43 research outputs found

    Citizen participation in the Plan for the Recovery of the Gomera Giant Lizard

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    [Resumo] Este programa forma parte do Proxecto Life denominado “Plano de Recuperación do Lagarto Xigante da Gomera”, cofinanciado pola Unión Europea, Ministerio de Medio Ambiente, Goberno de Canarias e Cabido Insular da Gomera.[Abstract] This programme forms a part of the Life Project entitled “Plan for the Recovery of the Gomera Giant Lizard” which is co-financed by the European Union, the Ministry of the Environment and the Government of the Canary Islands and the Island Council of La Gomera

    Gasdermin-B (GSDMB) takes center stage in antibacterial defense, inflammatory diseases, and cancer

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    One of the hottest topics in biomedical research is to decipher the functional implications of the Gasdermin (GSDM) protein family in human pathologies. These proteins are the key effectors of a lytic and pro-inflammatory cell death type termed pyroptosis (also known as “Gasdermin-mediated programmed cell death”). However, ever-growing evidence showed that GSDMs can play multiple and complex roles in a context-dependent manner. In this sense, Gasdermin-B (GSDMB; the only GSDM gene absent in mice and rats) has been implicated in antibacterial defense, numerous inflammatory pathologies (e.g., asthma, ulcerative colitis), and cancer, but both cell death-dependent and -independent functions have been reported in these diseases, fueling the debate on whether GSDMB has genuine pyroptotic capacity. Recently, a series of seminal papers cast light on the GSDMB multitasking capacity by showing that different GSDMB transcriptional isoforms have distinct biological activities. Nonetheless, there are still obscure areas to be clarified on the precise functional involvement of GSDMB translated variants in physiological and pathological conditions. In this viewpoint, we critically discuss the most recent and exciting data on this topic and propose a series of relevant challenges that need to be overcome before GSDMB-driven biomedical applications (as a biomarker of disease risk/progression/outcome or as specific therapeutic target) become a reality in clinical settingsPID2019-104644RB-I00, PDC2022-133252-I00, PID2022-136854OB-I0

    Distinct GSDMB protein isoforms and protease cleavage processes differentially control pyroptotic cell death and mitochondrial damage in cancer cells

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    Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMGasdermin (GSDM)-mediated pyroptosis is functionally involved in multiple diseases, but Gasdermin-B (GSDMB) exhibit cell death-dependent and independent activities in several pathologies including cancer. When the GSDMB pore-forming Nterminal domain is released by Granzyme-A cleavage, it provokes cancer cell death, but uncleaved GSDMB promotes multiple pro-tumoral effects (invasion, metastasis, and drug resistance). To uncover the mechanisms of GSDMB pyroptosis, here we determined the GSDMB regions essential for cell death and described for the first time a differential role of the four translated GSDMB isoforms (GSDMB1-4, that differ in the alternative usage of exons 6-7) in this process. Accordingly, we here prove that exon 6 translation is essential for GSDMB mediated pyroptosis, and therefore, GSDMB isoforms lacking this exon (GSDMB1-2) cannot provoke cancer cell death. Consistently, in breast carcinomas the expression of GSDMB2, and not exon 6-containing variants (GSDMB3-4), associates with unfavourable clinical-pathological parameters. Mechanistically, we show that GSDMB N-terminal constructs containing exon-6 provoke cell membrane lysis and a concomitant mitochondrial damage. Moreover, we have identified specific residues within exon 6 and other regions of the N-terminal domain that are important for GSDMBtriggered cell death as well as for mitochondrial impairment. Additionally, we demonstrated that GSDMB cleavage by specific proteases (Granzyme-A, Neutrophil Elastase and caspases) have different effects on pyroptosis regulation. Thus, immunocytederived Granzyme-A can cleave all GSDMB isoforms, but in only those containing exon 6, this processing results in pyroptosis induction. By contrast, the cleavage of GSDMB isoforms by Neutrophil Elastase or caspases produces short N-terminal fragments with no cytotoxic activity, thus suggesting that these proteases act as inhibitory mechanisms of pyroptosis. Summarizing, our results have important implications for understanding the complex roles of GSDMB isoforms in cancer or other pathologies and for the future design of GSDMB-targeted therapie

    Evaluación de los niveles de ruido para la implementación de un programa de conservación auditiva en la planta de procesamiento de mineral de la empresa Gold Processing & Research Group S.A.C.

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    La presente investigación se realizó con la finalidad de implementar un programa de conservación auditiva (PCA.) a partir de los resultados obtenidos de la evaluación de los niveles de ruido (NR) a los que se encuentran expuestos los trabajadores (ET) de la planta de procesamiento (PP) de mineral de la empresa Gold Processing & Research Group S.A.C. (GPR Group S.A.C.). El estudio consistió en realizar una auditoría inicial aplicando el Anexo B de la guía de diseño de la NIOSH, para realizar un diagnóstico inicial de las medidas que adopta la empresa para conservar la audición (CA.), teniendo como resultado que, de todos los ítems evaluados, el 76% no cumple, el 17 % no aplica, y sólo el 7% si cumple. Se realizó una evaluación de los NR a los trabajadores de la planta, usando la metodología 2 de la NTP ISO 9612-2010, obteniéndose como resultado que los trabajadores de la planta reciben un NR diario ponderado “A” de 92.11 dB, superando los 85 dBA permitidos en una jornada de 8 horas. A partir de los resultados obtenidos, se implementaron medidas de control (MC), considerando la jerarquía de controles, tales son el aislamiento del laboratorio, capacitaciones a los trabajadores y supervisores, elaboración del programa de exámenes audiométricos y entrega de equipos de protección auditiva. Y por último se realizó una segunda auditoría para verificar la efectividad de la implementación del PCA, en la empresa GPR Group S.A.C, haciendo uso del mismo cuestionario usado en la auditoría inicial. Se obtuvo como resultado que, el 8% de los Ítems evaluados no son cumplidos por la empresa, el 17 % de los ítems evaluados no aplican, y el 75% de los ítems evaluados si cumplen.Campus Arequip

    Identification and antimicrobial susceptibility of Streptomyces and other unusual Actinobacteria clinical isolates in Spain

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    Two hundred and eighty-six isolates from human clinical samples were identified between 1996 and 2019 as belonging to 8 families, 19 genera and 88 species of Actinobacteria. The most identified genera were Streptomyces (182 strains from 45 species), Actinomadura (29 strains, 5 species), Nocardiopsis (21 strains, 6 species) and Dietzia (18 strains, 5 species). The rest of the identified genera (15) contained 27 species with 36 isolates. Of the species studied, only 13/88 had been documented previously as isolates from clinical samples, and in some cases, as true pathogens. In this sense, a literature review of the species found in infections or in clinical samples without clear involvement in pathology has been carried out. Finally, the susceptibility to 8 antimicrobial agents has been studied. Streptomyces showed high resistance (80.8%) against cefotaxime and cotrimoxazole (55.5%), and no isolate resistance to amikacin and linezolid have been found. Lower percentages of resistance have been found in other genera, except in Dietzia (100% against cotrimoxazole and 44.4% against erythromycin). The greatest resistance in these genera was to cotrimoxazole (29.8) and erythromycin (27,9%), and no resistance to linezolid has been found in these genera. In Microbispora, Nonomuraea and Umezawaea, no resistant isolates have been found against any antibiotic studied. Only 3/104 isolates were resistant to amikacin in Amycolatopsis, Crossiella, and Micromonosopora. One isolate of Amycolatopsis was resistant to imipenem.S

    Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain

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    To determine whether the neurotoxin BoNT/B2 causing botulism in Spain is clonal, the genetic diversity and phylogenetic relationships of Clostridium botulinum from food-borne episodes and infant cases of the condition were explored. The botulinum toxin gene (bont) subtype, the variable region of the flagellin gene (flaVR), and a seven-gene multi-locus sequence type were examined by sequencing 37 BoNT-positive cultures obtained over the period 2010 to 2022. Out of 37 botulism events, 16 food-borne episodes and 16 infant cases were associated with bont/b2. Eight bont/b2 alleles were detected [nucleotide distance range 0.0259-0.415%, Hunter and Gaston discrimination index (HGDI) 0.71]. The most common bont/b2 allele corresponded to that of strain Prevot 25 NCASE and its single and double locus variations (87.5%). Four known flaVR types were identified (HGDI 0.79), along with one previously unknown (flaVR-15). Sixteen sequence types (STs) (HGDI 0.89) were recorded including seven new STs (ST164-ST170; 10 new alleles) and five new STs (ST171-ST175; with new allele combinations) were also noted. Correlations among some STs and flaVR types were seen. Overall, the present results show that the combined analysis of bont/b2-flaVR-ST at the nucleotide level could be used to track botulism events in Spain. The neurotoxin BoNT/B2 has largely been responsible for human botulism in Spain. The polymorphism analysis of bont/b2, flaVR typing, and sequence type determinations, revealed a wide variety of clones to be responsible for human botulism, ruling out a common source of acquisition. IMPORTANCE Botulism, a potentially fatal disease, is classically characterized by a symmetrical descending flaccid paralysis, which if left untreated can lead to respiratory failure and death. Botulinum neurotoxin (BoNT), produced by certain species of Clostridium, is the most potent biological toxin known, and the direct cause of botulism. This study characterizes the acquisition in Spain of two forms of botulism, i.e., food-borne and infant botulism, which are largely caused by the main neurotoxin BoNT/B2. Polymorphism analysis of the bont/b2 gene, typing of the flagellin variable region sequence (flaVR), and multilocus sequence typing, were used to explore the genetic background of Clostridium botulinum group I. To our knowledge, this is the first phylogenetic and typing study of botulism undertaken in Spain.This study was partially funded via Ministerio de Ciencia e Innovación (MCIN) and the Agencia Estatal de Investigación (AEI) grant PID2021127477OBI00 through the Plan Estatal de Investigación Científica, Técnica y de Innovación. N.G. is contracted via MCIN/AEI grant PTA-2019-016623-I. M.V. is contracted via grant PEJ CAM 2021-/TL/BMD-21100 from the Programa Operativo Empleo Juvenil e Iniciativa Empleo Juvenil (YEI).S

    El Paciente Pediatrico en NAP4

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    En el Reino Unido, la población pediátrica en el sistema sanitario, está definida por una edad inferior a los 16 años; en nuestro país, el punto de corte es la edad inferior a 15 años. Sin embargo, este límite no es real, pues en la mayoría de los centros exclusivamente pediátricos, se atiende a población con edad superior a los 15 años, sobre todo, aquellos pacientes con patología congénita o hereditaria. En el manejo del paciente pediátrico es excepcional, la situación de vía aérea difícil, pero hay dos importantes puntos a tener en cuenta: por un lado, cualquier paciente pediátrico sometido a procedimiento diagnóstico o terapéutico con sedación o técnica regional, va a precisar control de la vía aérea, y los pacientes pediátricos graves atendidos en los servicios de urgencia, requieren control de su vía aérea, antes del traslado dentro del mismo centro o a un centro de referencia

    La negociación colectiva como vehículo para la implantación efectiva de medidas de igualdad

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    Esta monografía tiene su origen en el Proyecto “Ciclo de seminarios. La negociación colectiva como vehículo para la implantación efectiva de medidas de Igualdad”, que ha sido financiado por el Instituto de la Mujer del Ministerio de Sanidad, Servicios Sociales e Igualdad (Resolución de 30 de noviembre de 2015, del Instituto de la Mujer y para la Igualdad de Oportunidades, por la que se conceden subvenciones destinadas a la realización de postgrados de estudios de género y actividades del ámbito universitario relacionadas con la igualdad de oportunidades entre mujeres y hombres, para el año 2015)

    Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans

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    Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches

    Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

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    BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348
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