Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Introduction to the science of sociology,

Bibliography at end of each chapter.Mode of access: Internet

The PHD and Chromo Domains Regulate the ATPase Activity of the Human Chromatin Remodeler CHD4

The NuRD (nucleosome remodeling and deacetylase) complex serves as a crucial epigenetic regulator of cell differentiation, proliferation, and hematopoietic development by coupling the deacetylation and demethylation of histones, nucleosome mobilization, and the recruitment of transcription factors. The core nucleosome remodeling function of the mammalian NuRD complex is executed by the helicase-domain-containing ATPase CHD4 (Mi-2β) subunit, which also contains N-terminal plant homeodomain (PHD) and chromo domains. The mode of regulation of chromatin remodeling by CHD4 is not well understood, nor is the role of its PHD and chromo domains. Here, we use small-angle X-ray scattering, nucleosome binding ATPase and remodeling assays, limited proteolysis, cross-linking, and tandem mass spectrometry to propose a three-dimensional structural model describing the overall shape and domain interactions of CHD4 and discuss the relevance of these for regulating the remodeling of chromatin by the NuRD complex

Prostitución: qué modelo jurídico-político para portugal?

A prostituição em Portugal conheceu diversos modelos jurídico-políticos, como a regulamentação, o proibicionismo e o abolicionismo, prevalecendo este último na atualidade. No discurso social e científico encontramos sobretudo duas posições: os defensores da prostituição como trabalho e os que a consideram uma violação dos direitos humanos. Este artigo apresenta a evolução histórico-legal dos modelos de intervenção na prostituição em Portugal, de forma a contextualizarmos e compreendermos a influência dos discursos. Em seguida, expõe as opiniões dos profissionais das instituições, que dirigem respostas a esta população, sobre a atual moldura jurídico-política, com a finalidade de analisar as diferentes perspectivas sobre o trabalho sexual. Baseando-se em pesquisa de natureza qualitativa que contemplou 23 entrevistas, conclui-se que embora não exista uma ideia clara sobre qual modelo adotar, a preocupação com o respeito pelos direitos humanos e o combate ao estigma estão patentes, independentemente do paradigma em questão.Different political-juridical models have framed prostitution in Portugal: regulation, prohibition and abolition, the latter of which is currently prevalent. There are two main standpoints in social and scientific discourse: those who defend prostitution as a valid form of labor and those who consider it a violation of human rights. This article presents the legal and historical evolution of models of interventions concerning prostitution in Portugal, so as to contextualize and understand the influence of discourses. Next, the article exposes the opinion of professionals within institutions that respond to the demands of this population, under the current political-juridical framework, with the objective of analyzing different perspectives on sexual labor. Based on qualitative research which tooks into account 23 interviews, it was concluded that although there is not a clear idea as to which model to adopt, the concern regarding respect for human rights and the combatting stigma is well-established, regardless of the paradigm in question.La prostitution au Portugal a connu divers modèles juridico-politiques, tels que la réglementation, la prohibition et l’abolitionnisme, ce dernier étant celui qui prévaut actuellement. Dans le discours social et scientifique, deux positions dominantes se dessinent: la défense de la prostitution comme travail et l’idée selon laquelle elle constituerait une violation des droits humains. Cet article présentera l’évolution historico-légale des modèles d’intervention dans la prostitution au Portugal, de façon à contextualiser et à comprendre l’influence des différents discours. Nous exposerons ensuite les opinions sur le cadre juridico-politique émises par des professionnels d’institutions prenant en charge cette population spécifique, dans le but d’analyser les différentes perspectives sur le travail sexuel. Sur la base d’une étude qualitative comprenant 23 entretiens, nous avons conclu que même s’il n’existait pas d’idée claire sur le modèle à adopter, le respect des droits humains et la lutte contre la stigmatisation constituaient des préoccupations centrales, et ce indépendamment du paradigme en question.La prostitución en Portugal ha conocido a lo largo del tiempo diversos modelos jurídico-políticos: la reglamentación, el prohibicionismo y el abolicionismo, siendo este último todavía prevaleciente en la actualidad. En el discurso social y científico encontramos sobre todo dos posiciones: los defensores de la prostitución como trabajo y aquellos que la consideran una violación de los derechos humanos. Este artículo presenta la evolución histórico-letal de los modelos de intervención en la prostitución en Portugal, como forma de contextualizar y comprender la influencia de los discursos. Enseguida, expone las opiniones de los profesionales de las instituciones, que dirigen respuestas a esta población, sobre el actual marco jurídico-político, con la finalidad de analizar las diferentes perspectivas sobre el trabajo sexual. Basándose en una investigación cualitativa que contempló 23 entrevistas, la conclusión sugiere que aunque no exista una idea clara sobre que modelo adoptar, la preocupación con el respeto a los derechos humanos y el combate al estigma están patentes, independiente del paradigma en cuestión