22. juli kommisjonen. Organisering, styring og ansvar [The 22. July Commission. Organization, steering and accountability].

INNLEIING 22. juli 2011 vart Norge ramma av to sjokkerande terroristangrep. Ei bilbombe øydela fleire sentrale regjeringsbygningar i Oslo og 8 personar vart drepne i angrepet. Nokre få timar seinare vart 69 politisk aktive ungdomar frå Arbeiderpartiet si ungdomsorganisasjon massakrert på ein leir på Utøya – like nordvest for Oslo. Dei fleste av dei 69 offera var mellom 15 og 18 år. Terroristen vart arrestert på Utøya same kvelden og vedgjekk straks ugjerningane. Rettsaka vist at han var ein ‘einsam ulv’ som opererte åleine utan å vera tilknytt nokon organisasjon. 24. august 2012 vart han dømt til 21 års forvaring

The governance of social cohesion: innovative coordination practices in public management

Introduction This report presents the main findings and policy implications of the COCOPS Work Package 5 (WP5) “The Governance of Social Cohesion: Innovative Coordination Practices in Public Management” (April 2012-May 2013). WP5 focused on searching and identifying innovative coordination practices and related steering instruments in public management in European public sectors, analysing their functioning and assessing their contribution to countering public-sector fragmentation and delivering public value. The WP was led by the University of Bergen (Professor Per Lægreid and Dr. Lise H. Rykkja) in close cooperation with Tallinn University of Technology (Professor Tiina Randma-Liiv and Dr. Külli Sarapuu). In total eleven COCOPS partners were engaged in WP5 (see Table 1). In addition, four non-COCOPS researchers working on the public sector coordination contributed to the study of emerging coordination practices

Association of \u3ci\u3eEscherichia coli\u3c/i\u3e O157:H7 \u3ci\u3etir\u3c/i\u3e polymorphisms with human infection

Background: Emerging molecular, animal model and epidemiologic evidence suggests that Shigatoxigenic Escherichia coli O157:H7 (STEC O157) isolates vary in their capacity to cause human infection and disease. The translocated intimin receptor (tir) and intimin (eae) are virulence factors and bacterial receptor-ligand proteins responsible for tight STEC O157 adherence to intestinal epithelial cells. They represent logical genomic targets to investigate the role of sequence variation in STEC O157 pathogenesis and molecular epidemiology. The purposes of this study were (1) to identify tir and eae polymorphisms in diverse STEC O157 isolates derived from clinically ill humans and healthy cattle (the dominant zoonotic reservoir) and (2) to test any observed tir and eae polymorphisms for association with human (vs bovine) isolate source. Results: Five polymorphisms were identified in a 1,627-bp segment of tir. Alleles of two tir polymorphisms, tir 255 T\u3eA and repeat region 1-repeat unit 3 (RR1-RU3, presence or absence) had dissimilar distributions among human and bovine isolates. More than 99% of 108 human isolates possessed the tir 255 T\u3eA T allele and lacked RR1-RU3. In contrast, the tir 255 T\u3eA T allele and RR1-RU3 absence were found in 55% and 57%, respectively, of 77 bovine isolates. Both polymorphisms associated strongly with isolate source (p \u3c 0.0001), but not by pulsed field gel electrophoresis type or by stx1 and stx2 status (as determined by PCR). Two eae polymorphisms were identified in a 2,755-bp segment of 44 human and bovine isolates; 42 isolates had identical eae sequences. The eae polymorphisms did not associate with isolate source. Conclusion: Polymorphisms in tir but not eae predict the propensity of STEC O157 isolates to cause human clinical disease. The over-representation of the tir 255 T\u3eA T allele in human-derived isolates vs the tir 255 T\u3eA A allele suggests that these isolates have a higher propensity to cause disease. The high frequency of bovine isolates with the A allele suggests a possible bovine ecological niche for this STEC O157 subset

Small ruminant lentivirus genetic subgroups associate with sheep TMEM154 genotypes.

Abstract: Small ruminant lentiviruses (SRLVs) are prevalent in North American sheep and a major cause of production losses for the U.S. sheep industry. Sheep susceptibility to SRLV infection is influenced by genetic variation within the ovine transmembrane 154 gene (TMEM154). Animals with either of two distinct TMEM154 haplotypes that both encode glutamate at position 35 of the protein (E35) are at greater risk of SRLV infection than those homozygous with a lysine (K35) haplotype. Prior to this study, it was unknown if TMEM154 associations with infection are influenced by SRLV genetic subgroups. Accordingly, our goals were to characterize SRLVs naturally infecting sheep from a diverse U.S. Midwestern flock and test them for associations with TMEM154 E35K genotypes. Two regions of the SRLV genome were targeted for proviral amplification, cloning, sequence analysis, and association testing with TMEM154 E35K genotypes: gag and the transmembrane region of env. Independent analyses of gag and env sequences showed that they clustered in two subgroups (1 and 2), they were distinct from SRLV subtypes originating from Europe, and that subgroup 1 associated with hemizygous and homozygous TMEM154 K35 genotypes and subgroup 2 with hemi- and homozygous E35 genotypes (gag p < 0.001, env p = 0.01). These results indicate that SRLVs in the U.S. have adapted to infect sheep with specific TMEM154 E35K genotypes. Consequently, both host and SRLV genotypes affect the relative risk of SRLV infection in sheep

In-Depth Global Analysis of Transcript Abundance Levels in Porcine Alveolar Macrophages Following Infection with Porcine Reproductive and Respiratory Syndrome Virus

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide and causes considerable economic loss. Identifying specific cell signaling or activation pathways that associate with variation in PRRSV replication and macrophage function may lead to identification of novel gene targets for the control of PRRSV infection. Serial Analysis of Gene Expression (SAGE) was used to create and survey the transcriptome of in vitro mock-infected and PRRSV strain VR-2332-infected porcine alveolar macrophages (PAM) at 0, 6, 12, 16, and 24 hours after infection. The transcriptome data indicated changes in transcript abundance occurring in PRRSV-infected PAMs over time after infection with more than 590 unique tags with significantly altered transcript abundance levels identified (P < .01). Strikingly, innate immune genes (whose transcript abundances are typically altered in response to other pathogens or insults including IL-8, CCL4, and IL-1β) showed no or very little change at any time point following infection

Single nucleotide polymorphism (SNP) discovery and linkage mapping of bovine cytokine genes

Polymorphic markers at bovine gene loci facilitate the integration of cattle genetic maps with those of humans and mice. To this end, 31 single nucleotide polymorphism (SNP) markers were developed for seven bovine chemokine genes. Loci were amplified from bovine genomic DNA by the polymerase chain reaction, and candidate amplicons were sequenced to determine their identity. Amplified loci from 24 founding parents and select progeny from a beef cattle reference population were sequenced and analyzed for SNPs. SNP haplotype alleles were determined by examining segregation patterns and used to establish the locus position on the bovine linkage map. Loci for growth-related proteins (GRO3, GRO1, and GROX) were clustered with the related CXC chemokine genes, interleukin (IL) 8, and epithelial cell inflammatory protein 1, at 84 cM from the centromeric end of the bovine chromosome (BTA) 6 linkage group. Bovine loci for a cluster of IL8 receptors, a stromal cell-derived factor 1, interferong, and tumor necrosis factor-a were mapped at 90, 55, 59, and 34 cM, respectively, from the centromeric ends of the BTA 2, 28, 5, and 23 linkage groups. The positions of these bovine loci were compared with those of orthologous loci on the human map to refine the boundaries of conserved synteny. These seven loci provide examples of SNP development in which the efficiency was largely dependent on the availability of bovine genomic or cDNA sequence. The polymorphic nature of these SNP haplotype markers suggests that they will be useful for mapping complex traits in cattle, such as resistance to infectious disease

Ovine reference materials and assays for prion genetic testing

<p>Abstract</p> <p>Background</p> <p>Genetic predisposition to scrapie in sheep is associated with several variations in the peptide sequence of the prion protein gene (<it>PRNP</it>). DNA-based tests for scoring <it>PRNP </it>codons are essential tools for eradicating scrapie and for evaluating rare alleles for increased resistance to disease. In addition to those associated with scrapie, there are dozens more <it>PRNP </it>polymorphisms that may occur in various flocks. If not accounted for, these sites may cause base-pair mismatching with oligonucleotides used in DNA testing. Thus, the fidelity of scrapie genetic testing is enhanced by knowing the position and frequency of <it>PRNP </it>polymorphisms in targeted flocks.</p> <p>Results</p> <p>An adaptive DNA sequencing strategy was developed to determine the 771 bp <it>PRNP </it>coding sequence for any sheep and thereby produce a consensus sequence for targeted flocks. The strategy initially accounted for 43 known polymorphisms and facilitates the detection of unknown polymorphisms through an overlapping amplicon design. The strategy was applied to 953 sheep DNAs from multiple breeds in U.S. populations. The samples included two sets of reference sheep: one set for standardizing <it>PRNP </it>genetic testing and another set for discovering polymorphisms, estimating allele frequencies, and determining haplotype phase. DNA sequencing revealed 16 previously unreported polymorphisms, including a L237P variant on the F₁₄₁haplotype. Two mass spectrometry multiplex assays were developed to score five codons of interest in U.S. sheep: 112, 136, 141, 154, and 171. Reference tissues, DNA, trace files, and genotypes from this project are publicly available for use without restriction.</p> <p>Conclusion</p> <p>Identifying ovine <it>PRNP </it>polymorphisms in targeted flocks is critical for designing efficient scrapie genetic testing systems. Together with reference DNA panels, this information facilitates training, certification, and development of new tests and knowledge that may expedite the eradication of sheep scrapie.</p

Formalization of gene regulation knowledge using ontologies and gene ontology causal activity models

Gene regulation computational research requires handling and integrating large amounts of heterogeneous data. The Gene Ontology has demonstrated that ontologies play a fundamental role in biological data interoperability and integration. Ontologies help to express data and knowledge in a machine processable way, which enables complex querying and advanced exploitation of distributed data. Contributing to improve data interoperability in gene regulation is a major objective of the GREEKC Consortium, which aims to develop a standardized gene regulation knowledge commons. GREEKC proposes the use of ontologies and semantic tools for developing interoperable gene regulation knowledge models, which should support data annotation. In this work, we study how such knowledge models can be generated from cartoons of gene regulation scenarios. The proposed method consists of generating descriptions in natural language of the cartoons; extracting the entities from the texts; finding those entities in existing ontologies to reuse as much content as possible, especially from well known and maintained ontologies such as the Gene Ontology, the Sequence Ontology, the Relations Ontology and ChEBI; and implementation of the knowledge models. The models have been implemented using Protégé, a general ontology editor, and Noctua, the tool developed by the Gene Ontology Consortium for the development of causal activity models to capture more comprehensive annotations of genes and link their activities in a causal framework for Gene Ontology Annotations. We applied the method to two gene regulation scenarios and illustrate how to apply the models generated to support the annotation of data from research articles

Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor

BACKGROUND: Zellweger syndrome (ZS) is a fatal inherited disease caused by peroxisome biogenesis deficiency. Patients are characterized by multiple disturbances of lipid metabolism, profound hypotonia and neonatal seizures, and distinct craniofacial malformations. Median live expectancy of ZS patients is less than one year. While the molecular basis of peroxisome biogenesis and metabolism is known in considerable detail, it is unclear how peroxisome deficiency leads to the most severe neurological symptoms. Recent analysis of ZS mouse models has all but invalidated previous hypotheses. HYPOTHESIS: We suggest that a regulatory rather than a metabolic defect is responsible for the drastic impairment of brain function in ZS patients. TESTING THE HYPOTHESIS: Using microarray analysis we identify diazepam binding inhibitor/acyl-CoA binding protein (DBI) as a candidate protein that might be involved in the pathogenic mechanism of ZS. DBI has a dual role as a neuropeptide antagonist of GABA(A) receptor signaling in the brain and as a regulator of lipid metabolism. Repression of DBI in ZS patients could result in an overactivation of GABAergic signaling, thus eventually leading to the characteristic hypotonia and seizures. The most important argument for a misregulation of GABA(A) in ZS is, however, provided by the striking similarity between ZS and "benzodiazepine embryofetopathy", a malformation syndrome observed after the abuse of GABA(A) agonists during pregnancy. IMPLICATIONS OF THE HYPOTHESIS: We present a tentative mechanistic model of the effect of DBI misregulation on neuronal function that could explain some of the aspects of the pathology of Zellweger syndrome

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion