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| 2. |
- Davidson, D. J., et al.
(författare)
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IRAK-4 mutation (Q293X): rapid detection and characterization of defective post-transcriptional TLR/IL-1R responses in human myeloid and non-myeloid cells
- 2006
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Ingår i: J Immunol. ; 177:11, s. 8202-11
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Tidskriftsartikel (refereegranskat)abstract
- Innate immunodeficiency has recently been reported as resulting from the Q293X IRAK-4 mutation with consequent defective TLR/IL-1R signaling. In this study we report a method for the rapid allele-specific detection of this mutation and demonstrate both cell type specificity and ligand specificity in defective IL-1R-associated kinase (IRAK)-4-deficient cellular responses, indicating differential roles for this protein in human PBMCs and primary dermal fibroblasts and in LPS, IL-1beta, and TNF-alpha signaling. We demonstrate transcriptional and post-transcriptional defects despite NF-kappaB signaling and intact MyD88-independent signaling and propose that dysfunctional complex 1 (IRAK1/TRAF6/TAK1) signaling, as a consequence of IRAK-4 deficiency, generates specific defects in MAPK activation that could underpin this patient's innate immunodeficiency. These studies demonstrate the importance of studying primary human cells bearing a clinically relevant mutation; they underscore the complexity of innate immune signaling and illuminate novel roles for IRAK-4 and the fundamental importance of accessory proinflammatory signaling to normal human innate immune responses and immunodeficiencies.
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| 4. |
- Currie, Bronwen, et al.
(författare)
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Living dangerously: implications of hydrogen sulphide events for marine life along the Namibian coast : A.G.V. Salvanes6, R. Bahlo5
- 2008
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Ingår i: International Symposium on Eastern Boundary Upwelling Ecosystems: Spain.
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Hypoxia, anoxia and free hydrogen sulphide in the water column are characteristic of the inner shelf coastal upwelling system off central Namibia. Biogeochemical monitoring of the diatomaceous sediments along the central coast over a 3-year period, coupled with acoustic studies and ROV video coverage, indicated a major role played by the seafloor in the generation and control of H2S into the water column. We determined the sedimentary processes resulting in the generation and dispersal of hydrogen sulphide, and its effect on some of the locally important fishes and invertebrates.Marked interannual variability with no obvious seasonal trends was apparent in methane contents of sediments even over the short three-year period, whilst sulphate reduction rates in the sediment showed little change. The large sulphur bacteria Thiomargarita namibiensis and Beggiatoa spp. form dense mats over extensive areas of mud and oxidize sulphide at the sediment-water interface, thereby regulating its flux into the overlying water. During episodic events however, hydrogen sulphide pervades the entire water column, followed by severe hypoxia. Under experimental conditions, the survival of juvenile horse mackerel Trachurus trachurus capensis was limited to less than two hours in water containing <0.7ml.l-1 dissolved oxygen. If sulphide was also present survival time was reduced to less than 30 minutes. In contrast, pelagic gobies Sufflogobius bibarbatus survive exposure to extended periods of anoxia and water containing sulphide. Gobies are found abundantly on the muddy seafloor where they evidently possess both physiological and behavioural strategies to survive sulphide and anoxia, accounting for the success of this species in Namibian waters and its importance as a key diet species for predatory fish, seabirds and marine mammals.
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| 5. |
- Due, P., et al.
(författare)
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Socioeconomic position, macroeconomic environment and overweight among adolescents in 35 countries
- 2009
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 33:10, s. 1084-1093
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Tidskriftsartikel (refereegranskat)abstract
- Objective: It is important to understand levels and social inequalities in childhood overweight within and between countries. This study examined prevalence and social inequality in adolescent overweight in 35 countries, and associations with macroeconomic factors. Design: International cross-sectional survey in national samples of schools. Subjects: A total of 11-, 13- and 15-year-olds from 35 countries in Europe and North America in 2001-2002 (N = 162 305). Measurements: The main outcome measure was overweight based on self-reported height and weight ( body mass index cut-points corresponding to body mass index of 25 kg/m(2) at the age of 18 years). Measures included family and school affluence (within countries), and average country income and economic inequality (between countries). Results: There were large variations in adolescent overweight, from 3.5% in Lithuanian girls to 31.7% in boys from Malta. Prevalence of overweight was higher among children from less affluent families in 21 of 24 Western and 5 of 10 Central European countries. However, children from more affluent families were at higher risk of overweight in Croatia, Estonia and Latvia. In Poland, Lithuania, Macedonia and Finland, girls from less affluent families were more overweight whereas the opposite was found for boys. Average country income was associated with prevalence and inequality in overweight when considering all countries together. However, economic inequality as measured by the Gini coefficient was differentially associated with prevalence and socioeconomic inequality in overweight among the 23-high income and 10-middle income countries, with a positive relationship among the high income countries and a negative association among the middle income countries. Conclusion: The direction and magnitude of social inequality in adolescent overweight shows large international variation, with negative social gradients in most countries, but positive social gradients, especially for boys, in some Central European countries. Macroeconomic factors are associated with the heterogeneity in prevalence and social inequality of adolescent overweight. International Journal of Obesity (2009) 33, 1084-1093; doi:10.1038/ijo.2009.128; published online 21 July 2009
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| 6. |
- Edwards, Howell G.M., et al.
(författare)
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Raman spectroscopy of natron : Shedding light on ancient Egyptian mummification
- 2007
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 388:3, s. 683-689
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Tidskriftsartikel (refereegranskat)abstract
- The mummification ritual in ancient Egypt involved the evisceration of the corpse and its desiccation using natron, a naturally occurring evaporitic mineral deposit from the Wadi Natrun, Egypt. The deposit typically contains sodium carbonate, sodium bicarbonate and impurities of chloride and sulfate as its major elemental components. It is believed that the function of the natron was to rapidly remove the water from the cadaver to prevent microbial attack associated with subsequent biological tissue degradation and putrefaction. Several specimens of natron that were recently collected from the Wadi Natrun contained coloured zones interspersed with the mineral matrix that are superficially reminiscent of extremophilic cyanobacterial colonisation found elsewhere in hot and cold deserts. Raman spectroscopy of these specimens using visible and near-infrared laser excitation has revealed not only the mineral composition of the natron, but also evidence for the presence of cyanobacterial colonies in several coloured zones observed in the mineral matrix. Key Raman biosignatures of carotenoids, scytonemin and chlorophyll have been identified
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| 7. |
- van der Most, Robbert G., et al.
(författare)
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Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy
- 2009
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 1432-0851 .- 0340-7004. ; 58:8, s. 1219-1228
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Tidskriftsartikel (refereegranskat)abstract
- Tumor cell death potentially engages with the immune system. However, the efficacy of anti-tumor chemotherapy may be limited by tumor-driven immunosuppression, e.g., through CD25(+) regulatory T cells. We addressed this question in a mouse model of mesothelioma by depleting or reconstituting CD25(+) regulatory T cells in combination with two different chemotherapeutic drugs. We found that the efficacy of cyclophosphamide to eradicate established tumors, which has been linked to regulatory T cell depletion, was negated by adoptive transfer of CD25(+) regulatory T cells. Analysis of post-chemotherapy regulatory T cell populations revealed that cyclophosphamide depleted cycling (Ki-67(hi)) T cells, including foxp3(+) regulatory CD4(+) T cells. Ki-67(hi) CD4(+) T cells expressed increased levels of two markers, TNFR2 and ICOS, that have been associated with a maximally suppressive phenotype according to recently published studies. This suggest that cyclophosphamide depletes a population of maximally suppressive regulatory T cells, which may explain its superior anti-tumor efficacy in our model. Our data suggest that regulatory T cell depletion could be used to improve the efficacy of anti-cancer chemotherapy regimens. Indeed, we observed that the drug gemcitabine, which does not deplete cycling regulatory T cells, eradicates established tumors in mice only when CD25(+) CD4(+) T cells are concurrently depleted. Cyclophosphamide could be used to achieve regulatory T cell depletion in combination with chemotherapy.
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