1,566 research outputs found

    Hypothyroidism decreases the biogenesis in free mitochondria and neuronal oxygen consumption in the cerebral cortex of developing rats

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    Thyroid hormone plays a critical role in mitochondrial biogenesis in two areas of the developing brain, the cerebral cortex and the striatum. Here we analyzed, in the cerebral cortex of neonatal rats, the effect of hypothyroidism on the biogenesis in free and synaptosomal mitochondria by analyzing, in isolated mitochondria, the activity of respiratory complex I, oxidative phosphorylation, oxygen consumption, and the expression of mitochondrial genome. In addition, we studied the effect of thyroid hormone in oxygen consumption in vivo by determining metabolic flow through C-13 nuclear magnetic resonance spectroscopy. Our results clearly show that in vivo, hypothyroidism markedly reduces oxygen consumption in the neural population of the cerebral cortex. This effect correlates with decreased free mitochondria biogenesis. In contrast, no effect was observed in the biogenesis in synaptosomal mitochondria. The parameters analyzed were markedly improved after T-3 administration. These results suggest that a reduced biogenesis and the subsequent reduction of respiratory capacity in free mitochondria could be the underlying cause of decreased oxygen consumption in the neurons of the cerebral cortex of hypothyroid neonates.This work was supported by Ministerio de Educaciín y Ciencia Grants SAF2004-06263-CO2-02 (to A.S.), SAF2004-06263-CO2-01, and SAF2007-62811 and Comunidad de Madrid Grant GR/SAL/0033/2004 (to A.P.-C.). Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas is funded by the Instituto de Salud Carlos III. T.B.R. is a recipient of a fellowship from the Fundaçâo para a Ciência e Tecnologia, Portugal (SFRH/BPD/26881/2006).Peer reviewe

    PELFI Project: Recruitment and Sociodemographic Characteristics of Immigrant and Autochthonous Families from Alicante and Barcelona City Subcohorts

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    Este artículo corresponde al “Proyecto de Estudios Longitudinales de Familias Inmigradas (PELFI)” del Subprograma de Inmigración y Salud del CIBERESP y describe el trabajo de campo basal y principales características socio-demográficas de dos sub-cohortes de familias inmigrantes y autóctonas. El diseño es observacional prospectivo. La población de estudio se definió como una muestra no probabilística de 180 familias de origen colombiano, ecuatoriano y marroquí y 50 españolas. Se entrevistó a 473 personas adultas entre 18 y 65 años (59,8% mujeres, 68,5% ocupados/as) y a 304 adolescentes entre 12 y17 años (53,9% mujeres, 27,1% nacidos en España pero de padres inmigrados) de cada familia, mediante dos cuestionarios diseñados ad hoc. La tasa de cooperación fue del 82,0% con una velocidad media de reclutamiento de 1,3 familias diarias. En total, se reclutó a 250 familias, 82 procedentes de Ecuador, 82 de Colombia, 29 de Marruecos y 57 españolas. Los adultos inmigrados llevaban una media de 13 años en España. La combinación de técnicas no probabilísticas permitió el acceso y velocidad de reclutamiento. Este estudio aporta información clave para el diseño y mejora de este tipo de cohortes en familias inmigradas.This study is a part of the multi-centre project “Platform of Longitudinal Studies of Immigrant Families (PELFI)” of the Immigration and Health Subprogram of the CIBER-ESP. It describes the field work and data collection of two sub-cohorts of immigrant and native families, and their main socio-demographic characteristics. Prospective observational cohort study in carried out in Barcelona and Alicante, Spain. The study population is a non-probabilistic sample of 180 families of Colombian, Ecuadorian and Moroccan origin and 50 families of Spanish origin. We interviewed adults aged 18-65 years and adolescents aged 12-17 years in each family, through two questionnaires (adolescent/adult). The cooperation rate was 82.0% with an average recruitment rate of 1.3 families per day. In total, 250 families have been recruited, 82 from Ecuador, 82 from Colombia, 29 from Morocco and 57 from Spain. A total of 473 adults (59.8% women and 68.5% employed) were surveyed. Immigrant adults have an average of 13 years living in Spain. A total of 304 adolescents (53.9% female, 27.1% born in Spain but with immigrant parents) were surveyed. The combination of non-probabilistic techniques promoted access and improved recruitment speed. This study provides key information for the design and improvement of cohort studies with immigrant families.Proyectos Fondo Investigación Sanitaria números PI14/01146 y PI14/02005 e Instituto de Salud Carlos III-FEDER

    The Sas3p and Gcn5p histone acetyltransferases are recruited to similar genes

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    A macroarray platform was used to identify binding sites of yeast histone acetyltransferase catalytic subunits and to correlate their positions with acetylation of lysine 14 of histone H3, revealing that Sas3p and Gcn5p are recruited to similar sets of intensely transcribed genes

    Androgen receptor gene and sociosexuality. Does fighting ability moderate the effect of genetics in reproductive strategies?

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    Springer Nature remains neutral with regard to juris dictional claims in published maps and institutional affiliations.Sociosexuality is a reliable proxy to evaluate the trade-off between short-term and long-term human mating strategies. The androgen receptor (AR) gene CAG-repeats polymorphism regulates the effect of testosterone and the expression of testosterone-related traits commonly associated with short-term mating strategies. According to the strategic pluralism hypothesis, a more effective receptor would prompt a short-term mating strategy to maximize the number of sexual partners, but studies are inconclusive and contradictory. The effect of a particular gene in behavior is frequently small and affected by the social environment and other variables, particularly psychological and personality traits. In the current study we propose the effect of the AR gene polymorphism in sociosexuality to be moderated by self-perceived fighting ability, a psychological attribute relevant in intrasexual competition. Our objective is to reveal if the CAG polymorphism is associated with a short-term strategy as expected from the strategic pluralism hypothesis, or conversely with long-term investments to maximize parental care. We fail to find any effect of the CAG polymorphism over mating strategies. However, self-perceived fighting ability is related to short-term mating orientation but not to the number of past sexual partners. In conclusion, we find no clear evidence about the potential role of CAG polymorphism of the AR gene over sociosexual attitudes and behavior. However, results from other studies suggest that there is evidence that genetic factors influence sociosexuality, but it is necessary to consider simultaneously more than a single genetic polymorphism and other psychological and physiological variablesThis study was supported by a postdoctoral proj ect from Universidad del Desarrollo for author Nohelia T. Valenzuela and funded by the project BIOUAM03-2019 of the Departmento de Biología of the Universidad Autónoma de Madri

    A morphological study of galaxies in ZwCl0024+1652, a galaxy cluster at redshift z ∼ 0.4

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    ABSTRACT: he well-known cluster of galaxies ZwCl0024+1652 at z ∼ 0.4 lacks an in-depth morphological classification of its central region. While previous studies provide a visual classification of a patched area, we used the public code called galaxy Support Vector Machine GALSVM) and HST/ACS data as well as the WFP2 master catalogue to automatically classify all cluster members up to 1 Mpc. GALSVM analyses galaxy morphologies through support vector machine (SVM). From the 231 cluster galaxies, we classified 97 as early types (ETs) and 83 as late types (LTs). The remaining 51 stayed unclassified (or undecided). By cross-matching our results with the existing visual classification, we found an agreement of 81 per cent. In addition to previous Zwcl0024 morphological classifications, 121 of our galaxies were classified for the first time in this work. In addition, we tested the location of classified galaxies on the standard morphological diagrams, colour–colour and colour–magnitude diagrams. Out of all cluster members, ∼20 per cent are emission-line galaxies, taking into account previous GLACE results. We have verified that the ET fraction is slightly higher near the cluster core and decreases with the clustercentric distance, while the opposite trend has been observed for LT galaxies. We found a higher fraction of ETs (54 per cent) than LTs (46 per cent) throughout the analysed central region, as expected. In addition, we analysed the correlation between the five morphological parameters (Abraham concentration, Bershady–Concelice concentration, asymmetry, Gini, and M20 moment of light) and the clustercentric distance, without finding a clear trend. Finally, as a result of our work, the morphological catalogue of 231 galaxies containing all the measured parameters and the final classification is available in the electronic form of this paper.MP also acknowledges support from the Spanish MINECO under projects AYA2013-42227-P and AYA2016-76682-C3-1-P- This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) under the grants AYA2014-58861-C3-2-P, AYA2014-58861-C3-3-P, AYA2017-88007-C3-1-P, and AYA2017-88007-C3-2-P

    Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy

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    <p>Abstract</p> <p>Background</p> <p>The epidermal specific ablation of <it>Trp53 </it>gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of <it>Rb </it>gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies.</p> <p>Results</p> <p>To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy.</p> <p>Conclusions</p> <p>Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.</p

    Effect of RecA inactivation on quinolone susceptibility and the evolution of resistance in clinical isolates of Escherichia coli

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    This study was presented in part at the Twenty-Ninth European Congress of Clinical Microbiology and Infectious Diseases, Amsterdam, The Netherlands, 2019 (Poster Presentation P1339).[Background] SOS response suppression (by RecA inactivation) has been postulated as a therapeutic strategy for potentiating antimicrobials against Enterobacterales.[Objectives] To evaluate the impact of RecA inactivation on the reversion and evolution of quinolone resistance using a collection of Escherichia coli clinical isolates.[Methods] Twenty-three E. coli clinical isolates, including isolates belonging to the high-risk clone ST131, were included. SOS response was suppressed by recA inactivation. Susceptibility to fluoroquinolones was determined by broth microdilution, growth curves and killing curves. Evolution of quinolone resistance was evaluated by mutant frequency and mutant prevention concentration (MPC).[Results] RecA inactivation resulted in 2–16-fold reductions in fluoroquinolone MICs and modified EUCAST clinical category for several isolates, including ST131 clone isolates. Growth curves and time–kill curves showed a clear disadvantage (up to 10 log10 cfu/mL after 24 h) for survival in strains with an inactivated SOS system. For recA-deficient mutants, MPC values decreased 4–8-fold, with values below the maximum serum concentration of ciprofloxacin. RecA inactivation led to a decrease in mutant frequency (≥103-fold) compared with isolates with unmodified SOS responses at ciprofloxacin concentrations of 4×MIC and 1 mg/L. These effects were also observed in ST131 clone isolates.[Conclusions] While RecA inactivation does not reverse existing resistance, it is a promising strategy for increasing the effectiveness of fluoroquinolones against susceptible clinical isolates, including high-risk clone isolates.This study was funded by the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad—co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015 and RD16/0016). Supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de InvestigaciónCooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (PI14/00940, PI17/01501, AC16/00072, RD16/0016/0001 and REIPI RD16/0016/0009) ‐ co-financed by European Development Regional Fund ‘A way to achieve Europe’, Operative Programme Intelligent Growth 2014‐2020.Peer reviewe
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