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Convergent evolution in European and Rroma populations reveals pressure exerted by plague on Toll-like receptors
No full textRecent historical periods in Europe have been characterized by severe epidemic events such as plague, smallpox, or influenza that shaped the immune system of modern populations. This study aims to identify signals of convergent evolution of the immune system, based on the peculiar demographic history in which two populations with different genetic ancestry, Europeans and Rroma (Gypsies), have lived in the same geographic area and have been exposed to similar environments, including infections, during the last millennium. We identified several genes under evolutionary pressure in European/Romanian and Rroma/Gipsy populations, but not in a Northwest Indian population, the geographic origin of the Rroma. Genes in the immune system were highly represented among those under strong evolutionary pressures in Europeans, and infections are likely to have played an important role. For example, Toll-like receptor 1 (TLR1)/TLR6/TLR10 gene cluster showed a strong signal of adaptive selection. Their gene products are functional receptors for Yersinia pestis, the agent of plague, as shown by overexpression studies showing induction of proinflammatory cytokines such as TNF, IL-1B, and IL-6 as one possible infection that may have exerted evolutionary pressures. Immunogenetic analysis showed that TLR1, TLR6, and TLR10 single-nucleotide polymorphisms modulate Y. pestis-induced cytokine responses. Other infections may also have played an important role. Thus, reconstruction of evolutionary history of European populations has identified several immune pathways, among them TLR1/TLR6/TLR10, as being shaped by convergent evolution in two human populations with different origins under the same infectious environment.This work was funded by Grant BFU2010-19443 (to J.B.) from the Ministerio de Ciencia y Tecnología (Spain) and the Direccío General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2009 SGR 1101). P.L. was supported by a PhD fellowship from "Acción Estratégica de Salud, en el Marco del Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008-2011" from Instituto de Salud Carlos III. B.K.T. was supported by Grant BT/01/COE/07/UDSC from the Department of Biotechnology, Government of India, New Delhi
Role of polycomb-like proteins in mouse embryonic stem cell differentiation
No full textPolycomb repressive complex (PRC) 2 is one of the key regulators of the transcriptional programs, it maintains stem cell properties and guides cell lineage specification. It is a multiprotein complex formed by a core and the associated factors that are assembled and dynamically expressed in a cell type-specific manner. Although extensive studies have elucidated the role and composition of PRC2 in mouse embryonic stem cells (ESCs), little is known about its architecture and function during cellular differentiation. Polycomb-Like proteins (PCLs) are three mutually exclusive accessory factors of PRC2, crucial for chromatin recruitment of the complex. This thesis aims to characterise the role of PCLs during ESCs differentiation into mesodermal embryoid bodies (mesoEBs), pinpointing the essential MTF2 protein timeframe to address its molecular functions during this cellular fate transition.El complejo de represión Polycomb (PRC) 2 es uno de los reguladores clave de los programas de transcripción, mantiene las propiedades de las células madre y guía la especificación de la línea celular. Es un complejo multiproteico formado por un núcleo y los factores asociados que se ensamblan y expresan dinámicamente al nucleo de manera específica a cada tipo celular. A pesar de que estudios extensos han dilucidado el papel y la composición del PRC2 en las células madre embrionarias de ratón (ESCs), se sabe poco sobre su arquitectura y función durante la diferenciación celular. Las proteines Polycomb-Like (PCLs) son tres factores accesorios mutuamente exclusivos de PRC2, cruciales para el reclutamiento a la cromatina del complejo. Esta tesis tiene como objetivo caracterizar el papel de las PCLs durante la diferenciación de las células madre embrionarias (ESCs) en embryoid bodies mesodérmicos (mesoEBs), identificando el período esencial de la proteína MTF2 para abordar sus funciones moleculares durante esta transición en el destino celular.Programa de Doctorat en Biomedicin
A Reformulation Proposal of the Mutual Agreement Procedure: The Inclusion of Meditation as Alternative Dispute Resolution Mechanism of Transfer Pricing Conflicts
No full textTransfer pricing disputes have significantly increased, requiring efficient and effective dispute resolution procedures. Despite the availability of domestic remedies and the MAP, due to the features of the procedure and transfer pricing disputes, the latter is more suitable. Nevertheless, according to the carried investigations, the MAP has crucial failures for dispute settlement, which urge to be addressed, as some disputes remain unresolved or pending resolution. After assessing ADR mechanisms to be included in the MAP considering features of transfer pricing disputes, mediation demonstrated to be more inclusive, transparent, more acceptable among jurisdictions, while able to deliver fairer and more satisfactory settlements quickly and effectively. Given the importance of legal certainty, efficiency and effectiveness in dispute resolution when performing transfer pricing transactions, the main contribution of this research is a reformulation of the MAP with the inclusion of mediation, besides the framework proposal to better conduct the MAP with mediation.Los litigios en materia de precios de transferencia han aumentado significativamente, lo que exige contar con mecanismos de resolución de conflictos eficientes y eficaces. A pesar de la disponibilidad de recursos internos y del procedimiento amistoso, este último resulta ser el método más adecuado. Sin embargo, según las investigaciones realizadas, este procedimiento presenta fallos cruciales para la resolución de dichos conflictos, que requieren ser abordados con urgencia (pues algunos de ellos no llegan a resolverse nunca o quedan pendientes de resolución). Tras evaluar los mecanismos alternativos de resolución de conflictos que pueden incluirse en el MAP, en atención a las características de los conflictos en materia de precios de transferencia, la mediación demostró ser más inclusiva, transparente y aceptable entre jurisdicciones, al tiempo que permite alcanzar acuerdos más justos y satisfactorios de forma rápida y eficaz. Dada la importancia de la seguridad jurídica, la eficiencia y la eficacia en la resolución de conflictos en materia de precios de transferencia, la principal contribución de esta investigación consiste en presentar una reformulación del MAP con la inclusión de la mediación, así como una propuesta marco para mejorar la aplicación del MAP a través de la mediación.Programa de Doctorat en Dre
Effect of a multifactorial weight loss intervention on HDL cholesterol efflux capacity and immunosenescence: a randomized controlled trial
No full textObjective: Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence. Method: CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m2 and metabolic syndrome were included. Results: Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (-3.32% ± 12.54% and -6.74% ± 11.2%, p < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention. Conclusions: A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.The PREDIMED-Plus-IMDEA trial was supported by CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (coordinated FIS projects led by JSS and JV, including the following projects: PI14/0137 and PI17/00508). ECS acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades, FJC2020-045377-I, funded by MCIN/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR. APF has been funded by the Spanish Association Against Cancer-AECC (PRDMA18011PAST). PJFM has been funded by a Ramon y Cajal Award from the Spanish Ministry of Science, Innovation and Universities (MICINN) (RYC-2017-22335). This study has been carried out thanks to the funds provided by Ministerio de Ciencia e Investigación through grants from PROYECTOS DE I + D + I «RETOS INVESTIGACIÓN» (RTI2018-095569-B-I00 and RTI2018-098113-B-I00) and «PROGRAMACIÓN CONJUNTA INTERNACIONAL» (PCI2018-093009). JSS was partially supported by ICREA under the ICREA Academia program
La puntuació en les traduccions de Konstantinos P. Kavafis per Carles Riba i per Alexis Eudald Solà: el cas del guió
No full textLes traduccions de Konstantinos P. Kavafi s de Carles Riba i d’Alexis Eudald Solà comparteixen l’objectiu de voler ser “la més literal i alhora la més literària”. Segons el mateix Solà, això implica la recerca de la més gran precisió en cada paraula i expressió, combinada amb la recreació d’una llengua dotada de força expressiva i amb atenció al ritme. Pel que fa al tercer d’aquests punts, cal tenir en compte com, més enllà de la mètrica, la poesia de Kavafi s es distingeix per un joc de pauses i canvis de ritme modulats per una puntuació peculiar. Aquest article es qüestiona com se’n pot fer una traducció, a través de l’estudi concret del guió. Es tracta d’un signe de ruptura, que s’ajusta perfectament al to dialogal de la poesia de Kavafi s. La riquesa d’aquest signe es fa manifesta en les tres opcions que presenten, sense cap explicació per part dels seus autors, els tres volums de traduccions de Riba i de Solà de què disposem, i ens porta a plantejarnos de nou la significació del que és literal i el que és literari
Evaluation checklist for the multidisciplinary approach to patients with asthma or suspected asthma in united airway disease
No full textPurpose: To generate an evaluation checklist for the multidisciplinary approach to patients with asthma or suspected asthma. Patients and methods: This was a qualitative study based on a literature review and expert opinions. A multidisciplinary steering committee with knowledge and experience in asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) was established and comprised two pneumologists, two allergologists, and two otorhinolaryngologists. They designed a preliminary evaluation checklist based on the best evidence available and their experience. An extra panel of 21 experts (five pneumologists, five allergologists, and 11 otorhinolaryngologists) analyzed and discussed the checklist, leading to the final version. Results: The checklist for the multidisciplinary approach to patients with asthma or suspected asthma includes the first and the follow-up visits. It is organized into several sections covering 1) current asthma and past history (diagnosis, symptoms, severity, control, etc.); 2) comorbidities (CRSwNP, atopic dermatitis, etc.); 3) physical examination and diagnostic tests (spirometry, bronchodilator reversibility test, fractional exhaled nitric oxide, etc.); 4) complementary tests (imaging, laboratory, allergy tests, etc.); 5) red flags (near-fatal asthma, CRSwNP complications); and 6) biological treatment (indication, response to treatment, decision making, etc.). Each section is divided into sub-sections detailing the recommended evaluation items. These items contain explanations, definitions, or variable lists that can be measured using direct questions, validated questionnaires, or other procedures such as imaging techniques or biomarkers. The checklist also proposes clinical actions. Conclusion: This evaluation checklist might help improve and standardize the clinical management of patients with asthma or suspected asthma
Cognitive and synaptic outcomes of targeting peripheral cannabinoid type-1 receptor: focus on naïve and intellectual disability mouse models
No full textCognition is a physiological brain function that refers to the process of acquiring and managing knowledge and understanding. It embraces multiple domains, including memory. Intellectual disability disorders such as fragile X syndrome, show in most cases deficits in learning and memory performance. The endocannabinoid system is an endogenous neuromodulatory network widely distributed in the central nervous system and peripheral tissues. It is under study as a potential therapeutic target, but its overall modulation may trigger several unwanted effects. In this thesis we have evaluated the cognitive and synaptic outcomes of inhibiting the peripheral cannabinoid type-1 receptor (CB1R) in naïve mice and in a mouse model of fragile X syndrome, showing that this peripheral approach may enhance memory persistence and synaptic plasticity in both mouse models. Altogether, combining behavioral, pharmacological, biochemical, electrophysiological, microbiological and transcriptomic approaches, we have identified the peripheral CB1R as a modulator of memory processes in health conditions, and as a potential therapeutic target in the treatment of intellectual disability.La cognició és una funció fisiològica del cervell que fa referència al procés d’adquisició i gestió del coneixement i la comprensió. Comprèn múltiples dominis, inclosa la memòria. Els trastorns de discapacitat intel·lectual, com ara la síndrome del X fràgil, mostren en la majoria de casos dèficits en l’aprenentatge i la memòria. El sistema endocannabinoide és una xarxa neuromoduladora endògena àmpliament distribuïda al sistema nerviós central i als teixits perifèrics. Està en estudi com a potencial diana terapèutica, però la seva modulació global pot provocar efectes adversos. En aquesta tesi hem avaluat els efectes cognitius i sinàptics de la inhibició del receptor cannabinoide perifèric tipus 1 (CB1R) en ratolins naïf i en un model de ratolí del síndrome del X fràgil, demostrant que aquesta aproximació perifèrica pot millorar la persistència de la memòria i la plasticitat sinàptica en ambdós models. En conjunt, combinant aproximacions conductuals, farmacològiques, bioquímiques, electrofisiològiques, microbiològiques i transcriptòmiques, hem identificat el CB1R perifèric com un modulador dels processos de memòria en condicions de salut, així com una diana terapèutica en el tractament de la discapacitat intel·lectual.La cognición es una función fisiológica del cerebro que hace referencia al proceso de adquisición y gestión del conocimiento y la comprensión. Comprende múltiples dominios, incluyendo la memoria. Los trastornos de discapacidad intelectual, como el síndrome del X frágil, muestran en la mayoría de casos déficits en el aprendizaje y la memoria. El sistema endocannabinoide es una red neuromoduladora endógena ampliamente distribuida en el sistema nervioso central y los tejidos periféricos. Está en estudio como potencial diana terapéutica, pero su modulación global puede desencadenar varios efectos adversos. En esta tesis hemos evaluados los efectos cognitivos y sinápticos de la inhibición del receptor cannabinoide periférico tipo 1 (CB1R) en ratones naíf y en un modelo de ratón del síndrome del X frágil, demostrando que esta aproximación periférica puede mejorar la persistencia de la memoria y la plasticidad sináptica en ambos modelos de ratón. En conjunto, combinando aproximaciones conductuales, farmacológicas, bioquímicas, electrofisiológicas, microbiológicas y transcriptómicas, hemos identificado el CB1R periférico como un modulador de los procesos de memoria en condiciones de salud, así como una posible diana terapéutica en el tratamiento de la discapacidad intelectual.Programa de Doctorat en Biomedicin
Interactive metadiscourse markers in abstracts written by undergraduate students
No full textThe abstract is a specialized type of academic discourse, like a lecture, literature review or research article, and therefore related to the expression and transmission of knowledge. The scientific literature offers numerous studies on the abstract as an academic genre based on corpora created by researchers who are themselves experts in their respective disciplines (Cavalieri 2014, Dos Santos 1996, Lorés & Bondi 2014, Saeeaw & Tangkiengsirisin 2014). Nonetheless, there exist relatively few studies which analyse how student writers acquire mastery over this genre (Aktas & Cortes 2008, Díez Prados 2018). As a contribution to filling this gap in the research, in the present study we will examine a corpus of abstracts written by undergraduates, focusing in particular on their use of interactive metadiscourse markers and the relationship between such markers and the rhetorical structure of the texts.This work was supported by the Assessment of Discourse Competence in Adult Plurilingual Learners: Detecting Learners’ Needs and Instructions for Autonomous Learning project (EDU2016-75874-P) under the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2016 of the Spanish Ministry of Economy, Industry and Competitiveness and co-financed by the Spanish State Research Agency (AEI) and the European Union’s Regional Development Fund (FEDER). The authors of this article belong to the Gr@el research group (Grup de recerca sobre aprenentatge i ensenyament de llengües ‘Language Learning and Teaching Research Group’), which is funded by a Catalan government AGAUR 2017-2019 grant (ref. 2017 SGR 915)
Pluralismo jurídico y mecanismos de coordinación entre los sistemas de justicia indígena y el sistema nacional de justicia en Colombia
No full textEl método negocial -como mecanismo para la elaboración de políticas que definan los límites y parámetros de coordinación entre la jurisdicción ordinaria y las jurisdicciones indígenas- es un imperativo constitucional bajo el ordenamiento establecido por la Constitución Política de 1991. No obstante, el método negocial ha fracasado, porque dos décadas después de la aprobación de la Constitución no se ha desarrollado una verdadera concertación que permita la aprobación de una ley de coordinación entre jurisdicciones. El fracaso del método negocial se hace patente en que el establecimiento de los criterios de coordinación, la fijación de los límites y la resolución de los conflictos de competencia se ha hecho y deberá hacerse -hasta que el método negocial no tenga éxito- caso a caso por parte de los jueces del Consejo Superior de la Judicatura y de la Corte Constitucional. Finalmente, el éxito del método negocial no garantiza la inexistencia de conflictos, ni debe ser excluyente de una aplicación conjunta con el método jurisprudencial
Essays on the Expected Credit Loss Model
No full textThe implementation of the Expected Credit Loss (ECL) model represents a significant change in financial reporting for banks by requiring the recognition of loan loss provisions based on expected credit losses at loan origination. This thesis examines the impact of the ECL model on bank transparency and lending decisions. Chapter 1 shows that the ECL model reduces the ability of equity investors to interpret loan loss provisions in banks' earnings announcements. Investors face greater difficulty in assessing the credit risk of a bank and incorporating this information into their investment decisions. This may be due to the insufficient disclosures about the main assumptions that banks use to calculate loan loss provisions under the ECL model. Chapter 2 examines the effect of the ECL model on the supply of credit in relationship banking. The findings indicate that the new impairment model reduces the role of relationship lending in facilitating credit access for firms, implying a reduction in the availability of credit at the firm level. Chapter 3 studies the impact of the ECL model on the measurement of normal and abnormal loan loss provisions, suggesting that traditional models used to detect earnings management in banks need to be extended to account for the dynamics of expected credit losses.La aplicación del modelo de pérdidas crediticias esperadas (ECL) representa un cambio importante en la información financiera de los bancos al exigir reservar por pérdidas crediticias esperadas en el momento de la concesión del préstamo. Esta tesis examina el impacto del modelo ECL sobre la transparencia bancaria y las decisiones de préstamo. El capítulo 1 muestra que el modelo ECL reduce la capacidad de los inversores de capital para interpretar las provisiones durante la presentación de los resultados financieros de los bancos. Los inversores tienen más dificultades para evaluar el riesgo de crédito de un banco e integrar esta información en sus decisiones de inversión. Esto se puede deber a la falta de información sobre los principales supuestos necesarios para el cálculo de las provisiones por pérdidas crediticias con ECL. El capítulo 2 examina el efecto del modelo ECL sobre la oferta de crédito en la banca relacional. Los resultados indican que el nuevo modelo reduce el papel de la banca relacional a la hora de facilitar que las empresas puedan acceder a nuevo crédito, lo que implica una reducción de la disponibilidad de crédito a nivel de empresa. El capítulo 3 estudia el impacto del modelo ECL en la medición de las provisiones por pérdidas crediticias normales y discrecionales, mostrando que los modelos tradicionales que se usan para detectar la gestión de beneficios en los bancos se deben modificar incorporando la dinámica de las pérdidas crediticias esperadas.Programa de Doctorat en Economia, Finances i Empres