A general definition and nomenclature for alternative splicing events

Understanding the molecular mechanisms responsible for the regulation of the transcriptome present in eukaryotic cells isone of the most challenging tasks in the postgenomic era. In this regard, alternative splicing (AS) is a key phenomenoncontributing to the production of different mature transcripts from the same primary RNA sequence. As a plethora ofdifferent transcript forms is available in databases, a first step to uncover the biology that drives AS is to identify thedifferent types of reflected splicing variation. In this work, we present a general definition of the AS event along with anotation system that involves the relative positions of the splice sites. This nomenclature univocally and dynamically assignsa specific ‘‘AS code’’ to every possible pattern of splicing variation. On the basis of this definition and the correspondingcodes, we have developed a computational tool (AStalavista) that automatically characterizes the complete landscape of ASevents in a given transcript annotation of a genome, thus providing a platform to investigate the transcriptome diversityacross genes, chromosomes, and species. Our analysis reveals that a substantial part—in human more than a quarter—ofthe observed splicing variations are ignored in common classification pipelines. We have used AStalavista to investigate andto compare the AS landscape of different reference annotation sets in human and in other metazoan species and found thatproportions of AS events change substantially depending on the annotation protocol, species-specific attributes, andcoding constraints acting on the transcripts. The AStalavista system therefore provides a general framework to conductspecific studies investigating the occurrence, impact, and regulation of AS.

Transcription factor map alignment of promoter regions

We address the problem of comparing and characterizing the promoter regions of genes with similar expression patterns. This remains a challenging problem in sequence analysis, because often the promoter regions of co-expressed genes do not show discernible sequence conservation. In our approach, thus, we have not directly compared the nucleotide sequence of promoters. Instead, we have obtained predictions of transcription factor binding sites, annotated the predicted sites with the labels of the corresponding binding factors, and aligned the resulting sequences of labels—to which we refer here as transcription factor maps (TF-maps). To obtain the global pairwise alignment of two TF-maps, we have adapted an algorithm initially developed to align restriction enzyme maps. We have optimized the parameters of the algorithm in a small, but well-curated, collection of human–mouse orthologous gene pairs. Results in this dataset, as well as in an independent much larger dataset from the CISRED database, indicate that TF-map alignments are able to uncover conserved regulatory elements, which cannot be detected by the typical sequence alignments.

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.

Genome-wide screen of genes required for caffeine tolerance in fission yeast

Background: An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to atoxic dose of this drug, and the relationship between caffeine and oxidative stress pathways.Methodology/Principal Findings: We searched for Schizosaccharomyces pombe mutants with inhibited growth on caffeinecontainingplates. We screened a collection of 2,700 haploid mutant cells, of which 98 were sensitive to caffeine. The genes mutated in these sensitive clones were involved in a number of cellular roles including the H2O2-induced Pap1 and Sty1 stress pathways, the integrity and calcineurin pathways, cell morphology and chromatin remodeling. We have investigated the role of the oxidative stress pathways in sensing and promoting survival to caffeine. The Pap1 and the Sty1 pathways are both required for normal tolerance to caffeine, but only the Sty1 pathway is activated by the drug. Cells lacking Pap1 aresensitive to caffeine due to the decreased expression of the efflux pump Hba2. Indeed, ?hba2 cells are sensitive to caffeine, and constitutive activation of the Pap1 pathway enhances resistance to caffeine in an Hba2-dependent manner. Conclusions/Significance: With our caffeine-sensitive, genome-wide screen of an S. pombe deletion collection, we havedemonstrated the importance of some oxidative stress pathway components on wild-type tolerance to the drug.

THC prevents MDMA neurotoxicity in mice

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg ×4) were pretreated with THC (3 mg/kg ×4) at room (21°C) and at warm (26°C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB1 receptor antagonist AM251 and the CB2 receptor antagonist AM630, as well as in CB1, CB2 and CB1/CB2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB1 receptor antagonist AM251, neither in CB1 and CB1/CB2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB2 cannabinoid antagonist and in CB2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB1 receptor, although CB2 receptors may also contribute to attenuate neuroinflammation in this process.

LSTA Five Year Plan, 1998-2002, 2002

The LSTA goals for Iowa, FY98-FY02, are as follows: 1. Provide all Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network. 2. Improve library service to Iowans through knowledgeable, well-trained staff and wellinformed public library trustees and library users. 3. Meet Iowans’ increasing demands for information and library services by identifying and encouraging resource sharing and partnerships. 4. Provide state level leadership and services to accomplish the LSTA Five-Year Plan. The primary objectives of this evaluation are to provide: $ An assessment of the overall impact of Iowa’s LSTA funding and success in achieving the goals identified in the state’s five-year plan. $ An in-depth analysis of two specific goals from the plan: providing Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network; and improving library service to Iowans through knowledgeable, well-trained staff and well-informed public library trustees and library users. LSTA built on accomplishments made possible with the federal HEA II-B grant awarded to the State Library in 1995. This grant led the way in bringing technology to Iowa libraries by creating an electronic library network for resource sharing. SILO (State of Iowa Libraries Online) became fully functional in 1997. The State Library continued funding SILO with LSTA money when the grant ended. This funding supports the SILO infrastructure, providing equitable access to information through cutting edge technology to Iowans in both small and large, rural and urban, communities. Access to electronic material and information has encouraged public libraries to increase the number of computers and public access to the Internet. LSTA funding was used to increase training opportunities for library staff and trustees. Many programs, such as librarian certification, were strengthened by an increase in continuing education opportunities.

LSTA Five Year Plan 2003-2007, 2007

The Iowa Commission of Libraries, the State Library’s governing board, convened the Library Services Task Force in August 2000. This group consisted of 46 Iowans from across the state, including librarians from all types of libraries, library trustees, legislators, members of Iowa Regional Library system (now called Library Service Areas) and Area Education Agencies, and citizens. Their mission was to make recommendations to the Commission on positioning libraries to effectively and efficiently meet the future needs of Iowans. Needs and expectations of Iowa Library customers and funding authorities were identified and examined by the Task Force, and are reflected in its recommendations. The Commission received the Task Force recommendations in December 2000, carefully studied them, solicited input from the Iowa library community, and with a few changes, forwarded the recommendations to the Governor and the Iowa General Assembly. These recommendations are now known as Iowa Commission of Libraries priorities and serve as a blueprint for future development of the Iowa library system. A second need assessment was conducted in 2001 as part of the process to formulate the joint Library Service Area – State Library Plan of Service 2003-2005. Biennial development of this plan is mandated by the Code of Iowa. In 2001, Library Service Area and Library Development staff from the State Library chose to completely revamp this plan, and used the process outlined in the The New Planning for Results by Sandra Nelson (the Public Library Association planning model) to do so. The group conducted a strengths/weaknesses/opportunities/threat analysis of the Iowa library situation, identified needs and put them in priority order, and identified service responses. Needs identified by the Library Services Task Force were similar to those identified by the Library Service Area and Library Development staff group. These needs were further analyzed and documented by State Library staff during the development of the LSTA plan. Sources consulted are identified in the text of the LSTA plan and/or listed at the close of this document. The text of the Library Services Task Force report and the documents created during the development of the Plan of Service 2003-2005 are cited in the appendix to this document.

LSTA Five Year Plan, 1998-2002, 2002

The LSTA goals for Iowa, FY98-FY02, are as follows: 1. Provide all Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network. 2. Improve library service to Iowans through knowledgeable, well-trained staff and wellinformed public library trustees and library users. 3. Meet Iowans’ increasing demands for information and library services by identifying and encouraging resource sharing and partnerships. 4. Provide state level leadership and services to accomplish the LSTA Five-Year Plan. The primary objectives of this evaluation are to provide: $ An assessment of the overall impact of Iowa’s LSTA funding and success in achieving the goals identified in the state’s five-year plan. $ An in-depth analysis of two specific goals from the plan: providing Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network; and improving library service to Iowans through knowledgeable, well-trained staff and well-informed public library trustees and library users. LSTA built on accomplishments made possible with the federal HEA II-B grant awarded to the State Library in 1995. This grant led the way in bringing technology to Iowa libraries by creating an electronic library network for resource sharing. SILO (State of Iowa Libraries Online) became fully functional in 1997. The State Library continued funding SILO with LSTA money when the grant ended. This funding supports the SILO infrastructure, providing equitable access to information through cutting edge technology to Iowans in both small and large, rural and urban, communities. Access to electronic material and information has encouraged public libraries to increase the number of computers and public access to the Internet. LSTA funding was used to increase training opportunities for library staff and trustees. Many programs, such as librarian certification, were strengthened by an increase in continuing education opportunities.

LSTA Five Year Plan Evaluation, 1998-2002, 2002

The LSTA goals for Iowa, FY98-FY02, are as follows: 1. Provide all Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network. 2. Improve library service to Iowans through knowledgeable, well-trained staff and wellinformed public library trustees and library users. 3. Meet Iowans’ increasing demands for information and library services by identifying and encouraging resource sharing and partnerships. 4. Provide state level leadership and services to accomplish the LSTA Five-Year Plan. The primary objectives of this evaluation are to provide: $ An assessment of the overall impact of Iowa’s LSTA funding and success in achieving the goals identified in the state’s five-year plan. $ An in-depth analysis of two specific goals from the plan: providing Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network; and improving library service to Iowans through knowledgeable, well-trained staff and well-informed public library trustees and library users. LSTA built on accomplishments made possible with the federal HEA II-B grant awarded to the State Library in 1995. This grant led the way in bringing technology to Iowa libraries by creating an electronic library network for resource sharing. SILO (State of Iowa Libraries Online) became fully functional in 1997. The State Library continued funding SILO with LSTA money when the grant ended. This funding supports the SILO infrastructure, providing equitable access to information through cutting edge technology to Iowans in both small and large, rural and urban, communities. Access to electronic material and information has encouraged public libraries to increase the number of computers and public access to the Internet. LSTA funding was used to increase training opportunities for library staff and trustees. Many programs, such as librarian certification, were strengthened by an increase in continuing education opportunities.

Death and resurrection of the human IRGM gene

Immunity-related GTPases (IRG) play an important role in defense against intracellular pathogens. One member of this gene family in humans, IRGM, has been recently implicated as a risk factor for Crohn's disease. We analyzed the detailed structure of this gene family among primates and showed that most of the IRG gene cluster was deleted early in primate evolution, after the divergence of the anthropoids from prosimians ( about 50 million years ago). Comparative sequence analysis of New World and Old World monkey species shows that the single-copy IRGM gene became pseudogenized as a result of an Alu retrotransposition event in the anthropoid common ancestor that disrupted the open reading frame (ORF). We find that the ORF was reestablished as a part of a polymorphic stop codon in the common ancestor of humans and great apes. Expression analysis suggests that this change occurred in conjunction with the insertion of an endogenous retrovirus, which altered the transcription initiation, splicing, and expression profile of IRGM. These data argue that the gene became pseudogenized and was then resurrected through a series of complex structural events and suggest remarkable functional plasticity where alleles experience diverse evolutionary pressures over time. Such dynamism in structure and evolution may be critical for a gene family locked in an arms race with an ever-changing repertoire of intracellular parasites.

Archimed i els seus projectes

[eng] Archimed is a French company that has developed cultural portals for town governments, which have been promoted jointly with local cultural agents such as the public library. The text describes some of the more significant projects in the area of citizen information.

Les biblioteques per a pacients poden existir al marge de la biblioteca pública?: una panoràmica internacional

State-of-the-art report on experiences and models of library services for paediatric patients, with an emphasis on the relation that exists -if any- between the public library and the patients' library.

Internet, bibliotecas públicas y centros de atención primaria: información de calidad y formación al alcance de los ciudadanos

Propuesta de colaboración entre los centros de atención primaria y las bibliotecas públicas para dar respuesta a la demanda ciudadana de formación e información de calidad sobre salud en Internet. Se pretende optimizar así los recursos de estos dos servicios públicos en beneficio del paciente crónico.

Catalogació patrimoni bibliogràfic: goigs: segle XIX

Catalogació dels goigs impresos durant el segle XIX, de la Biblioteca Pública de Girona. Son exemplars inclosos en el Catálogo Colectivo del Patrimonio Bibliográfico (CCPB), base de dades del Ministeri de Cultura.

Tough adults, frail babies: an analysis of stress sensitivity across early life-history stages of widely introduced marine invertebrates

All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis) were studied after exposure to high temperature (30°C), low salinities (26 and 22 ) and high copper concentrations (25, 50 and 100 µg/L). Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis), fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success might be responsible for ensuring population survival.