Native homing endonucleases can target conserved genes in humans and in animal models.

In recent years, both homing endonucleases (HEases) and zinc-finger nucleases (ZFNs) have been engineered and selected for the targeting of desired human loci for gene therapy. However, enzyme engineering is lengthy and expensive and the off-target effect of the manufactured endonucleases is difficult to predict. Moreover, enzymes selected to cleave a human DNA locus may not cleave the homologous locus in the genome of animal models because of sequence divergence, thus hampering attempts to assess the in vivo efficacy and safety of any engineered enzyme prior to its application in human trials. Here, we show that naturally occurring HEases can be found, that cleave desirable human targets. Some of these enzymes are also shown to cleave the homologous sequence in the genome of animal models. In addition, the distribution of off-target effects may be more predictable for native HEases. Based on our experimental observations, we present the HomeBase algorithm, database and web server that allow a high-throughput computational search and assignment of HEases for the targeting of specific loci in the human and other genomes. We validate experimentally the predicted target specificity of candidate fungal, bacterial and archaeal HEases using cell free, yeast and archaeal assays.

A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network.

BACKGROUND: The nuclear receptors are a large family of eukaryotic transcription factors that constitute major pharmacological targets. They exert their combinatorial control through homotypic heterodimerisation. Elucidation of this dimerisation network is vital in order to understand the complex dynamics and potential cross-talk involved. RESULTS: Phylogeny, protein-protein interactions, protein-DNA interactions and gene expression data have been integrated to provide a comprehensive and up-to-date description of the topology and properties of the nuclear receptor interaction network in humans. We discriminate between DNA-binding and non-DNA-binding dimers, and provide a comprehensive interaction map, that identifies potential cross-talk between the various pathways of nuclear receptors. CONCLUSION: We infer that the topology of this network is hub-based, and much more connected than previously thought. The hub-based topology of the network and the wide tissue expression pattern of NRs create a highly competitive environment for the common heterodimerising partners. Furthermore, a significant number of negative feedback loops is present, with the hub protein SHP [NR0B2] playing a major role. We also compare the evolution, topology and properties of the nuclear receptor network with the hub-based dimerisation network of the bHLH transcription factors in order to identify both unique themes and ubiquitous properties in gene regulation. In terms of methodology, we conclude that such a comprehensive picture can only be assembled by semi-automated text-mining, manual curation and integration of data from various sources.

The implications of alternative splicing in the ENCODE protein complement.

Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.

Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

A press database on natural risks and its application in the study of floods in Northeastern Spain

The aim of this work is to introduce a systematic press database on natural hazards and climate change in Catalonia (NE of Spain) and to analyze its potential application to social-impact studies. For this reason, a review of the concepts of risk, hazard, vulnerability and social perception is also included. This database has been built for the period 1982¿2007 and contains all the news related with those issues published by the oldest still-active newspaper in Catalonia. Some parameters are registered for each article and for each event, including criteria that enable us to determine the importance accorded to it by the newspaper, and a compilation of information about it. This ACCESS data base allows each article to be classified on the basis of the seven defined topics and key words, as well as summary information about the format and structuring of the new itself, the social impact of the event and data about the magnitude or intensity of the event. The coverage given to this type of news has been assessed because of its influence on construction of the social perception of natural risk and climate change, and as a potential source of information about them. The treatment accorded by the press to different risks is also considered. More than 14 000 press articles have been classified. Results show that the largest number of news items for the period 1982¿2007 relates to forest fires and droughts, followed by floods and heavy rainfalls, although floods are the major risk in the region of study. Two flood events recorded in 2002 have been analyzed in order to show an example of the role of the press information as indicator of risk perception.

Towards a database on societal impact of Mediterranean floods in the framework of the HYMEX project

The NW Mediterranean region experiences every year heavy rainfall and flash floods that occasionally produce catastrophic damages. Less frequent are floods that affect large regions. Although a large number of databases devoted exclusively to floods or considering all kind of natural hazards do exist, usually they only record catastrophic flood events. This paper deals with the new flood database that is being developed within the framework of HYMEX project. Results are focused on four regions representative of the NW sector of Mediterranean Europe: Catalonia, Spain; the Balearic Islands, Spain; Calabria, Italy; and Languedoc-Roussillon, Midi-Pyrenées and PACA, France. The common available 30-yr period starts in 1981 and ends in 2010. The paper shows the database structure and criteria, the comparison with other flood databases, some statistics on spatial and temporal distribution, and an identification of the most important events. The paper also provides a table that includes the date and affected region of all the catastrophic events identified in the regions of study, in order to make this information available for all audiences.

ASP en biblioteques i centres de documentació: publicació d'una base de dades Microsoft Access en el web

Es descriuen els passos necessaris per publicar a Internet una base de dades creada amb Microsoft Access utilitzant la tecnologia ASP. Es parteix d'un exemple de base de dades creada per a controlar el procés d'adquisicions i es van resseguint, en forma de tutorial, els diferents passos que seran necessaris per a la seva consulta des del web. Finalment, s'indiquen algunes aplicacions de la tecnologia ASP que podren ser útils per a biblioteques i centres de documentació.

ASP en bibliotecas y centros de documentación: publicación de una base de datos Microsoft Access en el web

Se describen los elementos necesarios para publicar en Internet una base de datos creada con Microsoft Access utilizando la tecnología ASP. Se parte de un ejemplo de base de datos creada para controlar el proceso de adquisiciones y se van resiguiendo, en forma de tutorial, los diferentes pasos que serán necesarios para su consulta desde el web. Finalmente, se indican algunas aplicaciones de la tecnología ASP que pueden ser útiles para bibliotecas y centros de documentación.

Nous reptes per als proveïdors de serveis d'informació

Parlar de fonts primàries i secundàries i d'obtenció de documents originals potser passarà a la història d'aquí a molts pocs anys. Ens trobem en un sector en què l'única cosa clara és que ningú ho té clar. Sembla que abans tothom tenia el seu paper delimitat, però actualment la tradicional cadena de la informació és un veritable garbuix de possibles vies de transmissió. Ens trobem que tothom fa diversos papers i a l'usuari se li presenten mœltiples opcions. La competència entre els proveïdors-intermediaris és cada vegada més gran i alguns quasi s'estan quedant sense marges comercials. Al final, els que tenen el poder són els propietaris-productors de la informació.

FirstSearch: servei en línia per a l'usuari final

Descripció del servei en línia FirstSearch d'OCLC. Es detallen les bases de dades que ofereix, l'accés, tarificació, el llenguatge d'interrogació emprat i es presenta el mòdul d'obtenció de documents que pot gestionar cada un dels usuaris finals i amb el qual es poden aconseguir un gran nombre dels documents que contenen les bases de dades consultades.

The database industry in Catalonia: a ten year overview

Reviews growth in database production in Catalonia (ASCII, videotext, CD-ROM) over the past decade, with particular attention to the level of development, classification of producers, distribution, users and language. Examines the principal problems affecting the Catalan context: the lack of an informationand documentation policy, deficiencies in distribution of databases, the special situation in telecommunications, insufficient financial resources and the lack of specialized personnel.

La indústria de les bases de dades a Catalunya: panoràmica de deu anys

Es fa un repás a l'evolució en la producció de les bases de dades a Catalunya (ASCII, videotex, CD-ROM) en els darrers deu anys, fent especial esment al grau de desenvolupament, tipología dels productors, la distribució, els usuaris i l'idioma. A partir d'aquí es comenten els principals problemes que afecten el context cátala, i que fan referència principalment a la inexistencia d'una política d'informació i documentació, a una deficient distribució de les bases de dades, a l'especial situació de les telecomunicacions, a la insuficiència de recursos econòmics i a la manca de personal especialitzat.

Avaluació dels tutorials de PubMed i Eric

La societat de la informació ofereix noves vies d'experimentació en el camp dels materials formatius. D'una banda, les tecnologies de la informació proporcionen maneres més interactives i adients de presentar el material i, de l'altra, apareixen nous conceptes en el camp de la formació i de l'educació, com ara la necessitat d'una formació continuada, la concepció de nous entorns educatius virtuals i, en definitiva, la necessitat d'elaborar nous materials didàctics que s'adaptin a aquestes situacions. El present estudi defineix una sèrie d'indicadors formals i d'aprenentatge que ajuden a avaluar i millorar els tutorials sobre la recuperació de la informació i els aplica, de manera comparativa, a dos tutorials de bases de dades bibliogràfiques: ERIC i PubMed. Els indicadors de contingut s'obtenen d'aspectes relacionats amb la didàctica i el model instructiu, mentre que els indicadors formals s'extreuen dels conceptes d'usabilitat i disseny de pàgines web. La finalitat d'aquest estudi és la sistematització d'uns criteris que permetin avaluar i millorar el disseny de tutorials sobre recuperació de la informació.