El desarrollo en las organizaciones. La articulación entre el INTA y la Universidad como parte del cambio

El sector agropecuario y las comunidades que lo integran enfrentan el desafío de los actuales cambios en el contexto económico y social, tanto a nivel de país como del mundo en general. A partir de aquí la sociedad organizada, es decir las instituciones oficiales y privadas deben tener la suficiente capacidad de cambio para “amoldarse” y permanecer en el nuevo “escenario”.EEA OliverosFil: Fernandez Alsina, Mario. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; Argentin

SynGAP splice variants display heterogeneous spatio-temporal expression and subcellular distribution in the developing mammalian brain

Altres ajuts: Financial support for this work was provided by: Career Integration Grant (ref. 304111), Ramón y Cajal Fellowship (RYC-2011-08391p) IEDI-2017-00822; ; BES-2013-063720 (MINECO) to GG; MH096847 (NIH), MH108408 (NIH) and NS064079 (NIH) to GR and RO1 MH112151 (NIH) to RLH. All experiments were conducted in compliance with the ARRIVE guidelines.The SynGAP protein is a major regulator of synapse biology and neural circuit function. Genetic variants linked to epilepsy and intellectual disability disrupt synaptic function and neural excitability. SynGAP has been involved in multiple signaling pathways and can regulate small GTPases with very different roles. Yet, the molecular bases behind this pleiotropy are poorly understood. We hypothesize that different SynGAP isoforms will mediate different sets of functions and that deciphering their spatio-temporal expression and subcellular localization will accelerate understanding their multiple functions. Using isoform-specific antibodies recognizing SynGAP in mouse and human samples we found distinctive developmental expression patterns for all SynGAP isoforms in five mouse brain areas. Particularly noticeable was the delayed expression of SynGAP-α1 isoforms, which directly bind to postsynaptic density-95, in cortex and hippocampus during the first 2 weeks of postnatal development. Suggesting that during this period other isoforms would have a more prominent role. Furthermore, we observed subcellular localization differences between isoforms, particularly throughout postnatal development. Consistent with previous reports, SynGAP was enriched in the postsynaptic density in the mature forebrain. However, SynGAP was predominantly found in non-synaptic locations in a period of early postnatal development highly sensitive to SynGAP levels. While, α1 isoforms were always found enriched in the postsynaptic density, α2 isoforms changed from a non-synaptic to a mostly postsynaptic density localization with age and β isoforms were always found enriched in non-synaptic locations. The differential expression and subcellular distribution of SynGAP isoforms may contribute to isoform-specific regulation of small GTPases, explaining SynGAP pleiotropy. Syngap1 gene encodes for different synaptic Ras/Rap GTPase-activating (SynGAP) isoforms which are key for brain function. SynGAP C-termini splice variants show different spatio-temporal expression and subcellular localization in the developing mouse brain. This study reveals a non-synaptic and heterogenous role of SynGAP spliced variants. Depicted abundance differences only allow relative comparison within a given tissue (top panel), postnatal age (PND, middle panel), or subcellular distribution (bottom panel). Ctx, cortex; Hip, hippocampus; Str, striatum; OB, Olfactory Bulb; Crb, cerebellum and tSynGAP, total SynGAP

HAPLN1 potentiates peritoneal metastasis in pancreatic cancer

The presence of peritoneal metastasis in pancreatic cancers is associated with poor prognosis. Here the authors show that hyaluronan and proteoglycan link protein-1 (HAPLN1) promotes tumour cell plasticity and pro-tumoral immune microenvironment to facilitate peritoneal dissemination in pancreatic cancers. Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis. Bioinformatic analysis showed that HAPLN1 expression is enriched in the basal PDAC subtype and associated with worse overall patient survival. In a mouse model for peritoneal carcinomatosis, HAPLN1-induced immunomodulation favors a more permissive microenvironment, which accelerates the peritoneal spread of tumor cells. Mechanistically, HAPLN1, via upregulation of tumor necrosis factor receptor 2 (TNFR2), promotes TNF-mediated upregulation of Hyaluronan (HA) production, facilitating EMT, stemness, invasion and immunomodulation. Extracellular HAPLN1 modifies cancer cells and fibroblasts, rendering them more immunomodulatory. As such, we identify HAPLN1 as a prognostic marker and as a driver for peritoneal metastasis in PDAC

Case report : Challenges in immune reconstitution following hematopoietic stem cell transplantation for CTLA-4 insufficiency-like primary immune regulatory disorders

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is a T-cell hyperactivation disorder that can manifest with both immunodeficiency and immune dysregulation. Approximately one-third of patients may present mild symptoms and remain stable under supportive care. The remaining patients may develop severe multiorgan autoimmunity requiring lifelong immunosuppressive treatment. Hematopoietic stem cell transplantation (HSCT) is potentially curable for patients with treatment-resistant immune dysregulation. Nevertheless, little experience is reported regarding the management of complications post-HSCT. We present case 1 (CTLA-4 haploinsufficiency) and case 2 (CTLA-4 insufficiency-like phenotype) manifesting with severe autoimmunity including cytopenia and involvement of the central nervous system (CNS), lung, and gut and variable impairment of humoral responses. Both patients underwent HSCT for which the main complications were persistent mixed chimerism, infections, and immune-mediated complications [graft-versus-host disease (GVHD) and nodular lung disease]. Detailed management and outcomes of therapeutic interventions post-HSCT are discussed. Concretely, post-HSCT abatacept and human leukocyte antigen (HLA)-matched sibling donor lymphocyte infusions may be used to increase T-cell donor chimerism with the aim of correcting the immune phenotype of CTLA-4 haploinsufficiency

tumor infiltrating lymphocytes tils and pdl1 expression as prescreening enrichment biomarkers of clinical benefit to immune checkpoint inhibitors ci in early clinical trials ect

n/

Desarrollo de un mapa interactivo de recursos energéticos alternativos a partir de una experiencia pedagógica universitaria

El trabajo presenta la metodología destinada a desarrollar un mapa interactivo como herramienta de estudio del potencial de energía renovable disponible en distintas regiones del país. La relevancia del trabajo reside en que la existencia de datos globales organizados permitirá un acceso ordenado, no intuitivo, a información sobre las posibilidades de producción de energía térmica y eléctrica con recursos de bajo impacto ambiental, si bien existen antecedentes importantes en este campo, que en la mayoría de los casos no han sido ampliamente difundidos o no han llegado a plasmar los resultados de la investigación en una herramienta de estudio accesible y fácilmente aplicable para una rápida visualización de las posibilidades existentes. Una primera fase de aplicación del trabajo está destinada al ámbito educativo, específicamente en la carrera de Ingeniería en Ecología de la Universidad de Flores.This paper describes the methodology destinated to develop an interactive map in order to be used as a helping instrument the study of the different regions of the country that present renewable energy resources. The relevance of this paper lies on that the existence of organized data, will permit an ordered, not intuitive access to the information about the different possibilities of thermal and electrical energy production with low environmental impact resources. Some other important studies of this kind have been developed before, but they have not been widely spread. The first application of this paper is to be used in the educational field, specifically in subjects related to Environmental Engineering at Flores University.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Desarrollo de un mapa interactivo de recursos energéticos alternativos a partir de una experiencia pedagógica universitaria

El trabajo presenta la metodología destinada a desarrollar un mapa interactivo como herramienta de estudio del potencial de energía renovable disponible en distintas regiones del país. La relevancia del trabajo reside en que la existencia de datos globales organizados permitirá un acceso ordenado, no intuitivo, a información sobre las posibilidades de producción de energía térmica y eléctrica con recursos de bajo impacto ambiental, si bien existen antecedentes importantes en este campo, que en la mayoría de los casos no han sido ampliamente difundidos o no han llegado a plasmar los resultados de la investigación en una herramienta de estudio accesible y fácilmente aplicable para una rápida visualización de las posibilidades existentes. Una primera fase de aplicación del trabajo está destinada al ámbito educativo, específicamente en la carrera de Ingeniería en Ecología de la Universidad de Flores.This paper describes the methodology destinated to develop an interactive map in order to be used as a helping instrument the study of the different regions of the country that present renewable energy resources. The relevance of this paper lies on that the existence of organized data, will permit an ordered, not intuitive access to the information about the different possibilities of thermal and electrical energy production with low environmental impact resources. Some other important studies of this kind have been developed before, but they have not been widely spread. The first application of this paper is to be used in the educational field, specifically in subjects related to Environmental Engineering at Flores University.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease

Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance. Based on demonstrated pro-tolerogenic activity, sirolimus (rapamycin) is an agent with promise to achieve these goals. In a long-term follow-up analysis of a randomized phase II trial comparing sirolimus/tacrolimus versus methotrexate/tacrolimus for graft-versus-host disease prevention in matched sibling or unrelated donor transplant, we examined the impact of prolonged sirolimus administration (≥ 1 year post-transplant). Median follow-up time for surviving patients at time of this analysis was 41 months (range 27–60) for sirolimus/tacrolimus and 49 months (range 29–63) for methotrexate/tacrolimus. Sirolimus/tacrolimus patients had significantly lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease (34% vs. 65%; P=0.004) and late acute graft-versus-host disease (20% vs. 43%; P=0.04). While sirolimus/tacrolimus patients had lower prednisone exposure and earlier discontinuation of tacrolimus (median time to tacrolimus discontinuation 368 days vs. 821 days; P=0.002), there was no significant difference in complete immune suppression discontinuation (60-month estimate: 43% vs. 31%; P=0.78). Prolonged sirolimus administration represents a viable approach to mitigate risk for moderate-severe chronic and late acute graft-versus-host disease. Further study of determinants of successful immune suppression discontinuation is needed