas a cabo por el proyecto Legumbres Secas de la Estación ExperimentalAgroindustrial Obispo Colombres (EEAOC) en la búsqueda de resistencia genética a esta enfermedad. Los trabajos comenzaron con la introducción de germoplasma desde el Centro Internacional de Agricultura Tropical a partir del cual seliberó TUC 550, la primera variedad resistente a mancha angular en Argentina. En la siguiente etapa se realizaron cruzamientos locales, utilizando como parentales resistentes los materiales seleccionados en las primeras valuaciones. Se obtuvieron así líneas avanzadas de poroto negro con niveles de resistencia superiores a los conseguidos en la etapa previa. También se identificaron nuevos parentales para futuras combinaciones, teniendo en cuenta que el trabajo de mejoramiento genético debe ser continuo debido a la alta variabilidad patogénica que presenta P. griseola.Palabras clave: evaluación de germoplasma, resistencia a Pseudocercospora griseola; Angular leaf spot of common bean, caused by the fungus Pseudocercospora griseola, affects yield and quality of bean seed. In Argentina this disease became gradually a limiting factor for the crop, so its management is an important aspect to consider in common bean production. In this work, the activities carried out by the Legumbres Secas project of the Estación Experimental Agroindustrial Obispo Colombres (EEAOC) in the search for genetic resistance to this disease are presented briefly. This work began with the introduction of germplasm from the International Center for Tropical Agriculture from which the variety TUC 550 was released, the first variety with resistance to angular leaf spot in Argentina. In the next stage, the project has carried out local crosses using as resistant parents those genotypes selected in the first evaluations. Advanced black bean lines were obtained with higher levels of resistance than those obtained in the previous stages. Also, new potential parents were identified for future combinations, considering that breeding for angular leaf spot resistance should be continuous because of the high pathogenic variability exhibited by P. griseola.

Fungal diversity at fragmented landscapes: synthesis and future perspectives

Fungal diversity at fragmented landscapes: synthesis and future perspectives Grilli, Gabriel; Longo, Maria Silvana; Huais, Pablo Yair; Pereyra, Mariana; Verga, Ernesto Gustavo; Urcelay, Roberto Carlos; Galetto, Leonardo Fungi are organisms with important roles in ecosystem functioning and services, but knowledge about how habitat fragmentation affect fungal diversity is biased by experimental approaches and it is spread in different trophic groups. We analyzed the empirical evidences of fungal diversity in fragmented landscapes, and proposed future perspectives for the study of these organisms under land use changes. Fungal diversity might be negatively affected by habitat fragmentation; however, this trend may differ in magnitude depending on fungal groups and their nutritional habits. In addition, due to the fact that fungal diversity at fragmented landscapes has been studied mainly through few indicators (e.g. isolation, area and edge effect); we propose incorporating the landscape structure and accurate spatio-temporal scales to the study of fungal diversity responses to fragmented landscapes. Together, this methodological refinement may allow improving knowledge on fungi when designing proper strategies for landscape management.

Mapping inundation probability due to increasing sea level rise along El Puerto de Santa María (SW Spain)

Mapping inundation probability due to increasing sea level rise along El Puerto de Santa María (SW Spain) Fraile Jurado, Pablo; Álvarez Francoso, José I.; Guisado Pintado, Emilia; Sanchez Carnero, Noela Belen; Ojeda Zújar, José; Leatherman, Stephen P. Global sea levels have risen through the twentieth and twenty-first centuries. This rise will almost certainly continue and probably accelerate during the rest of the twenty-first century, albeit there is strong disagreement about the range of future sea level rise due to uncertainties regarding scenarios and emission of greenhouse gasses. Although the impacts of sea level rise are diverse, inundation during high tides is one of the most obvious and immediate consequences. A probabilistic methodology for mapping the inundation hazard because of sea level rise has been applied to the coast of El Puerto de Santa María in the province of Cádiz in southwest Spain. This methodology involves a step forward since represents the full range of probabilities, associated with each scenario of sea level rise considered, and thus offers a more realistic view of the probability of inundation in each area. Results show large differences in the spatial distribution of probable inundation in urban areas and wetlands leading to different consequences for management actions.

Bioactive glasses as delivery systems for antimicrobial agents

Bioactive glasses as delivery systems for antimicrobial agents Rivadeneira, Josefina; Gorustovich Alonso, Alejandro Adrian Most biomaterial-associated infections are caused by opportunistic pathogens and bacteria that are regularly found within the microflora of the implant site. In addition, a biomaterial implant or device remains at risk of infection by hematogenous spread of bacteria disseminated from infections elsewhere in the body or from infected peri-implant tissue in revision surgery. The resulting infections are frequently accompanied by patient morbidity and discomfort and can lead to surgical replacement of the implant after lengthy, unsuccessful attempts to mitigate infections with antibiotic treatments. Therefore, extensive study is aiming to find new infection-resistant antimicrobial biomaterials and coatings for implants and devices to effectively reduce the incidence of biomaterial-associated infections. An overview of the in vitro and in vivo antimicrobial efficacies of the numerous biomaterials currently available is beyond the scope of this review. Herein, we provide a comprehensive review of bioactive glasses as biomaterial delivery systems for antimicrobial agents.

Primer reporte de un Área de Congregación de Zánganos de Apis mellifera (Hymenoptera: Apidae) de Argentina

Primer reporte de un Área de Congregación de Zánganos de Apis mellifera (Hymenoptera: Apidae) de Argentina Galindo Cardona, Alberto; Quiroga, Oscar B.; Bianchi, Eliana Mariel; Ayup, María Marta Natural reproduction of honeybees occurs in zones called drone congregation areas (DCA), visited by drones (males) and queens of several colonies. These places are open areas, protected from the wind by high vegetation cover and are very common near an apiary. Until now, there was none DCA reported in Argentina. First, we determine the fly activity of drones, watching the entrance and exit to the hives from 8:00 to 18:00 hours. We found two peaks, in 11:00 to 12:00 hours and 15:00 to 17:30. To find a DCA, we track the path of movement of drones using helium-filled balloons, kites and remotes flying. Each contact point of drones in the bait was georeferenced with a GPS to determine the path to a DCA. We found the first DCA in northern Argentina, close to queen?s cabin breeding in Alberdi, Tucumán (ARG). This study is important in biology for health monitoring and estimating the structure and genetic diversity of Apis mellifera L. in northern Argentina and for apiculture, to preserve regional ecotypes through a reproductive planning for beekeepers.; La reproducción natural de las abejas melíferas ocurre en zonas denominadas áreas de congregación de zánganos (ACZ), visitadas por machos, denominados zánganos, y reinas integrantes de varias colonias. Dichas áreas se caracterizan por ser abiertas,protegidas del viento por cubierta vegetal alta y es muy común encontrarlas cerca de un apiario. En la Argentina, hasta el momento no se había localizado ninguna ACZ. Primero se determinó el horario de actividad de zánganos, observando la entrada y salida a las colmenas de 8:00 a 18:00 horas. La actividad de los zánganos tuvo dos picos, de 11:00 a 12:00 horas y de 15:00 a 17:30 horas. Luego se hizo la identificación de la ruta de movimiento de zánganos, utilizando globos inflados con helio y barriletes. Cada punto de contacto de zánganos en el cebo, fue georeferenciado con GPS. Encontramos la primera ACZ en el norte de Argentina, cerca de una cabaña de crianza de reinas en Alberdi, Tucumán (ARG). Este estudio es importante ya que implementa una metodología para monitorear ACZ, la cual ayudaría en el estudio de la salud de las abejas y en la estimación de la estructura y diversidad genética de Apis melliferaL., también en apicultura, ya que brindaría una herramienta a los apicultores para la conservación de los ecotipos regionales mediante el planeamiento reproductivo de las abejas.

Connectedness of the algebraic set of vectors generating planar normal sections of homogeneous isoparametric hypersurfaces

Connectedness of the algebraic set of vectors generating planar normal sections of homogeneous isoparametric hypersurfaces Sanchez, Cristian Urbano Let M Sn+1 Rn+2 be a homogeneous isoparametric hypersurfaceand consider the algebraic set of unit tangent vectors generating planarnormal sections at a point E 2 M (denoted by bXE [M] TE (M)). Th epresent paper is devoted to prove that bXE [M] is connected by arcs.. This in turn proves that its projective image X [M] RP (TE (M)) also has this property.

Light and matter diffraction from the unified viewpoint of Feynman’s Sum of all Paths

Light and matter diffraction from the unified viewpoint of Feynman’s Sum of all Paths Arlego, Marcelo José Fabián; Fanaro, Maria de Los Angeles In this work, we present a pedagogical strategy to describe the diffraction phenomenon based on a didactic adaptation of the Feynman’s path integrals method, which uses only high school mathematics. The advantage of our approach is that it allows to describe the diffraction in a fully quantum context, where superposition and probabilistic aspects emerge naturally. Our method is based on a time-independent formulation, which allows modelling the phenomenon in geometric terms and trajectories in real space, which is an advantage from the didactic point of view. A distinctive aspect of our work is the description of the series of transformations and didactic transpositions of the fundamental equations that give rise to a common quantum framework for light and matter. This is something that is usually masked by the common use, and that to our knowledge has not been emphasized enough in a unified way. Finally, the role of the superposition of nonclassical paths and their didactic potential are briefly mentioned.

Política y modernización en el radicalismo bonaerense: el Matadero Municipal de Bahía Blanca (1912-1918)

Política y modernización en el radicalismo bonaerense: el Matadero Municipal de Bahía Blanca (1912-1918); Politics and modernization in Buenos Aires Radicalism: the municipal slaughterhouse of Bahía Blanca (1912-1918) Costantini, Florencia Bahía Blanca, ciudad ubicada en el sudoeste bonaerense, constituyó por su emplazamiento costero un centro importador/exportador de una vasta zona de influencia que nucleaba el sur de la provincia. Hacia principios del siglo XX su especialización productiva fue principalmente el ovino, seguido en menor medida por vacunos. En el contexto de organización capitalista, la comuna de esta localidad desplegó una política orientada a regular la rama productiva cárnica hacia el abasto urbano como lo fue la construcción de un matadero municipal. El objetivo del presente artículo es analizar la planificación y edificación del Matadero Municipal de Bahía Blanca. Partimos de la hipótesis, que el mismo estuvo dirigido a modernizar el espacio urbano y la producción del alimento. En el marco de esta medida, vemos que los agentes políticos bahienses desarrollaron funciones de producción y control sobre la elaboración de este alimento destinado a los consumidores locales, lo cual nos permite aproximarnos a los debates en torno a este tópico problematizando el rol del Estado municipal en la economía bahiense.; Bahia Blanca, a city located in the southwestern Buenos Aires, constituted due to its coastal location, an importer/exporter center linked to a vast area of influence that nucleated south of the province. By the beginning of the 20th century its productive specialization was mainly sheep, followed to a lesser extent by bovine. In the context of capitalist organization, the commune of Bahia Blanca deployed a policy oriented to organize the productive branch of the meat to the urban supply as was the construction of a municipal slaughterhouse. The aim of this paper is to analyze the planning and the construction of the Municipal Slaughterhouse of Bahia Blanca. We assume that the slaughterhouse was intended to modernizing the urban space and food production. Under this measure, we see that the political actors developed functions of production, regulation and control over the meat for local consumers, which allows us to approach the debates around this topic by problematizing the role of the municipal state in the economy.

Probing electronic structure of stoichiometric and defective Sn O2

Probing electronic structure of stoichiometric and defective Sn O2 Moreno, Mario Sergio Jesus; Kas, J. J.; Ma, C.; Wang, F.; Rehr, J. J.; Malac, M. The electronic structure of stoichiometric tin dioxide (SnO2) is studied by probing its unoccupied states using the fine structure in the electron energy-loss spectra (EELS) at the oxygen-K (O-K) edge. The spectral measurements were performed both at room and at high temperatures (773 K) and compared to ab initio calculations carried out using the real-space multiple-scattering and linearized augmented-plane-wave methods. Important many-body effects are included via quasiparticle corrections calculated within the many-pole GW self-energy approximation. An additional energy-dependent damping is calculated to account for vibrational effects. Results from this paper demonstrated that quantitative agreement between theoretical and experimental spectra can be obtained when nonspherical potentials and quasiparticle self-energy effects are considered and vibrational broadening is included. Modifications of the electronic structure by single oxygen vacancies, both in the bulk and at the (110) surface, also are predicted. Our predictions support the use of O-K EELS as a probe of the defect structures in SnO2 surfaces and nanoparticles.

Micropillar Resonators for Optomechanics in the Extremely High 19-95-GHz Frequency Range

Micropillar Resonators for Optomechanics in the Extremely High 19-95-GHz Frequency Range Anguiano, S.; Bruchhausen, Axel Emerico; Jusserand, B.; Favero, I.; Lamberti, F. R.; Lanco, L.; Sagnes, I.; Lemaître, A.; Lanzillotti Kimura, Norberto Daniel; Senellart, P.; Fainstein, Alejandro Strong confinement, in all dimensions, and high mechanical frequencies are highly desirable for quantum optomechanical applications. We show that GaAs/AlAs micropillar cavities fully confine not only photons but also extremely high frequency (19-95 GHz) acoustic phonons. A strong increase of the optomechanical coupling upon reducing the pillar size is observed, together with record room-temperature Q-frequency products of 1014. These mechanical resonators can integrate quantum emitters or polariton condensates, opening exciting perspectives at the interface with nonlinear and quantum optics.

Primeros registros de guanacos albinos en las montañas de la precordillera andina austral (Mendoza, Argentina)

Primeros registros de guanacos albinos en las montañas de la precordillera andina austral (Mendoza, Argentina); First records of albine guanacos in the mountains of southern Andean Precordillera (Mendoza, Argentina) Puig, Silvia; Videla, Fernando; Rosi, Maria Irene; Seitz, Viviana Paola; Moreni, Jonathan; Pérez, Martín; Tobares, Roberto; Maldonado, Florencia; Martín, Sebastián La hipopigmentación, expresada como albinismo total, leucismo, xantismo o piebaldismo, ha sido registrada en gran variedad de vertebrados, generalmente con baja frecuencia. Este aporte documenta los primeros registros de guanacos con hipopigmentación en una población silvestre de la precordillera andina austral. Dichos registros se obtuvieron entre 2013 y 2017, en el marco de relevamientos científicos y recorridos de control y vigilancia efectuados en la reserva natural Villavicencio. Los hallazgos correspondieron a un adulto leucístico y una cría albina, integrados respectivamente a un grupo de solteros y a un grupo familiar. Ambos presentaban desplazamientos normales y activa interacción social, evidencias que permiten descartar dificultades en el crecimiento, obtención del alimento o integración intraespecífica. Los hallazgos descriptos, que se añaden a los previamente documentados en guanacos del norte de Argentina y Chile, no se alejan de las tasas de ocurrencia natural de hipopigmentación mencionadas en bibliografía. No obstante, el incremento de las actividades humanas en la región destaca la relevancia de monitorear sus posibles efectos sobre la población de guanacos. Si dichas actividades generasen fragmentación o contaminación ambiental, el guanaco podría sufrir estrés ambiental y endogamia, con potencial incidencia sobre la tasa de albinismo.; Hypopigmentation, expressed as complete albinism, leucism, xantism, or piebaldism, has been recorded in a great variety of vertebrates, generally with low frequency. This note documents the first records of guanacos with hypopigmentation in a wild population of the Southern Andean Precordillera. These records were obtained between 2013 and 2017, in the frame of scientific investigations and tasks of control and surveillance carried out in the Villavicencio protected area. The findings corresponded to a leucistic adult and an albino young, integrated to a bachelor group and a familial group, respectively. Both showed normal movements and active social interaction, evidences that allow to discard difficulties in growing, obtaining food or intraspecific integration. The described findings, together with those previously documented for the guanaco in northern Argentina and Chile, are not far from the rates of natural occurence of hypopigmentation mentioned in bibliography. However, the increase of human activities in the region highlights the relevance of monitoring their effects on the guanaco population. If such activities generate environmental fragmentation or contamination, the guanaco could present environmental stress and endogamy, with potential incidence on the albinism rate.

Análisis relacional de cálculos dentales y periodontitis en una colección osteológica documentada

Análisis relacional de cálculos dentales y periodontitis en una colección osteológica documentada Garizoain, Gonzalo; Petrone, Selene Se presentan los resultados del análisis de cálculos dentales y periodontitis realizados sobre 342 piezasdentales pertenecientes a 30 individuos adultos provenientes de la colección osteológica Lambre. Se realizóun análisis escópico de cada pieza dental, indicándose la presencia/ausencia de dichas patologías,así como su posición, tipo y severidad en el caso de los cálculos. El 26,31% de las piezas analizadas noexhibieron patología alguna, el 31% sólo presentaron periodontitis, 1,75% sólo cálculos dentales y porúltimo el 40,94% casos manifestaron ambas patologías. En cuanto a los cálculos dentales la mayoríaeran subgingivales con una severidad tipo 1 y se ubicaban en el maxilar inferior. A partir de los resultadosobtenidos se puede establecer cierta asociación entre cálculos dentales y periodontitis, así comotambién que las piezas dentarias más propensas a desarrollar cálculos dentales son las más cercanas alas glándulas salivales de mayor tamaño.

Applied Biotechnology: Isolation and Detection of an Efficient Biosurfactant from Pseudomonas sp. Comparative Studies against Chemical Surfactants

Applied Biotechnology: Isolation and Detection of an Efficient Biosurfactant from Pseudomonas sp. Comparative Studies against Chemical Surfactants Mainez, María Esperanza; Müller, Diana María; Murguia, Marcelo Cesar The use of biosurfactants became essential because of its multiple properties and applications. The high toxicity to the environment led to search for new alternatives such as the reduction or replacement by biological surfactants. Because of this, it is in our interest to produce biosurfactants from a non-pathogenic Pseudomonas. We obtained lower values of critical micelle concentration (CMC) from the culture broth than obtained from dodecyl sulfate sodium (SDS) and Pluronic F-68, used as pure surfactans. We found values of critical micellar concentration close to 0.15 mg/L in the purified fraction by adsorption chromatography. We determine by mass spectrometry this strain possibly produces two families of biosurfactants. Majority fraction might be formed by cyclic lipopeptides whose molecular weights could be located in the range of 1100-1200 Da. However, it is necessary perform confirmatory structural studies and to determine the specific structure of these analytes.

Advanced Modeling Reconciles Counterintuitive Decisions in Lead Optimization

Advanced Modeling Reconciles Counterintuitive Decisions in Lead Optimization Fernandez, Ariel; Ridgway Scott Lead optimization (LO) is essential to fulfill the efficacy and safety requirements of drug-based targeted therapy. The ease with which water may be locally removed from around the target protein crucially influences LO decisions. However, inferred binding sites often defy intuition and the resulting LO decisions are often counterintuitive, with nonpolar groups in the drug placed next to polar groups in the target. We first introduce biophysical advances to reconcile these apparent mismatches. We incorporate three-body energy terms that account for the net stabilization of preformed target structures upon removal of interfacial water concurrent with drug binding. These unexplored drug-induced environmental changes enhancing the target electrostatics are validated against drug–target affinity data, yielding superior computational accuracy required to improve drug design.

Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na+ and Cl- permeabilities

Nitric oxide reduces paracellular resistance in rat thick ascending limbs by increasing Na+ and Cl- permeabilities Monzón, Casandra Margarita; Occhipinti, Rossana; Pignataro, Omar Pedro; Garvin, Jeffrey L. About 50% of the Na+ reabsorbed in thick ascending limbs traverses the paracellular pathway. Nitric oxide (NO) reduces the permselectivity of this pathway via cGMP, but its effects on absolute Na+ ([Formula: see text]) and Cl- ([Formula: see text]) permeabilities are unknown. To address this, we measured the effect of l-arginine (0.5 mmol/l; NO synthase substrate) and cGMP (0.5 mmol/l) on [Formula: see text] and [Formula: see text] calculated from the transepithelial resistance (Rt) and [Formula: see text]/[Formula: see text] in medullary thick ascending limbs. Rt was 7,722 ± 1,554 ohm·cm in the control period and 6,318 ± 1,757 ohm·cm after l-arginine treatment (P < 0.05). [Formula: see text]/[Formula: see text] was 2.0 ± 0.2 in the control period and 1.7 ± 0.1 after l-arginine (P < 0.04). Calculated [Formula: see text] and [Formula: see text] were 3.52 ± 0.2 and 1.81 ± 0.10 × 10-5 cm/s, respectively, in the control period. After l-arginine they were 6.65 ± 0.69 (P < 0.0001 vs. control) and 3.97 ± 0.44 (P < 0.0001) × 10-5 cm/s, respectively. NOS inhibition with Nω-nitro-l-arginine methyl ester (5 mmol/l) prevented l-arginine´s effect on Rt Next we tested the effect of cGMP. Rt in the control period was 7,592 ± 1,470 and 4,796 ± 847 ohm·cm after dibutyryl-cGMP (0.5 mmol/l; db-cGMP) treatment (P < 0.04). [Formula: see text]/[Formula: see text] was 1.8 ± 0.1 in the control period and 1.6 ± 0.1 after db-cGMP (P < 0.03). [Formula: see text] and [Formula: see text] were 4.58 ± 0.80 and 2.66 ± 0.57 × 10-5 cm/s, respectively, for the control period and 9.48 ± 1.63 (P < 0.007) and 6.01 ± 1.05 (P < 0.005) × 10-5 cm/s, respectively, after db-cGMP. We modeled NO´s effect on luminal Na+ concentration along the thick ascending limb. We found that NO´s effect on the paracellular pathway reduces net Na+ reabsorption and that the magnitude of this effect is similar to that due to NO´s inhibition of transcellular transport.

Recognition and characterization of unit interval graphs with integer endpoints

Recognition and characterization of unit interval graphs with integer endpoints Duran, Guillermo Alfredo; Fernández Slezak, F.; Grippo, L.N.; Oliveira, F.de S.; Szwarcfiter, Jayme L. We study those unit interval graphs having a model with intervals of integer endpoints and prescribed length. We present a structural result for this graph subclass which leads to a quadratic-time recognition algorithm, giving as positive certificate a model of minimum total length and as negative certificate a forbidden induced subgraph. We also present a quadratic-time algorithm to build, given a unit interval graph, a unit interval model with integer endpoints for which the interval length is as minimum as possible.

Update on GLUT4 Vesicle Traffic: A Cornerstone of Insulin Action

Update on GLUT4 Vesicle Traffic: A Cornerstone of Insulin Action Jaldín Fincati, Javier Roberto; Pavarotti, Martin Alejandro; Frendo-Cumbo, Scott; Bilan, Philip J.; Klip, Amira Glucose transport is rate limiting for dietary glucose utilization by muscle and fat. The glucose transporter GLUT4 is dynamically sorted and retained intracellularly and redistributes to the plasma membrane (PM) by insulin-regulated vesicular traffic, or ‘GLUT4 translocation’. Here we emphasize recent findings in GLUT4 translocation research. The application of total internal reflection fluorescence microscopy (TIRFM) has increased our understanding of insulin-regulated events beneath the PM, such as vesicle tethering and membrane fusion. We describe recent findings on Akt-targeted Rab GTPase-activating proteins (GAPs) (TBC1D1, TBC1D4, TBC1D13) and downstream Rab GTPases (Rab8a, Rab10, Rab13, Rab14, and their effectors) along with the input of Rac1 and actin filaments, molecular motors [myosinVa (MyoVa), myosin1c (Myo1c), myosinIIA (MyoIIA)], and membrane fusion regulators (syntaxin4, munc18c, Doc2b). Collectively these findings reveal novel events in insulin-regulated GLUT4 traffic. Insulin promotes GLUT4 redistribution from recycling endosomes and specialized intracellular compartments to the plasma membrane (PM). Signaling bifurcates downstream of phosphatidylinositol 3-kinase towards Akt and Rac. Akt signaling leads to activation of Rab10 in adipocytes and Rab8a and Rab13 in myoblasts. Rab10 acts at several steps in GLUT4 translocation, whereas Rab8a promotes GLUT4 exit from the perinuclear region and Rab13 promotes tethering of GLUT4 vesicles near the PM. Rac1 signaling induces cortical actin remodeling that tethers GLUT4 vesicles beneath the PM. Additional proteins may also fine-tune actin remodeling through tropomyosin3.1 and tropomodulin3 via Akt2 input. Insulin increases [Ca2+] beneath the PM, which may regulate the SNARE complex that mediates the final step of GLUT4 vesicle fusion with the PM.

Downregulation of adaptor protein MyD88 compromises the angiogenic potential of B16 murine melanoma

Downregulation of adaptor protein MyD88 compromises the angiogenic potential of B16 murine melanoma Trucco, Lucas Daniel; Roselli, Emiliano; Araya, Paula; Nuñez, Nicolás Gonzalo; Mena, Hebe Agustina; Bocco, Jose Luis; Negrotto, Soledad; Maccioni, Mariana The mechanisms that link inflammatory responses to cancer development remain a subject of intense investigation, emphasizing the need to better understand the cellular and molecular pathways that create a tumor promoting microenvironment. The myeloid differentiation primary response protein MyD88 acts as a main adaptor molecule for the signaling cascades initiated from Toll-like receptors (TLRs) and the interleukin 1 receptor (IL-1R). MyD88 has been shown to contribute to tumorigenesis in many inflammation-associated cancer models. In this study, we sought to better define the role of MyD88 in neoplastic cells using a murine melanoma model. Herein, we have demonstrated that MyD88 expression is required to maintain the angiogenic switch that supports B16 melanoma growth. By knocking down MyD88 we reduced TLR-mediated NF-κB activation with no evident effects over cell proliferation and survival. In addition, MyD88 downregulation was associated with a decrease of HIF1α levels and its target gene VEGF, in correlation with an impaired capability to induce capillary sprouting and tube formation of endothelial cells. Melanomas developed from cells lacking MyD88 showed an enhanced secretion of chemoattractant ligands such as CCL2, CXCL10 and CXCL1 and have an improved infiltration of macrophages to the tumor site. Our results imply that cell-autonomous signaling through MyD88 is required to sustain tumor growth and underscore its function as an important positive modulator of tumor angiogenesis.

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