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- Gaulton, Kyle J, et al.
(author)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Journal article (peer-reviewed)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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- Lagergård, Teresa, 1946, et al.
(author)
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Distribution of Chlamydia trachomatis ompA genovars and the new variant of C. trachomatis in the Göteborg area, Sweden.
- 2010
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In: European journal of clinical microbiology & infectious diseases. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 29:5, s. 609-611
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Journal article (peer-reviewed)abstract
- The aims of this study were to assess the proportion of the new variant of Chlamydia trachomatis (nvCT) and the distribution of ompA genovars among C. trachomatis-positive patients in the Göteborg area, Sweden. Consecutive urine samples positive for C. trachomatis using BD ProbeTec ET (177 patients, 88 men and 89 women) were collected. An nvCT-specific real-time polymerase chain reaction (PCR) assay was used to investigate the nvCT prevalence. To identify the genovars, a 990-bp ompA DNA segment from 105 specimens was sequenced. Seventeen percent (30/177) of all specimens contained nvCT. Nine different genovars were identified. About 50% were of genovar E, followed by F 16%, G 11%, K 8%, and D 5%, representing about 90% of the specimens in Göteborg. The occurrence of nvCT and the dominance of genovar E in Göteborg is similar to those in other areas of Sweden. To cover about 90% of the C. trachomatis infections in Sweden, the serovars D, E, F, G, and K should be included in future vaccines based on the major outer membrane protein.
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- Lagergård, Teresa, 1946, et al.
(author)
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On the evolution of the sexually transmitted bacteria Haemophilus ducreyi and Klebsiella granulomatis.
- 2011
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In: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1230
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Journal article (peer-reviewed)abstract
- Haemophilus ducreyi and Klebsiella (Calymmatobacterium) granulomatis are sexually transmitted bacteria that cause characteristic, persisting ulceration on external genitals called chancroid and granuloma inguinale, respectively. Those ulcers are endemic in developing countries or exist, as does granuloma inguinale, only in some geographic "hot spots."H. ducreyi is placed in the genus Haemophilus (family Pasteurellacae); however, this phylogenetic position is not obvious. The multiple ways in which the bacterium may be adapted to its econiche through specialized nutrient acquisitions; defenses against the immune system; and virulence factors that increase attachment, fitness, and persistence within genital tissue are discussed below. The analysis of K. granulomatis phylogeny demonstrated a high degree of identity with other Klebsiella species, and the name K. granulomatis comb. nov. was proposed. Because of the difficulty in growing this bacterium on artificial media, its characteristics have not been sufficiently defined. More studies are needed to understand bacterial genetics related to the pathogenesis and evolution of K. granulomatis.
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- Vrede, Tobias, et al.
(author)
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Modeling the effects of locally sourced fish feed ingredients on net phosphorus loading to the Baltic Sea
- 2014
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Reports (other academic/artistic)abstract
- Phosphorus and nitrogen release from open cage fish farms is an environmental problem that may result in eutrophication. This concern needs to be addressed if aquaculture is to expand in the Baltic Sea area. All of the nutrients released from the fish farm come from the feed used in fish production. Currently, the vast majority of the nutrients are imported to the Baltic Sea in the form of raw ingredients used in feeds. In order to achieve a more sustainable industry, from the eutrophication point of view, it is thus important to develop more environmentally sound feeds. In order to reduce the import of nutrients, and to close nutrient cycles within the sea, the inclusion of Baltic Sea sourced ingredients in fish feeds could be a solution. Here we present a simple steady state model of phosphorus (P) fluxes in aquaculture in the Baltic Sea. By replacing half of the fishmeal used in the feed with Baltic Sea sourced fishmeal the net P loading can be reduced by 65% if the fish production remains constant, or alternatively, the fish production could be more than doubled while still meeting a target of a 20% P loading reduction. A zero net P load to the Baltic Sea can be achieved if a wider variety of raw ingredients sourced from the Baltic Sea are included. We also present other scenarios to illustrate the gains of using an increased amount of Baltic Sea sourced nutrients in fish feeds. Due to the probable increase in price for fish feeds if more local ingredients are used, incentives that favor an increased utiliza-tion of Baltic Sea sourced nutrients need to be put in place. Increased nutrient recirculation, potentially even a closed nutrient loop within the industry, would improve many aspects of the sustainability of fish farming, as well as show the dedication of Baltic Sea aquaculture to act in an environmentally responsible manner while developing to fulfil the increased demand for local high quality fish. In conclusion, the model presented here gives results that are relevant and of great value for strategic management purposes, and form a basis for discussions and decision making. The model output is qualitatively sound and gives a good understanding of potential net P loading in different scenarios, although the exact numbers should be interpreted with great care.
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- Wising, Catharina, 1973, et al.
(author)
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Toxic activity of the CdtB component of Haemophilus ducreyi cytolethal distending toxin expressed from an adenovirus 5 vector
- 2010
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In: APMIS. - : Wiley. - 1600-0463 .- 0903-4641. ; 118:2, s. 143-149
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Journal article (peer-reviewed)abstract
- The Haemophilus ducreyi cytolethal distending toxin (HdCDT) catalytic subunit CdtB has DNase-like activity and mediates DNA damage after its delivery into target cells. We constructed a replication-deficient adenovirus type 5 (Ad5) vector expressing CdtB and investigated the toxic properties of this vector on HeLa cells. Ad5CdtB caused loss of cell viability, morphologic changes, and cell cycle arrest, findings similar to HdCDT intoxication. This confirmed that CdtB is responsible for the toxicity of the holotoxin when expressed in cells following transduction by an adenoviral vector, and indicated a possible potential of this novel strategy in studies of activity of intracellular products and in gene therapy of cancer.
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