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Sökning: WFRF:(Stenberg Mia)

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2.
  • Hamers, Timo, et al. (författare)
  • In Vitro toxicity profiling of ultrapure non-dioxin-like polychlorinated biphenyl congeners and their relative toxic contribution to PCB mixtures in humans
  • 2011
  • Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 121:1, s. 88-100
  • Tidskriftsartikel (refereegranskat)abstract
    • The toxic equivalency concept used for the risk assessment of polychlorinated biphenyls (PCBs) is based on the aryl hydrocarbon receptor (AhR)-mediated toxicity of coplanar dioxin-like (DL) PCBs. Most PCBs in the environment, however, are non-dioxin-like (NDL) PCBs that cannot adopt a coplanar structure required for AhR activation. For NDL-PCBs, no generally accepted risk concept is available because their toxicity is insufficiently characterized. Here, we systematically determined in vitro toxicity profiles for 24 PCBs regarding 10 different mechanisms of action. Prior to testing, NDL-PCB standards were purified to remove traces of DL compounds. All NDL-PCBs antagonized androgen receptor activation and inhibited gap junctional intercellular communication (GJIC). Lower chlorinated NDL-PCBs were weak estrogen receptor (ER) agonists, whereas higher chlorinated NDL-PCBs were weak ER antagonists. Several NDL-PCBs inhibited estradiol-sulfotransferase activity and bound to transthyretin (TTR) but with much weaker potencies than reported for hydroxylated PCB metabolites. AhR-mediated expression of uridine-glucuronyl transferase isozyme UGT1A6 was induced by DL-PCBs only. Hierarchical cluster analysis of the toxicity profiles yielded three separate clusters of NDL-PCBs and a fourth cluster of reference DL-PCBs. Due to small differences in relative potency among congeners, the highly abundant indicator PCBs 28, 52, 101, 118, 138, 153, and 180 also contributed most to the antiandrogenic, (anti)estrogenic, antithyroidal, tumor-promoting, and neurotoxic potencies calculated for PCB mixtures reported in human samples, whereas the most potent AhR-activating DL-PCB-126 contributed at maximum 0.2% to any of these calculated potencies. PCB-168 is recommended as an additional indicator congener, given its relatively high abundance and antiandrogenic, TTR-binding, and GJIC-inhibiting potencies.
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3.
  • Johansson, Anna-Mia, et al. (författare)
  • msl2 mRNA is bound by free nuclear MSL complex in Drosophila melanogaster
  • 2011
  • Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 39:15, s. 6428-6439
  • Tidskriftsartikel (refereegranskat)abstract
    • In Drosophila, the global increase in transcription from the male X chromosome to compensate for its monosomy is mediated by the male-specific lethal (MSL) complex consisting of five proteins and two non-coding RNAs, roX1 and roX2. After an initial sequence-dependent recognition by the MSL complex of 150-300 high affinity sites, the spread to the majority of the X-linked genes depends on local MSL-complex concentration and active transcription. We have explored whether any additional RNA species are associated with the MSL complex. No additional roX RNA species were found, but a strong association was found between a spliced and poly-adenylated msl2 RNA and the MSL complex. Based on our results, we propose a model in which a non-chromatin-associated partial or complete MSL-complex titrates newly transcribed msl2 mRNA and thus regulates the amount of available MSL complex by feedback. This represents a novel mechanism in chromatin structure regulation.
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4.
  • Johansson, Anna-Mia, et al. (författare)
  • Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster.
  • 2007
  • Ingår i: EMBO J. - 0261-4189. ; 26:9, s. 2307-2316
  • Tidskriftsartikel (refereegranskat)abstract
    • Drosophila melanogaster exhibits two expression-regulating systems that target whole, specific chromosomes: the dosage compensation system whereby the male-specific lethal complex doubles transcription of genes on the male X-chromosome and the chromosome 4-specific protein Painting of fourth, POF. POF is the first example of an autosome-specific protein and its presence raises the question of the universality of chromosome-specific regulation. Here we show that POF and heterochromatin protein 1 (HP1) are involved in the global regulation of the 4th chromosome. Contrary to previous conclusions, Pof is not essential for survival of diplo-4th karyotype flies. However, Pof is essential for survival of haplo-4th individuals and expression of chromosome 4 genes in diplo-4th individuals is decreased in the absence of Pof. Mapping of POF using chromatin immunoprecipitation suggested that it binds within genes. Furthermore, we show that POF binding is dependent on heterochromatin and that POF and HP1 bind interdependently to the 4th chromosome. We propose a balancing mechanism involving POF and HP1 that provides a feedback system for fine-tuning expression status of genes on the 4th chromosome.
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5.
  • Johansson, Anna-Mia, et al. (författare)
  • POF and HP1 bind expressed exons, suggesting a balancing mechanism for gene regulation
  • 2007
  • Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404. ; 3:11, s. e209-
  • Tidskriftsartikel (refereegranskat)abstract
    • Two specific chromosome-targeting and gene regulatory systems are present in Drosophila melanogaster. The male X chromosome is targeted by the male-specific lethal complex believed to mediate the 2-fold up-regulation of the X-linked genes, and the highly heterochromatic fourth chromosome is specifically targeted by the Painting of Fourth (POF) protein, which, together with heterochromatin protein 1 (HP1), modulates the expression level of genes on the fourth chromosome. Here we use chromatin immunoprecipitation and tiling microarray analysis to map POF and HP1 on the fourth chromosome in S2 cells and salivary glands at high resolution. The enrichment profiles were complemented by transcript profiles to examine the link between binding and transcripts. The results show that POF specifically binds to genes, with a strong preference for exons, and the HP1 binding profile is a mirror image of POF, although HP1 displays an additional "peak" in the promoter regions of bound genes. HP1 binding within genes is much higher than the basal HP1 enrichment on Chromosome 4. Our results suggest a balancing mechanism for the regulation of the fourth chromosome where POF and HP1 competitively bind at increasing levels with increased transcriptional activity. In addition, our results contradict transposable elements as a major nucleation site for HP1 on the fourth chromosome.
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6.
  • Johansson, Anna-Mia, 1978-, et al. (författare)
  • POF Regulates the Expression of Genes on the Fourth Chromosome in Drosophila melanogaster by Binding to Nascent RNA
  • 2012
  • Ingår i: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 32:11, s. 2121-2134
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • In Drosophila, two chromosome-wide compensatory systems have been characterized: the dosage compensation system that acts on the male X chromosome and the chromosome-specific regulation of genes located on the heterochromatic fourth chromosome. Dosage compensation in Drosophila is accomplished by hypertranscription of the single male X chromosome mediated by the male-specific lethal (MSL) complex. The mechanism of this compensation is suggested to involve enhanced transcriptional elongation mediated by the MSL complex, while the mechanism of compensation mediated by the painting of fourth (POF) protein on the fourth chromosome has remained elusive. Here, we show that POF binds to nascent RNA, and this binding is associated with increased transcription output from chromosome 4. We also show that genes located in heterochromatic regions spend less time in transition from the site of transcription to the nuclear envelope. These results provide useful insights into the means by which genes in heterochromatic regions can overcome the repressive influence of their hostile environment.
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8.
  • Karlsson, Edvin, et al. (författare)
  • Airborne microbial biodiversity and seasonality in Northern and Southern Sweden
  • 2020
  • Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Microorganisms are essential constituents of ecosystems. To improve our understanding of how various factors shape microbial diversity and composition in nature it is important to study how microorganisms vary in space and time. Factors shaping microbial communities in ground level air have been surveyed in a limited number of studies, indicating that geographic location, season and local climate influence the microbial communities. However, few have surveyed more than one location, at high latitude or continuously over more than a year. We surveyed the airborne microbial communities over two full consecutive years in Kiruna, in the Arctic boreal zone, and Ljungbyhed, in the Southern nemoral zone of Sweden, by using a unique collection of archived air filters. We mapped both geographic and seasonal differences in bacterial and fungal communities and evaluated environmental factors that may contribute to these differences and found that location, season and weather influence the airborne communities. Location had stronger influence on the bacterial community composition compared to season, while location and season had equal influence on the fungal community composition. However, the airborne bacterial and fungal diversity showed overall the same trend over the seasons, regardless of location, with a peak during the warmer parts of the year, except for the fungal seasonal trend in Ljungbyhed, which fluctuated more within season. Interestingly, the diversity and evenness of the airborne communities were generally lower in Ljungbyhed. In addition, both bacterial and fungal communities varied significantly within and between locations, where orders like Rhizobiales, Rhodospirillales and Agaricales dominated in Kiruna, whereas Bacillales, Clostridiales and Sordariales dominated in Ljungbyhed. These differences are a likely reflection of the landscape surrounding the sampling sites where the landscape in Ljungbyhed is more homogenous and predominantly characterized by artificial and agricultural surroundings. Our results further indicate that local landscape, as well as seasonal variation, shapes microbial communities in air.
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9.
  • Lewerentz, Jacob, 1992-, et al. (författare)
  • The path to immortalization of cells starts by managing stress through gene duplications
  • 2023
  • Ingår i: Experimental Cell Research. - : Elsevier. - 0014-4827 .- 1090-2422. ; 422:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The genomes of immortalized cell lines (and cancer cells) are characterized by multiple types of aberrations, ranging from single nucleotide polymorphisms (SNPs) to structural rearrangements that have accumulated over time. Consequently, it is difficult to estimate the relative impact of different aberrations, the order of events, and which gene functions were under selective pressure at the early stage towards cellular immortalization. Here, we have established novel cell cultures derived from Drosophila melanogaster embryos that were sampled at multiple time points over a one-year period. Using short-read DNA sequencing, we show that copy-number gain in preferentially stress-related genes were acquired in a dominant fraction of cells in 300-days old cultures. Furthermore, transposable elements were active in cells of all cultures. Only a few (<1%) SNPs could be followed over time, and these showed no trend to increase or decrease. We conclude that the early cellular responses of a novel culture comprise sequence duplication and transposable element activity. During immortalization, positive selection first occurs on genes that are related to stress response before shifting to genes that are related to growth.
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10.
  • Lewerentz, Jacob, et al. (författare)
  • Transposon activity, local duplications and propagation of structural variants across haplotypes drive the evolution of the Drosophila S2 cell line
  • 2022
  • Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Immortalized cell lines are widely used model systems whose genomes are often highly rearranged and polyploid. However, their genome structure is seldom deciphered and is thus not accounted for during analyses. We therefore used linked short- and long-read sequencing to perform haplotype-level reconstruction of the genome of a Drosophila melanogaster cell line (S2-DRSC) with a complex genome structure.Results: Using a custom implementation (that is designed to use ultra-long reads in complex genomes with nested rearrangements) to call structural variants (SVs), we found that the most common SV was repetitive sequence insertion or deletion (> 80% of SVs), with Gypsy retrotransposon insertions dominating. The second most common SV was local sequence duplication. SNPs and other SVs were rarer, but several large chromosomal translocations and mitochondrial genome insertions were observed. Haplotypes were highly similar at the nucleotide level but structurally very different. Insertion SVs existed at various haplotype frequencies and were unlinked on chromosomes, demonstrating that haplotypes have different structures and suggesting the existence of a mechanism that allows SVs to propagate across haplotypes. Finally, using public short-read data, we found that transposable element insertions and local duplications are common in other D. melanogaster cell lines.Conclusions: The S2-DRSC cell line evolved through retrotransposon activity and vast local sequence duplications, that we hypothesize were the products of DNA re-replication events. Additionally, mutations can propagate across haplotypes (possibly explained by mitotic recombination), which enables fine-tuning of mutational impact and prevents accumulation of deleterious events, an inherent problem of clonal reproduction. We conclude that traditional linear homozygous genome representation conceals the complexity when dealing with rearranged and heterozygous clonal cells.
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