Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-βInduced Neuronal Death

Astrocytes actively participate in neuro-inflammatory processes associated to Alzheimer’s disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD associated pathological inflammation, suggesting a potential new druggable target for this devastating disease. We have now developed decoy molecules to interfere with calcineurin/FOXO3 interactions, and tested them in astrocytes and neuronal co-cultures exposed to amyloid-β (Aβ) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A-induced neuronal death and favors the production of a set of growth factors that we hypothesize form part of a cytoprotective pathway to resolve inflammation. Furthermore, interference of the A-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-β protein precursor (AβPP) synthesis, reduced the AβPP amyloidogenic pathway, resulting in lower Alevels, and blocked the expression of pro-inflammatory cytokines TNFα and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by Aβ accumulation in brain may constitute an effective new therapeutic approach in AD. Future studies with intranasal delivery, or brain barrier permeable decoy compounds, are warranted

Stakeholders y responsabilidad social universitaria en la Universidad Nacional de San Antonio Abad del Cusco

The objective of the research was to identify the perception of internal and external stakeholders regarding the university social responsibility fulfilled by the National University of San Antonio Abad in Cusco (UNSAAC). For this purpose, a qualitative, descriptive, and nonexperimental basic research was carried out, with a probabilistic sample of 211 internal stakeholders and a non-probabilistic sample of 49 external stakeholder representatives. Surveys and interview techniques were applied. The results showed that the most of the internal stakeholders perceive that the university social responsibility is moderately acceptable in the four axes of social responsibility (management, training, cognition and social perception), on the other hand, an important part of the external stakeholders perceive that the university is disconnected from the organizations of its local and regional environment, especially in the aspects of management and research, nevertheless consider that the university is an organization potentially allied to its institutional activities.El objetivo de la investigación fue identificar la percepción de los Stakeholders internos y externos respecto a la responsabilidad social universitaria que cumple la Universidad Nacional de San Antonio Abad del Cusco (UNSAAC).  Con tal propósito, se efectuó una investigación básica, cualitativa, descriptiva y no experimental, con una muestra probabilística de 211 de Stakeholders internos y una muestra no probabilística de 49 representantes de stakeholder externos. Se aplicaron las técnicas de encuesta y entrevista. Los resultados evidenciaron que la mayor parte de los Stakeholders internos perciben que la responsabilidad social universitaria de la entidad es medianamente aceptable en los cuatro ejes de la responsabilidad social (gestión, formación, cognición y participación social), en cambio, una parte importante de los Stakeholders externos perciben que la universidad se encuentra desvinculada de las organizaciones de su entorno local y regional, especialmente en los aspectos de gestión e investigación, no obstante consideran que la universidad es una organización potencialmente aliada a sus actividades institucionales

Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

One important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dendriplex, consequently leading to low transfection efficiencies. Therefore, biodegradable cationic dendritic structures have been eagerly awaited. However, the development of these dendritic nanocarriers is challenging because of the undesired and/or premature degradation observed during their synthesis and/or application. Here, we report new hybrid-biodegradable, biocompatible, non-toxic, and water-soluble azide-terminated PEG–GATGE dendritic block copolymers, based on a gallic acid (GA) core and triethylene glycol (TG) butanoate arms, incorporating ester bonds (E) at the dendritic arms/shell. Their successful functionalization by “click” chemistry with unprotected alkynated amines allowed complexation and delivery of siRNA. The hydrophobic character of the GATGE building unit confers to these hydrolyzable dendritic bionanomaterials a great ability to complex, protect and mediate the cellular internalization of siRNA. Moreover, the localization of the degradation points at the dendritic periphery, close to the complexed siRNA, was found to be important for nucleic acid release from the nanoparticles, rendering a significant improvement of the transfection efficiency compared to their hydrolytically stable PEG–GATG copolymer counterparts. The present study puts forward these biodegradable PEG–dendritic block copolymers not only as suitable vectors for nucleic acids, but also as new avenues for further developments exploring their use in theranosticsThe authors would like to acknowledge the FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE and the Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia (PTDC/CTM-NAN/112428/2009 and PTDC/CTM-NAN/3547/2014) that supported this work and the FCT / MEC through National Funds and, when applicable, co-financed by the FEDER via the PT2020 Partnership Agreement under the 4293 Unit I&D. V. Leiro acknowledges the support by FCT (SFRH/BPD/69110/2010) and by the project NORTE-01-0145-FEDER-000012, financed by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). P.M.D. Moreno acknowledges the support from the Marie Curie Actions of the European Community’s Seventh Framework Program (PIEF-GA-2011-300485) and FCT fellowship (SFRH/BPD/108738/2015). This work was also financially supported by the Spanish Government (MINECO: CTQ2012-34790, CTQ2012-33436) and the Xunta de Galicia (CN2011/037)S

Promoción de exportación para las PyMEs

El presente trabajo tiene por finalidad revelar la incidencia que tienen las pequeñas y medianas empresas argentinas en el mercado internacional y los instrumentos con los que cuentan para acceder a dicho mercado. Para ello, se analizó el comercio exterior en su conjunto, principalmente, sus actores, operatoria, incoterms, entre otros. Se aplicaron métodos cuantitativos a través de la presentación de gráficos con datos estadísticos para conocer los porcentajes de exportación de las PyMEs en la Argentina. Los resultados obtenidos por un lado, indican la gran importancia que tienen estas empresas en las operaciones de extracción de mercadería que se realizan en nuestro país y por el otro, la falta de formación para insertarse al comercio exterior de una manera más competitiva. El objetivo de este informe es dar a conocer herramientas existentes que provocan beneficios y facilitan la introducción al mercado externo para las pequeñas y medianas empresas.Fil: Gazze, Omar Carim. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Naranjo Vega, Ana Victoria Lourdes. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Ticli, Brunela Elena. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas

Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-beta-Induced Neuronal Death

Astrocytes actively participate in neuro-inflammatory processes associated to Alzheimer's disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD-associated pathological inflammation, suggesting a potential new druggable target for this devastating disease. We have now developed decoy molecules to interfere with calcineurin/FOXO3 interactions, and tested them in astrocytes and neuronal co-cultures exposed to amyloid-beta (A beta) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A beta-induced neuronal death and favors the production of a set of growth factors that we hypothesize form part of a cytoprotective pathway to resolve inflammation. Furthermore, interference of the A beta-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-beta protein precursor (A beta PP) synthesis, reduced the A beta PP amyloidogenic pathway, resulting in lower A beta levels, and blocked the expression of pro-inflammatory cytokines TNF alpha and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by A beta accumulation in brain may constitute an effective new therapeutic approach in AD. Future studies with intranasal delivery, or brain barrier permeable decoy compounds, are warranted.Peer ReviewedPostprint (author's final draft

Social services for the elderly: a multivariate perspective study

IntroductionToday’s society is aware that healthy aging favors quality of life in the future, even more so as life expectancy increases in populations such as Europe. As in countries such as Japan, it is necessary for institutions to provide social services to support the elderly, with the aim of achieving an optimal quality of life for these people. The aim of this study is to analyze the different types of social services and activities that certain institutions provide to the elderly in order to find areas for improvement or to propose relationships between them that will benefit both users and institutions.MethodsOfficial data from Junta de Castilla y León (Spain) on social services for the elderly in the 9 provinces of the autonomous community of Castilla y León from 2007 to 2021 were analysed using multivariate statistical techniques.ResultsThroughout the period under analysis, there is an association between the number of places in public and private non-profit residential centers for the elderly and the number of places in day-care centers or the number of students in the Inter-University Experience Programme. The variables associated with the telecare programme are related to the number of people under guardianship. On the other hand, three well-differentiated clusters of provinces of Castilla y León were observed.DiscussionOur findings have implications for the quality of life of the elderly, as the differences in social services in the areas analysed have a direct impact on the health of the elderly

Clinical and ultrasound thyroid nodule characteristics and their association with cytological and histopathological outcomes: A retrospective multicenter study in high-resolution thyroid nodule clinics

Introduction: Thyroid nodules are a common finding. A high-resolution thyroid nodule clinic (HR-TNC) condenses all tests required for the evaluation of thyroid nodules into a single appointment. We aimed to evaluate the clinical outcomes at HR-TNCs. Design and Methods: A retrospective cross-sectional multicenter study including data from four HR-TNCs in Spain. We evaluated fine-needle aspiration (FNA) indications and the association between clinical and ultrasound characteristics with cytological and histopathological outcomes. Results: A total of 2809 thyroid nodules were included; FNA was performed in 82.1%. Thyroid nodules that underwent FNA were more likely larger, isoechoic, with microcalcifications, and in younger subjects. The rate of nondiagnostic FNA was 4.3%. A solid component, irregular margins or microcalcifications, significantly increased the odds of Bethesda IV-V-VI (vs. Bethesda II). Irregular margins and a solid component were independently associated with increased odds of malignancy. Thyroid nodules <20 mm and ≥20–<40 mm had a 6.5-fold and 3.3-fold increased risk for malignancy respectively in comparison with those ≥40 mm. Conclusion: In this large multicenter study, we found that the presence of a solid component and irregular margins are factors independently related to malignancy in thyroid nodules. Since nodule size ≥40 mm was associated with the lowest odds of malignancy, this cut-off should not be a factor leading to indicate thyroid surgery. HR-TNCs were associated with a low rate of nondiagnostic FNA

La Imagen y la Narrativa como Herramientas para el Abordaje Psicosocial en Escenarios de Violencia. Municipios de Barrancabermeja, Sabana de Torres y Vélez.

El presente documento aborda una temática importante en nuestro contexto sociocultural e histórico como es el conflicto armado en Colombia ya que muchas regiones han tenido que soportar diferentes formas de violaciones a los derechos humanos. Este trabajo permitió dar paso al desarrollo de habilidades importantes como la comprensión de los fenómenos de violencia desde diferentes puntos de vista y su correspondiente intervención psicosocial, lo cual es vital para las comunidades víctimas de estos hechos bélicos que requieren de estrategias que transformen su realidad. Este texto presenta reflexiones analíticas sobre narrativas como el relato de Modesto Pacayá, víctima del conflicto armado, las cuales se obtuvieron mediante la formulación de diferentes tipos de preguntas: circulares, reflexivas y estrategias para examinar todo el suceso traumático; luego se realiza el planteamiento psicosocial del Caso de Pandurí mediante acciones y estrategias de intervención, finalmente se anexa el informe analítico y reflexivo de una foto intervención que se realizó en los municipios de Sabana de Torres, Barrancabermeja y Vélez (Departamento de Santander), que describe con detalle toda esta problemática y experiencia de dolor y la huella que dejó en la región. Según Villa (2012) "un enfoque psicosocial incluye principios como los de dignidad, apoyo mutuo, solidaridad, vida con calidad, enfoque de derechos, enfoque de género y desarrollo humano integral en salud mental". (p.353). Podemos decir que todos estos acontecimientos de violencia, producen una onda explosiva psicosocial que destruye todo lo que está a su alrededor, esto se incluye: proyectos de vida, prosperidad regional, desarrollo económico, educación y en general afecta todo el entramado social. Esta exploración de los distintos contextos de nuestros territorios víctimas de la violencia sociopolítica que genera la guerra nos hace un llamado a los profesionales en psicología a profundizar en la investigación de nuevas técnicas de intervención psicosocial enfocada en las víctimas y victimarios en su entorno para que puedan mejorar el tratamiento y propongan mejores formas de afrontar estos hechos anormales dando paso al empoderamiento de los sujetos y a la necesaria transformación social.This document addresses a critical issue in our sociocultural and historical context, such as the armed conflict in Colombia, since many regions have had to endure different forms of human rights violations. The work allowed to give way to the development of valuable skills, such as the understanding of the phenomena that is violence, analyzed from diverse points of view and their corresponding psychosocial intervention, which is vital for these communities that are victims of those war acts and that require strategies to transform their reality. This text presents analytical reflections on narratives like the story of Modesto Pacayá, a victim of the armed conflict. Those were obtained by formulating varied types of questions such as, circular, reflective, and some strategies to examine the entire traumatic event. Regarding the psychosocial approach, the Pandurí Case is carried out through action and intervention strategies, while the analytical and reflective report of a photo intervention was carried out in the municipalities of Sabana de Torres, Barrancabermeja and Vélez (Department of Santander). The report is attached and aims at describing this problem in detail portraying the experience of pain and the painful footprint it left in the region. According to Villa (2012) "a psychosocial approach includes principles like dignity, mutual support, solidarity, quality life, a rights approach, a gender approach and integral human development in mental health." (p.353). We can say all these violent events produce a psychosocial explosive wave that demolishes everything that is around it, including life projects, regional prosperity, economic development, thus affecting the social framework in general. This exploration of the various contexts of our territories, victims of the sociopolitical violence generated by the war, calls on psychology professionals to deepen the investigation of new psychosocial intervention techniques, focused on the victims and culprits in their environment that can improve treatment and propose better ways to face these abnormal events, giving way to the empowerment of the subjects and the necessary social transformation

Manual municipal sobre control de vertidos

El agua, como motor de desarrollo y fuente de riqueza, ha constituido uno de los pilares fundamentales para el progreso del hombre. La ordenación y gestión de los recursos hídricos, que ha sido desde siempre un objetivo prioritario para cualquier sociedad, se ha realizado históricamente bajo directrices orientadas a satisfacer la demanda en cantidades suficientes, bajo una perspectiva de política de oferta. El incremento de la oferta de agua como herramienta para el impulso económico, el mayor nivel de contaminación, irremisiblemente asociado a un mayor nivel de desarrollo, algunas características naturales (sequías prolongadas, inundaciones) y en definitiva una sobreexplotación de los recursos hídricos, han conducido a un deterioro importante de los mismos. El desarrollo de la Directiva Europea y Nacional respecto a control de vertido responsabiliza al Ayuntamiento directamente de los vertidos del municipio al exterior, y consecuentemente al Alcalde Presidente de cada Municipio. Por ello la Diputación de Sevilla, cumpliendo su labor de auxilio técnico al municipio ha encargado al Grupo TAR este manual municipal de control de vertidos para asesorar continuamente a todos los pueblos de la provincia de Sevilla, con la vocación de que sea una herramienta permanente de consulta que ayude a conseguir que la provincia lidere el cumplimiento de las normas y el desarrollo sostenible de todo su entorno. Real Decreto Legislativo 1/2001, de 20 de julio, por el que se aprueba el texto refundido de la Ley de Aguas de 1.985, junto con la nueva Directiva Marco europea para la política de agua suponen un cambio importante en los conceptos y criterios utilizados en la planificación hidrológica e introducen la calidad de las aguas y la protección de los recursos hídricos como puntos fundamentales para estructurar dicha planificación. El estado ecológico de un agua sería una expresión de la calidad de la estructura y del funcionamiento del ecosistema y cuyos criterios de clasificación (muy bueno, bueno y aceptable), en función del tipo de ecosistema acuático de que se trate, se recogen en los anexos de la directiva

Compartmentalization of distinct cAMP signaling pathways in mammalian sperm.

Fertilization competence is acquired in the female tract in a process known as capacitation. Capacitation is needed for the activation of motility (e.g. hyperactivation) and to prepare the sperm for an exocytotic process known as acrosome reaction. While the HCO3--dependent soluble adenylyl cyclase Adcy10 plays a role in motility, less is known about the source of cAMP in the sperm head. Transmembrane adenylyl cyclases (tmACs) are another possible source of cAMP. These enzymes are regulated by stimulatory heterotrimeric Gs proteins; however, the presence of Gs or tmACs in mammalian sperm has been controversial. In this manuscript, we used Western blotting and cholera toxin-dependent ADP ribosylation to show Gs presence in the sperm head. Also, we showed that forskolin, a tmAC specific activator, induces cAMP accumulation in sperm from both WT and Adcy10 null mice. This increase is blocked by the tmAC inhibitor SQ-22536 but not by the Adcy10 inhibitor KH7. While Gs immunoreactivity and tmAC activity are detected in the sperm head, PKA is only found in the tail, where Adcy10 was previously shown to reside. Consistent with an acrosomal localization, Gs reactivity is lost in acrosome reacted sperm, and forskolin is able to increase intracellular Ca2+ and induce the acrosome reaction. Altogether, these data suggest that cAMP pathways are compartmentalized in sperm, with Gs and tmAC in the head and Adcy10 and PKA in the flagellum.Fil: Wertheimer Hermitte, Eva Victoria. University Of Massachussets; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Krapf, Dario. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: de la Vega Beltran, José L.. Universidad Nacional Autónoma de México; MéxicoFil: Sánchez Cárdenas, Claudia. Universidad Nacional Autónoma de México; MéxicoFil: Navarrete, Felipe. University Of Massachussets; Estados UnidosFil: Haddad, Douglas. University Of Massachussets; Estados UnidosFil: Escoffier, Jessica. University Of Massachussets; Estados UnidosFil: Salicioni, Ana M.. University Of Massachussets; Estados UnidosFil: Levin, Lonny R.. Cornell University; Estados UnidosFil: Buck, Jochen. Cornell University; Estados UnidosFil: Mager, Jesse. University Of Massachussets; Estados UnidosFil: Darszon, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Visconti, Pablo E.. University Of Massachussets; Estados Unido