Tipification methods and molecular epidemiology of staphylocuccus aureus with methicillin resistance

El interés actual del estudio de Staphylococcus aureus deriva de su elevada frecuencia de cepas resistentes a los antibióticos que causa frecuentes brotes de infección, especialmente, el S. aureus con resistencia a meticilina (SARM). El objetivo de esta revisión fue estudiar la estructura genética poblacional y el origen de los aislamientos de SARM. La tipificación del cassette cromosómico mec estafilocócico es el método más importante para identificar y definir la naturaleza clonal del S. aureus con resistencia a meticilina. Los estudios de epidemiología molecular evidencian un patrón de diseminación de unas pocas cepas que son las responsables del importante problema mundial. Existe el predominio de clones pandémicos de SARM asociado a infecciones hospitalarias (SARM-AH), que ha han sido reemplazados en la actualidad por clones de origen comunitario (SARM-AC). En Colombia, predomina el clon pediátrico y el chileno entre los aislamientos hospitalarios. Sin embargo, en la actualidad una variante del clon comunitario USA300 prevalece en las infecciones adquiridas en la comunidad y en el hospital, desplazando los clones hospitalarios como ocurre en el resto de mundo. El entendimiento de la epidemiología y clonalidad de las infecciones por S. aureus tiene importantes implicaciones en el control de la emergencia de cepas con multirresistencia y el esparcimiento de clones resistentes y sensibles a meticilina.Recent interest in the study of Staphylococcus aureus derives from the high frequency of antibiotic-resistant strains that cause frequent outbreaks of infection, especially Methicillinresistant S. aureus (MRSA). The objective of this review was to study the population genetic structure and the origin of MRSA isolation. Classification of staphylococcal cassette chromosomemec (SCCmec) is the most important method to identify and define the S. aureus methicillin-resistant clonal nature. Molecular epidemiologic studies have demonstrated dissemination patterns of few strains which are responsible for the important worldwide problem. There is a predominance of pandemic clones of MRSA associated to hospital-acquired infections (HA-MRSA) which has been replaced today by community-acquired strains (CA-MRSA). In Colombia, the pediatric clone and the Chilean clone predominate between hospital isolations. However, currently, there is a variant community clone USA300 prevailing in infections acquired in the community and in the hospital, displacing HA-MRSA as it happens in the rest of world. Understanding the epidemiology and clonality of S. aureus infections has important implications for future efforts to control of the emergence of multidrug-resistant strains and the spread of clones resistant and sensible to methicillin

Análisis de las competencias y perfiles profesionales de los programas de máster en el ámbito de las TIC

El objetivo de este trabajo es realizar un análisis comparativo de la oferta actual de programas de máster en el ámbito de las TICs ofertados en España. Como punto de partida se tomarán las competencias definidas en diversas iniciativas Europeas y los perfiles profesionales específicos al ámbito de las TICs definidos por el consorcio Career-Space. Como resultado se obtendrá el grado de cobertura en España de los perfiles profesionales demandados por la industria, identidad las principales carencias existente

Experiencia práctica de tipo interdisciplinar para manejo de dispositivos de potencia, instrumentación electrónica, sistemas microprocesadores e identificación paramétrica de sistemas dinámicos

El cambio en el entorno y en las dimensiones internas de las instituciones de educación superior provoca la necesidad de revisar el modelo educativo. Actualmente asistimos a la transformación de la Universidad provocada en gran medida por la revolución del conocimiento y las nuevas tecnologías de la información, que generan cambios tanto en el entorno como en los recursos internos disponibles en las universidades. El reto imperativo durante la próxima década es el cambio que debe producirse tanto en los productos que la Universidad ofrece (titulaciones, programas de postgrado, investigación, difusión, etc.) como en la forma en la que ofrece estos produ ctos, resultando necesario revisar los procesos docentes y haciéndose imperativa la introducción de la formación multidisciplinar. En este trabajo se presenta una experiencia práctica de tipo multidisciplinar, que aúna conceptos relacionados c on el manejo de herramientas de simulación basadas en Matlab y Simulink para el estudio de sistemas electrónicos digitales, analógicos y de potencia, así como el procesamiento de la señal y la identificación paramétrica de sistemas dinámicos. Se describirá el sistema con el que se trabajará (una máquina de inducción de 5 fases gobernada por un convertidor de potencia de 2 nivel es), para posteriormente definir su modelado empleando Matlab y Simulink y plantear los objetivos del trabajo de si mulación a realizar por los alumnos

Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8

53BP1 is a well-known mediator of the cellular response to DNA damage. Two alternative mechanisms have been proposed to explain 53BP1’s interaction with DNA double-strand breaks (DSBs), one by binding to methylated histones and the other via an RNF8 E3 ligase–dependent ubiquitylation pathway. The formation of RNF8 and 53BP1 irradiation-induced foci are both dependent on histone H2AX. To evaluate the contribution of the RNF8-dependent pathway to 53BP1 function, we generated RNF8 knockout mice. We report that RNF8 deficiency results in defective class switch recombination (CSR) and accumulation of unresolved immunoglobulin heavy chain–associated DSBs. The CSR DSB repair defect is milder than that observed in the absence of 53BP1 but similar to that found in H2AX−/− mice. Moreover, similar to H2AX but different from 53BP1 deficiency, RNF8−/− males are sterile, and this is associated with defective ubiquitylation of the XY chromatin. Combined loss of H2AX and RNF8 does not cause further impairment in CSR, demonstrating that the two genes function epistatically. Importantly, although 53BP1 foci formation is RNF8 dependent, its binding to chromatin is preserved in the absence of RNF8. This suggests a two-step mechanism for 53BP1 association with chromatin in which constitutive loading is dependent on interactions with methylated histones, whereas DNA damage–inducible RNF8-dependent ubiquitylation allows its accumulation at damaged chromatin

Reduction of ureteral stent encrustation by modulating the urine pH and inhibiting the crystal film with a new oral composition: a multicenter, placebo controlled, double blind, randomized clinical trial

Background: Encrustation of ureteral double J stents is a common complication that may affect its removal. The aim of the proposed study is to evaluate the efficacy and safety of a new oral composition to prevent double J stent encrustation in indwelling times up to 8 weeks. Methods: A double-blinded, multicenter, placebo-controlled trial was conducted with 105 patients with indwelling double J stents enrolled across 9 public hospitals in Spain. The patients were randomly assigned (1:1) into intervention (53 patients) or placebo (52 patients) groups for 3 to 8 weeks and both groups self-monitored daily their morning urine pH levels. The primary outcome of analysis was the degree of stent ends encrustation, defined by a 4-point score (0 - none; 3 - global encrustation) using macroscopic and electron microscopy analysis of crystals, after 3 to 8-w indwelling period. Score was exponentially transformed according to calcium levels. Secondary endpoints included urine pH decrease, stent removal, and incidence of adverse events. Results: The intervention group benefits from a lower global encrustation rate of stent ends than placebo group (1% vs 8.2%; p < 0.018). Mean encrustation score was 85.12 (274.5) in the placebo group and 18.91 (102.27) in the intervention group (p < 0.025). Considering the secondary end points, treated patients reported greater urine pH decreases (p = 0.002). No differences in the incidence of adverse events were identified between the groups. Conclusions: Our data suggest that the use of this new oral composition is beneficial in the context of ureteral double J indwelling by decreasing mean, as well as global encrustation

Les Houches 2013: Physics at TeV Colliders: Standard Model Working Group Report

This Report summarizes the proceedings of the 2013 Les Houches workshop on Physics at TeV Colliders. Session 1 dealt primarily with (1) the techniques for calculating standard model multi-leg NLO and NNLO QCD and NLO EW cross sections and (2) the comparison of those cross sections with LHC data from Run 1, and projections for future measurements in Run 2.Comment: Proceedings of the Standard Model Working Group of the 2013 Les Houches Workshop, Physics at TeV Colliders, Les houches 3-21 June 2013. 200 page

Paleopatología en la necrópolis mudéjar de El Raval (Crevillent, Alicante)

Presentamos el estudio osteoarqueológico de las inhumaciones procedentes de la necrópolis mudéjar del Raval (Crevillent, Alicante). Se han identificado un mínimo de 83 individuos de diferentes edades y de ambos sexos. Las patologías observadas son variadas, evidenciándose un alto número de patologías dentales (caries, pérdidas dentales, etc.). Se ha constatado la presencia de patología traumática, osteoarticular, signos infecciosos, etc. Igualmente, hemos señalado la existencia de malformaciones congénitas, y diversas variaciones epigenéticas.In this paper we present the paleopathological study of inhumations from a Mudejar necropolis in El Raval (Crevillent, Alicante). We have identified at least 83 individuals of different ages and both sexes. The recognized pathology is varied, showing a high number of dental diseases (tooth decay, tooth loss, etc.). It is evident the presence of trauma, osteoarthropathy, infectious signs, etc. We have also noticed the existence of congenital malformations, and several epigenetic variations

Molecular and Structural Discrimination of Proline Racemase and Hydroxyproline-2-Epimerase from Nosocomial and Bacterial Pathogens

The first eukaryotic proline racemase (PRAC), isolated from the human Trypanosoma cruzi pathogen, is a validated therapeutic target against Chagas' disease. This essential enzyme is implicated in parasite life cycle and infectivity and its ability to trigger host B-cell nonspecific hypergammaglobulinemia contributes to parasite evasion and persistence. Using previously identified PRAC signatures and data mining we present the identification and characterization of a novel PRAC and five hydroxyproline epimerases (HyPRE) from pathogenic bacteria. Single-mutation of key HyPRE catalytic cysteine abrogates enzymatic activity supporting the presence of two reaction centers per homodimer. Furthermore, evidences are provided that Brucella abortus PrpA [for ‘proline racemase’ virulence factor A] and homologous proteins from two Brucella spp are bona fide HyPREs and not ‘one way’ directional PRACs as described elsewhere. Although the mechanisms of aminoacid racemization and epimerization are conserved between PRAC and HyPRE, our studies demonstrate that substrate accessibility and specificity partly rely on contraints imposed by aromatic or aliphatic residues distinctively belonging to the catalytic pockets. Analysis of PRAC and HyPRE sequences along with reaction center structural data disclose additional valuable elements for in silico discrimination of the enzymes. Furthermore, similarly to PRAC, the lymphocyte mitogenicity displayed by HyPREs is discussed in the context of bacterial metabolism and pathogenesis. Considering tissue specificity and tropism of infectious pathogens, it would not be surprising if upon infection PRAC and HyPRE play important roles in the regulation of the intracellular and extracellular amino acid pool profiting the microrganism with precursors and enzymatic pathways of the host

Genomic Instability, Defective Spermatogenesis, Immunodeficiency, and Cancer in a Mouse Model of the RIDDLE Syndrome

Eukaryotic cells have evolved to use complex pathways for DNA damage signaling and repair to maintain genomic integrity. RNF168 is a novel E3 ligase that functions downstream of ATM,γ-H2A.X, MDC1, and RNF8. It has been shown to ubiquitylate histone H2A and to facilitate the recruitment of other DNA damage response proteins, including 53BP1, to sites of DNA break. In addition, RNF168 mutations have been causally linked to the human RIDDLE syndrome. In this study, we report that Rnf168−/− mice are immunodeficient and exhibit increased radiosensitivity. Rnf168−/− males suffer from impaired spermatogenesis in an age-dependent manner. Interestingly, in contrast to H2a.x−/−, Mdc1−/−, and Rnf8−/− cells, transient recruitment of 53bp1 to DNA double-strand breaks was abolished in Rnf168−/− cells. Remarkably, similar to 53bp1 inactivation, but different from H2a.x deficiency, inactivation of Rnf168 impairs long-range V(D)J recombination in thymocytes and results in long insertions at the class-switch junctions of B-cells. Loss of Rnf168 increases genomic instability and synergizes with p53 inactivation in promoting tumorigenesis. Our data reveal the important physiological functions of Rnf168 and support its role in both γ-H2a.x-Mdc1-Rnf8-dependent and -independent signaling pathways of DNA double-strand breaks. These results highlight a central role for RNF168 in the hierarchical network of DNA break signaling that maintains genomic integrity and suppresses cancer development in mammals