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La relación entre Lukács y la tragedia será uno de los elementos más importantes para poder entender el desarrollo de sus concepciones éticas y estéticas. El papel que juega el personaje principal en el desarrollo de la novela: el héroe, su búsqueda interior, el puesto en el desarrollo histórico de la misma y los demás aspectos relacionados con la refiguración artística. Veremos cómo Lukács emprende esta búsqueda desde la Antigüedad Clásica, pasando por la Edad Media, el Renacimiento, la Ilustración, el Realismo Crítico y su posterior recuperación con el Realismo Socialista.

Editorial do número América Latina, experiências socialistas e educação

O afogamento é um problema de saúde pública universal que não recebeu a atenção necessária e impacta desproporcionalmente as crianças. Diversos fatores podem causar afogamento, por isso, existe a necessidade de se preveni-lo com o uso de conteúdos, não apenas procedimental, mas também atitudinal e conceitual. Objetivo deste texto foi refletir sobre as habilidades, conceitos e atitudes necessárias para a prevenção do afogamento e a respeito dos conteúdos procedimentais, atitudinais e conceituais que devem compor as aulas de natação de crianças para aumentar a segurança aquática. A metodologia foi de revisão bibliográfica com a base nas publicações de artigos disponíveis, nos últimos 10 anos, na base de dados Pub Med, com as palavras chaves: natação e afogamento. Os resultados mostraram que o conteúdo procedimental, que devem compor as aulas de natação de crianças para aumentar a segurança aquática, devem fazer com que o aluno aprenda a saber fazer, executar ações na água relacionadas ao desenvolvimento da aquacidade. Já os conteúdos conceituais devem fazer com que o aluno aprenda a saber sobre fatos, conceitos, símbolos, imagens, princípios materiais, e por fim os conteúdos atitudinais, o aluno aprenda a saber respeitar, conviver com normas, posturas, valores e atitudes. Pode-se concluir que o ensino da natação com os três conteúdos interligados (procedimental, conceitual e atitudinal) é mais uma ferramenta para ajudar a prevenir o afogamento. Os alunos precisam saber realizar a técnica procedimental para utilizar os braços e pernas com eficiência para sustentação e deslocamento, flutuar na vertical e horizontal, mudar de decúbito, conseguir se deslocar por alguns segundos em busca de local seguro, além disso, é importante também fornecer conteúdos para que ele possa adquirir conhecimento conceituais e desenvolver atitudes corretas, sobre os riscos de afogamento, aprender a ter controle emocional e discernimento em situações de perigo.

The various analyses guided by the concept of development as a utopian horizon and how to achieve it inform an ideology of development in that they tend to dehistoricize “development” and thus present as natural its relations of domination and exploitation through a system of ideas that treats particular historical processes as if they could be universalized and particular political projects as if they were universal. This perception leads to hypotheses about this ideology of development focusing on its contemporary presence, its origins, its roots, its unfolding, its hegemony, its tendency toward economicism, and possible ways of moving beyond it. A focus on its contemporary presence contributes to the current critique of it in connection with the construction of a socialist strategy in Our America. As variadas análises orientadas pelo horizonte utópico do desenvolvimento e pautadas pela questão motora de “como se desenvolver” informam a ideologia do desenvolvimento, na medida em que tendem a desistoricizar o “desenvolvimento” e, desta forma, naturalizam as relações de dominação e exploração vigentes através de um sistema de ideias que apresenta determinados processos históricos particulares como passíveis de universalização e determinados projetos políticos particulares como sendo universais. Esta percepção traz consigo sete hipóteses sobre a ideologia do desenvolvimento, tratando de sua presença atual, origem, enraizamento, desdobramentos, hegemonia, tendência ao economicismo e, finalmente, possíveis formas de sua superação. O foco aqui se concentra na primeira hipótese, tendo em vista a relevância política atual da crítica à ideologia do desenvolvimento na construção de uma estratégia socialista em Nuestra América.

The endocannabinoid system plays a key role in the intersection of the nervous, endocrine, and immune systems, regulating not only their functions but also how they interplay with each other. Endogenous ligands, named endocannabinoids, are produced “on demand” to finely regulate the synthesis and secretion of hormones and neurotransmitters, as well as to regulate the production of cytokines and other proinflammatory mediators. It is well known that immune challenges, such as exposure to lipopolysaccharide, the main component of the Gram-negative bacteria cell wall, disrupt not only the hypothalamic–pituitary–adrenal axis but also affects other endocrine systems such as the hypothalamic–pituitary–gonadal axis and the release of oxytocin from the neurohypophysis. Here we explore which actors and molecular mechanisms are involved in these processes.

This book presents an original proposal through a social history of ideas on Latin American economic development: although its structure addresses the life trajectory of each of the main representatives of the first generation of development theorists in the region, in itineraries that unfold from the first decades of the 20th century to the present, it shows an intellectual and ideological plot that goes beyond the individual paths and ties them to a historical moment in the evolution of ideas and to a certain context of social, cultural and material conditions in which they were developed. We consider that (economic) ideas are discernible structures of meaning, perspective and fidelity to a purpose and, like institutions, have their own relationships, tensions and continuities. It evolves independently in a dialogue and in a cultural fabric that each intellectual has with other thinkers who preceded and accompany him in a specific historical moment. This snippet of reality -the reality of ideas- contains explanatory force in its relative autonomy. Without ideas, without thought, without mentalities, there is no possibility of entering the field of social history. Therefore, on a general level, the book's proposal converges, in research practice and historiographic theorizing, economic and social history with the history of ideas. In this way, each chapter illuminates fundamental aspects of the biographical trajectory of ten great intellectuals of 20th century Latin American economic thought: Raúl Prebisch, Aníbal Pinto, Víctor Urquidi, Celso Furtado, Juan Noyola Vázquez, Horacio Flores de la Peña, Helio Jaguaribe, Aldo Ferrer, Osvaldo Sunkel and María Maria Maria da Conceição Tavares. The collection enables an approach to the analysis of the economic and social potentialities and limitations of the countries in the region, as well as the public policies implemented and the debates that arose regarding the possibilities of accelerating their economic development. It also provides an important part of the history of ECLAC (Economic Commission for Latin America and the Caribbean), the UN agency to which most of them were linked. The intellectuals discussed here have been chosen for the relevance and transcendence of their original contributions to the analysis of the problems of Latin American development, respecting a sufficiently wide range of national origins so as to cover different traditions and experiences. The studies are arranged chronologically according to the date of birth of each thinker, as this gives a first idea of the historical place of their actions and theoretical formulation. In sum, this book constitutes an important step from the perspective of the history of ideas by allowing us to identify a clear "epistemic community"; that is, the functioning of a network of actors with experience and competence in a particular professional domain from which we can distinguish an organizing problem-area, Latin American development.

Se tenía como fin determinar el impacto en las importaciones y exportaciones de Risaralda con la implementación del TLC entre Colombia y EE. UU el cual entró en vigencia en el año 2012.Mediante recopilación de información estadística entre los periodos de 2010 a 2019, aunque existen diferentes referencias que afirman un panorama positivo para el país, no es claro si es así o por lo contrario es negativo.Conforme a las gráficas, la región presenta un superávit frente a Estados Unidos durante estos periodos. Sin embargo, en los últimos 4 años la región ha tenido una caída en comercio por la desaceleración de la economía global. Finalmente, todo parece indicar que el TLC no trajo consigo muy buenos resultados para el departamento a pesar de que exporta más de lo que importa, la tendencia de esto es a la baja lo cual indicaría preocupantes resultados para el departamento.

Resumen Objetivo: describir la percepción de calidad de vida de las personas que han sufrido amputación por un accidente laboral. Metodología: investigación cualitativa con la aplicación de entrevista semiestructurada de 10 preguntas abiertas a seis trabajadores que sufrieron un accidente laboral que terminó en amputación. La información fue recolectada, analizada y clasificada de forma manual en categorías emergentes. Resultados: los participantes son de sexo masculino, de 34 y 52 años de edad, su domicilio son los municipios del eje cafetero y norte del valle, el estado civil es 5 casados y 1 separado, el nivel educativo 2 en primaria, 3 con secundaria y 1 técnico profesional. Todos afiliados al sistema de salud. Los segmentos corporales amputados son: 3 amputados del Miembro Superior, los otros tres amputados del Miembro Inferior. Conclusiones: su calidad de vida según las capacidades funcionales humanas centrales definidas por Nussbaum reflejan que posterior al siniestro fue afectada en la pérdida seguridad y confianza en sí mismos, impidiendo las actividades de tipo social. Su condición actual los limita en mejorar sus ingresos por su condición de discapacidad. El dolor crónico y la desadaptación protésica son comunes. Al igual que el uso de aditamentos y las dificultades en el traslado. Es evidente el fortalecimiento de la red de apoyo familiar primaria, sin embargo, al finalizar su rehabilitación hay desinterés en actividades sociales. Los participantes tienen proyectos a futuro concretos que involucran su familia. Finalmente, su proceso de rehabilitación se limitó a lo básico y no contaron con otro tipo de apoyo. Abstract Objective: to describe the perception of quality of life of people who have suffered amputation due to a work accident. Methodology: qualitative research with the application of a 10 open questions semi-structured interview to six workers who had suffered an occupational accident that ended in amputation. The information was collected, analyzed and classified manually in emerging categories. Results: the participants are 34 and 52 years old males from the municipalities of the coffee triangle area and north of the Department of Valle del Cauca. Their marital status is 5 married and 1 separated, their educational level is 2 primary school, 3 secondary school and 1 professional technician. All of them are affiliated to the health system. The body segments amputated are: 3 upper limb amputees and 3 lower limb amputees. Conclusions: their quality of life, according to the central human functional capacities defined by Nussbaum, reflects that after the accident they were affected by the loss of security and self-confidence, preventing social activities. Their current condition limits them from improving their income due to their disabling condition. Chronic pain and prosthetic maladjustment are common, as well as the use of accessories and the difficulties to move. The strengthening of the primary family support network is evident but, at the end of their rehabilitation, there is a lack of interest in social activities. Participants have concrete future projects that involve their family. Finally, their rehabilitation process was limited to the basics and they did not have any other type of support. Resumo Objetivo: descrever a percepção da qualidade de vida das pessoas que têm sofrido amputação por um acidente laboral. Metodologia: pesquisa qualitativo com a aplicação de entrevista semiestruturadas de 10 perguntas abertas a seis trabalhadores que sofreram um acidente laboral (trabalho) que acabou em amputação. A informação foi coletada, analisada e classificada de forma manual em categorias emergentes. Resultados: os participantes são de sexo masculino, de 34 e 52 anos de idade, seu domicílio são os municípios do eixo Cafeeiro e norte do departamento do Valle (Colômbia), o estado civil é 5 casados e 1 separado, o nível educativo 2 no ensino primário, 3 com ensino médio e 1 técnico profissional. Todos cadastrados no sistema de saúde. Os segmentos corpóreos amputados são: 3 amputados do Membro Superior, os outros três amputados do Membro Inferior. Conclusões: De acordo com a lista das capacidades humanas de Nussbaum evidencia-se que, após do sinistro, a qualidade de vida das pessoas amputadas foi afetada na perda de segurança e de confiança dos indivíduos em si mesmos, o qual os impede de realizarem atividades de tipo social. Sua condição atual de deficiência limita sua capacidade de melhorar seus ingressos, sendo a dor crónica e a desadaptação protésica fatores comuns, junto com o uso de aditamentos e as dificuldades na locomoção. É evidente o fortalecimento da rede de apoio familiar primária; entretanto, ao finalizar sua reabilitação há desinteresse em atividades sociais. Os participantes têm projetos concretos envolvendo sua família. Finalmente, seu processo de reabilitação se limitou a uma atenção básica e não contaram com outro tipo de apoio.

A vitamina D é um hormônio esteróide lipossolúvel que exerce inúmero funções no organismo. A elevada prevalência de níveis inadequados de vitamina D é hoje em dia encarado como um problema de saúde pública que afeta vários países, não somente os países europeus como os países da América do Sul. Por este motivo e pelo conhecimento do crescente número de doenças associadas a esta deficiência, a medição exata dos níveis de vitamina D tem assumido elevada relevância na clínica. Desta forma, o número de análises para avaliação da quantidade de vitamina D para fins diagnósticos aumentou significativamente. O presente trabalho contou com o objetivo principal de buscar na literatura disponível artigos e trabalhos publicados sobre a vitamina D, através de uma revisão narrativa nos bancos de dados PubMed, Scielo e ScienceDirect nos idiomas inglês e português. Conclui-se que a vitamina D tem um importante papel nutricional e regulador do sistema imunológico. Outros estudos devem ser realizados para determinar os riscos e benefícios da reposição de vitamina D.

Shiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) produces hemorrhagic colitis, hemolytic uremic syndrome (HUS), and acute encephalopathy. The mortality rate in HUS increases significantly when the central nervous system (CNS) is involved. Besides, EHEC also releases lipopolysaccharide (LPS). Many reports have described cognitive dysfunctions in HUS patients, the hippocampus being one of the brain areas targeted by EHEC infection. In this context, a translational murine model of encephalopathy was employed to establish the deleterious effects of Stx2 and the contribution of LPS in the hippocampus. The purpose of this work is to elucidate the signaling pathways that may activate the inflammatory processes triggered by Stx2, which produces cognitive alterations at the level of the hippocampus. Results demonstrate that Stx2 produced depression-like behavior, pro-inflammatory cytokine release, and NF-kB activation independent of the ERK1/2 signaling pathway, while co-administration of Stx2 and LPS reduced memory index. On the other hand, LPS activated NF-kB dependent on ERK1/2 signaling pathway. Cotreatment of Stx2 with LPS aggravated the pathologic state, while dexamethasone treatment succeeded in preventing behavioral alterations. Our present work suggests that the use of drugs such as corticosteroids or NF-kB signaling inhibitors may serve as neuroprotectors from EHEC infection.

A la memoria de María Helena Henao. Caruquia

Hacer un recorrido por las influencias que recibió la obra de Georg Lukács de los dramaturgos Ibsen, Strindberg y Shakespeare. Ver que los inicios de su rechazo hacia la burguesía, los primeros conatos de aspectos revolucionarios y la posterior inclinación hacia la estética vienen marcados desde esta temprana influencia que ejercieron sobre él los dramaturgos antes nombrados. Destacar de manera clara los giros dados por Lukács a lo largo de su vida intelectual. La cual desde luego estuvo marcada por la influencia en las respectivas épocas por autores diferentes. hacer énfasis en los aspectos más destacados de la influencia recibida: la teoría del reflejo, la periodicidad, el dinero, la singularidad privada, la soledad, la relación del público con el drama etc.

Jurisdiction specialization is a topic of interest in the administration the justice system. Pros and cons have been vastly discussed, but few papers discuss the pratical details connected to the application of this policy. In this study, we discuss the creation of business courts in the County of São Paulo Brazil, and introduce innovating data analysis methodologies for solving pratical problems. In São Paulo, new courts, specialized or not, must follow two main criteria. New courts must have a minimum number of lawsuits per year and must have some estimate of the future worka load. In the performed analyses, we found evidence that a business lawsuit requires almost twice the amount of effort of a common lawsuit. By correcting the volume of lawsuits, based on a matter-treatment model, we arrived at the conclusion that two business courts can handle the existing demand adequately. Also, we were able to develop a robust methodology to verify if and how business courts should be created.

espanolLa relacion que existe entre Lukacs y Vattimo esta determinada por la manera diferente en que se enfrentan a los postulados del materialismo, tanto historico como dialectico. La radicalidad del filosofo hungaro es suavizada por el filosofo italiano. Los presupuestos de absolutismo que tienen los juicios esteticos y eticos lukacsianos son tomados de una manera menos radical por Gianni Vattimo. En este articulo haremos un recorrido a traves de este tipo de interacciones. Veremos que los momentos historicos a los que se enfrentaron son totalmente distintos, por lo que los resultados y las posteriores maneras de aplicacion son tambien diferentes. EnglishThe relationship between Lukacs and Vattimo is determined by the different way in which they confront the postulatesof materialism, both historical and dialectical. The radicality of the Hungarian philosopher is softened by the Italian philosopher. The presuppositions of absolutism that Lukacs's aesthetic and ethical judgments have are taken in a far less radical way by Gianni Vattimo. In this article we will guide you through the type of interactions encountered. We will see that the historical moments with which they faced were totally different, so that the results and subsequent ways of application were also different.

El presente documento enuncia la Estrategia de Seguridad Aérea y Espacial Nacional que reviste una alta importancia en la seguridad del espacio aéreo y ultraterrestre de la nación, y cuyos conceptos se encuentran ampliamente descritos y desarrollados en el presente documento, con base a la referencia propuesta en la Estrategia Multdimensional de Seguridad Nacional (2018- 2028). En esta dirección, se proponen unos objetivos y líneas de acción que por supuesto buscan dar cumplimiento a los fnes establecidos en la presente estrategia. La Estrategia de Seguridad Aérea y Espacial Nacional que se plantea, se encuentra organizada en cinco capítulos. El primero de ellos titulado “Antecedentes”, se describen los antecedentes normativos e históricos de la seguridad aeroespacial que tenen como elemento común la evolución conforme se iba desarrollando las guerras, ya que el actuar militar generaba interés y alternatvas para enriquecer y robustecer todas las herramientas espaciales. De esta manera se muestra cómo nació la preocupación por la regulación de esta modalidad de estrategia militar y como el Derecho Internacional pone su mirada en este ámbito dirigiendo la ruta normativa mediante la cual los Estados establecieran sus facultades sobre el espacio aéreo con un conjunto de límites y libertades en ejercicio de su soberanía.

La intención de este libro es recoger los contenidos, los procesos y los emprendimientos de la innovación social. Cierto es que una revisión de los discursos y las representaciones sobre innovación, y particularmente sobre la innovación social, deja una sensación de confusión en las formas y las estrategias para acotar el objeto. Tal vez cueste admitirlo, pero esa sí que es una característica transversal en los tiempos actuales: el hecho de que los procesos, los objetos, los métodos y los enfoques tienden a rechazar las definiciones, las delimitaciones y las acotaciones definitivas. Sin embargo, un mínimo de bases se requiere para que podamos hablar de cualquier tema. Las diversas experiencias, procedencias y enmarcaciones conceptuales (que no teóricas) respecto a la innovación invitan a avanzar en sus páginas con una visión abierta, flexible y que busque, no tanto teorías definitivas, sino fuerzas de interacción que tienden a esa acotación, delimitación y definición que mencionamos anteriormente como retos del trabajo de investigación actual en el ámbito de lo social.

The production of pro-inflammatory cytokines during inflammatory processes has been associated with preterm birth (PTB) and fetal injury in humans and mice. We previously demonstrated that exposition to an enriched environment (EE), defined as a noninvasive and biological significant stimulus of the sensory pathway combined with voluntary physical activity, prevented PTB and perinatal death induced by the systemic administration of bacterial lipopolysaccharide (LPS) in mice. This work aimed to analyze whether EE modulates the immune response to the inflammatory process induced by LPS in peripheral blood and the amniotic fluid (AF). We observed that EE modulated maternal white blood cell count and its response to LPS. Furthermore, we found higher levels of IL-10 and a higher percentage of B cells in AF from EE exposed mothers compared to controls. Albeit LPS significantly increased IL-6 levels in AF from both groups, it was 3.6 times higher in control environment (CE) exposed group when compared to EE. Similarly, levels of IL-22 were significantly increased by LPS in both groups, but it was 6.7 times higher in EE group. Interestingly, levels of PGE2 in AF were only increased in the EE-LPS treated group, and a positive correlation between IL-22 and PGE2 levels was observed. During lactation, EE prevented LPS-induced delay in physical landmarks analyzed to assess offspring development. Our results suggest that EE modulates the immune response to systemic LPS-administration protecting the offspring. We propose that an EE-like protocol could be designed for pregnant women aiming at preventing the sequelae present in premature children.

Prenatal exposure to glucocorticoids (GC) is a central topic of interest in medicine since GCs are essential for the maturation of fetal organs and intrauterine growth. Synthetic glucocorticoids, which are used in obstetric practice, exert beneficial effects on the fetus, but have also been reported to lead to intrauterine growth retardation (IUGR). In this study, a model of growth restriction in mice was established through maternal administration of dexamethasone during late gestation. We hypothesised that GC overexposure may adversely affect placental angiogenesis and fetal and placental growth. Female BALB/c mice were randomly assigned to control or dexamethasone treatment, either left to give birth or euthanised on days 15, 16, 17 and 18 of gestation followed by collection of maternal and fetal tissue. The IUGR rate increased to 100% in the dexamethasone group (8 mg/kg body weight on gestational days 14 and 15) and pups had clinical features of symmetrical IUGR at birth. Dexamethasone administration significantly decreased maternal body weight gain and serum corticosterone levels. Moreover, prenatal dexamethasone treatment not only induced fetal growth retardation but also decreased placental weight. In IUGR placentas, VEGFA protein levels and mRNA expression of VEGF receptors were reduced and NOS activity was lower. Maternal dexamethasone administration also reduced placental expression of the GC receptor, αGR. We demonstrated that maternal dexamethasone administration causes fetal and placental growth restriction. Furthermore, we propose that the growth retardation induced by prenatal GC overexposure may be caused, at least partially, by an altered placental angiogenic profile.

Maternal overnutrition negatively impacts the offspring's health leading to an increased risk of developing chronic diseases or metabolic syndrome in adulthood. What we eat affects the endocannabinoid system (eCS) activity, which in turn modulates lipogenesis and fatty acids utilization in hepatic, muscle, and adipose tissues. This study aimed to evaluate the transgenerational effect of maternal obesity on cannabinoid receptor 1 knock-out (CB1 KO) animals in combination with a postnatal obesogenic diet on the development of metabolic disturbances on their offspring. CB1 KO mice were fed a control diet (CD) or a high-fat diet (HFD; 33% more energy from fat) for 3 months. Offspring born to control and obese mothers were also fed with CD or HFD. We observed that pups born to an HFD-fed mother presented higher postnatal weight, lower hepatic fatty acid amide hydrolase activity, and increased blood cholesterol levels when compared to the offspring born to CD-fed mothers. When female mice born to HFD-fed CB1 KO mothers were exposed to an HFD, they gained more weight, presented elevated blood cholesterol levels, and more abdominal adipose tissue accumulation than control-fed adult offspring. The eCS is involved in several reproductive physiological processes. Interestingly, we showed that CB1 KO mice in gestational day 15 presented resistance to LPS-induced deleterious effects on pregnancy outcome, which was overcome when these mice were obese. Our results suggest that an HFD in CB1 receptor-deficient mice contributes to a "nutritional programming" of the offspring resulting in increased susceptibility to metabolic challenges both perinatally and during adulthood.

PURPOSE Trastuzumab has shown an overall survival (OS) benefit in patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC), in both the adjuvant and the metastatic setting. We assessed the effectiveness of trastuzumab in patients treated in daily practice according to national treatment coverage protocols and compared our results with those reported by randomized clinical trials. These coverage protocols included patient selection criteria similar to those of those clinical trials and were developed by the Uruguayan National Resource Fund (FNR), the agency that has funded these prescriptions for more than a decade. PATIENTS AND METHODS We included all patients with HER2-positive BC treated with trastuzumab under FNR coverage approved between January 1, 2006, and December 31, 2016. The source of data was the FNR database, and primary outcome was OS, analyzed through Cox proportional hazards regression analysis. RESULTS A total of 1,944 women were included: 1,085 women (55.8%) were postmenopausal and 1,240 (63.7%) had HER2 and hormone receptor–positive BC. Trastuzumab was administered as adjuvant therapy to 1,233 patients (63.5%), of whom 154 also received it as a neoadjuvant treatment. Three hundred nineteen patients (16.4%) received trastuzumab for advanced disease. Five-year OS in the adjuvant setting was 86.4% (95% CI, 84.0% to 88.7%). The median survival of patients with advanced BC was 25.1 months (95% CI, 10.1 to 42.5 months). CONCLUSION Our survival results are not inferior to those reported in clinical trials, in both adjuvant and advanced settings. Importantly, these results support the relevance and the feasibility of treating patients in routine practice, following coverage protocols based on patient selection criteria and methods supported by positive clinical trials. In addition, these results favor quality and appropriate access to BC treatment in our country.

This study aims at comparing the pathological complete response rate of women submitted to neoadjuvant chemotherapy for breast cancer in the world with the community from Hospital do Câncer do Mato Grosso, to verify which histological subtypes have higher chances of reaching the pathological complete response. Therefore, we will analyze the medical records of the patients who underwent neoadjuvant chemotherapy followed by surgery. Besides the initial clinical staging from I to III between 2014 to 209. The criteria in RECIST 1.1 were used (Response Evaluation Criteria in Solid Tumors) to define pathological complete response for the breast and the axilla. We concluded that the benefit of neoadjuvant chemotherapy is mostly seen in patients with negative hormone receptors and positive HER2, and they have higher chances of reaching pathological complete response. In the triple negative subtype, neoadjuvant chemotherapy with the objective of reaching pCR is, until this moment, the best strategy for higher survival rates in these patients, according to data from the global literature.

Mucosal ulcerations are an oral complication that can often affect kidney transplant patients, mostly due to the effect of immunosuppression. It has been frequently reported drug-induced ulceration or lymphoproliferative disorders with buccal manifestations however, some unusual disorders should also be considered, such as fungal infections, viruses, as well as opportunistic infection by other microorganisms. Determining the etiology and differential diagnose from other causes of mouth ulcers is very important for the adequate treatment of said lesion. Dental health of patients should also be taken into the account prior to the transplant surgery, since periodontal pockets are the main niche of microbial reservoir. Moreover, mixed with oral microbiota, parasites such as Trichomonas spp. can be found in the dental plaque of patients with periodontal disease. Particularly, Trichomonas spp. are anaerobic motile-flagellated protozoa that can both induce tissue damage and exacerbate preexistent injuries in vaginal and oral mucosa. Parasitic infection in the oral cavity has not been well studied and it is thought to be underreported. In the present study we report the first case in literature of presence of Trichomonas spp. as a potential etiological factor of the oral ulcerations of a kidney transplanted patient that remitted after antibiotic treatment. Fil: Dmytrenko, Ganna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Tana, Lorena. Instituto de Transplante de Alta Complejidad; Argentina Fil: Cachau, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Bravo, Martín. Instituto Argentino de Transplante de Alta Complejidad; Argentina Fil: Gonzalez, Silvina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Correa, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Fernández Solari, José Javier. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: de Laurentiis, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina

El presente trabajo tiene como propósito, analizar los criterios del operador jurídico para la valoración de la responsabilidad empleador por los daños causados al empleado en Colombia. En la realización de este estudio, se empleó un análisis jurisprudencial y doctrinal sobre la responsabilidad subjetiva y objetiva del empleador ante lesiones laborales que traen consigo, la pérdida de la capacidad laboral o incluso, la muerte del trabajador. El estudio se enmarcó dentro del paradigma cualitativo con una fase de tipo descriptiva-documental; a su vez, presenta un diseño bibliográfico para el cual se utilizó como técnica de la recolección de información, la observación documental.

espanolHacer un recorrido por las diferentes recepciones del concepto de la religion de Hegel, especialmente el estudio llevado a cabo por Manuel Valls, las diversas criticas realizadas por: Lukacs, Garaudy, Marx entre otros. En primer lugar, se vera en detalle cuales fueron los presupuestos que llevaron a Hegel a subordinar la filosofia a la religion; en segundo lugar, se trataran de encontrar los vinculos entre la religion y la politica; por ultimo, tambien es importante hacer un breve comentario sobre la disputa que se origino entre los hegelianos de derecha, o sea, los viejos hegelianos y los hegelianos de izquierda. EnglishTake a tour on the different aspects surrounding the figure and the philosophy of Hegel’s concept of religion, especially the study carried out by Manuel Valls, the various criticisms made by: Lukacs, Garaudy, Marx among others. In the first place, it’ll be seen in detail which where the Budget that carried Hegel to subordinate the philosophy to the religion; at second place, it’ll be treated to find the connection between religion and politics; and in the last place, it’s important to make a short commentary about what was originated between right wing hegelians, I mean, the old hegelians and the left wing hegelians.

En las últimas décadas, y particularmente en los años transcurridos de la actual, los avances tecnológicosalcanzados en los campos de la informática y las comunicaciones, han despertado un entusiasmo inusitadoy un afán por obtener provecho de aquellos, en todos los sectores del quehacer humano.Poner en duda la utilidad de la tecnología informática en su estado actual, sería un absurdo, como lo sería también desconocer su capacidad de transformación de la realidad social, económica y cultural. En cuanto al primer aspecto, no es posible negar que hoy día, gracias a esta tecnología, existen grandes facilidades para la realización de lo que en otro tiempo (en un pasado bastante cercano), representaban dispendiosas tareas, o simplemente pertenecían al mundo de la ficción. En cuanto al segundo aspecto, el de su capacidad de transformación, es claro que su aplicación ha inundado todo el entorno más inmediato de las personas provocandocambios en sus costumbres y tradiciones, sus prioridades y formas de realizar diferentes actividades, "desplazando el concepto de realidad".

STUDY QUESTION: What is the role of the endocannabinoid system (eCS) on the lipopolysaccharide (LPS) effects on uterine explants from 7-day pregnant mice in a murine model of endotoxin-induced miscarriage? SUMMARY ANSWER: We found evidence for cannabinoid receptor type2 (CB2) involvement in LPS-induced increased prostaglandin-F2α (PGF2α) synthesis and diminished cyclic adenosine monophosphate (cAMP) intracellular content in uterine explants from early pregnant mice. WHAT IS KNOWN ALREADY: Genital tract infections by Gram-negative bacteria are a common complication of human pregnancy that results in an increased risk of pregnancy loss. LPS, the main component of the Gram-negative bacterial wall, elicits a strong maternal inflammatory response that results in embryotoxicity and embryo resorption in a murine model endotoxin-induced early pregnancy loss. We have previously shown that the eCS mediates the embryotoxic effects of LPS, mainly via CB1 receptor activation. STUDY DESIGN, SIZE, DURATION: An in vitro study of mice uterine explants was performed to investigate the eCS in mediating the effects of LPS on PGF2α production and cAMP intracellular content. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eight to 12-week-old virgin female BALB/c or CD1 (wild-type [WT] or CB1-knockout [CB1-KO]) mice were paired with 8- to 12-week-old BALB/c or CD1 (WT or CB1-KO) males, respectively. On day 7 of pregnancy, BALB/c, CD1 WT or CD1 CB1-KO mice were euthanized, the uteri were excised, implantation sites were removed and the uterine tissues were separated from decidual and embryo tissues. Uterine explants were cultured and exposed for an appropriate amount of time to different pharmacological treatments. The tissues were then collected for cAMP assay and PGF2α content determination by radioimmunoassay. MAIN RESULTS AND THE ROLE OF CHANCE: In vitro treatment of uteri explants from 7-day pregnant BALB/c or CD1 (WT or CB1-KO) mice with LPS induced an increased production of PGF2α (P < 0.05) and a reduction of the tissue content of cAMP (P < 0.05). These effects were mediated by CB2 receptors since exposure to AM630 (a specific CB2 receptor antagonist) prevented these LPS-induced effects (P < 0.05). Collectively, our results suggest a role for the eCS mediating LPS-induced deleterious effects on reproductive tissues. LIMITATIONS, REASONS FOR CAUTION: Since our experimental design involves in vitro experiments of uterine explants, the extrapolation of the results presented here to humans is limited. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide evidence for the role of CB2 receptors in reproductive events as well as their participation as a mediator of LPS deleterious effects on reproductive tissues. LARGE SCALE DATA: None. STUDY FUNDING AND COMPETING INTEREST(S): Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2010/0813 and PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Carlos Davio was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/2050). The authors have no competing interests. Fil: Salazar, Ana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Carozzo, Alejandro Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Correa, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Franchi, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina

Background:Stimulation of serotonergic neurons within the dorsal raphe dorsomedial subnucleus facilitates inhibitory avoidance acquisition in the elevated T-maze. It has been hypothesized that such anxiogenic effect is due to serotonin release in the basolateral nucleus of the amygdala, where facilitation of serotonin 2C receptor-mediated neurotransmission increases anxiety. Besides the dorsal raphe dorsomedial subnucleus, the dorsal raphe caudal subnucleus is recruited by anxiogenic stimulus/situations. However, the behavioral consequences of pharmacological manipulation of this subnucleus are still unknown.Aims:Investigate whether blockade of serotonin 2C receptors in the basolateral nucleus of the amygdala counteracts the anxiogenic effect caused by the stimulation of dorsal raphe dorsomedial subnucleus serotonergic neurons. Evaluate the effects caused by the excitatory amino acid kainic acid or serotonin 1A receptor-modulating drugs in the dorsal raphe caudal subnucleus.Methods:Male Wistar rats were tested in the elevated T-maze and light-dark transition tests after intra-basolateral nucleus of the amygdala injection of the serotonin 2C receptor antagonist SB-242084 (6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride) followed by intra-dorsal raphe dorsomedial subnucleus administration of the serotonin 1A receptor antagonist WAY-100635 (N-[2-[4-2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinil-cyclohexanecarboxamide maleate). In the dorsal raphe caudal subnucleus, animals were injected with kainic acid, WAY-100635 or the serotonin 1A receptor agonist 8-OH-DPAT ((±)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide) and tested in the elevated T-maze.Results:SB-242084 in the basolateral nucleus of the amygdala blocked the anxiogenic effect caused by the injection of WAY-100635 in the dorsal raphe dorsomedial subnucleus. Kainic acid in the dorsal raphe caudal subnucleus increased anxiety, but also impaired escape expression in the elevated T-maze. Neither WAY-100635 nor 8-OH-DPAT in the dorsal raphe caudal subnucleus affected rat’s behavior in the elevated T-maze.Conclusion:Serotonin 2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect caused by the stimulation of serotonergic neurons in the dorsal raphe dorsomedial subnucleus. The dorsal raphe caudal subnucleus regulates anxiety- and panic-like behaviors, presumably by a serotonin 1A receptor-independent mechanism.

Summary Information transmission in biological signaling networks is commonly considered to be a unidirectional flow of information between protein partners. According to this view, many bacterial response regulator proteins utilize input receiver (REC) domains to "switch" functional outputs, using REC phosphorylation to shift pre-existing equilibria between inactive and active conformations. However, recent data indicate that output domains themselves also shift such equilibria, implying a "mutual inhibition" model. Here we use solution nuclear magnetic resonance to provide a mechanistic basis for such control in a PhyR-type response regulator. Our structure of the isolated, non-phosphorylated REC domain surprisingly reveals a fully active conformation, letting us identify structural and dynamic changes imparted by the output domain to inactivate the full-length protein. Additional data reveal transient structural changes within the full-length protein, facilitating activation. Our data provide a basis for understanding the changes that REC and output domains undergo to set a default "inactive" state.

Straighthead is a physiological disorder in rice that causes yield losses and is a serious threat to rice production worldwide. Identification of QTL conferring resistance will help develop resistant cultivars for straighthead control. We conducted linkage mapping to identify QTL involved with straighthead. The study was based on a F2 population developed from a cross between ‘Zhe733(resistant)/R312(susceptible)’. Using phenotypic data of F2 plants and their F2:3 families, two major QTL, qSTH-2 and qSTH-8, were identified using bulked segregant analysis, explaining 11.1 and 28.1 % of the phenotypic variation on chromosome 2 and 8, respectively. The qSTH-2 for straighthead resistance was identified by linkage mapping. qSTH-2 was situated near a QTL “AsS” responsible for arsenic accumulation. Straighthead is frequently observed on land where As has accumulated. The result suggests a kind of internal connection between qSTH-2 and AsS. Additionally, the QTL qSTH-8 was located close to HD5 related with heading date. The close location may be associated with the observation of early heading among straighthead resistant varieties. These findings should be useful for further genetic study of straighthead.

We analyze the main factors influencing the attractiveness of public-private partnerships (PPP) applied to Brazil. Considering the Brazilian regulatory framework, the risks involved in a railroad PPP in Brazil are quantified and the attractiveness of this investment is evaluated through Monte Carlo simulations. Results suggest that Capex and regulatory risks are the main obstacles to PPP projects in Brazil. In addition, measures have been proposed to be implemented by the government to improve the return of these enterprises. New attractiveness analyses confirm a reduction in venture risk with the proposed measures.

Maternal obesity has been shown to impact the offspring health during childhood and adult life. This study aimed to evaluate whether maternal obesity combined with postnatal exposure to an obesogenic diet could induce metabolic alterations in offspring. Female CD1 mice were fed a control diet (CD, 11.1% of energy from fat) or with a high-fat diet (HFD, 44.3% of energy from fat) for 3 months. After weaning, pups born from control and obese mothers were fed with CD or HFD for 3 months. Both mothers and offspring were weighted weekly and several blood metabolic parameters levels were evaluated. Here, we present evidence that the offspring from mothers exposed to a HFD showed increased acetylation levels of histone 3 on lysine 9 (H3K9) in the liver at postnatal Day 1, whereas the levels of acetylation of H4K16, dimethylation of H3K27, and trimethylation of H3K9 showed no change. We also observed a higher perinatal weight and increased blood cholesterol levels when compared to the offspring on postnatal Day 1 born from CD-fed mothers. When mice born from obese mothers were fed with HFD, we observed that they gained more weight, presented higher blood cholesterol levels, and abdominal adipose tissue than mice born to the same mothers but fed with CD. Collectively, our results point toward maternal obesity and HFD consumption as a risk factor for epigenetic changes in the liver of the offspring, higher perinatal weight, increased weight gain, and altered blood cholesterol levels.

To survive and adapt to environmental changes, bacteria commonly use two-component signaling systems. Minimally, these pathways use histidine kinases (HKs) to detect environmental signals, harnessing these to control phosphorylation levels of receiver (REC) domains of downstream response regulators that convert this signal into physiological responses. Studies of several prototypical REC domains suggest that phosphorylation shifts these proteins between inactive and active structures that are globally similar and well-folded. However, it is unclear how globally these findings hold within REC domains in general, particularly when they are considered within full-length proteins. Here, we present EL_LovR, a full-length REC-only protein that is phosphorylated in response to blue light in the marine α-proteobacterium, Erythrobacter litoralis HTCC2594. Notably, EL_LovR is similar to comparable REC-only proteins used in bacterial general stress responses, where genetic evidence suggests that their potent phosphatase activity is important to shut off such systems. Size exclusion chromatography, light scattering, and solution NMR experiments show that EL_LovR is monomeric and unfolded in solution under conditions routinely used for other REC structure determinations. Addition of Mg(2+) and phosphorylation induce progressively greater degrees of tertiary structure stabilization, with the solution structure of the fully activated EL_LovR adopting the canonical receiver domain fold. Parallel functional assays show that EL_LovR has a fast dephosphorylation rate, consistent with its proposed function as a phosphate sink that depletes the HK phosphoryl group, promoting the phosphatase activity of this enzyme. Our findings demonstrate that EL_LovR undergoes substantial ligand-dependent conformational changes that have not been reported for other RRs, expanding the scope of conformational changes and regulation used by REC domains, critical components of bacterial signaling systems.

The burgeoning demand for rice in Latin America and Caribbean (LAC) exceeds supply, resulting in a rice deficit. To overcome this challenge, rice production should be increased, albeit sustainably. However, since rice production is associated with increases in the atmospheric concentration of two greenhouse gases (GHGs), namely methane (CH4) and nitrous oxide (N2O), the challenge is on ensuring that production increases are not associated with an increase in GHG emissions and thus do not cause an increase in GHG emission intensities. Based on current understanding of drivers of CH4 and N2O production, we provide here insights on the potential climate change mitigation benefits of management and technological options (i.e., seeding, tillage, irrigation, residue management) pursued in the LAC region. Studies conducted in the LAC region show intermittent irrigation or alternate wetting and drying of rice fields to reduce CH4 emissions by 25–70% without increasing N2O emissions. Results on yield changes associated with intermittent irrigation remain inconclusive. Compared to conventional tillage, no-tillage and anticipated tillage (i.e., fall tillage) cause a 21% and 25% reduction in CH4 emissions, respectively. From existing literature, it was unambiguous that the mitigation potential of most management strategies pursued in the LAC region need to be quantified while acknowledging country-specific conditions. While breeding high yielding and low emitting rice varieties may represent the most promising and possibly sustainable approach for achieving GHG emission reductions without demanding major changes in on-farm management practices, this is rather idealistic. We contend that a more realistic approach for realizing low GHG emitting rice production systems is to focus on increasing rice yields, for obvious food security reasons, which, while not reducing absolute emissions, should translate to a reduction in GHG emission intensities. Moreover, there is need to explore creative ways of incentivizing the adoption of promising combinations of management and technological options EEA Corrientes Fil: Chirinda, Ngonidzashe. Centro Internacional de Agricultura Tropical (CIAT); Colombia Fil: Arenas, Laura. Centro Internacional de Agricultura Tropical (CIAT); Colombia Fil: Katto, María. Centro Internacional de Agricultura Tropical (CIAT); Colombia Fil: Loaiza, Sandra. Centro Internacional de Agricultura Tropical (CIAT); Colombia Fil: Correa, Fernando. Centro Internacional de Agricultura Tropical (CIAT); Colombia Fil: Isthitani, Manabu. Centro Internacional de Agricultura Tropical (CIAT); Colombia Fil: Loboguerrero, Ana María. Centro Internacional de Agricultura Tropical (CIAT); Colombia. Consultative Group on International Agricultural Research (CGIAR) Research Program on Climate Change, Agriculture and Food Security (CCAFS); Colombia Fil: Martínez-Barón, Deissy. Centro Internacional de Agricultura Tropical (CIAT); Colombia. Consultative Group on International Agricultural Research (CGIAR) Research Program on Climate Change, Agriculture and Food Security (CCAFS); Colombia Fil: Graterol, Eduardo. Fondo Latinoamericano para Arroz de Riego (FLAR); Colombia Fil: Jaramillo, Santiago. Fondo Latinoamericano para Arroz de Riego (FLAR); Colombia Fil: Torres, Carlos Felipe. Instituto de Hidrología, Meteorología y Estudios Ambientales (IDEAM); Colombia Fil: Arango, Miguel. Corporación Colombiana de Investigación Agropecuaria (CORPOICA); Colombia Fil: Guzmán, Myriam. Federación Nacional de Arroceros (FEDEARROZ); Colombia Fil: Avila, Ivan. Federación Nacional de Arroceros (FEDEARROZ); Colombia Fil: Hube, Sara. Instituto de Investigaciones Agropecuarias (INIA); Chile Fil: Kurtz, Ditmar Bernardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Corrientes; Argentina Fil: Zorrilla, Gonzalo. National Agricultural Research Institute (INIA); Uruguay Fil: Terra, Jose. National Agricultural Research Institute (INIA); Uruguay Fil: Irisarri, Pilar. Universidad de la República. Facultad de Agricultura. Department of Plant Biology; Uruguay Fil: Tarlera, Silvana. Universidad de la República. Facultad de Química y Ciencia. Department of Biosciences; Uruguay Fil: LaHue, Gabriel. University of California, Davis. Land, Air and Water Resources. Department Plant Sciences; Estados Unidos Fil: Scivittaro, Walkyria Bueno. Embrapa Clima Temperado (CPACT); Brasil Fil: Noguera, Aldo. Paraguay. Ministerio de Agricultura y Ganadería (MAG); Paraguay Fil: Bayer, Cimelio. Universidad Federal de Río Grande del Sur. Department of Soil Science; Brasil

Activation of the hypothalamic-pituitary-adrenal axis (HPA) is critical for survival when the organism is exposed to a stressful stimulus. The endocannabinoid system (ECS) is currently considered an important neuromodulator involved in numerous pathophysiological processes and whose primary function is to maintain homeostasis. In the tissues constituting the HPA axis, all the components of the ECS are present and the activation of this system acts in parallel with changes in the activity of numerous neurotransmitters, including nitric oxide (NO). NO is widely distributed in the brain and adrenal glands and recent studies have shown that free radicals, and in particular NO, may play a crucial role in the regulation of stress response. Our objective was to determine the participation of the endocannabinoid and NOergic systems as probable mediators of the neuroendocrine HPA axis response to a psychophysical acute stress model in the adult male rat. Animals were pre-treated with cannabinoid receptors agonists and antagonists at central and systemic level prior to acute restraint exposure. We also performed in vitro studies incubating adrenal glands in the presence of ACTH and pharmacological compounds that modifies ECS components. Our results showed that the increase in corticosterone observed after acute restraint stress is blocked by anandamide administered at both central and peripheral level. At hypothalamic level both cannabinoid receptors (CB1 and CB2) are involved, while in the adrenal gland, anandamide has a very potent effect in suppressing ACTH-induced corticosterone release that is mainly mediated by vanilloid TRPV1 receptors. We also observed that stress significantly increased hypothalamic mRNA levels of CB1 as well as adrenal mRNA levels of TRPV1 receptor. In addition, anandamide reduced the activity of the nitric oxide synthase enzyme during stress, indicating that the anti-stress action of endocannabinoids may involve a reduction in NO production at hypothalamic and adrenal levels. In conclusion, an endogenous cannabinoid tone maintains the HPA axis in a stable basal state, which is lost with a noxious stimulus. In this case, the ECS dampens the response to stress allowing the recovery of homeostasis. Moreover, our work further contributes to in vitro evidence for a participation of the endocannabinoid system by inhibiting corticosterone release directly at the adrenal gland level. Fil: Surkin, Pablo Nicolas. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gallino, Sofia Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Luce, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Correa, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Fernández Solari, José Javier. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: de Laurentiis, Andrea. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina

Preterm birth is a major contributor to early and delayed physical and cognitive impairment. Epidemiological and experimental data indicate that maternal infections are a significant and preventable cause of preterm birth. Recently, melatonin has been suggested to exert neuroprotective effects in several models of brain injury. Here, we sought to investigate whether the administration of melatonin is able to prevent lipopolysaccharide (LPS)-induced fetal brain damage in a model of LPS-induced preterm labor. For this purpose, 15-day pregnant BALB/c mice received intraperitoneally 2 doses of LPS or vehicle: the first one at 10:00 hours (0.26 mg/kg) and the second at 13:00 hours (0.52 mg/kg). On day 14 of pregnancy, a group of mice was subcutaneously implanted with a pellet of 25 mg melatonin. This experimental protocol resulted in 100% of preterm birth and pup death in the LPS group and a 50% of term birth and pup survival in the melatonin + LPS group. In the absence of melatonin, fetuses from LPS-treated mothers showed histological signs of brain damage, microglial/macrophage activation, and higher levels of IL-1β, inducible nitric oxide synthase (NOS), and neuronal NOS mRNAs as well as increased histone acetyltransferase activity and histone H3 hyperacetylation. In contrast, antenatal administration of melatonin prevented LPS-induced fetal brain damage. Moreover, when behavioral traits were analyzed in the offspring from control, melatonin, and melatonin + LPS, no significant differences were found, suggesting that melatonin prevented LPS-induced long-term neurodevelopmental impairments. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent fetal brain damage and its long-term consequences induced by maternal inflammation. Fil: Domínguez Rubio, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Correa, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Aisemberg, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Dorfman, Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Bariani, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Zorrilla Zubilete, María Aurelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Franchi, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina

Although histidine kinases (HKs) are critical sensors of external stimuli in prokaryotes, the mechanisms by which their sensor domains control enzymatic activity remain unclear. Here, we report the full-length structure of a blue light-activated HK from Erythrobacter litoralis HTCC2594 (EL346) and the results of biochemical and biophysical studies that explain how it is activated by light. Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer. Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain. The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark. Upon light stimulation, interdomain interactions weaken to facilitate activation. Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation. We suggest parallels between EL346 and dimeric HKs, with sensor-induced movements in the DHp similarly remodeling the DHp/CA interface as part of activation.

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The kinetics of the nopol synthesis by Prins condensation of β-pinene and paraformaldehyde over Sn-MCM-41 synthesized by impregnation was evaluated using the initial reaction rate method. The reaction rate equation obtained from a kinetic model based on the Langmuir–Hinshelwood formalism with the surface reaction of adsorbed reactants on catalytic sites of the same nature as the limiting step, gave a good prediction of the experimental data. The effect of temperature on the kinetics of nopol synthesis over Sn-MCM-41 obtained by impregnation was studied between 75 and 100 °C. The robustness analysis of the kinetic model showed that the surface reaction constant, k sr ′ , should be about 0.185 mol g−1 h−1 at 90 °C, while the ratio between the adsorption equilibrium constant of β-pinene, KA, and formaldehyde species, KB, is approximately 1.2:1 (KA:KB). The obtained apparent activation energy and pre-exponential factor are 78 kJ/mol and 2.3 × 1010 mol g−1 h−1, respectively, but compensation effect analysis using both experimental and simulated data gave strong evidence of the dependency in temperature of the apparent Arrhenius parameters.

Maternal infections with gram-negative bacteria are associated with miscarriage and are one of the most common complications during pregnancy. Previous studies from our group have shown that lipopolysaccharide (LPS)-activated infiltrating peripheral blood mononuclear cells (PBMC) into decidual tissue plays an important role in the establishment of a local inflammatory process that results in embryo cytotoxicity and early embryo resorption. Moreover, we have also shown that an increased endocannabinoid tone mediates LPS-induced deleterious effects during early pregnancy loss. Here, we sought to investigate whether the infiltrating PBMC modulates the decidual endocannabinoid tone and the molecular mechanisms involved. PBMC isolated from 7-day pregnant mice subjected to different treatments were co-cultured in a transwell system with decidual tissue from control 7-day pregnant mice. Decidual fatty acid amide hydrolase (FAAH) activity was measured by radioconvertion, total decidual protein nitration by Western blot (WB), and decidual FAAH nitration by immunoprecipitation followed by WB. We found that co-culture of PBMC obtained from LPS-treated mice increased the level of nitration of decidual FAAH, which resulted in a negative modulation of decidual FAAH activity. Interestingly, co-treatment with progesterone or aminoguanidine prevented this effect. We found that LPS-treated PBMC release high amounts of nitric oxide (NO) which causes tyrosine nitration of decidual FAAH, diminishing its enzymatic activity. Inactivation of FAAH, the main degrading enzyme of anandamide and similar endocannabinoids, could lead to an increased decidual endocannabinoid tone with embryotoxic effects. J. Cell. Physiol. 232: 1441-1447, 2017. © 2016 Wiley Periodicals, Inc.

Miscarriage caused by Gram-negative bacteria infecting the female genital tract is one of the most common complications of human pregnancy. Intraperitoneal administration of LPS to 7-days pregnant mice induces embryo resorption after 24 h. Here, we show that LPS induced apoptosis on uterine explants from 7-days pregnant mice and that CB1 receptor was involved in this effect. On the other hand, heparin has been widely used for the prevention of pregnancy loss in women with frequent miscarriage with or without thrombophilia. Besides its anticoagulant properties, heparin exerts anti-inflammatory, immunomodulatory and anti-apoptotic effects. Here, we sought to investigate whether the administration of heparin prevented LPS-induced apoptosis in uterine explants from 7-days pregnant mice. We found that heparin enhanced cell survival in LPS-treated uterine explants and that this effect was mediated by increasing uterine FAAH activity. Taken together, our results point towards a novel mechanism involved in the protective effects of heparin.

Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors central to hypoxia response and cancer development. Within the HIF-2 complex, one domain (HIF-2α PAS-B) contains a large (290 A3) buried cavity filled with water molecules within its hydrophobic core. Such cavities are uncommon except in the case of ligand-binding proteins, leading to the hypothesis that HIF-2α can be regulated by small molecules. The development of artificial HIF-2α inhibitors validates this hypothesis but raises questions about the impact of this cavity on HIF-2α PAS-B structure and function. To answer these points, we used computational methods to construct a repacked protein containing a smaller cavity within the native fold. Experimental validation of a five-mutation variant confirms achieving these objectives and stabilizing the folded structure. Complementary functional data establish that ligands cannot bind this variant although heterodimerization remains unchanged. Altogether, our strategy innovatively addresses the roles of solvated cavities in maintaining protein stability and function.

Companies involved in water and forest resource extraction in Colombia are obliged to compensate for any resulting impacts stemming from their activities, as agreed with the environmental authorities. Compensation usually relates to reforestation or the development of public service infrastructure. However, these initiatives should be more relevant to the local community and ensure that the protection of biodiversity is efficiently undertaken and optimized to support the greatest number of benefits to fauna and flora and the provision of ecosystem services. This paper shows how a partnership between Mansarovar Energy Colombia Ltd., a heavy oil extraction company, and the national and local environmental authorities, resulted in the establishment of buffer zones to support the conservation of the Regional Natural Park "Serranía de las Quinchas". In total one thousand hectares were added to the already existing 21,000 ha that legally constitute the park. This synergy led to a greater impact within the local community, compared to when each entity worked separately.