“El hombre de mayor fama”: el mito de Hércules en Mira de Amescua

La comedia El hombre de mayor fama recoge algunas de las hazañas guerreras y amorosas más sobresalientes de Hércules. El carácter heroico del protagonista se ve amenazado por un amor ilegítimo que absorbe todas sus energías, y del que sólo el sacrificio de su muerte podrá salvarlo. La comedia puede ser interpretada alegóricamente como el triunfo de la fama sobre el amor, de la virtud sobre el vicio. Se caracteriza esta comedia por la acción continua, la abundancia de episodios diversos y el poco relieve psicológico de la mayoría de los personajes. Entre sus valores más positivos destacan la variedad y fuerza de algunas situaciones dramáticas, la desenvoltura de los personajes y el acierto de la versificación. The comedy El hombre de mayor fama is about the love affairs of Hercules and his most successful deeds. The main character’s heroism is threatened by an unlawful love that consumes his energy and whose only salvation is the sacrifice of his life. The play can be interpreted allegorically like the triumph of fame over love, virtue over vice. This comedy is characterized by continuous action, the number of different episodes and the slight psychological profile of its characters. Its greatest valúes are the variety and description of the diverse dramatics situations, the self-assurance of the characters and the accurate use of versification

Revisión del género Cantabrogeus Salgado, 2000, con la descripción de tres nuevas especies hipogeas endémicas de la Cordillera Cantábrica (Coleoptera, Leiodidae, Cholevinae, Leptodirini)

Se revisan las dos especies previamente descritas del género Cantabrogeus (Coleoptera, Leiodidae, Cholevinae, Leptodirini), y se describen tres especies nuevas: Cantabrogeus antimachus sp. n., C. cultellus sp. n. y C. fresnedai sp. n. Una de ellas (C. antimachus sp. n.) es triploide (3n = 33) y la primera especie partenogenética conocida de Leiodidae. Se analizan y se discuten las relaciones existentes entre los diferentes taxones a partir de los caracteres morfológicos externos y las estructuras de los aparatos genitales masculino y femenino, así como las áreas cársticas que colonizan las diferentes especies en la zona cantábrica (NO ibérico). El análisis de datos moleculares (fragmentos de siete genes mitocondriales y nucleares) confirma la monofilia de Cantabrogeus y su proximidad filogenética con el género Fresnedaella, así como su inclusión dentro de la serie Quaestus, que es parafilética. La especie partenogenética (C. antimachus sp. n.) ocupa una posición derivada dentro del género Cantabrogeus, que, de acuerdo con estimas de la tasa de variación molecular basadas en estudios previos, probablemente se diversificó durante el Plioceno–Pleistoceno en las zonas cársticas cántabras, que son de una alta complejidad tectónica.The two previously known species of the genus Cantabrogeus (Coleoptera, Leiodidae, Cholevinae, Leptodirini) are redescribed, and three new species are described: Cantabrogeus antimachus n. sp., C. cultellus n. sp. and C. fresnedai n. sp. One of these (C. antimachus n. sp.) is tripliod (3n = 33) and the first known parthenogenetic species of Leiodidae. The relationships between the different taxa are discussed based on external morphological characters and the structure of male and female genitalia, as well as the distribution of the species in the different areas in the Cantabrian mountains (NW Iberia). Analyses of molecular data (fragments of seven mitochondrial and nuclear genes) confirms the monophyly of Cantabrogeus and its sister–group relationship with Fresnedaella, as well as its inclusion within the paraphyletic series Quaestus. The parthenogenetic species (C. antimachus n. sp.) has a derived position within Cantabrogeus, which, according to previous estimates of the molecular rate, probably diversified during the Pliocene–Pleistocene in the Cantabrian karst areas, of a high tectonic complexity.Se revisan las dos especies previamente descritas del género Cantabrogeus (Coleoptera, Leiodidae, Cholevinae, Leptodirini), y se describen tres especies nuevas: Cantabrogeus antimachus sp. n., C. cultellus sp. n. y C. fresnedai sp. n. Una de ellas (C. antimachus sp. n.) es triploide (3n = 33) y la primera especie partenogenética conocida de Leiodidae. Se analizan y se discuten las relaciones existentes entre los diferentes taxones a partir de los caracteres morfológicos externos y las estructuras de los aparatos genitales masculino y femenino, así como las áreas cársticas que colonizan las diferentes especies en la zona cantábrica (NO ibérico). El análisis de datos moleculares (fragmentos de siete genes mitocondriales y nucleares) confirma la monofilia de Cantabrogeus y su proximidad filogenética con el género Fresnedaella, así como su inclusión dentro de la serie Quaestus, que es parafilética. La especie partenogenética (C. antimachus sp. n.) ocupa una posición derivada dentro del género Cantabrogeus, que, de acuerdo con estimas de la tasa de variación molecular basadas en estudios previos, probablemente se diversificó durante el Plioceno–Pleistoceno en las zonas cársticas cántabras, que son de una alta complejidad tectónica

Substituting Rabbit All-Purpose Foodstuff by Brewing Bran Meal (Hordeum distichum) to Reach Optimal FemaleWeigt at First Breeding.

Forty-eight Cuban Brown genotype female rabbits with an initial liveweight of 567,0 ± 12 g were sampled to de-termine their growth rate at rabbit raising facilities from this species breeding center in Santiago de Cuba. A com-pletely randomized design with four treatments and six replicas each was used to evaluate the effect of partially substituting rabbit all-purpose foodstuff by brewing bran meal (Hordeum distichum) at 0 %, 7 %, 14 %, and 21 % inclusion levels. This diet was also supplemented with Phil nodiflora L. forage, mineral salts, and water ad libitum. Treatments did not affect dry matter consumption. Food conversion rate increased due to the greater inclusion level percentage (P < 0,05); in turn, final liveweight decreased because of commercial foodstuff substitution

Recalling the Biological Significance of Immune Checkpoints on NK Cells: A Chance to Overcome LAG3, PD1, and CTLA4 Inhibitory Pathways by Adoptive NK Cell Transfer?

Immune checkpoint receptors (IC) positively or negatively regulate the activation of the host immune response, preventing unwanted reactions against self-healthy tissues. In recent years the term IC has been mainly used for the inhibitory ICs, which are critical to control Natural Killer (NK) and Cytotoxic CD8(+) T cells due to its high cytotoxic potential. Due to the different nature of the signals that regulate T and NK cell activation, specific ICs have been described that mainly regulate either NK cell or T cell activity. Thus, strategies to modulate NK cell activity are raising as promising tools to treat tumors that do not respond to T cell-based immunotherapies. NK cell activation is mainly regulated by ICs and receptors from the KIR, NKG2 and NCRs families and the contribution of T cell-related ICs is less clear. Recently, NK cells have emerged as contributors to the effect of inhibitors of T cell-related ICs like CTLA4, LAG3 or the PD1/PD-L1 axes in cancer patients, suggesting that these ICs also regulate the activity of NK cells under pathological conditions. Strikingly, in contrast to NK cells from cancer patients, the level of expression of these ICs is low on most subsets of freshly isolated and in vitro activated NK cells from healthy patients, suggesting that they do not control NK cell tolerance and thus, do not act as conventional ICs under non-pathological conditions. The low level of expression of T cell-related ICs in "healthy" NK cells suggest that they should not be restricted to the detrimental effects of these inhibitory mechanisms in the cancer microenvironment. After a brief introduction of the regulatory mechanisms that control NK cell anti-tumoral activity and the conventional ICs controlling NK cell tolerance, we will critically discuss the potential role of T cell-related ICs in the control of NK cell activity under both physiological and pathological (cancer) conditions. This discussion will allow to comprehensively describe the chances and potential limitations of using allogeneic NK cells isolated from a healthy environment to overcome immune subversion by T cell-related ICs and to improve the efficacy of IC inhibitors (ICIs) in a safer way

The influence of lung microbiota on lung carcinogenesis, immunity and immunotherapy

Microbiota have emerged as key modulators of both the carcinogenic process and the immune response against cancer cells, and, thus, it seems to influence the efficacy of immunotherapy. While most studies have focused on analyzing the influence of gut microbiota, its composition substantially differs from that in the lung. Here, we describe how microbial life in the lungs is associated with host immune status in the lungs and, thus, how the identification of the microbial populations in the lower respiratory tract rather than in the gut might be key to understanding the lung carcinogenic process and to predict the efficacy of different treatments. Understanding the influence of lung microbiota on host immunity may identify new therapeutic targets and help to design new immunotherapy approaches to treat lung cancer

Ecoturismo marino en el golfo de California y península de Baja California: tendencias de investigación y vacíos de información

Achieving equitable and sustainable ecotourism requires a wide range of multidisciplinary and cross-scale information, particularly given the growing scale of ecotourism operations and continuing governance and climate challenges. Ecosystems in Mexico’s Gulf of California and Baja California Peninsula support a thriving ecotourism industry that has quickly expanded over the last few decades, potentially outpacing research into current performance and future sustainable development opportunities. We develop and apply a formal literature review approach to characterize academic marine ecotourism literature, highlight key insights and identify research strengths and gaps, and thus analyse almost 50 publications for the region from 1994 to 2014. There has been a significant increase in the number of various types of publications; most (68%) focus on ecological themes, 25% on economics, and 7% on social aspects of human wellbeing. There are also trends towards research on specific species (e.g. mammals, fish and sharks) and in specific areas. A common theme in publication conclusions is the need for collaboration from all stakeholder groups. We discuss these findings, and address potential limitations of our method, with a view to informing sound policies to ensure that ecotourism can provide equitable benefits to local communities while incentivizing sustainable practices and nature conservation.El desarrollo equitativo y sostenible del ecoturismo debe considerar una amplia gama de información multidisciplinaria y a varias escalas, particularmente dada la creciente magnitud de las operaciones de ecoturismo y los retos de gobernanza y climáticos. Los ecosistemas en el golfo de California y península de Baja California en México mantienen a una próspera industria de ecoturismo que se ha expandido rápidamente a lo largo de las últimas décadas, posiblemente dejando atrás a la investigación respecto a sus operaciones actuales y las oportunidades para el desarrollo sostenible a futuro. Desarrollamos y aplicamos una revisión formal de literatura para caracterizar a las publicaciones académicas respecto al ecoturismo, señalar tendencias clave e identificar fortalezas y vacíos de investigación, analizando casi 50 publicaciones para la región desde 1994 al 2014. Ha habido un incremento significativo en la cantidad de publicaciones de varios tipos; la mayoría (68%) se enfocan en temas ecológicos, 25% en economía y 7% en aspectos sociales del bienestar humano. También existe una tendencia hacia investigación de ciertas especies (e.g. mamíferos, peces, tiburones) y en regiones específicas. Un tema común en las conclusiones de las publicaciones analizadas es la necesidad de colaboración por todos los grupos de actores. Discutimos estos resultados, y las posibles limitaciones de nuestro método, en el contexto de informar políticas adecuadas para asegurar que el ecoturismo pueda proveer beneficios equitativos a comunidades locales al mismo tiempo que se incentivan las prácticas sostenibles y la conservación de la naturaleza

Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed. © 2013 Pérez, Romeu, Cabrera, González, Batista-Duharte, Labrada, Pérez, Reyes, Ramírez, Sifontes, Fernández and Lastre

A surface groove essential for viral Bcl-2 function during chronic infection in vivo

Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the gamma-herpesvirus 68 (gammaHV68) Bcl-2 family protein (gammaHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the gammaHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type gammaHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of gammaHV68 from latency and efficient persistent gammaHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection

The Multifaceted Function of Granzymes in Sepsis: Some Facts and a Lot to Discover

Sepsis is a serious global health problem. In addition to a high incidence, this syndrome has a high mortality and is responsible for huge health expenditure. The pathophysiology of sepsis is very complex and it is not well-understood yet. However, it is widely accepted that the initial phase of sepsis is characterized by a hyperinflammatory response while the late phase is characterized by immunosuppression and immune anergy, increasing the risk of secondary infections. Granzymes (Gzms) are a family of serine proteases classified according to their cleavage specificity. Traditionally, it was assumed that all Gzms acted as cytotoxic proteases. However, recent evidence suggests that GzmB is the one with the greatest cytotoxic capacity, while the cytotoxicity of others such as GzmA and GzmK is not clear. Recent studies have found that GzmA, GzmB, GzmK, and GzmM act as pro-inflammatory mediators. Specially, solid evidences show that GzmA and GzmK function as extracellular proteases that regulate the inflammatory response irrespectively of its ability to induce cell death. Indeed, studies in animal models indicate that GzmA is involved in the cytokine release syndrome characteristic of sepsis. Moreover, the GZM family also could regulate other biological processes involved in sepsis pathophysiology like the coagulation cascade, platelet function, endothelial barrier permeability, and, in addition, could be involved in the immunosuppressive stage of sepsis. In this review, we provide a comprehensive overview on the contribution of these novel functions of Gzms to sepsis and the new therapeutic opportunities emerging from targeting these proteases for the treatment of this serious health problem

Sustitución del pienso cunícula todo propósito por afrecho de cebada cervecera (Hordeum distichum) en la obtención del peso de incorporación de la hembra de reemplazo.

Se determinó la tasa de crecimiento de 48 conejas en desarrollo del genotipo Pardo Cubano, con peso vivo inicial de 567,0 ± 12 g, durante 70 días, en instalaciones cunícolas del centro multiplicador para la especie, en Santiago de Cuba. Se utilizó un diseño completamente aleatorio, con cuatro tratamientos y seis repeticiones en cada uno, para evaluar el efecto de la sustitución parcial del concentrado todo propósito cunícola por harina de afrecho de cebada cervecera (Hordeum distichum) a niveles de inclusión en la dieta de 0; 7; 14 y 21 %. La dieta incluía además forraje oro azul (Phil nodiflora L), sales minerales y suministro de agua ad libitum. El consumo de materia seca no varió por efecto de los tratamientos. La conversión alimentaria incrementó con el aumento del por ciento de inclusión (P < 0,05); así mismo, con la sustitución del pienso comercial disminuyó el peso vivo final (P < 0,05).Substituting Rabbit All-Purpose Foodstuff by Brewing Bran Meal (Hordeum distichum) to Reach Optimal Female Weigt at First Breeding.ABSTRACTForty-eight Cuban Brown genotype female rabbits with an initial liveweight of 567,0 ± 12 g were sampled to determine their growth rate at rabbit raising facilities from this species breeding center in Santiago de Cuba. A com-pletely randomized design with four treatments and six replicas each was used to evaluate the effect of partially subs-tituting rabbit all-purpose foodstuff by brewing bran meal (Hordeum distichum) at 0 %, 7 %, 14 %, and 21 % inclusion levels. This diet was also supplemented with Phil nodiflora L. forage, mineral salts, and water ad libitum. Treatments did not affect dry matter consumption. Food conversion rate increased due to the greater inclusion level percentage (P < 0,05); in turn, final liveweight decreased because of commercial foodstuff substitution