| 1. |
- Björklund, Patrik, et al.
(författare)
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Västerås slott : Slott och borgar
- 2000
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Rapport (populärvet., debatt m.m.)abstract
- En majoritet av dagens byggnadsuppgifter gäller att hantera det redan byggda. När vi står inför situationen att restaurera en befintlig byggnad är det viktigt att förstå olika tidsperioders stilideal liksom byggnadsteknik och material. Först då kan vi göra en väl avvägd analys, som tar tillvara och utvecklar de kvaliteter som byggnaderna själva besitter. Därför är utbildningen upplagd som ett växelspel mellan föreläsningar, seminarier, exkursioner och en för året vald studieuppgift.Slott och borgar har varit läsårets tema. Vi har valt att arbeta med Västerås och Örebro slott - två ganska bortglömda Vasaslott som är väl värda att lyfta fram. Särskilt har vi studerat de senaste 300 årens förändringar, som inte tidigare ägnats lika stora forskarmöda som medelitden och Vasatiden. I dessa två exempel finns en provkarta på estetiska, praktiska och tekniska ingrepp från Carl Hårlemans tid och fram till idag.Studierna har således omfattat både gestaltning, funktion och byggnadsteknik. Avsikten är att visa på kvaliteter i de omvandlingar och restaureringar som skett, men också att peka på problem och analysera olika möjligheter inför framtiden. Arbetet har skett i samarbete med Statens fastighetsverk och är tänkt att utgöra ett underlag till vårdprogram och framtida restaureringsinsatser.
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| 2. |
- Nilsson, Emil, 1973-
(författare)
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Breeding System Evolution and Pollination Success in the Wind-Pollinated Herb Plantago maritima
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, I examined variation in sex expression and mating patterns in the sexually polymorphic, wind-pollinated herb Plantago maritima. With a combination of field studies, greenhouse experiments, and genetic analyses, I (a) examined factors influencing sex ratio variation in gynodioecious plants (in which hermaphrodites and females coexist), (b) discovered variation in breeding system, (c) investigated density-dependence of seed production, and (d) documented genetic variation within and among populations close to the northern range margin in Europe. In a survey of 104 P. maritima populations, I documented considerable variation in sex ratio (range 0-70% females, median 6.3% females). As predicted, females were more frequently missing from small than from large populations, and the variance in sex ratio increased with decreasing population size. Among twelve populations sampled for seed production, the frequency of females was positively related to relative fecundity of females and negatively related to population size. The results suggest that the local sex ratio is influenced both by the relative fecundity of females and hermaphrodites, and by stochastic processes in small populations.A comparative field study showed that plant fecundity decreased with increasing distance to nearest pollen donor both within and among populations in an archipelago in southern Sweden, where self-incompatibility was confirmed in controlled crosses. In contrast, plant fecundity was overall higher and was not density-dependent in the Skeppsvik archipelago in northern Sweden, where controlled crosses showed that plants are self-compatible. The results were consistent with the prediction that evolution of self-fertility should reduce density-dependence of pollination success.I quantified the genetic structure within and among populations from eastern Sweden and western Finland based on variation at four polymorphic microsatellite loci. The genetic diversity was low in northern Sweden, which may be the result of a history of small population sizes and periods of frequent self-fertilization.
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| 3. |
- Nilton, Anna, et al.
(författare)
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Targeting Zfp148 activates p53 and reduces tumor initiation in the gut
- 2016
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Ingår i: OncoTarget. - : Impact Journals, LLC. - 1949-2553. ; 7:35, s. 56183-56192
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor Zinc finger protein 148 (Zfp148, ZBP-89, BFCOL, BERF1, htβ) interacts physically with the tumor suppressor p53, but the significance of this interaction is not known. We recently showed that knockout of Zfp148 in mice leads to ectopic activation of p53 in some tissues and cultured fibroblasts, suggesting that Zfp148 represses p53 activity. Here we hypothesize that targeting Zfp148 would unleash p53 activity and protect against cancer development, and test this idea in the APCMin/+ mouse model of intestinal adenomas. Loss of one copy of Zfp148 markedly reduced tumor numbers and tumor-associated intestinal bleedings, and improved survival. Furthermore, after activation of β-catenin-the initiating event in colorectal cancer-Zfp148 deficiency activated p53 and induced apoptosis in intestinal explants of APCMin/+ mice. The anti-tumor effect of targeting Zfp148 depended on p53, as Zfp148 deficiency did not affect tumor numbers in APCMin/+ mice lacking one or both copies of Trp53. The results suggest that Zfp148 controls the fate of newly transformed intestinal tumor cells by repressing p53 and that targeting Zfp148 might be useful in the treatment of colorectal cancer.
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| 4. |
- Sayin, Volkan I., 1983, et al.
(författare)
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Loss of One Copy of Zfp148 Reduces Lesional Macrophage Proliferation and Atherosclerosis in Mice by Activating p53
- 2014
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Ingår i: Circulation Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7330 .- 1524-4571. ; 115:9, s. 781-791
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Cell proliferation and cell cycle control mechanisms are thought to play central roles in the pathogenesis of atherosclerosis. The transcription factor Zinc finger protein 148 (Zfp148) was shown recently to maintain cell proliferation under oxidative conditions by suppressing p53, a checkpoint protein that arrests proliferation in response to various stressors. It is established that inactivation of p53 accelerates atherosclerosis, but whether increased p53 activation confers protection against the disease remains to be determined. Objective: We aimed to test the hypothesis that Zfp148 deficiency reduces atherosclerosis by unleashing p53 activity. Methods and Results: Mice harboring a gene-trap mutation in the Zfp148 locus (Zfp148(gt/+)) were bred onto the apolipoprotein E (Apoe)(-/-) genetic background and fed a high-fat or chow diet. Loss of 1 copy of Zfp148 markedly reduced atherosclerosis without affecting lipid metabolism. Bone marrow transplantation experiments revealed that the effector cell is of hematopoietic origin. Peritoneal macrophages and atherosclerotic lesions from Zfp148(gt/+)Apoe(-/-) mice showed increased levels of phosphorylated p53 compared with controls, and atherosclerotic lesions contained fewer proliferating macrophages. Zfp148(gt/+) Apoe(-/-) mice were further crossed with p53-null mice (Trp53(-/-) [the gene encoding p53]). There was no difference in atherosclerosis between Zfp148(gt/+) Apoe(-/-) mice and controls on a Trp53(+/-) genetic background, and there was no difference in levels of phosphorylated p53 or cell proliferation. Conclusions: Zfp148 deficiency increases p53 activity and protects against atherosclerosis by causing proliferation arrest of lesional macrophages, suggesting that drugs targeting macrophage proliferation may be useful in the treatment of atherosclerosis.
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| 5. |
- Sayin, Volkan I., 1983, et al.
(författare)
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Zfp148 Deficiency Causes Lung Maturation Defects and Lethality in Newborn Mice That Are Rescued by Deletion of p53 or Antioxidant Treatment
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor Zfp148 (Zbp-89, BFCOL, BERF1, htβ) interacts physically with the tumor suppressor p53 and is implicated in cell cycle control, but the physiological role of Zfp148 remains unknown. Here we show that Zfp148 deficiency leads to respiratory distress and lethality in newborn mice. Zfp148 deficiency prevented structural maturation of the prenatal lung without affecting type II cell differentiation or surfactant production. BrdU analyses revealed that Zfp148 deficiency caused proliferation arrest of pulmonary cells at E18.5–19.5. Similarly, Zfp148-deficient fibroblasts exhibited proliferative arrest that was dependent on p53, raising the possibility that cell stress is part of the underlying mechanism. Indeed, Zfp148 deficiency lowered the threshold for activation of p53 under oxidative conditions. Moreover, both in vivo and cellular phenotypes were rescued on Trp53+/− or Trp53−/− backgrounds and by antioxidant treatment. Thus, Zfp148 prevents respiratory distress and lethality in newborn mice by attenuating oxidative stress–dependent p53-activity during the saccular stage of lung development. Our results establish Zfp148 as a novel player in mammalian lung maturation and demonstrate that Zfp148 is critical for cell cycle progression in vivo.
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