Fernando Birri: la Poesía, Raíz de Todas las Flores

Fernando Birri (1925-2017) fue titiritero, escritor,artista plástico, director, teórico del cine y profesor. El intelectualsantafesino hizo de la síncresis y de la heterogeneidad la marcadistintiva de su arte. Al terminar sus estudios en Italia, en1956, volvió a su Santa Fe natal, donde fundó el Instituto deCinematografía, primera escuela de cine del país. A través de suobra y de su actividad académica, Birri redefinió la función delarte cinematográfico, que se convirtió en un medio educativo parala creación de una conciencia social latinoamericana. De hecho,Birri revolucionó el mundo del cine del continente, tanto que sele atribuye el título de «padre del nuevo cine latinoamericano».El reconocimiento internacional, sin embargo, no se correspondecon una adecuada investigación sobre su obra, cuyos estudiosresultan fragmentarios y poco exhaustivos. Su actividad poéticadespertó aún menos interés por parte de la crítica, a pesar dela importancia de la palabra escrita en la carrera del autor. Estetrabajo no pretende ser un análisis exhaustivo de la poesía deFernando Birri, sino un acercamiento para despertar interés enesta faceta del artista que quedó a la sombra de su actividadcinematográfica y que, a su vez, es la clave para entender suproducción

The neuro-cardiac junction: the hotline for bidirectional dialogue between neurons and cardiomyocytes

Rationale: The heart is mainly innervated by the sympathetic nervous system that is involved in the fight or flight response. Sympathetic neurons (SNs), whose cell bodies are placed in the stellate and superior cervical ganglia, mediate the main physiological mechanism increasing the frequency and force of cardiac contraction through release of norepinephrine. Recently, we have reported that SNs regulate heart trophism through stimulation of β2 adrenergic receptors and repression of muscle specific ubiquitin ligases (i.e. Murf1 and Atrogin1) but not much is known about the effects of SNs on sarcomeres. Nerve growth factor (NGF) released by the myocardium controls cardiac innervation by SNs after binding to its receptor (TrkA) and is required for neuronal survival. Thus, bidirectional coupling between SGNs and the heart takes place: the heart needs to be coupled to the SNs to receive norepinephrine stimulation for an efficient increase in heart contraction, and conversely, SNs are coupled to the heart for neurotrophic stimulation that is required for neuronal viability. However, whether a cell-cell interaction occurs in the SN-heart coupling is not known. An interaction between the muscle and the neuron that has been well described both in terms of function and structure, is the neuro-muscular junction (NMJ), characterized by membrane thickenings, acetylcholinergic receptor clustering, reduced intermembrane space (70-50 nm) and neurotrophin release by the postsynaptic myocyte (e.g. NT3, NT4). Considering the interaction between the SNs and the heart (neuro-cardiac junction, NCJ), this study aims i) to evaluate the effects of anterograde SN stimulation on sarcomeric structures, ii) to determine whether specific cellular structures are present at the SN/Cardiomyocyte (CM) contact site, iiI) to investigate the role of SGN/CM contact in NGF-mediated signaling. Results: To analyze changes in sarcomere structure, cultured CMs were treated with adrenergic stimuli (clenbuterol, phenylephrine and norepinephrine) or nutrient/serum deprived by HBSS incubation. Since starvation and sympathetic denervation share common targets (e.g. ubiquitin ligases), we can make a parallelism between the two pro-atrophic stimuli for alterations in the sarcomeres. Incubation with adrenergic agonists did not cause significant changes, whereas starvation caused a 41.86% decrease in sarcomere area, suggesting that sarcomere degradation is faster than its synthesis. This result was confirmed by experiments of in live imaging performed on CMs transfected with a construct encoding for the z-line localized RFP-zasp. To understand whether all sarcomeric proteins share the same fate during HBSS treatment, immunofluorescence (IF) and western blot (WB) analyses were performed on different proteins localized in the sarcomeres. While α actinin and cardiac tropoinin (cTn) I showed delocalization and degradation, no significant changes were measured for cTnT upon HBSS treatment, suggesting that sarcomeric proteins are degraded in different ways. To understand which protein degradation system is involved in sarcomere disassembly, we considered the autophagy-lysosome and ubiquitin proteasome systems (UPS). WB and IF analyses supported the activation of both systems in cells treated with HBSS. In live imaging of CMs co-transfected with constructs encoding for RFP-zasp and EGFP-LC3 showed LC3 enrichment near sarcomeres in nutrient/serum deprived cells, suggesting that autophagy may be involved in sarcomere degradation. Moreover, IF staining showed ubiquitin marked sites near the M-line of sarcomeres in cells incubated with HBSS, suggesting that ubiquitin ligases may be involved in sarcomere disassembly. Since Murf1 is a muscle specific ubiquitin ligase, localized in the M-line of sarcomeres and upregulated upon nutrient/serum deprivation, we evaluated its role. Its overexpression caused a 88.57% decrease in the sarcomere area, when compared to controls, whereas its silencing in starved CMs did not prevent sarcomere degradation (446.19 ±35.65 vs 144.91 ±26.25 μm2 of sarcomeric area in controls and silenced CMs respectively). These results were confirmed by in live imaging on RFP-zasp transfected CMs, and suggest that UPS and in particular Murf1 are involved in HBSS induced sarcomeric disassembly and that Murf1-mediated degradation is not the only process. Considering the analysis of the neuro-cardiac interaction, IF staining on rat heart cryosections showed dense innervation of the heart by sympathetic neurons that mainly interact with CMs when compared to other cardiac cell types that are well represented in the heart (e.g. cardiac fibroblasts, CFs). Electron microscopy on mouse heart slices and rat SN/CM co-cultures showed a close association between SNs and CMs (intermembrane distance around 70 nm), neurotransmitter vesicle accumulation and increased membrane protein density. These data support that a direct interaction between the sympathetic neurons and the CMs exists. To analyze such interaction, SN/CM co-cultures were developed by isolating sympathetic ganglia neurons (SGN) from the superior cervical ganglia and CMs from the hearts of neonatal rats. Both cell types were characterized using IF staining for dopamine β-hydroxylase, a maker for noradrenergic neurons, and for α actinin, a sarcomeric protein. Moreover, IF staining showed an enrichment of cell-to-cell adhesion molecules including β-catenin and cadherin at the contact sites between processes and CMs. Such enrichment developed after 2 weeks of co-culture, suggesting that SGN/CM co-cultures are subjected to time dependent maturation. In spotted co-cultures allowing to identify processes on wither CMs or non CM cardiac cells (mainly fibroblasts), a higher area occupied by processes was measured on CMs when compared to the other cardiac cells after NGF withdrawal (67.11 ±12.36% vs 3.79 ±1.12% of area occupied by processes respectively), supporting the preferential interaction of SGNs with CMs. This idea is further supported by the observation that SGNs develop larger contact sites on CMs than in other cardiac cells (82.88 ±1.3% decrease in contact area on non CM cardiac cells when compared to CMs). Taken together, all these data suggest that SGNs establish a direct and stable interaction with CMs and not other cardiac cells. Since the myocardium is known to produce NGF that is required for SN viability, the functional role of the NCJ was assessed considering NGF signaling. This neurotrophin is synthesized by CMs, as detected by the western blot analysis. Transfection of CMs with siRNA against NGF caused a 72.91% decrease of the neurotrophin expression, reducing neuronal density in SGN/CM co-cultures (65.72 ±9.33% decrease in mean neuronal density when compared to the scramble siRNA). This effect was abolished by the addition of NGF in the culture medium and supports that SGNs are dependent on CM derived NGF. NGF binding to its receptor enables TrkA activation, endocytosis and retrograde transport to the neuronal soma. TrkA retrograde movements were assessed by monitoring transport velocity, using imaging in transiently TrkA-DsRed2 transfected SGNs. The speed of retrograde TrkA-DsRed2 movements depended on the presence of NGF (0.32 ±0.06 vs 0.19 ±0.03μm/s in presence or absence of NGF). In co-cultures, retrograde movements were higher and faster in processes contacting CMs than those contacting other cardiac cells (0.24 ±0.05 vs 0.11 ±0.02μm/s respectively), supporting the idea that TrkA is activated on CMs and not on the other cardiac cells and that SGN survival requires CM derived NGF. Since SGNs interact with CMs and depend on CM released NGF, we tested the hypothesis that the NCJ is necessary for neuronal survival. IF on mouse heart slices showed TrkA enrichment at SGN/CM contact site, suggesting that NGF signaling may be involved in the NCJ. Moreover, CM-conditioned medium did not prevent neuronal death (58.21 ±10.42% decrease in mean neuronal density when compared to SGN/CM co-cultures), suggesting that NGF in the medium is not sufficient for neuronal survival. Consistently, we measured NGF concentration in CM-conditioned medium and it was a 1000-fold lower than the minimal dose required for neuronal survival (0.13 ±0.08pM). To evaluate whether a single cell-to-single cell NGF signaling occurs between SGNs and CMs, co-cultures were co-transfected with siRNA against NGF and a plasmid encoding for the GFP that allows the identification of NGF silenced CMs. Sympathetic processes on NGF-silenced CMs showed a 19.56 ±4.01% decrease in the neuro-cardiac contact area when compared to those on untransfected CMs of the same co-culture, supporting that direct cell-cell NGF mediated signaling is present. Moreover, co-cultures were transfected with a construct encoding NGF in order to detect NGF accumulation in processes using the IF. Only processes in contact with transfected CM contained NGF puncta, while those in contact with untransfected cells of the same co-culture did not contain NGF (43.43 ±10.77 vs 4.17 ± 4.1% of processes on transfected or un-transfected CMs). Taken together, these data suggest that the establishment of a neuro-cardiac interaction is necessary to allow NGF signaling. In the end of this work, we interfered with NGF signaling using different strategies. First, we used an anti-NGF antibody to sequester NGF. Second, since from TEM analysis we detected sites of cell-to-cell distance of 10nm, we used the smaller TrkA antagonist c(92-96). Third, we used k252a that has a size comparable to that of c(92-96) and that is membrane permeable. Whereas every approach worked on SGNs alone leading to a significant reduction in neuronal density, only k252a was able to reduce neuronal density in co-cultures (73.24 ±4.18% decrease in mean neuronal density when compared to the control), suggesting that the NCJ is an isolated microenvironment protected from diffusion. Since k252a led to neuronal loss in co-cultures, we used this inhibitor to estimate NGF concentration at the contact site, incubating SGNs alone with k252a and NGF at increasing concentrations. The estimated concentration was 1.4 ±0.03nM, 3.5 times higher than the minimal dose required for neuronal survival, supporting that the NCJ is characterized by high NGF concentration. Conclusions: Taken together, our results suggest that sympathetic neurons establish a direct interaction with CMs and that they are dependent on CM derived NGF. Morever, NGF-dependent pro-survival signal to the SGN needs this direct interaction that facilitates NGF activation of TrkA thanks to the development of an isolated microdomain characterized by a high NGF concentration and TrkA enrichment. Finally, sarcomere dismantlement during atrophic remodeling involves the activation of protein degradation systems and in particular of the ubiquitin ligase Murf1, whose regulation by SNs may affect sarcomere structur

IMPORTACIONES ITALIANAS EN "SUR" (1945-1955)

En aquest treball tractarem de dibuixar un mapa preliminar de la recepció d'alguns textos italians a l'Argentina i d'entendre l'entrada en circulació de determinades idees sobre art i literatura al país a partir de 1945. Ens enfocarem a la revista “SUR”, en particular en el núm. 225. El que intentarem mostrar és que la "intelligentsia" liberal de “SUR”, a través de les seves idees cosmopolites, va introduir, potser inconscientment, textos i autors italians clau per a les generacions intel·lectuals argentines dels anys 60.If we were to choose a prototype of a literary journal, the Argentine journal “SUR” would undoubtedly be one of the models to adopt because of the influence it had on artistic, cultural and political debates in Argentina in the second half of the twentieth century. From 1945 one can observe that certain new ideas about art and culture started to circulate in the country. Our hypothesis is that this was due to the import of Italian texts published in the Italian “dopoguerra” (that is the post-war period after the II World War). Our purpose is to show in what sense and by what means this import process of Italian texts in SUR affected the artistic ideas in Argentina after the 1950s. The always recurring tension between the foreign and the local, which has characterized Argentine cultural history for decades, was partly sort out in those years with the reception of Italian Neorealism in the Argentine literary scene, since this new trend brought a new aesthetics and a new literary language both close to “the local” and, at the same time, “universal”. In this paper we will try to draw a preliminary map of the reception of some Italian literary texts in Argentina. We will also study the circulation of certain ideas about art and literature in the country from 1945. We will focus on “SUR”, namely on its issue #225. By doing so, we will try to light up the fact that the liberal intelligentsia collaborating with “SUR” introduced, probably unconsciously, Italian works and authors that would be key for the Argentine next literary generation in the sixties.En este trabajo trataremos de dibujar un mapa preliminar de la recepción de algunos textos italianos en Argentina y de entender la entrada en circulación de determinadas ideas sobre arte y literatura en el país a partir de 1945. Nos enfocaremos en la revista Sur, en particular en el número 225. Lo que se intentará poner a la luz es que la “intelligentsia” liberal de Sur, a través de sus ideas cosmopolitas, introdujo, quizás in-conscientemente, textos y autores italianos clave para las generaciones intelectuales argentinas de los años 60

La compensazione statale delle vittime di reato negli Stati Membri dell’UE: uno studio comparativo

State compensation for victims of crime could be described as a young but problematic institution. During its relatively short history, which begins with the origins of victimology during the second post-war period, it has raised a heated debate, rich in considerations regarding the figure of the victim of crime, the foundations of the institute itself but also its critical issues. After having summarized these aspects and the main evolutionary steps of the compensatory institution, especially in the context of the European Union, this article will report the results of a comparative research which aimed to collect data on the level of implementation of compensation in the 27 Member States of the Union. In this context, legislative sources, as well as study carried out with uniform methodologies in the Member States and additional information obtained through other channels were used. Results were then critically compared around some particularly meaningful thematic nodes, which made it possible to identify trends and divergences in the solutions proposed from time to time to resolve the most problematic issues. In the last section, the author will carry out a brief reflection on the plausible future of compensation and on the opportunity of its absorption in the broader concept of reparation

Lactic acid bacteria : reviewing the potential of a promising delivery live vector for biomedical purposes

Lactic acid bacteria (LAB) have a long history of safe exploitation by humans, being used for centuries in food production and preservation and as probiotic agents to promote human health. Interestingly, some species of these Gram-positive bacteria, which are generally recognized as safe organisms by the US Food and Drug Administration (FDA), are able to survive through the gastrointestinal tract (GIT), being capable to reach and colonize the intestine, where they play an important role. Besides, during the last decades, an important effort has been done for the development of tools to use LAB as microbial cell factories for the production of proteins of interest. Given the need to develop effective strategies for the delivery of prophylactic and therapeutic molecules, LAB have appeared as an appealing option for the oral, intranasal and vaginal delivery of such molecules. So far, these genetically modified organisms have been successfully used as vehicles for delivering functional proteins to mucosal tissues in the treatment of many different pathologies including GIT related pathologies, diabetes, cancer and viral infections, among others. Interestingly, the administration of such microorganisms would suppose a significant decrease in the production cost of the treatments agents since being live organisms, such vectors would be able to autonomously amplify and produce and deliver the protein of interest. In this context, this review aims to provide an overview of the use of LAB engineered as a promising alternative as well as a safety delivery platform of recombinant proteins for the treatment of a wide range of diseases

The regulation of the JNK cascade and programmed cell death by NF-κB: mechanisms and functions

The nuclear factor κB (NF-κB) family is an evolutionarily conserved family of transcription factors that play a central role in immune and inflammatory responses. They also play a pivotal role in cell survival, whereby activation of NF-κB antagonizes programmed cell death induced by tumor necrosis factor receptors and other cell death signals. The prosurvival function of NF-κB has been implicated in a wide range of biological processes, including the development and homeostasis of the immune system and liver. It has also been implicated in the pathogenesis of numerous diseases, including cancer, chronic inflammation, and certain hereditary disorders. The protective activity of NF-κB can also hamper tumor cell killing inflicted by radiation or chemotherapeutic drugs, thereby promoting resistance to cancer treatments. This prosurvival activity of NF-κB involves the suppression of sustained c-Jun N-terminal kinase (JNK) activation and of the accumulation of cytotoxic reactive oxygen species. NF-κB mediates this function by inducing the transcription of target genes, whose products inhibit the JNK signaling pathway and suppress accumulation of reactive oxygen species through their antioxidant functions. The development of specific inhibitors that target the critical downstream NF-κB-regulated genes that promote survival in cancer and other diseases potentially holds a key to developing specific and effective therapeutic strategies to combat these disorders

Editorial: High added-value nanoparticles: Rethinking and recycling cell protein waste

info:eu-repo/semantics/publishedVersio

NF-κB: blending metabolism, immunity, and inflammation

The procurement and management of nutrients and ability to fight infections are fundamental requirements for survival. These defense responses are bioenergetically costly, requiring the immune system to balance protection against pathogens with the need to maintain metabolic homeostasis. NF-κB transcription factors are central regulators of immunity and inflammation. Over the last two decades, these factors have emerged as a pivotal node coordinating the immune and metabolic systems in physiology and the etiopathogenesis of major threats to human health, including cancer, autoimmunity, chronic inflammation, and others. In this review, we discuss recent advances in understanding how NF-κB-dependent metabolic programs control inflammation, metabolism, and immunity and how improved knowledge of them may lead to better diagnostics and therapeutics for widespread human diseases