78 research outputs found

    Fernando de Castro and the discovery of the arterial chemoreceptors

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    Producción CientíficaWhen de Castro entered the carotid body(CB)field,the organ was considered to be a small autonomic ganglion,a gland,a glomusorglomerulus,or a paraganglion. In his 1928 paper,de Castro concluded:“Insum,the Glomuscarotic umisinnervated by centripetal fibers,whose trophic center sare located in thesensory ganglia of the glossopharyngeal, and not by centrifugal[efferent] or secret o motor fibers a sisthe case for glands ; these are precisely the facts which lead to suppose that the Glomuscaroticumisa sensory organ.”A few pages down,de Castro wrote:“The Glomus represents an organ with multiplereceptors furnished with specialized receptor cells like those of the sensory organs [tastebuds?]...As aplausible hypothesis we propos et hattheGlomuscaroti cum represents a sensory organ, at present the only one in its kind, dedicated to capture certain qualitative variations in the composition of blood, a function that,possibly by are flex mechanism would have an effect on the functionalactivity of other organs... Therefore, thesensory fiber would not be directly stimulated by blood, but via the intermediation of the epithelial cell soft he organ, which, as their structures suggests, possess a secretory function which would participate in the stimulation of the centripetal fibers.”In our article we will recreat et he experiments that allowed Fernando de Castrotoreach this first conclusion. Also, we will scrutinize the natural endowment sand the scientific knowledge that drove de Castrotomaket the triple hypotheses : the CBaschemoreceptor (variationsinbloodcomposition),as a secondary sensory receptor which functioning involves a chemical synapse, and as a center, origin of systemicreflexes. After a brief account of the systemic reflex effects resulting from the CB stimulation, we wil lcomplete our article with a general view of the cellular-molecular mechanisms currently thought to be involved in the functionin go fthis arterial chemoreceptor

    Metal-Catalyzed Cascade Reactions between Alkynoic Acids and Dinucleophiles: A Review

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    Cascade reactions provide a straightforward access to many valuable compounds and reduce considerably the number of steps of a synthetic sequence. Among the domino and multicomponent processes that involve alkynes, the cascade reaction between alkynoic acids and C-, N-, O- and S-aminonucleophiles stands out as a particularly powerful tool for the one-pot construction of libraries of nitrogen-containing heterocyclic compounds with scaffold diversity and molecular complexity. This reaction, based on an initial metal-catalyzed cycloisomerization that generates an alkylidene lactone intermediate, was originally catalyzed by gold(I) catalysts, along with silver salts or Brönsted acid additives, but other alternative metal catalysts have emerged in the last decade as well as different reaction media. This review examines the existing literature on the topic of metal-catalyzed cascade reactions of acetylenic acids and dinucleophiles and discusses aspects concerning substrate/catalyst ratio for every catalyst system, nature of the aminonucleophile involved and substrate scope. In addition, alternative solvents are also considered, and an insight into the pathway of the reaction and possible intermediates is also provided.This research was funded by the Basque Government (IT1583-22) and the Spanish Ministry of Economy and Competitiveness (CTQ2017-86630-P)

    Age protects from harmful effects produced by chronic intermittent hypoxia

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    Producción CientíficaObstructive sleep apnoea (OSA) affects an estimated 3–7% of the adult population, the frequency doubling at ages >60–65 years. As it evolves, OSA becomes frequently associated with cardiovascular, metabolic and neuropsychiatric pathologies defining OSA syndrome (OSAS). Exposing experimental animals to chronic intermittent hypoxia (CIH) can be used as a model of the recurrent hypoxic and O2 desaturation patterns observed in OSA patients. CIH is an important OSA event triggering associated pathologies; CIH induces carotid body (CB)-driven exaggerated sympathetic tone and overproduction of reactive oxygen species, related to the pathogenic mechanisms of associated pathologies observed in OSAS. Aiming to discover why OSAS is clinically less conspicuous in aged patients, the present study compares CIH effects in young (3–4 months) and aged (22–24 months) rats. To define potential distinctive patterns of these pathogenic mechanisms, mean arterial blood pressure as the final CIH outcome was measured. In young rats, CIH augmented CB sensory responses to hypoxia, decreased hypoxic ventilation and augmented sympathetic activity (plasma catecholamine levels and renal artery content and synthesis rate). An increased brainstem integration of CB sensory input as a trigger of sympathetic activity is suggested. CIH also caused an oxidative status decreasing aconitase/fumarase ratio and superoxide dismutase activity. In aged animals, CIH minimally affected CB responses, ventilation and sympathetic-related parameters leaving redox status unaltered. In young animals, CIH caused hypertension and in aged animals, whose baseline blood pressure was augmented, CIH did not augment it further. Plausible mechanisms of the differences and potential significance of these findings for the diagnosis and therapy of OSAS are discussed.Ministerio de Ciencia, Innovación y Universidades (grant BFU2012-37459)Instituto de Salud Carlos III (grant CIBER CB06/06/0050)Portuguese Foundation for Science and Technology (grant EXP/NEU-SCC/2813/2013

    Creación del primer Grupo iGEM (Competición Internacional de Biología Sintética) de Madrid: Facultad de Biología-UCM

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    En este Trabajo se describe la creación del primer Grupo iGEM de Madrid así como la elaboración de un biosensor que permite la detección de polen de olivo a tiempo real empleando metodos de ingeniería genética y robótica

    Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population

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    Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population
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