miR-127-5p targets the 3'UTR of human β-F1-ATPase mRNA and inhibits its translation

IMW and IMR are the recipients of pre-doctoral fellowships from the Plan de Formación de Profesorado Universitario (AP2007-03035) from the Ministerio de Educación and JAE-CSIC, respectively. The work was supported by grants from the Ministerio de Educación y Ciencia (BFU2010- 18903), by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII and by Comunidad de Madrid (S2011/BMD-2402), Spain. The CBMSO receives an institutional grant from Fundación Ramón Arece

Leucemia linfocítica crónica y su respuesta al tratamiento en un perro

Se presenta un caso clínico de leucemia linfocítica crónica en una perra, describiendo el curso de la enfermedad, los métodos diagnósticos empleados y su respuesta al tratamiento quimioterápico.A case of chronic lymphocytic leukemia in a bitch is presented. In this paper we describe the evolution of the disease, the diagnosis protocol and the response to a chemotherapeutic treatment

Efficient execution of cell death in non-glycolytic cells requires the generation of ROS controlled by the activity of mitochondrial H+-ATP synthase

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Carcinogenesis following peer review. The definitive publisher-authenticated version Carcinogenesis 2006 27(5):925-935 is available at: http://dx.doi.org/10.1093/carcin/bgi315There is a large body of clinical data documenting that most human carcinomas contain reduced levels of the catalytic subunit of the mitochondrial H+-ATP synthase. In colon and lung cancer this alteration correlates with a poor patient prognosis. Furthermore, recent findings in colon cancer cells indicate that downregulation of the H+-ATP synthase is linked to the resistance of the cells to chemotherapy. However, the mechanism by which the H+-ATP synthase participates in cancer progression is unknown. In this work, we show that inhibitors of the H+-ATP synthase delay staurosporine (STS)-induced cell death in liver cells that are dependent on oxidative phosphorylation for energy provision whereas it has no effect on glycolytic cells. Efficient execution of cell death requires the generation of reactive oxygen species (ROS) controlled by the activity of the H+-ATP synthase in a process that is concurrent with the rapid disorganization of the cellular mitochondrial network. The generation of ROS after STS treatment is highly dependent on the mitochondrial membrane potential and most likely caused by reverse electron flow to Complex I. The generated ROS promote the carbonylation and covalent modification of cellular and mitochondrial proteins. Inhibition of the activity of the H+-ATP synthase blunted ROS production prevented the oxidation of cellular proteins and the modification of mitochondrial proteins delaying the release of cytochrome c and the execution of cell death. The results in this work establish the downregulation of the H+-ATP synthase, and thus of oxidative phosphorylation, as part of the molecular strategy adapted by cancer cells to avoid ROS-mediated cell death. Furthermore, the results provide a mechanistic explanation to understand chemotherapeutic resistance of cancer cells that rely on glycolysis as the main energy provision pathway.G.S. and M.M-D. were supported by pre-doctoral fellowships from the Ministerio de Ciencia y Tecnología. This work was supported by grants from the Ministerio de Sanidad y Consumo (PI041255), Comunidad de Madrid (SAL/0026/2004) and Ministerio de Ciencia y Tecnología (BMC2001-0710). The CBMSO receives an institutional grant from Fundación Ramón Areces.Peer reviewe

Nuevo índice para evaluar anomalías de elementos traza en suelos: el caso del SE español

In this work, an index is established to detect anomalies in trace elements in the soil. This index, which relates the total concentration of each element with the regional geochemical background value of the element considered, was defined by studying the levels of trace elements from different soils located in SE Spain. In the area, a previous screening of trace elements detected seven zones with anomalies and revealed two conflictive areas: Sierra Gador and Cabo de Gata. In each zone, a second sampling was undertaken at two different depths (0-20 cm and 20-40 cm). The results indicate that the main anomalies were due to arsenic (As), lead (Pb), and zinc (Zn). In Sierra Gador Pb was the element that registered the highest rate of enrichment with respect to the regional geochemical background, reaching values up to 270-fold higher in some samples. In this zone, more than 50% of the samples were anomalous in any of the trace elements studied (higher than regional geochemical background). In Cabo de Gata, As concentration was higher than the geochemical background in more than 40% of the samples; meanwhile Pb concentration was higher in 50% of the samples.En este trabajo establecemos un índice para detectar anomalías en el contenido de elementos traza en suelos. Este índice relaciona el contenido total de cada elemento traza con el fondo geoquímico regional, definido mediante el estudio de los niveles de elementos traza en diferentes suelos localizados en el sureste español. En un primer estudio sobre niveles de elementos traza en suelos del área de estudio detectaron siete zonas con anomalías, de las cuales dos fueron consideradas conflictivas: Sierra de Gádor y Cabo de Gata. En cada una de estas dos zonas se realizó un segundo estudio más exhaustivo a dos niveles de profundidad (0-20 y 20-40 cm). Los resultados indican que las principales anomalías correspondes a los niveles de As, Pb y Zn. En Sierra de Gádor el Pb es el elemento que presenta una mayor tasa de enriquecimiento con respecto al fondo geoquímico regional, con valores puntuales que lo superan hasta 270 veces. También en esta zona más del 50% de las muestras presentan anomalías en alguno de los elementos analizados. En Cabo de Gata el As supera el fondo geoquímico regional en más del 40% de las muestras; mientras que el Pb lo supera en el 50% de las muestras.This study has been made possible by the research Project no. 1550 of the Regional Environmental Department of the Andalusian Government

The origins of economic growth and regional income inequality in South-West Europe 1870-1950

This study focuses on South-West Europe, an area comprising France, Italy, Spain and Portugal, to evaluate inequality in regional income between 1870 and 1950. To do this, information on a decadal basis on regional population and Gross Domestic Product (GDP) for 171 regions (84 French départements, 22 Italian regioni, 18 Portuguese distritos and 49 Spanish provincias) has been collected. Regional inequalities increased between 1870 and 1910 but subsequently tended to flatten out through until 1950. In the first period, regional disparities increased mainly driven by a handful of French and Spanish regions in northern France, such as the Paris basin, Catalonia, the Basque-Country and northern Italy. In the second period, inequality flattened out, driven by the incorporation of new regions on the path of modern economic growth. The study also shows the evolution towards a bimodal, polarized pattern of regional income distribution in 1910-1950 with two convergence clubs. The richest regions were clustering in northern France, the Paris basin and the north of Italy. Meanwhile, most of southern Italy and the vast majority of the Spanish and Portuguese regions already occupied the bottom positions in the income distribution ranking. This point to the emergence of the core-periphery pattern that characterizes much of South-West Europe today

Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity

Background and Purpose: Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E2 production in inflammatory con ditions. We evaluated the role of mPGES-1 in the development and the metabolic and cardiovascular alterations of obesity. Experimental Approach: mPGES-1+/+ and mPGES-1 / mice were fed with normal or high fat diet (HFD, 60% fat). The glycaemic and lipid profile was evaluated by glu cose and insulin tolerance tests and colorimetric assays. Vascular function, structure and mechanics were assessed by myography. Histological studies, q-RT-PCR, and western blot analyses were performed in adipose tissue depots and cardiovascular tissues. Gene expression in abdominal fat and perivascular adipose tissue (PVAT) from patients was correlated with vascular damage. Key Results: Male mPGES-1 / mice fed with HFD were protected against body weight gain and showed reduced adiposity, better glucose tolerance and insulin sensi tivity, lipid levels and less white adipose tissue and PVAT inflammation and fibrosis, compared with mPGES-1+/+ mice. mPGES-1 knockdown prevented cardiomyocyte hypertrophy, cardiac fibrosis, endothelial dysfunction, aortic insulin resistance, and vascular inflammation and remodelling, induced by HFD. Obesity-induced weight gain and endothelial dysfunction of resistance arteries were ameliorated in female mPGES-1 / mice. In humans, we found a positive correlation between mPGES-1 expression in abdominal fat and vascular remodelling, vessel stiffness, and systolic blood pressure. In human PVAT, there was a positive correlation between mPGES-1 expression and inflammatory markers. Conclusions and Implications: mPGES-1 inhibition might be a novel therapeutic approach to the management of obesity and the associated cardiovascular and meta bolic alterations

CRISPR-spacer integration reporter plasmids reveal distinct genuine acquisition specificities among CRISPR-Cas I-E variants of Escherichia coli

Prokaryotes immunize themselves against transmissible genetic elements by the integration (acquisition) in clustered regularly interspaced short palindromic repeats (CRISPR) loci of spacers homologous to invader nucleic acids, defined as protospacers. Following acquisition, mono-spacer CRISPR RNAs (termed crRNAs) guide CRISPR-associated (Cas) proteins to degrade (interference) protospacers flanked by an adjacent motif in extrachomosomal DNA. During acquisition, selection of spacer-precursors adjoining the protospacer motif and proper orientation of the integrated fragment with respect to the leader (sequence leading transcription of the flanking CRISPR array) grant efficient interference by at least some CRISPR-Cas systems. This adaptive stage of the CRISPR action is poorly characterized, mainly due to the lack of appropriate genetic strategies to address its study and, at least in Escherichia coli, the need of Cas overproduction for insertion detection. In this work, we describe the development and application in Escherichia coli strains of an interference-independent assay based on engineered selectable CRISPR-spacer integration reporter plasmids. By using this tool without the constraint of interference or cas overexpression, we confirmed fundamental aspects of this process such as the critical requirement of Cas1 and Cas2 and the identity of the CTT protospacer motif for the E. coli K12 system. In addition, we defined the CWT motif for a non-K12 CRISPR-Cas variant, and obtained data supporting the implication of the leader in spacer orientation, the preferred acquisition from plasmids harboring cas genes and the occurrence of a sequential cleavage at the insertion site by a ruler mechanism.This work was funded by the Ministerio de Economía y Competitividad (BIO2011-24417)

Uso de un compuesto de fórmula (I) como bactericida frente a Streptococcus

Uso de al menos un compuesto de fórmula (I) donde R1 es alquilo C1-C6 o forma Ncicloalquilo C5-C8 junto con R2 ; R 2 es alquilo C1-C6, forma Ncicloalquilo C5-C8 junto con R1 , o es una cadena alquílica que se une a (CH2)n formando una amina bicíclica; R3 es alquilo C1-C2 o ausente; R4 es un sustituyente aromático que comprende al menos dos anillos aromáticos; n es un valor entre 1 y 2; y m es un valor entre 0 y 1; como bactericida frente a Streptococcus, preferiblemente frente a Streptococcus pneumoniae. Adicionalmente, compuesto de fórmula (Ia) y una composición bactericida que lo comprenda.Peer reviewedConsejo Superior de Investigaciones Científicas, Universidad Miguel HernándezB1 Patente sin examen previ

Straight access to highly fluorescent angular indolocarbazoles via merging Au- and Mo-catalysis

A straightforward and efficient synthesis of the two less explored types of indolocarbazoles has been developed. Two different processes for the carbazole nucleus preparation, a gold-catalysed regioselective cyclization followed by the dioxomolybdenum-catalysed version of Cadogan reductive cyclization, enables the sequential construction of two carbazole cores. The procedure features total regioselectivity and high overall yields. The required starting α-indol-3-ylalkyl propargylic alcohols are easily and efficiently accessed from commercially available reagents. In addition, the photoluminescent properties of two indolo[2,3-c]carbazoles, with fluorescence quantum yields around 0.7, have been studied.Junta de Castilla y León and FEDER (BU291P18) and Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P

A Semantic Web methodological framework to evaluate the support of integrity in thesaurus tools

12 p.With the Semantic Web, thesauri recover a relevant role supporting semantic searches and other added-value services. Thesaurus standards define what constructs a thesaurus can have and the integrity rules it must comply with. Thesaurus editors can be helped in their work if thesaurus tools offer them support for integrity, warning when integrity rules are violated and/or helping them to correct these mistakes. The most recent thesaurus standard is ISO 25964, which supersedes ISO 2788, evolving towards concept-based thesauri, better aligned with the Semantic Web approach than the term-based thesauri of ISO 2788. However, the W3C recommendation for KOS (Knowledge Organization System) representation in the semantic web context is SKOS, which is in fact prior to ISO 25964. This paper focuses on thesaurus integrity and the evolution from ISO 2788 to ISO 25964. Its effect on integrity issues is analyzed. A methodological proposal for evaluating integrity support in thesaurus tools, arising from the results of this work, is presented. Its target audience is professionals in charge of thesaurus edition. Besides being adapted to the most recent thesaurus standard, ISO 25964, it also includes the comparison of ISO standards with SKOS. The paper is completed with the presentation of the results of applying it to three thesaurus tools