Phylogenetic surveillance of viral genetic diversity and the evolving molecular epidemiology of human immunodeficiency virus type 1

With ongoing generation of viral genetic diversity and increasing levels of migration, the global human immunodeficiency virus type 1 (HIV-1) epidemic is becoming increasingly heterogeneous. In this study, we investigate the epidemiological characteristics of 5,675 HIV-1 pol gene sequences sampled from distinct infections in the United Kingdom. These sequences were phylogenetically analyzed in conjunction with 976 complete-genome and 3,201 pol gene reference sequences sampled globally and representing the broad range of HIV-1 genetic diversity, allowing us to estimate the probable geographic origins of the various strains present in the United Kingdom. A statistical analysis of phylogenetic clustering in this data set identified several independent transmission chains within the United Kingdom involving recently introduced strains and indicated that strains more commonly associated with infections acquired heterosexually in East Africa are spreading among men who have sex with men. Coalescent approaches were also used and indicated that the transmission chains that we identify originated in the late 1980s to early 1990s. Similar changes in the epidemiological structuring of HIV epidemics are likely to be taking in place in other industrialized nations with large immigrant populations. The framework implemented here takes advantage of the vast amount of routinely generated HIV-1 sequence data and can provide epidemiological insights not readily obtainable through standard surveillance methods.</p

Crisi econòmica i gestió de la inseguretat ciutadana: els mapes de la delinqüència

El context econòmic actual de crisi ha derivat cap a un discurs polític centrat, principalment, en la reducció dels pressupostos públics. Per tal de mantenir el nivell actual de serveis, l'aposta ha de passar per una major eficiència i eficàcia de la gestió pública, evitant la despesa innecessària i maximitzant l'impacte dels serveis prestats. La introducció i l'ús d'aplicacions informàtiques es preveu com una de les solucions a l'hora d'abaratir costos i processos de l'Administració. En l'àmbit de la seguretat, aquesta aposta es centra en un major desenvolupament d'eines de georeferenciació o sistemes d'informació geogràfica que tinguin com a finalitat millorar la gestió i visualització de la informació i facilitar-ne l'intercanvi entre plataformes policials. Però un ús eficient d'aquestes aplicacions requereix afrontar prèviament un conjunt de reptes relacionats amb les estructures organitzatives que les gestionaran i les possibilitats i expectatives tècniques que en deriven, així com una reflexió per mesurar les externalitats tant positives com negatives en un camp tan sensible com és el de la seguretat.El contexto económico actual de crisis ha derivado hacia un discurso político centrado, principalmente, en la reducción de los presupuestos públicos. Para mantener el nivel actual de servicios, la apuesta debe pasar por una eficiencia y eficacia mayor de la gestión pública, evitando el gasto innecesario y maximizando el impacto de los servicios prestados. La introducción y el uso de aplicaciones informáticas se prevé como una de las soluciones a la hora de abaratar costes y procesos de la Administración. En el ámbito de la seguridad, esta apuesta se centra en un desarrollo mayor de herramientas de georreferenciación o sistemas de información geográfica que tengan como finalidad mejorar la gestión y visualización de la información y facilitar el intercambio entre plataformas policiales. Pero un uso eficiente de estas aplicaciones requiere afrontar previamente un conjunto de retos relacionados con las estructuras organizativas que las gestionarán y las posibilidades y expectativas técnicas que se derivan, así como una reflexión para medir las externalidades tanto positivas como negativas en un campo tan sensible como es el de la seguridadThe current economic crisis has turned towards a path of political discourse based mainly on the reduction of public budgets. To maintain our current level of services, we need to increase the efficiency and efficacy of public administration, avoiding unnecessary expense and maximising the impact of the services provided. The introduction and use of IT applications is predicted to be one of the solutions that will help to cut costs and administrative procedures. In the area of safety, this solution focuses on further developing georeferencing tools or geographic information systems intended to improve the way information is managed, visualised and exchanged across police platforms. But before efficient use of these applications can be made, it is necessary to confront a series of challenges relating to the organizational structures that will be used to manage them and to their technical capacities and expectations, and to weigh up the positive and negative external factors at play in such a sensitive area as safety and security

A phylogenetic method for detecting positive epistasis in gene sequences and its application to RNA virus evolution

RNA virus genomes are compact, often containing multiple overlapping reading frames and functional secondary structure. Consequently, it is thought that evolutionary interactions between nucleotide sites are commonplace in the genomes of these infectious agents. However, the role of epistasis in natural populations of RNA viruses remains unclear. To investigate the pervasiveness of epistasis in RNA viruses, we used a parsimony-based computational method to identify pairs of co-occurring mutations along phylogenies of 177 RNA virus genes. This analysis revealed widespread evidence for positive epistatic interactions at both synonymous and nonsynonymous nucleotide sites and in both clonal and recombining viruses, with the majority of these interactions spanning very short sequence regions. These findings have important implications for understanding the key aspects of RNA virus evolution, including the dynamics of adaptation. Additionally, many comparative analyses that utilize the phylogenetic relationships among gene sequences assume that mutations represent independent, uncorrelated events. Our results show that this assumption may often be invalid.</p

Entre l'excepcionalitat i la informalitat: apunts per a un urbanisme postbombolla

Segons els autors l’esclat de la bombolla immobiliària ha tallat en sec la lògica de la plusvàlua que ha governat l’urbanisme fins ara. Aquest fet ha produït dos tipus de respostes que no solucionen pas els problemes derivats de la crisi: la resposta institucional basada en la promoció de megaprojectes (Eurovegas, BCNWorld, etc.), i l’urbanisme autogestionat (pràctiques urbanístiques de microtransformacions, de recuperació temporal d’espais, etc.). Les solucions que plantegen els autors passen per considerar l’urbanisme com a instrument polític, com a eina per al canvi social. Un urbanisme que ha de ser multidisciplinar i col·laboratiu i que gestioni (indivisiblement) tant l’urbanització i l’edificació del sòl, com els canvis del seu valor que la planificació genera.Según los autores del estallido de la burbuja inmobiliaria ha cortado en seco la lógica de la plusvalía que ha gobernado el urbanismo hasta ahora. Este hecho ha producido dos tipos de respuestas que no solucionan los problemas derivados de la crisis: la respuesta institucional basada en la promoción de megaproyectos (Eurovegas, BCNWorld, etc.), Y el urbanismo autogestionado (prácticas urbanísticas de microtransformaciones, de recuperación temporal de espacios, etc.). Las soluciones que plantean los autores pasan por considerar el urbanismo como instrumento político, como herramienta para el cambio social. Un urbanismo que debe ser multidisciplinar y colaborativo y que gestione (indivisiblemente) tanto la urbanización y la edificación del suelo, como los cambios de su valor que la planificación genera

The art and science of winning: professional cricket coaching as transdisciplinary practice

This context statement examines the thirty-year evolution of my coaching and leadership in professional sport through my work in the public domain. It focuses on how to optimally coach and manage teams to win across multiple formats in professional cricket. Examining and reflecting on the process of how this took place: the campaigns, the engagement with the team and performer, with the ultimate goal of optimizing (designing) team performance to win leagues and championships. To do this, I began by utilising my training in education. I designed a coaching and performance programme, which I divided into a time phased performance curriculum. Over time I began to see the holistic nature of performance and I evolved this thinking into a coaching system bringing together the mental, technical, physical and strategic aspects of performance, into the overarching design of 'winning' performance for individuals and teams. The system was centred both on the individual performer and the team, coaching them to set clear, precise performance goals, with the aim that they would go on to proactively take responsibility for their own learning process. The coaching and performance system evolved through research and constant testing with different teams and players. A ‘thought architecture’ (a term I coined) emerged, which is a design process to attain a goal or objective. The ‘thought architecture’ evolved into a specific coaching approach focused on performance design to create the neural circuitry of optimal performance. The goal was for the learning process to become unconscious thinking and action, both individually and collectively within the team. This submission examines and summarises the stages of learning, the role of mentors, the championships won and lost, the evolution of the transdisciplinary coaching model and the optimal performance system. This text analyses the professional context in which this work took place with reference to the theoretical frameworks that informed this study. I conclude by looking at both the applications of optimal performance in other professional fields and the implications of this practice

HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

Histone deacetylases (HDACs) regulate the acetylation of histones in the control of gene expression. Many non-histone proteins are also targeted for acetylation, including TGF-ß signalling pathway components such as Smad2, Smad3 and Smad7. Our studies in mouse C3H10T1/2 fibroblasts suggested that a number of TGF-ß-induced genes that regulate matrix turnover are selectively regulated by HDACs. Blockade of HDAC activity with trichostatin A (TSA) abrogated the induction of a disintegrin and metalloproteinase 12 (Adam12) and tissue inhibitor of metalloproteinases-1 (Timp-1) genes by TGF-ß, whereas plasminogen activator inhibitor-1 (Pai-1) expression was unaffected. Analysis of the activation of cell signalling pathways demonstrated that TGF-ß induced robust ERK and PI3K activation with delayed kinetics compared to the phosphorylation of Smads. The TGF-ß induction of Adam12 and Timp-1 was dependent on such non-Smad signalling pathways and, importantly, HDAC inhibitors completely blocked their activation without affecting Smad signalling. Analysis of TGF-ß-induced Adam12 and Timp-1 expression and ERK/PI3K signalling in the presence of semi-selective HDAC inhibitors valproic acid, MS-275 and apicidin implicated a role for class I HDACs. Furthermore, depletion of HDAC3 by RNA interference significantly down-regulated TGF-ß-induced Adam12 and Timp-1 expression without modulating Pai-1 expression. Correlating with the effect of HDAC inhibitors, depletion of HDAC3 also blocked the activation of ERK and PI3K by TGF-ß. Collectively, these data confirm that HDACs, and in particular HDAC3, are required for activation of the ERK and PI3K signalling pathways by TGF-ß and for the subsequent gene induction dependent on these signalling pathways