A genomic analysis identifies a novel component in the genetic structure of sub-Saharan African populations

Studies of large sets of SNP data have proven to be a powerful tool in the analysis of the genetic structure of human populations. In this work, we analyze genotyping data for 2,841 SNPs in 12 Sub-Saharan African populations, including a previously unsampled region of south-eastern Africa (Mozambique). We show that robust results in a world-wide perspective can be obtained when analyzing only 1,000 SNPs. Our main results both confirm the results of previous studies, and show new and interesting features in Sub-Saharan African genetic complexity. There is a strong differentiation of Nilo-Saharans, much beyond what would be expected by geography. Hunter-gatherer populations (Khoisan and Pygmies) show a clear distinctiveness with very intrinsic Pygmy (and not only Khoisan) genetic features. Populations of the West Africa present an unexpected similarity among them, possibly the result of a population expansion. Finally, we find a strong differentiation of the south-eastern Bantu population from Mozambique, which suggests an assimilation of a pre-Bantu substrate by Bantu speakers in the region.

A variant in the gene FUT9 is associated with susceptibility to placental malaria infection

Malaria in pregnancy forms a substantial part of the worldwide burden of malaria, with an estimated annual death toll of up to 200,000 infants, as well as increased maternal morbidity and mortality. Studies of genetic susceptibility to malaria have so far focused on infant malaria, with only a few studies investigating the genetic basis of placental malaria, focusing only on a limited number of candidate genes. The aim of this study therefore was to identify novel host genetic factors involved in placental malaria infection. To this end we carried out a nested case-control study on 180 Mozambican pregnant women with placental malaria infection, and 180 controls within an intervention trial of malaria prevention. We genotyped 880 SNPs in a set of 64 functionally related genes involved in glycosylation and innate immunity. A SNP located in the gene FUT9, rs3811070, was significantly associated with placental malaria infection (OR = 2.31, permutation p-value = 0.028). Haplotypic analysis revealed a similarly strong association of a common haplotype of four SNPs including rs3811070. FUT9 codes for a fucosyl-transferase that is catalyzing the last step in the biosynthesis of the Lewis-x antigen, which forms part of the Lewis blood group-related antigens. These results therefore suggest an involvement of this antigen in the pathogenesis of placental malaria infection.

Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.

A targeted association study of immunity genes and networks suggests novel associations with placental malaria infection

A large proportion of the death toll associated with malaria is a consequence of malaria infection during pregnancy, causing up to 200,000 infant deaths annually. We previously published the first extensive genetic association study of placental malaria infection, and here we extend this analysis considerably, investigating genetic variation in over 9,000 SNPs in more than 1,000 genes involved in immunity and inflammation for their involvement in susceptibility to placental malaria infection. We applied a new approach incorporating results from both single gene analysis as well as gene-gene interactionson a protein-protein interaction network. We found suggestive associations of variants in the gene KLRK1 in the single geneanalysis, as well as evidence for associations of multiple members of the IL-7/IL-7R signalling cascade in the combined analysis. To our knowledge, this is the first large-scale genetic study on placental malaria infection to date, opening the door for follow-up studies trying to elucidate the genetic basis of this neglected form of malaria.

African signatures of recent positive selection in human FOXI1

Background: The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene underhuman-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences.Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans,20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39worldwide human populations from the HGDP-CEPH diversity panel.Results: The genome sequences recently available from other primate and non-primate species showed that FOXI1divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant inEuropeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsbstatistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recentepisode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on theputatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies stronglycorrelated with the absolute geographical latitude of the populations sampled.Conclusions: We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate mightbe related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediatedwater-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.

¿Es obligatorio interpretar la normativa española de origen interno sobre precios de transferencia según las Directices de la OCDE?

Este trabajo cuenta con financiación del Ministerio de Ciencia e Innovación y del Fondo Social Europeo (ayuda BES-2008-003252)

La introducción del inglés en la docencia y su influencia en los contenidos de las asignaturas de Derecho Financiero y Tributario

A pesar de que numerosos juristas (jueces, notarios, registradores de la propiedad...) puedan desarrollarsu carrera profesional sin necesitar conocer lenguas extranjeras, el dominio del inglés es una competenciaimprescindible para desarrollar una carrera profesional como jurista en los principalesdespachos de abogados españoles, en empresas multinacionales o en organizaciones internacionales.Así pues, es lógico que en el actual contexto del espacio europeo de educación superior los nuevosestudios de Grado promuevan el dominio de esta competencia introduciendo el inglés en la docencia.En el ámbito particular del Derecho Financiero y Tributario ello no resulta frecuentemente posible ya quefundamentalmente se estudia el ordenamiento jurídico español y por lo tanto las fuentes se encuentrandisponibles únicamente en castellano. Sin embargo, existen varias estrategias que permiten introducir elinglés en la docencia, aunque sea de forma parcial y afectando ligeramente a los contenidos tradicionalesde las asignaturas. Una posibilidad consiste en tratar cuestiones de Derecho Comparado en lasactividades que se desarrollan en las asignaturas centradas en el Derecho español. Otra posibilidadconsiste en impartir la asignatura de Fiscalidad Internacional en inglés, si bien ello requiere reformularsu contenido y centrarlo en los principios generales en vez de en la normativa española que regula latributación de supuestos de hecho con elementos internacionales. A pesar de que la introducción delinglés en la docencia plantee un importante reto tanto para el alumnado como para el profesorado, entendemosque es algo necesario en los tiempos actuales.

Aplicación de buenas prácticas para la mejora de la calidad de los trabajos fin de grado en Ing. en Diseño Industrial

El trabajo presentado en esta comunicación se enmarca en un proyecto financiado por la Secretaría de Estado de Universidades, Ministerio de Educación Cultura y Deporte en su Programa de Estudios y Análisis, mejora de la calidad de la enseñanza superior y de la actividad del profesorado universitario en el Eje de Nuevos avances y determinación del impacto de las misiones universitarias, Modalidad de Trabajos de análisis, lideradopor la Universitat Pompeu Fabra y en el que participan docentes de las universidades de Valladolid, Cádiz, Las Palmas de Gran Canaria, Sevilla, Autónoma de Barcelona, Carlos III de Madrid y Universidat Oberta de Catalunya.En el proyecto se ha realizado un trabajo de análisis de las prácticas programadas en las distintas universidades para velar por la calidad de los trabajos fin de grado, actualmente proyectos fin carrera. Se han recopilado diferentes procedimientos de evaluación llevados a cabo en diferentes Universidades que van desde plantillas de verificación para los tribunales de los proyectos a guías de procedimiento completas que verifican elestablecimiento y cumplimiento de hitos intermedios.En esta comunicación se muestra la aplicación de algunas de las prácticas propuestas en el caso real de proyectos fin de carrera en la titulación de Ingeniería Técnica en Diseño Industrial de la Escuela de Ingenierías Industriales. Se pone de manifiesto la utilidad del uso de dichas prácticas frente a enfoques más clásicos o simplistas.

La Lectura crítica en los libros de educación secundaria : concepción y tratamiento metodológico

La presente investigación propone comparar y analizar la concepción y la forma cómo abordan la lectura crítica los libros de texto del Ministerio de Educación y las editoriales privadas de educación secundaria en el Perú. El estudio se desarrolla desde la perspectiva de los Nuevos Estudios de Literacidad y la Literacidad crítica, que conciben la lectura como una práctica social situada. La metodología es descriptiva y explorativa; se sustenta en el análisis cuantitativo y cualitativo. El corpus de análisis lo constituyen los textos de lectura y las actividades de comprensión crítica de 4 manuales del Ministerio de Educación y 3 de las editoriales Norma y Santillana. Los resultados demuestran que tanto los objetivos como el tratamiento de los textos de lectura se desarrollan desde la perspectiva psicolingüística y lingüística de la lectura. Leer críticamente significa opinar sobre el texto y la práctica de la literacidad crítica es aún incipiente, porque las actividades siguen concentradas en la comprensión literal del texto y, generalmente, se callan las ideologías y las relaciones de poder. En conclusión, no existen diferencias significativas entre los dos tipos de manuales.

Hotusa hotels

Hotusa nace en 1977 fruto de la iniciativa de un grupo de hoteleros de Barcelona (España) que, ante la pujanza de las nuevas cadenas hoteleras, deciden unir sus fuerzas creando una organización que les preste servicios de comercialización de forma conjunta. Hoy en día Hotusa cuenta con más de 2.500 hoteles en 48 países de cuatro continentes y se configura como uno de los principales consorcios hoteleros a nivel mundial y el primero a nivel europeo. La organización está formada, entre otras, por las cadenas de hoteles independientes Hotusa Hotels y Elysées West Hotels; el representante hotelero Keytel; el tour operador Restel; la website de gestión y reserva on-line Hotelius.com, la compañía tecnológica IGM Web; la cadena Eurostars Hotels. El objetivo de Hotusa es el de dotar a hoteles independientes y pequeños grupos, de todas aquellas herramientas que puedan ayudarles a competir en igualdad de condiciones con las grandes cadenas hoteleras a nivel internacional. Comercialización, distribución, representación, tecnología, sistemas de calidad y aprovisionamientos son los puntos fuertes de la compañía, sobre los que gira la actividad tradicional. La segmentación en diferentes marcas y, en consecuencia, la adaptación a ellas de los servicios, constituye el gran reto de futuro de la organización. La sede central se encuentra en Barcelona (España), si bien cuentan con oficinas en Roma, Paris, Londres, Viena, Lisboa y Buenos Aires. En 2008 recibió el Premio Príncipe Felipe a la Excelencia Turística, otorgado por el Ministerio de Industria, Turismo y Comercio de España como reconocimiento a su contribución al incremento de la competitividad de la industria turística española así como a la consolidación de su posición en el mercado turístico internacional.

Aitchison Geometry for Probability and Likelihood as a new approach to mathematical statistics

The Aitchison vector space structure for the simplex is generalized to a Hilbert space structure A2(P) for distributions and likelihoods on arbitrary spaces. Centralnotations of statistics, such as Information or Likelihood, can be identified in the algebraical structure of A2(P) and their corresponding notions in compositional data analysis, such as Aitchison distance or centered log ratio transform.In this way very elaborated aspects of mathematical statistics can be understoodeasily in the light of a simple vector space structure and of compositional data analysis. E.g. combination of statistical information such as Bayesian updating,combination of likelihood and robust M-estimation functions are simple additions/perturbations in A2(Pprior). Weighting observations corresponds to a weightedaddition of the corresponding evidence.Likelihood based statistics for general exponential families turns out to have aparticularly easy interpretation in terms of A2(P). Regular exponential families formfinite dimensional linear subspaces of A2(P) and they correspond to finite dimensionalsubspaces formed by their posterior in the dual information space A2(Pprior).The Aitchison norm can identified with mean Fisher information. The closing constant itself is identified with a generalization of the cummulant function and shown to be Kullback Leiblers directed information. Fisher information is the local geometry of the manifold induced by the A2(P) derivative of the Kullback Leibler information and the space A2(P) can therefore be seen as the tangential geometry of statistical inference at the distribution P.The discussion of A2(P) valued random variables, such as estimation functionsor likelihoods, give a further interpretation of Fisher information as the expected squared norm of evidence and a scale free understanding of unbiased reasoning

Some last thoughts on compositional data analysis

One of the disadvantages of old age is that there is more past than future: this,however, may be turned into an advantage if the wealth of experience and, hopefully,wisdom gained in the past can be reflected upon and throw some light on possiblefuture trends. To an extent, then, this talk is necessarily personal, certainly nostalgic,but also self critical and inquisitive about our understanding of the discipline ofstatistics. A number of almost philosophical themes will run through the talk: searchfor appropriate modelling in relation to the real problem envisaged, emphasis onsensible balances between simplicity and complexity, the relative roles of theory andpractice, the nature of communication of inferential ideas to the statistical layman, theinter-related roles of teaching, consultation and research. A list of keywords might be:identification of sample space and its mathematical structure, choices betweentransform and stay, the role of parametric modelling, the role of a sample spacemetric, the underused hypothesis lattice, the nature of compositional change,particularly in relation to the modelling of processes. While the main theme will berelevance to compositional data analysis we shall point to substantial implications forgeneral multivariate analysis arising from experience of the development ofcompositional data analysis…

Compositional Data in Biomedical Research

Modern methods of compositional data analysis are not well known in biomedical research.Moreover, there appear to be few mathematical and statistical researchersworking on compositional biomedical problems. Like the earth and environmental sciences,biomedicine has many problems in which the relevant scienti c information isencoded in the relative abundance of key species or categories. I introduce three problemsin cancer research in which analysis of compositions plays an important role. Theproblems involve 1) the classi cation of serum proteomic pro les for early detection oflung cancer, 2) inference of the relative amounts of di erent tissue types in a diagnostictumor biopsy, and 3) the subcellular localization of the BRCA1 protein, and it'srole in breast cancer patient prognosis. For each of these problems I outline a partialsolution. However, none of these problems is \solved". I attempt to identify areas inwhich additional statistical development is needed with the hope of encouraging morecompositional data analysts to become involved in biomedical research

Compositions in life science data

The aim of this talk is to convince the reader that there are a lot of interesting statisticalproblems in presentday life science data analysis which seem ultimately connected withcompositional statistics.Key words: SAGE, cDNA microarrays, (1D-)NMR, virus quasispecies

Experimental design on the simplex

Optimum experimental designs depend on the design criterion, the model andthe design region. The talk will consider the design of experiments for regressionmodels in which there is a single response with the explanatory variables lying ina simplex. One example is experiments on various compositions of glass such asthose considered by Martin, Bursnall, and Stillman (2001).Because of the highly symmetric nature of the simplex, the class of models thatare of interest, typically Scheff´e polynomials (Scheff´e 1958) are rather differentfrom those of standard regression analysis. The optimum designs are also ratherdifferent, inheriting a high degree of symmetry from the models.In the talk I will hope to discuss a variety of modes for such experiments. ThenI will discuss constrained mixture experiments, when not all the simplex is availablefor experimentation. Other important aspects include mixture experimentswith extra non-mixture factors and the blocking of mixture experiments.Much of the material is in Chapter 16 of Atkinson, Donev, and Tobias (2007).If time and my research allows, I would hope to finish with a few comments ondesign when the responses, rather than the explanatory variables, lie in a simplex.ReferencesAtkinson, A. C., A. N. Donev, and R. D. Tobias (2007). Optimum ExperimentalDesigns, with SAS. Oxford: Oxford University Press.Martin, R. J., M. C. Bursnall, and E. C. Stillman (2001). Further results onoptimal and efficient designs for constrained mixture experiments. In A. C.Atkinson, B. Bogacka, and A. Zhigljavsky (Eds.), Optimal Design 2000,pp. 225–239. Dordrecht: Kluwer.Scheff´e, H. (1958). Experiments with mixtures. Journal of the Royal StatisticalSociety, Ser. B 20, 344–360.1