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Sökning: WFRF:(Ng S.) > (2000-2004)

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1.
  • Fong, L. G., et al. (författare)
  • Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice
  • 2004
  • Ingår i: Proc Natl Acad Sci U S A. ; 101:52, s. 18111-18116
  • Tidskriftsartikel (refereegranskat)abstract
    • Zmpste24 is a metalloproteinase required for the processing of prelamin A to lamin A, a structural component of the nuclear lamina. Zmpste24 deficiency results in the accumulation of prelamin A within cells, a complete loss of mature lamin A, and misshapen nuclear envelopes. Zmpste24-deficient (Zmpste24(-/-)) mice exhibit retarded growth, alopecia, micrognathia, dental abnormalities, osteolytic lesions in bones, and osteoporosis, which are phenotypes shared with Hutchinson-Gilford progeria syndrome, a human disease caused by the synthesis of a mutant prelamin A that cannot undergo processing to lamin A. Zmpste24(-/-) mice also develop muscle weakness. We hypothesized that prelamin A might be toxic and that its accumulation in Zmpste24(-/-) mice is responsible for all of the disease phenotypes. We further hypothesized that Zmpste24(-/-) mice with half-normal levels of prelamin A (Zmpste24(-/-) mice with one Lmna knockout allele) would be subjected to less toxicity and be protected from disease. Thus, we bred and analyzed Zmpste24(-/-)Lmna(+/-) mice. As expected, prelamin A levels in Zmpste24(-/-)Lmna(+/-) cells were significantly reduced. Zmpste24(-/-)Lmna(+/-) mice were entirely normal, lacking all disease phenotypes, and misshapen nuclei were less frequent in Zmpste24(-/-)Lmna(+/-) cells than in Zmpste24(-/-) cells. These data suggest that prelamin A is toxic and that reducing its levels by as little as 50% provides striking protection from disease.
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  • Gerhardsson, Lars, et al. (författare)
  • Cadmium, copper and zinc in tissues of deceased copper smelter workers
  • 2002
  • Ingår i: Journal of Trace Elements in Medicine and Biology. - 1878-3252. ; 16:4, s. 261-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Workers at a copper and lead smelter in northern Sweden have a multifactorial exposure to a number of heavy metals. The concentrations of cadmium, copper and zinc in Liver, Lung, kidney and brain tissues have been deters mined by atomic absorption spectrometry in 32 deceased tong-term exposed male lead smelter workers, and compared with those of 10 male controls. Furthermore, copper and zinc Levels in hair and nails were determined by energy-dispersive X-ray fluorescence. The highest cadmium concentrations among both workers and controls were observed in kidney, followed in order by liver, lung and brain. The levels in kidney, Liver and Lung were all significantly higher in the workers than in the controls (p < 0.03). Among the workers relatively strong positive correlations (p < 0.03) were observed between cadmium concentrations in liver and lung, liver and kidney, liver and brain, and lung and brain. In the exposed workers a positive correlation was observed between cadmium and zinc concentrations in the kidney (r(s) = 0.38; p = 0.034). This is probably mainly due to the protein metallothionein, which is stored in the kidney, binding equimolar amounts of these two metals. The highest concentrations of copper were found in hair and nails among both workers and controls, followed in order by liver, brain, kidney and Lung. The tissue concentrations of copper in brain, Lung and kidney were all significantly higher among the smelter workers than in the controls (p less than or equal to 0.036). Copper Levels in lung and age at time of death were positively correlated among the exposed workers (r(s) = 0.39; p = 0.029). In the same group, positive correlations between copper and zinc concentrations in kidney (r(s) = 0.45; p = 0.009) and nails (r(s) = 0.68; p < 0.001) were also observed, reflecting possible biological interactions between these two metals. Among both workers and controls, the highest zinc concentrations were found in hair, followed in order by nails, liver, kidney, brain and lung. Significantly higher tissue concentrations among the workers as compared with the reference group were noted in kidney, liver and brain (p &LE; 0.033). Neither copper nor zinc concentrations in hair and nails seemed to provide a useful measure of the trace element status of the smelter workers.Workers at a copper and lead smelter in northern Sweden have a muttifactodal exposure to a number of heavy metals. The concentrations of cadmium, copper and zinc in Liver, Lung, kidney and brain tissues have been deters mined by atomic absorption spectrometry in 32 deceased tong-term exposed male lead smelter workers, and compared with those of 10 male controls. Furthermore, copper and zinc Levels in hair and nails were determined by energy-dispersive X-ray fluorescence. The highest cadmium concentrations among both workers and controls were observed in kidney, followed in order by liver, lung and brain. The levels in kidney, Liver and Lung were all significantly higher in the workers than in the controls (p < 0.03). Among the workers reLativety strong positive correlations (p < 0.03) were observed between cadmium concentrations in liver and lung, liver and kidney, liver and brain, and lung and brain. In the exposed workers a positive correlation was observed between cadmium and zinc concentrations in the kidney (r, = 0.38; p = 0.034). This is probably mainly due to the protein meta llothionei n, which is stored in the kidney, binding equimolar amounts of these two metals. The highest concentrations of copper were found in hair and nails among both workers and controls, followed in order by liver, brain, kidney and Lung. The tissue concentrations of copper in brain, Lung and kidney were all significantLy higher among the smelter workers than in the controls (p &LE;0.036). Copper Levels in lung and age at time of death were positively correlated among the exposed workers (r(s) = 0.39; p = 0.029). In the same group, positive correlations between copper and zinc concentrations in kidney (r(s) = 0.45; p = 0.009) and nails (r(x) = 0.68; p < 0.001) were also observed, reflecting possible biological interactions between these two metals. Among both workers and controls, the highest zinc concentrations were found in hair, followed in order by naits, liver, kidney, brain and lung. Significantly higher tissue concentrations among the workers as compared with the reference group were noted in kidney, liver and brain (p < 0.033). Neither copper nor zinc concentrations in hair and nails seemed to provide a useful measure of the trace element status of the smelter workers.
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8.
  • Hanson, Hans, et al. (författare)
  • Modelling of coastal evolution on yearly to decadal time scales
  • 2003
  • Ingår i: Journal of Coastal Research. - 0749-0208. ; 19:4, s. 790-811
  • Tidskriftsartikel (refereegranskat)abstract
    • There is still no universal model for analysing and predicting coastal evolution and its governing processes on yearly to decadal time scales. Instead, depending on the nature of the problem and project objectives, there is a wide range of models available, each focusing on the problem complex from a specific standpoint. The present paper gives an overview of available numerical model types. A differentiation is made between equilibrium and non-equilibrium model types as well as between longshore uniform and non-longshore uniform model types. These models are discussed in terms of their general assumptions, approaches, and applicability. Most of the model descriptions are supplemented by an illustrative example. In addition, generic issues, such as level of knowledge on different scales, selection of model type on the basis of the nature of the application, the concept of equilibrium, model validation and utilisation are discussed.
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