Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are ‘primed’ to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β

Luis Jiménez de Asúa and the gestation of ‘Non Intervention Policy’ in the Spanish Civil War

El 27 de julio de 1936 Luis Jiménez de Asúa llegó precipitadamente a París. Allí le esperaba Fernando de los Ríos. Tras el golpe militar del día 18, ambos dirigentes socialistas debían encabezar las gestiones diplomáticas conducentes a conseguir el auxilio de las democracias europeas en forma de venta de material bélico y suministros. Para entonces había comenzado la defección escalonada y calculada del cuerpo diplomático español parisino. Con su epicentro en el Quai d’Orsay, la sucesión de acontecimientos en las semanas siguientes adelantó dos circunstancias sustanciales del conflicto: la trascendencia desde primera hora del vector internacional, y el abandono que sufrió la República por parte de las democracias occidentales. Este artículo revisa la vía interpretativa de un actor –y testigo– de primer orden en la gestación del sistema de ‘No Intervención’. Su testimonio constituye una introducción privilegiada en la reconstrucción de este capítulo tan relevante de la Guerra Civil Española.On July 27, 1936, Luis Jiménez de Asúa arrived hurriedly in Paris there to meet Fernando de los Ríos. After the military coup on July 18th, both socialist leaders had to lead diplomatic efforts to obtain the help of the European democracies in the form of the sale of military equipment and supplies. By then the gradual, calculated defection of the Spanish diplomatic corps in Paris had begun. Located mainly in the Quai d’Orsay, the sequence of events in the following weeks speeded up two substantial circumstances of the conflict: the relevance, from the very beginning, of the international vector, and the abandonment of the western democracies suffered by the Republic. This work revises the interpretative path of a prime protagonist –and witness– in the development of the ‘Non Intervention’ system. His testimony provides a privileged introduction to the rebuilding of an outstanding chapter of the Spanish Civil War

“Mensaje a la juventud”. Luis Jiménez de Asúa y el movimiento estudiantil opositor a la Dictadura de Primo de Rivera

During the Primo de Rivera Dictatorship, the student movement underwent a series of changes so profound that they brought it from its traditional atony attitude to the forefront of Spanish public life. His manifestations of dissidence against the regime were based not only on the interventionist policy of the Dictatorship, but also on subversive attitudes towards widely established social conventions and customs. On the other hand, not few of those youthful protagonists, as well as some of the most notable historiographical works, have considered Luis Jiménez de Asúa to be the most outstanding of the protester professors. He is a professor of criminal law at the Central University and is considered a spiritual guide among liberal youths. During that decade, Asúa also experienced a deep process of personal transformation. The following article approaches this convergent process, taking as a symbolic-chronological frame of reference two representative manifestos of the Madrid jurist, tributary as well as two radically different contexts: Impressions of Argentina (15/10/1923) and Message to the Youth. Re-turn to Science (17/04/1931).Durante la Dictadura de Primo de Rivera, el movimiento estudiantil experimentó una serie de cambios tan profundos que le llevaron de su tradicional actitud de atonía a la primera línea de la vida pública española. Sus manifestaciones de disidencia frente al régimen se fundamentaron no solo en su política intervencionista, sino también sobre actitudes subversivas respecto a convenciones y usos sociales ampliamente establecidos. Por otra parte, no pocos de aquellos protagonistas juveniles, así como algunos de los trabajos historiográficos más notables, han considerado a Luis Jiménez de Asúa como el más destacado de los catedráticos contestatarios. Titular de la cátedra de Derecho penal de la Universidad Central y considerado entre los ambientes juveniles liberales como un guía espiritual, también Asúa experimentó durante aquella década un profundo proceso de transformación personal. El siguiente artículo se aproxima a este proceso convergente, tomando como marcos de referencia simbólico-cronológicos dos manifiestos representativos del jurista madrileño, tributarios además de dos contextos radicalmente distintos: Impresiones de la Argentina (15/10/1923) y Mensaje a la juventud. Retorno a la ciencia (17/04/1931)

LCG Service Challenge 3 at the Spanish Tier-1 and Tier-2 sites

This note describes the participation of the Spanish centres PIC and CIEMAT in the LCG Service Challenge 3 as Tier-1 and Tier-2 sites respectively. Data transfer, job submission and data throughput from mass storage to the data processing jobs have been successfully exercised at the desired level. Very valuable experience has been gained running the complex computing system under realistic conditions at a signi cant scale

Efectos del establecimiento de las áreas marinas protegidas en la pesquería argentina de la merluza negra (Dissostichus eleginoides)

At the beginning of the 1990s, the Argentine toothfish fishery gained prominence as a consequence of the rapid expansion of trawler and longliner fleets targeting this species. This fishing area covers the slope and shelf from 60° S to 37° S in the Argentine Exclusive Economic Zone. The main fishing ground is located in the southern area, bordering Namuncurá-Burdwood Bank II (NBBII) and Yaganes (Y) marine protected areas (MPA) established in 2018. In order to determine the impact generated by MPAs on effort distribution, 308 fishing trips carried out between 2010 and 2020, which reported 82% of the total fishing effort of Argentine toothfish declared in that period, were spatially analyzed. The Y-MPA sector categorized as National Marine Reserve and located to the south of Tierra del Fuego reported more than half (58%) of the toothfish catch recorded throughout that period, while the NBBII-MPA located to the east of Tierra del Fuego and south of De los Estados Island represented 17%. The NBBII-MPA sector established as a Strict National Marine Reserve and located to the south of the Burdwood Bank represented 25%. With the establishment of the MPAs, 7.11% of the international requirement has been met. At the moment, effects resulting from the creation of MPAs can only be speculated upon qualitatively, but should be quantified in the near future.A principios de la década de 1990, la pesquería de merluza negra argentina ganó protagonismo gracias a la rápida expansión de las flotas de arrastre y palangre que se dirigían a esta especie. Esta zona de pesca cubre el talud y plataforma desde los 60° S hasta los 37° S en la Zona Económica Exclusiva argentina. El principal caladero se encuentra en la zona sur, colindando con las áreas marinas protegidas (AMP) Banco Namuncurá-Burdwood II (NBBII) y Yaganes (Y), establecidas en 2018. Para determinar el impacto que generan las AMP en la distribución del esfuerzo, se analizaron espacialmente 308 viajes de pesca realizados entre 2010 y 2020, que reportaron 82% del total del esfuerzo pesquero declarado de merluza negra argentina en ese período. El sector Y-AMP categorizado como Reserva Nacional Marina y ubicado al sur de Tierra del Fuego, reportó más de la mitad (58%) de la captura de merluza negra registrada durante ese período, mientras que el NBBII-AMP ubicado al este de Tierra del Fuego y sur de la Isla de los Estados representaron 17%. El sector NBBII-AMP establecido como Reserva Nacional Marina Estricta y ubicado al sur del Banco Burdwood representó el 25%. Con el establecimiento de las AMP se ha cumplido 7,11% del requerimiento internacional. En la actualidad, los efectos resultantes de la creación de AMP solo pueden especularse cualitativamente, pero deberían cuantificarse en un futuro próximo.

The La Luna/Río Negro(.) Petroleum system at the Urdaneta West Field, lake Maracaibo basin, NW Venezuela: ID basin modelling and secondary oil migration

This paper investigates the timing of hydrocarbon generation in the northern part of the Urdaneta West field in the NW of the Lake Maracaibo Basin, NW Venezuela, based on ID basin modelling at three wells referred to as wells X, Y and Z. Kitchen areas were identified and secondary migration directions were inferred based on analyses of the thermal and burial history of the Upper Cretaceous La Luna Formation source rock and the geochemistry of 20 oil samples from the Río Negro Formation reservoir. Aliphatic hydrocarbons in the oil samples were analysed by gas chromatography - mass spectrometry (GC-MS) while the vanadium- nickel and sulphur contents were determined by energy dispersive X-ray spectrometry and inductively coupled plasma optical emission spectroscopy, respectively. Bulk and molecular characterizations indicated that the oils originated from a marine carbonate source rock containing oil-prone Type II kerogen, consistent with generation by the La Luna Formation. Burial and thermal history modelling in the study area indicated that the La Luna source rock at wells X, Y and Z reached the oil window during the late Eocene, mid-Eocene and early Paleocene respectively. ID model results from the three wells showed that hydrocarbon generation began in the early Eocene. The transformation ratio of the La Luna Formation source rock in the modelled wells reached values of 35%, 98% and 100% by the end of the Eocene. In the Urdaneta West field, two different oil charges appear to have mixed in the Río Negro reservoir. Both oil charges were generated by the La Luna Formation source rock but at different times. A first charge of less mature oil occurred in the middle-late Eocene (Phase 1 generation), and a second, more mature oil charge took place in the Miocene - Quaternary (Phase 2 generation). The kitchen area for the first oil charge is inferred to have been located to the north and NE of Urdaneta West; that for the second oil charge to the south of the field. This migration model is supported by observed variations in the geochemical compositions of the oil samples analysed from different wells in the Urdaneta West field.J.G. Diaz acknowledges the support of the PDVSA Western Exploration Project Management and the University of Zulia. The authors are grateful to Iván Chirino and Patricia Marín for their scientific assistance. We are also grateful to the JPG referees (Karla Quintero-Bonilla, Katya Reategui and anonymous) whose comments helped to improve the original version of this manuscript. Carlos Boente obtained a post-doctoral contract within the program PAIDI 2020 (Ref 707 DOC 01097), co-financed by the Junta de Andalucía (Andalusian Government) and the EU

Analysis of the rumen microbiome and metabolome to study the effect of an antimethanogenic treatment applied in early life of kid goats

This work aimed to gain insight into the transition from milk to solid feeding at weaning combining genomics and metabolomics on rumen contents from goat kids treated with a methanogenic inhibitor (bromochloromethane, BCM). Sixteen goats giving birth to two kids were used. Eight does were treated (D+) with BCM after giving birth and over 2 months. One kid per doe in both groups was treated with BCM (k+) for 3 months while the other was untreated (k–). Rumen samples were collected from kids at weaning (W) and 1 (W + 1) and 4 (W + 4) months after and from does at weaning and subjected to 16S pyrosequencing and metabolomics analyses combining GC/LC-MS. Results from pyrosequencing showed a clear effect of age of kids, with more diverse bacterial community as solid feed becomes more important after weaning. A number of specific OTUs were significantly different as a result of BCM treatment of the kid at W while at W + 1 and W + 4 less OTUs were significantly changed. At W + 1, Prevotella was increased and Butyrivibrio decreased in BCM treated kids. At W + 4 only the effect of treating mothers resulted in significant changes in the abundance of some OTUs: Ruminococcus, Butyrivibrio and Prevotella. The analysis of the OTUs shared by different treatments revealed that kids at weaning had the largest number of unique OTUs compared with kids at W + 1 (137), W + 4 (238), and does (D) (23). D + k+ kids consistently shared more OTUs with mothers than the other three groups at the three sampling times. The metalobomic study identified 473 different metabolites. In does, lipid super pathway included the highest number of metabolites that were modified by BCM, while in kids all super-pathways were evenly affected. The metabolomic profile of samples from kids at W was different in composition as compared to W + 1 and W + 4, which may be directly ascribed to the process of rumen maturation and changes in the solid diet. This study shows the complexity of the bacterial community and metabolome in the rumen before weaning, which clearly differ from that after weaning and highlight the importance of the dam in transmitting the primary bacterial community after birth.</p

Defense of a rebellion: the trial for the Revolutionary Manifesto of 1930. Political purposes, responsibilities and legitimacy

Tras el fracaso de la Sublevación de Jaca del 12 de diciembre de 1930 y la ejecución de los capitanes Fermín Galán y Ángel García Hernández, las autoridades gubernamentales consiguieron detener a seis de los dirigentes del Comité Revolucionario. Acusados de conspiración para la rebelión militar, se instruyó un sumarísimo cuya vista se celebraría durante los días 20 y 21 de marzo de 1931. Entre estas dos fechas, la iniciativa del Comité Revolucionario — con epicentro en la cárcel Modelo de Madrid— logró trasladar a la opinión pública la existencia de un conflicto de poderes que fue sintetizado durante la vista: la legitimidad de la actitud insurreccional frente a un régimen que había perdido la suya desde septiembre de 1923.After the failure of the Jaca Uprising of 12 December 1930 and the execution of Captains Fermín Galán and Ángel García Hernández, the government authorities managed to arrest six of the leaders of the Revolutionary Committee. Charged with conspiracy to military rebellion. Charge with to conspiracy for the military rebellion, a summary trial was instructed whose hearing would be held between 20 and 21 March of the following year. Between these two dates, the initiative of the Revolutionary Committee - with its epicentre in the Madrid Model prison - managed to convey to public opinion the existence of a conflict of powers synthesized during the trial: the legitimacy of the insurrectional attitude towards a regime that had lost its own since September 1923