Molecular-genetic analysis of the structural determinants and primary functions of eukaryotic ribosomal proteins L16 y L19 in Saccharomyces cerevisiae

Resumen del póster presentado al "XXXV Congreso de la SEB-BM/37th FEBS/22nd IUBMB" celebrados en Sevilla del 4 al 9 de septiembre de 2012.Peer Reviewe

Plan de Negocio para una empresa de comercio electrónico

Trabajo de fin de grado, del grado de Administración y Dirección de Empresas, en el cual se elabora un plan de negocio de una empresa de comercio electrónico enfocado en la ciudad de Zaragoza y sobre los espacios de coworking y la propia creación de una aplicación para reservar un espacio en ellos. Se realiza la creación de una empresa de comercio electrónico, en la que se estudia el análisis del entorno general, del mercado y de la competencia. Posteriormente se realiza una viabilidad comercial y técnica del producto, además de explicar la estructura legal y organizativa que llevara a cabo nuestra empresa. Finalmente se elabora un análisis económico-financiero donde se realizan los estados financieros para analizar si el proyecto es viable o no viable. Además añadimos una valoración del riesgo a la hora de realizar el proyecto, con los futuros riesgos que nos podemos encontrar en la realización del proyecto.<br /

6th International Conference on Mechanical Models in Structural Engineering

Producción CientíficaThis ebook contains the 37 full papers submitted to the 6th International Conference on Mechanical Models in Structural Engineering (CMMOST 2021) held in Valladolid on December 2021

Assessment of the Association of Health with the Liberalisation of Trade in Services under the World Trade Organisation

Background: The liberalisation of trade in services which began in 1995 under the General Agreement on Trade in Services (GATS) of the World Trade Organisation (WTO) has generated arguments for and against its potential health effects. Our goal was to explore the relationship between the liberalisation of services under the GATS and three health indicators – life expectancy (LE), under-5 mortality (U5M) and maternal mortality (MM) - since the WTO was established. Methods and Findings: This was a cross-sectional ecological study that explored the association in 2010 and 1995 between liberalisation and health (LE, U5M and MM), and between liberalisation and progress in health in the period 1995–2010, considering variables related to economic and social policies such as per capita income (GDP pc), public expenditure on health (PEH), and income inequality (Gini index). The units of observation and analysis were WTO member countries with data available for 2010 (n = 116), 1995 (n = 114) and 1995–2010 (n = 114). We conducted bivariate and multivariate linear regression analyses adjusted for GDP pc, Gini and PEH. Increased global liberalisation in services under the WTO was associated with better health in 2010 (U5M: 20.358 p,0.001; MM: 20.338 p = 0.001; LE: 0.247 p = 0.008) and in 1995, after adjusting for economic and social policy variables. For the period 1995–2010, progress in health was associated with income equality, PEH and per capita income. No association was found with global liberalisation in services. Conclusions: The favourable association in 2010 between health and liberalisation in services under the WTO seems to reflect a pre-WTO association observed in the 1995 data. However, this liberalisation did not appear as a factor associated with progress in health during 1995–2010. Income equality, health expenditure and per capita income were more powerful determinants of the health of populations.This study was funded by the Carlos III Health Institute and the Programme for Promotion of Biomedical and Health Sciences (http://www.isciii.es/) of the Spanish Ministry of Health and Consumer Affairs (Ref. PI060295)

Sociedad y cultura en los puentes de Madrid

Bridges are not just functional structures; they usually assume social and cultural values. This fact is perceived with greater intensity in urban bridges. We study here the bond created between Madrid city bridges and citizens and social life, as well as their presence in different cultural expressions from the 16th century up to the present. From the older bridges over Manzanares river to the most modern ones on the city outskirts, including the city center, Rondas and M-30 highway, the study offers an itinerary of the bridges which have been relevant in literature, paintings and films, analyzing their current worth and social significance for Madrilenians. The bridges of Madrid help build up a society and enhance its cultural heritage.Los puentes no son sólo estructuras funcionales; casi siempre asumen valores sociales y culturales. Este hecho se percibe con mayor intensidad en los puentes urbanos. Se estudia aquí la vinculación de estos puentes del municipio de Madrid con la ciudadanía y la vida social, y su presencia en diferentes expresiones culturales desde el siglo XVI hasta la actualidad. Desde los más antiguos puentes sobre el Manzanares hasta los más modernos de la periferia, pasando por los urbanos, las Rondas y la M-30, se realiza un recorrido por sus apariciones más relevantes en la literatura, la pintura y el cine, así como por su actual valor y significación social para los madrileños. Los puentes de Madrid construyen sociedad y son cultura

Safety and Efficacy of Crizotinib in Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma: Phase Ib GEINO 1402 Trial

Simple Summary Most patients with glioblastoma, the most frequent primary brain tumor in adults, develop resistance to standard first-line treatment combining temozolomide and radiotherapy. Signaling through the hepatocyte growth factor receptor (c-MET) and the midkine (ALK ligand) promotes gliomagenesis and glioma stem cell maintenance, contributing to the resistance of glioma cells to anticancer therapies. This trial reports for the first time that the addition of crizotinib, an ALK, ROS1, and c-MET inhibitor, to standard RT and TMZ is safe and resulted in a promising efficacy for newly diagnosed patients with glioblastoma. Background: MET-signaling and midkine (ALK ligand) promote glioma cell maintenance and resistance against anticancer therapies. ALK and c-MET inhibition with crizotinib have a preclinical therapeutic rationale to be tested in newly diagnosed GBM. Methods: Eligible patients received crizotinib with standard radiotherapy (RT)/temozolomide (TMZ) followed by maintenance with crizotinib. The primary objective was to determine the recommended phase 2 dose (RP2D) in a 3 + 3 dose escalation (DE) strategy and safety evaluation in the expansion cohort (EC). Secondary objectives included progression-free (PFS) and overall survival (OS) and exploratory biomarker analysis. Results: The study enrolled 38 patients. The median age was 52 years (33-76), 44% were male, 44% were MGMT methylated, and three patients had IDH1/2 mutation. In DE, DLTs were reported in 1/6 in the second cohort (250 mg/QD), declaring 250 mg/QD of crizotinib as the RP2D for the EC. In the EC, 9/25 patients (32%) presented grade >= 3 adverse events. The median follow up was 18.7 months (m) and the median PFS was 10.7 m (95% CI, 7.7-13.8), with a 6 m PFS and 12 m PFS of 71.5% and 38.8%, respectively. At the time of this analysis, 1 died without progression and 24 had progressed. The median OS was 22.6 m (95% CI, 14.1-31.1) with a 24 m OS of 44.5%. Molecular biomarkers showed no correlation with efficacy. Conclusions: The addition of crizotinib to standard RT and TMZ for newly diagnosed GBM was safe and the efficacy was encouraging, warranting prospective validation in an adequately powered, randomized controlled study

Studies on the Coordination of Ribosomal Protein Assembly Events Involved in Prosessing and Stabiliz

Cellular production of ribosomes involves the formation of highly defined interactions between ribosomal proteins (r-proteins) and ribosomal RNAs (rRNAs). Moreover in eukaryotic cells, efficient ribosome maturation requires the transient association of a large number of ribosome biogenesis factors (RBFs) with newly forming ribosomal subunits. Here, we investigated how r-protein assembly events in the large ribosomal subunit (LSU) rRNA domain II are coordinated with each other and with the association of RBFs in early LSU precursors of the yeast Saccharomyces cerevisiae. Specific effects on the pre-ribosomal association of RBFs could be observed in yeast mutants blocked in LSU rRNA domain II assembly. Moreover, formation of a cluster of r-proteins was identified as a downstream event in LSU rRNA domain II assembly. We analyzed in more detail the functional relevance of eukaryote specific bridges established by this r-protein cluster between LSU rRNA domain II and VI and discuss how they can support the stabilization and efficient processing of yeast early LSU precursor RNAs

Antithrombin is incorporated into exosomes produced by antithrombin non-expressing cells

Antithrombin is a serine protease inhibitor that exerts a crucial role in hemostasis as the main inhibitor of the coagulation cascade. It plays also critical roles in other processes, such as inflammation and cancer. Here we show that exosomes released by Madin-Darby canine kidney (MDCK) cells cultured in the presence of heparin incorporate antithrombin from the serum. Exosomal antithrombin is found complexed with the serine protease high temperature requirement A1 (HTRA1), whose cellular levels are increased after serum deprival, the condition used to collect exosomes. Although the biological relevance of the presence of antithrombin in exosomes remains to be investigated, our results suggest a functional interplay between antithrombin and HTRA1.Ginés Luengo-Gil holds a grant from the Spanish Society of Hematology and Hemotherapy (SEHH-FEHH), Irene Martínez-Martínez holds a Miguel Servet contract from the ISCIII. Miguel Quintanilla holds a grant (SAF2017-84183-R) from the Spanish Ministry of Science, Innovation and Universities and Irene Martínez-Martínez holds grants from ISCIII (CP13/00126 & FEDER and PI17/00050 & FEDER)

Association of the ACTN3 rs1815739 Polymorphism with Physical Performance and Injury Incidence in Professional Women Football Players.

The p.R577X polymorphism (rs1815739) in the ACTN3 gene causes individuals with the XX genotype to be deficient in functional α-actinin-3. Previous investigations have found that XX athletes are more prone to suffer non-contact muscle injuries, in comparison with RR and RX athletes who produce a functional α-actinin-3 in their fast-twitch fibers. This investigation aimed to determine the influence of the ACTN3 R577X polymorphism on physical performance and injury incidence of players competing in the women’s Spanish first division of football (soccer). Using a cross-sectional experiment, football-specific performance and epidemiology of non-contact football-related injuries were recorded in a group of 191 professional football players. ACTN3 R577X genotype was obtained for each player using genomic DNA samples obtained through buccal swabs. A battery of physical tests, including a countermovement jump, a 20 m sprint test, the sit-and-reach test and ankle dorsiflexion, were performed during the preseason. Injury incidence and characteristics of non-contact injuries were obtained according to the International Olympic Committee (IOC) statement for one season. From the study sample, 28.3% of players had the RR genotype, 52.9% had the RX genotype, and 18.8% had the XX genotype. Differences among genotypes were identified with one-way analysis of variance (numerical variables) or chi-square tests (categorical variables). Jump height (p = 0.087), sprint time (p = 0.210), sit-and-reach distance (p = 0.361), and dorsiflexion in the right (p = 0.550) and left ankle (p = 0.992) were similar in RR, RX, and XX football players. A total of 356 non-contact injuries were recorded in 144 football players while the remaining 47 did not sustain any non-contact injuries during the season. Injury incidence was 10.4 ± 8.6, 8.2 ± 5.7, and 8.9 ± 5.3 injuries per/1000 h of football exposure, without differences among genotypes (p = 0.222). Injury rates during training (from 3.6 ± 3.7 to 4.8 ± 2.1 injuries per/1000 h of training exposure, p = 0.100) and match (from 47.8 ± 9.5 to 54.1 ± 6.3 injuries per/1000 h of match exposure, p = 0.209) were also similar in RR, RX, and XX football players. The ACTN3 genotype did not affect the mode of onset, the time needed to return to play, the type of injury, or the distribution of body locations of the injuries. In summary, women football players with different genotypes of the p.R577X ACTN3 polymorphism had similar values of football-specific performance and injury incidence. From a practical perspective, the ACTN3 genotyping may not be useful to predict performance or injury incidence in professional women football players.pre-print840 K

Evaluation of ECA Gesture strategies for robust Human-Computer Interaction

Embodied Conversational Agents (ECAs) offer us the possibility to design pleasant and efficient human-machine interaction. In this paper we present an evaluation scheme to compare dialogue-based speaker authentication and information retrieval systems with and without ECAs on the interface. We used gestures and other visual cues to improve fluency and robustness of interaction with these systems. Our tests results suggest that when an ECA is present users perceive fewer system errors, their frustration levels are lower, turn-changing goes more smoothly, the interaction experience is more enjoyable, and system capabilities are generally perceived more positively than when no ECA is present. However, the ECA seems to intensify the users' privacy concerns