207 research outputs found

    A common copy-number variant within SIRPB1 correlates with human Out-of-Africa migration after genetic drift correction

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    Previous reports have proposed that personality may have played a role on human Out-Of- Africa migration, pinpointing some genetic variants that were positively selected in the migrating populations. In this work, we discuss the role of a common copy-number variant within the SIRPB1 gene, recently associated with impulsive behavior, in the human Out-Of-Africa migration. With the analysis of the variant distribution across forty-two different populations, we found that the SIRPB1 haplotype containing duplicated allele significantly correlated with human migratory distance, being one of the few examples of positively selected loci found across the human world colonization. Circular Chromosome Conformation Capture (4C-seq) experiments from the SIRPB1 promoter revealed important 3D modifications in the locus depending on the presence or absence of the duplication variant. In addition, a 3' enhancer showed neural activity in transgenic models, suggesting that the presence of the CNV may compromise the expression of SIRPB1 in the central nervous system, paving the way to construct a molecular explanation of the SIRPB1 variants role in human migration

    Methylation alterations are not a major cause of PTTG1 missregulation

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    Background: On its physiological cellular context, PTTG1 controls sister chromatid segregation during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity for which gained the over name of securin. PTTG1 was found to promote malignant transformation in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently, PTTG1 has been also related to different processes such as DNA repair and found to trans-activate different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be excluded that this effect may also occur in other tumor types. Despite the clinical relevance and the increasing molecular characterization of PTTG1, the reason for its up-regulation remains unclear. Method: We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1 immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix 50 K microarray technology and FRET analysis to search for allelic imbalances comprising the PTTG1 locus. Conclusion: Our data suggest that neither methylation alterations nor LOH are involved in PTTG1 over-expression. These data, together with those previously reported, point towards a post-transcriptional level of missregulation associated to PTTG1 over-expression.This project was funded by The Fundación de Investigación Biomédica Mutua Madrileña Automovilista. Neocodex have been partially funded by the Ministerio de Educación y Ciencia of Spain (FIT-010000-2004-69, PTQ04-1-0006, PTQ2003-0549, PTQ2003-0546 and PTQ2003-0783). MAJ was also supported by SAF2005- 07713-C03-03 and CS by FIS 06/757

    A new generation of vectors with increased induction ratios by overimposing a second regulatory level by attenuation

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    A major drawback of regulated gene expression from vectors bearing strong promoters is the associated high basal expression level. Simple regulatory systems have an intrinsic limitation in the range of induction, and attempts to mutate promoters to reduce basal expression usually result in concomitant reduction of induced levels. We have explored the possibility of reducing basal levels of gene expression while keeping induced levels intact by incorporating an additional regulatory circuit controlling a different step of the expression process. We have integrated the nasFEDCBA transcriptional attenuation system of Klebsiella oxytoca into a cascade expression circuit based on different regulatory elements of Pseudomonas putida, and also into a system based on the tac promoter, to expand their regulatory capacity. Basal expression from the promoters of these circuits was reduced by more than 10-fold by the nasF attenuator sequence while keeping the induced levels intact in the presence of the antiterminator protein, thus increasing the induction ratio by up to 1700-fold. In addition, using different combinations of regulatory elements and inducing conditions, we were able to obtain a broad range of expression levels. These vectors and the concept of their design will be very useful in regulating overproduction of heterologous proteins both at laboratory and industrial scales

    The dynamics of cluster entrepreneurship: Knowledge legacy from parents or agglomeration effects? The case of the Castellon ceramic tile district

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    [EN] What are the main mechanisms driving the process of industry clustering? There is a tension between two different perspectives as regards explaining entrepreneurship and spatial concentration: the roles played by agglomeration economies and knowledge legacies passed on from parents to spawns or spinoffs. Using qualitative interviews and archival data analysis, this paper tracks the evolution and the organizational reproduction of the ceramic tile cluster of Castellon (Spain) since its inception in 1727. Results show the existence of agglomeration and socially-based co-operation forces. Beyond de novo spinoffs, abundant social capital in highly agglomerated regions facilitates co-operation and new firm formation, and even co-operation amongst competitors to create new firms. Socially-based networks, reinforced by agglomeration externalities, all act as learning mechanisms to build pre-entry capabilities in new ventures, complementing Klepper¿s inheritance perspective. Spatial concentration of an industry can be attributed to the benefits of agglomeration and socially-based co-operation, in combination with the influence of knowledge legacies in a complementary and synergistic process. Conclusions are framed within the knowledge spillover theory of entrepreneurship, shedding light on how entrepreneurship occurs in clusters.We thank Editor Martin Kenney, David Audretsch and Guido Buenstorf for their fantastic and constructive comments. Jose-Luis Hervas-Oliver also thanks Fiorenza Belussi, Andrea Furlani and Roberto Grandinetti for their comments at the presentation in the Padova PhD course. Carlos Camahort and the Porcelanosa co-owner Maria Jose Soriano were both very helpful with data and insights, as well as ASCER (Michel Toumi). We are thankful to financial support from the Spanish Ministry of Economics (MINECO) under research grant ECO2015:63645-R (MINECO/FEDER) Open Innovation in Clusters.Hervás Oliver, JL.; Lleo, M.; Cervelló Royo, RE. (2017). The dynamics of cluster entrepreneurship: Knowledge legacy from parents or agglomeration effects? The case of the Castellon ceramic tile district. Research Policy. 46(1):73-92. https://doi.org/10.1016/j.respol.2016.10.006S739246

    Trypsin/α-amylase inhibitors and thionins: possible defence proteins from barley

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    This chapter reviews recent work on the trypsin/α-amylase inhibitor and thionin protein families. The genomic distribution of protein genes in barley and related species, gene expression and in vitro activities are considered. Some of the evidence of a possible defence role against stored products pests for inhibitors and thionins is briefly discusse

    Market value vs. legal value in land use change in Spain

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    [EN] The Spanish Land Law of May 28, 2007 gave rise to a radical change in the determination of the legal value of the land for agricultural use under compulsory purchase proceedings linked to the transformation of their use. Under this new law the compulsory purchase value is calculated based on the real or potential discounted cash flow at a determined rate set in the rule, with the aim of avoiding the negative effects of speculation. The aim of this work was to compare if there are significant differences between the values obtained when applying the methodology provided under the new law and the values presented in the national land prices survey. We have considered whether differences actually exist between the values obtained when applying the methodology provided under the new law and the values presented in the national survey; and the aim of this work is to compare these values. For this purpose the variables relevant for the application of the capitalization method were estimated based on the data published in the Spanish official statistics. Significant differences were found between the legal rate and the one which estimates the market values, with an average value for the studied period of 3.45% and 1.75%, respectively; additionally, different trends were observed. Also the existence of different discount rates for the market value depending on the land use against the unique rate set in the rule has been verified; therefore, the real distortion which a single capitalization rate could give rise to is very significant.Segura García Del Río, B.; Pérez-Salas Sagreras, JL.; Cervelló Royo, RE.; Vidal, F. (2010). Market value vs. legal value in land use change in Spain. Journal of Food Agriculture & Environment. 8(3&4):1208-1211. http://hdl.handle.net/10251/108620S1208121183&

    New GOLD classification: longitudinal data on group assignment

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    Rationale: Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). Objective: To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. Methods: We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. Results: At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). Conclusions: In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index

    A method for detecting epistasis in genome-wide studies using case-control multi-locus association analysis

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    <p>Abstract</p> <p>Background</p> <p>The difficulty in elucidating the genetic basis of complex diseases roots in the many factors that can affect the development of a disease. Some of these genetic effects may interact in complex ways, proving undetectable by current single-locus methodology.</p> <p>Results</p> <p>We have developed an analysis tool called Hypothesis Free Clinical Cloning (HFCC) to search for genome-wide epistasis in a case-control design. HFCC combines a relatively fast computing algorithm for genome-wide epistasis detection, with the flexibility to test a variety of different epistatic models in multi-locus combinations. HFCC has good power to detect multi-locus interactions simulated under a variety of genetic models and noise conditions. Most importantly, HFCC can accomplish exhaustive genome-wide epistasis search with large datasets as demonstrated with a 400,000 SNP set typed on a cohort of Parkinson's disease patients and controls.</p> <p>Conclusion</p> <p>With the current availability of genetic studies with large numbers of individuals and genetic markers, HFCC can have a great impact in the identification of epistatic effects that escape the standard single-locus association analyses.</p

    ACTIVAPP

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    Activapp se origina a partir para cubrir una necesidad en el mercado peruano, buscamos ofrecer a los potenciales usuarios una alternativa novedosa que permita mejorar la salud y el rendimiento en el trabajo mediante pausas activas, ya que se ha demostrado que realizar estas actividades durante la jornada de trabajo generan una disminución del estrés, de la carga laboral y se mejora la circulación sanguínea promoviendo el bienestar de la persona. Asimismo, no solo se ofrecerá este servicio, vamos a complementar con sesiones de psicología, nutrición, yoga. De esta manera, las personas tendrán un servicio novedoso que brinda distintas opciones. Este proyecto no solo impactará en la salud y rendimiento laboral sino también ayudará a las empresas a tener colaboradores con mayor rendimiento y mantener el estado tanto físico como mental en niveles óptimos. Para el modelo de negocio es necesario contar un un aplicativo, el cual va a desarrollarse y dentro de las funciones el usuario podrá registrarse, separar una sesión y usar el servicio. Asimismo, también se tendrá un área de soporte tecnológico para ayudarlos en cualquier duda respecto al uso del aplicativo o de los servicios. Al ofrecer un producto digital, nuestra estrategia comunicacional estará dirigida en su mayoría en los medios digitales y en el uso de redes sociales, la cual estará segmentada para trabajadores y permitirá una adecuada llegada a los potenciales consumidores. El objetivo del proyecto busca que, en un período de 5 años, convertirse en una aplicación líder en mejorar la salud y bienestar a los trabajadores remotos mediante el uso de este servicio.Activapp originates from to cover a need in the Peruvian market, we seek to offer potential users a novel alternative that allows improving health and performance at work through active breaks, since it has been shown that carrying out these activities during the day of work generate a decrease in stress, workload and improves blood circulation promoting the well-being of the person. Likewise, not only will this service be offered, we will complement it with psychology, nutrition, and yoga sessions. In this way, people will have a new service that offers different options. This project will not only impact health and work performance, but will also help companies to have higher-performing employees and maintain both physical and mental state at optimal levels. For the business model it is necessary to have an application, which will be developed and within the functions the user will be able to register, separate a session and use the service. Likewise, there will also be a technological support area to help them with any questions regarding the use of the application or the services. By offering a digital product, our communication strategy will be directed mostly to digital media and the use of social networks, which will be segmented for workers and will allow an adequate reach to potential consumers. The objective of the project is to become, in a period of 5 years, a leading application in improving the health and well-being of remote workers through the use of this service.Trabajo de investigació
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