A powerful and rapid approach to human genome scanning in small quantities of genomic DNA

Dense maps of short-tandem-repeat polymorphisms (STRPs) have allowed genome-wide searches for genes involved in a great variety of diseases with genetic influences, including common complex diseases. Generally for this purpose, marker sets with a 10 cM spacing are genotyped in hundreds of individuals. We have performed power simulations to estimate the maximum possible intermarker distance that still allows for sufficient power. In this paper we further report on modifications of previously published protocols, resulting in a powerful screening set containing 229 STRPs with an average spacing of 18·3 cM. A complete genome scan using our protocol requires only 80 multiplex PCR reactions which are all carried out using one set of conditions and which do not contain overlapping marker allele sizes. The multiplex PCR reactions are grouped by sets of chromosomes, which enables on-line statistical analysis of a set of chromosomes, as sets of chromosomes are being genotyped. A genome scan following this modified protocol can be performed using a maximum amount of 2.5 μg of genomic DNA per individual, isolated from either blood or from mouth swabs.link_to_subscribed_fulltex

The combined impact of urban heat island, thermal bridge effect of buildings and future climate change on the potential overwintering of Phlebotomus species in a Central European metropolis

Leishmaniasis is one of the most important emerging vector-borne diseases in Western Eurasia. Although winter minimum temperatures limit the present geographical distribution of the vector Phlebotomus species, the heat island effect of the cities and the anthropogenic heat emission together may provide the appropriate environment for the overwintering of sand flies. We studied the climate tempering effect of thermal bridges and the heat island effect in Budapest, Hungary. Thermal imaging was used to measure the heat surplus of heat bridges. The winter heat island effect of the city was evaluated by numerical analysis of the measurements of the Aqua sensor of satellite Terra. We found that the surface temperature of thermal bridges can be at least 3-7 °C higher than the surrounding environment. The heat emission of thermal bridges and the urban heat island effect together can cause at least 10 °C higher minimum ambient temperature in winter nights than the minimum temperature of the peri-urban areas. This milder micro-climate of the built environment can enable the potential overwintering of some important European Phlebotomus species. The anthropogenic heat emission of big cities may explain the observed isolated northward populations of Phlebotomus ariasi in Paris and Phlebotomus neglectus in the agglomeration of Budapest

Relative power and sample size analysis on gene expression profiling data

Background: With the increasing number of expression profiling technologies, researchers today are confronted with choosing the technology that has sufficient power with minimal sample size, in order to reduce cost and time. These depend on data variability, partly determined by sample type, preparation and processing. Objective measures that help experimental design, given own pilot data, are thus fundamental. Results: Relative power and sample size analysis were performed on two distinct data sets. The first set consisted of Affymetrix array data derived from a nutrigenomics experiment in which weak, intermediate and strong PPARα agonists were administered to wild-type and PPARα-null mice. Our analysis confirms the hierarchy of PPARα-activating compounds previously reported and the general idea that larger effect sizes positively contribute to the average power of the experiment. A simulation experiment was performed that mimicked the effect sizes seen in the first data set. The relative power was predicted but the estimates were slightly conservative. The second, more challenging, data set describes a microarray platform comparison study using hippocampal δC-doublecortin-like kinase transgenic mice that were compared to wild-type mice, which was combined with results from Solexa/Illumina deep sequencing runs. As expected, the choice of technology greatly influences the performance of the experiment. Solexa/Illumina deep sequencing has the highest overall power followed by the microarray platforms Agilent and Affymetrix. Interestingly, Solexa/Illumina deep sequencing displays comparable power across all intensity ranges, in contrast with microarray platforms that have decreased power in the low intensity range due to background noise. This means that deep sequencing technology is especially more powerful in dete

Decolonizar la investigación sobre migraciones : apuntes desde una etnografía colaborativa

En este artículo analizamos los significados asumidos por la idea de "(in)migración(es)" y la categoría de "(in)migrante(s)" en los contextos sociales, políticos y académicos contemporáneos. Resaltando su estrecha relación con el pensamiento de Estado y la colonialidad del poder/saber, nos preguntamos por otros posibles acercamientos a la movilidad humana. Discutimos la etnografía colaborativa, entendida como una metodología decolonial que rechaza las representaciones pasivizantes hegemónicas y aspira a visibilizar los procesos de subjetivación política de las personas junto a las que se investiga. Aportando ejemplos de nuestra propia investigación colaborativa junto a Stop Desahucios-Granada 15M, ilustramos cómo la idea de (in)migración(es) y la categoría "(in)migrante(s)" se han materializado en nuestro contexto, que se encuentra definido por el activismo político y no había sido previamente alterizado como "migratorio". Concluimos resaltando la ambivalencia implícita en estas dos expresiones y reflexionamos sobre los pros y los contras implícitos en su uso.In this paper we analyze the meaning of "immigration" and "immigrant" within contemporary social, political and academic contexts. We emphasize their narrow relation with State thought and the coloniality of power/knowledge and search for alternative approaches to human mobility. With this aim, we discuss collaborative ethnography as a decolonial methodology addressed to visibilize the political subjectivation processes of the people we research with. Drawing on examples from our own collaborative research with Stop Evictions-Granada 15M, we show how the idea of "immigration" and the category "immigrants" have come into being within our field, a space of political activism which had not been previously constructed as a "migratory context". We conclude underlining the ambivalence implicit in the two aforementioned concepts and discuss the pros and cons of using them

Social Change and Betty Friedan's The Feminine Mystique: A Study of the Charismatic Author-Leader

In this thesis I explore the significance of the publication of Betty Friedan's The Feminine Mystique (1963) to the emergence of the second wave Women's Liberation Movement in the US in the late 1960s. To this end, I deploy key concepts provided through social movement theory (eg collective identity, collective action frames, social problem construction). I also incorporate Max Weber and Antonio Gramsci's insights on the indispensable role played by leaders who demonstrate a clear and effective political will. Weber's three part model of pure charisma is used as a general template for understanding the impact of Friedan's text. I critique aspects of Weber's theory of charisma, in particular his failure to appreciate that the written word can mark the initial emergence phase of charisma rather than its routinisation. I augment Weber's insights on charismatic leadership by attending to Gramsci's emphasis on the necessity of winning the 'war of ideas' that must be waged at the level of civil society within advanced capitalist societies. I examine Gramsci's understanding of the power available to the organic intellectual who is aligned with the interests of subaltern groups and who succeeds in revealing the hegemonic commitments of accepted 'common sense'. In the latter part of this thesis, I apply these many useful concepts to my case study analysis of Betty Friedan's The Feminine Mystique. I argue that Friedan's accessible, middlebrow text gave birth to a new discursive politics which was critically important not only for older women, but for a younger generation of more radicalised women. I emphasise how Friedan's text mounted a concerted attack on the discursive construction of femininity under patriarchal capitalism. I question Friedan's diagnostic claim that the problems American women faced were adequately captured by the terminology of the trapped housewife syndrome. I conclude by arguing that social movement researchers have to date failed to appreciate the leadership potential of the charismatic author-leader who succeeds in addressing and offering a solution to a pressing social problem through the medium of a best-selling, middlebrow text

The Implicitome: A Resource for Rationalizing Gene-Disease Associations

High-throughput experimental methods such as medical sequencing and genome-wide association studies (GWAS) identify increasingly large numbers of potential relations between genetic variants and diseases. Both biological complexity (millions of potential gene-disease associations) and the accelerating rate of data production necessitate computational approaches to prioritize and rationalize potential gene-disease relations. Here, we use concept profile technology to expose from the biomedical literature both explicitly stated gene-disease relations (the explicitome) and a much larger set of implied gene-disease associations (the implicitome). Implicit relations are largely unknown to, or are even unintended by the original authors, but they vastly extend the reach of existing biomedical knowledge for identification and interpretation of gene-disease associations. The implicitome can be used in conjunction with experimental data resources to rationalize both known and novel associations. We demonstrate the usefulness of the implicitome by rationalizing known and novel gene-disease associations, including those from GWAS. To facilitate the re-use of implicit gene-disease associations, we publish our data in compliance with FAIR Data Publishing recommendations [https://www.force11.org/group/fairgroup] using nanopublications. An online tool (http://knowledge.bio) is available to explore established and potential gene-disease associations in the context of other biomedical relations.UB – Publicatie

Advances in therapeutic RNA-targeting

Mechanisms of disease, diagnostics and therap

[Dutch government invests in existing biobanks].,Dutch government invests in existing biobanks

Contains fulltext : 87383.pdf (publisher's version ) (Closed access)Modern research, aimed at discovering factors that influence health and disease, requires large collections of data and samples. Collaboration between biobanks is therefore essential. The Dutch hub in the network of biobanks, the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), is one of the major Dutch biobanking initiatives. It is sponsored by the Dutch government through the Netherlands Organization for Scientific Research (NWO). BBMRI-NL sets up collaboration between approximately 150 existing clinical and population biobanks in the Netherlands, and forms the link with the European BBMRI initiative. BBMRI-NL aims at enrichment and harmonization of existing Dutch biobanks, at data management and analysis, and at laying the legal, social and ethical foundations, in order to improve access and inter-operability, and to render the information and organization up to date. Other major Dutch initiatives are String of Pearls and LifeLines. Together these will create the conditions needed for Dutch researchers to further develop their strong position in the international biobanking field