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Sökning: WFRF:(Nilsson Karina)

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2.
  • Nilsson, Helena Jernmark, et al. (författare)
  • The transcriptional coregulator NAB2 is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells
  • 2017
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:50, s. 87136-87150
  • Tidskriftsartikel (refereegranskat)abstract
    • The Wilms' tumor gene 1 (WT1) is recurrently mutated in acute myeloid leukemia. Mutations and high expression of WT1 associate with a poor prognosis. In mice, WT1 cooperates with the RUNX1/RUNX1T1 (AML1/ETO) fusion gene in the induction of acute leukemia, further emphasizing a role for WT1 in leukemia development. Molecular mechanisms for WT1 are, however, incompletely understood. Here, we identify the transcriptional coregulator NAB2 as a target gene of WT1. Analysis of gene expression profiles of leukemic samples revealed a positive correlation between the expression of WT1 and NAB2, as well as a non-zero partial correlation. Overexpression of WT1 in hematopoietic cells resulted in increased NAB2 levels, while suppression of WT1 decreased NAB2 expression. WT1 bound and transactivated the proximal NAB2 promoter, as shown by ChIP and reporter experiments, respectively. ChIP experiments also revealed that WT1 can recruit NAB2 to the IRF8 promoter, thus modulating the transcriptional activity of WT1, as shown by reporter experiments. Our results implicate NAB2 as a previously unreported target gene of WT1 and that NAB2 acts as a transcriptional cofactor of WT1.
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3.
  • Ullmark, Tove, et al. (författare)
  • Anti-apoptotic quinolinate phosphoribosyltransferase (QPRT) is a target gene of Wilms' tumor gene 1 (WT1) protein in leukemic cells
  • 2017
  • Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 482:4, s. 802-807
  • Tidskriftsartikel (refereegranskat)abstract
    • Wilms' tumor gene 1 (WT1) is a zinc finger transcription factor that has been implicated as an oncogene in leukemia and several other malignancies. When investigating possible gene expression network partners of . WT1 in a large acute myeloid leukemia (AML) patient cohort, one of the genes with the highest correlation to . WT1 was quinolinate phosphoribosyltransferase (QPRT), a key enzyme in the . de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway. To investigate the possible relationship between . WT1 and . QPRT, we overexpressed . WT1 in hematopoietic progenitor cells and cell lines, resulting in an increase of . QPRT expression. WT1 knock-down gave a corresponding decrease in . QPRT gene and protein expression. Chromatin-immunoprecipitation revealed WT1 binding to a conserved site in the first intron of the . QPRT gene. Upon overexpression in leukemic K562 cells, QPRT conferred partial resistance to the anti-leukemic drug imatinib, indicating possible anti-apoptotic functions, consistent with previous reports on glioma cells. Interestingly, the rescue effect of QPRT overexpression was not correlated to increased NAD + levels, suggesting NAD + independent mechanisms. We conclude that . QPRT, encoding a protein with anti-apoptotic properties, is a novel and direct target gene of WT1 in leukemic cells.
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4.
  • Ullmark, Tove, et al. (författare)
  • Distinct global binding patterns of the Wilms' tumor gene 1 (WT1) -KTS and +KTS isoforms in leukemic cells
  • 2017
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 102:2, s. 336-345
  • Tidskriftsartikel (refereegranskat)abstract
    • The zinc finger transcription factor Wilms' tumor gene 1 (WT1) acts as an oncogene in acute myeloid leukemia. A naturally occurring alternative splice event between zinc fingers three and four, removing or retaining three amino acids (+/-KTS), is believed to change the DNA binding affinity of WT1, although there are conflicting data regarding the binding affinity and motifs of the different isoforms. Increased expression of WT1 -KTS at the expense of WT1 +KTS isoform associates with poor prognosis in acute myeloid leukemia. We determined the genome-wide binding pattern of WT1 -KTS and WT1 +KTS in leukemic K562 cells by chromatin immunoprecipitation and deep sequencing (ChIP-seq). Motif discovery revealed distinct binding motifs for the isoforms, some of which have been previously reported as WT1 binding sites. We discovered that the WT1 -KTS isoform predominantly binds close to transcription start sites and to enhancers, in a similar fashion to other transcription factors, whereas WT1 +KTS binding is rather enriched within gene bodies. We observed a significant overlap between WT1 -KTS and WT1 +KTS target genes, despite the binding sites being distinct. Motif discovery revealed distinct binding motifs for the isoforms, some of which have been previously reported as WT1 binding sites. Additional analyses showed that both WT1 -KTS and WT1 +KTS target genes are more likely to be transcribed than non-targets, and are involved in cell proliferation, cell death, and development. Our study provides evidence that WT1 -KTS and WT1 +KTS share target genes yet still bind distinct locations, indicating isoform-specific regulation in transcription of genes related to cell proliferation and differentiation, consistent with involvement of WT1 in acute myeloid leukemia.
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6.
  • Adbo, Karina, 1969-, et al. (författare)
  • Moving beyond the language–Visualizing chemical concepts through one’s own creative expression
  • 2022
  • Ingår i: Frontiers in Education. - : Frontiers Media S.A.. - 2504-284X. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to explore university students’ interpretations of chemical content in the form of physical constructions of atomic nuclei. Playdough was chosen as the means for expression, since it provided the students with the task of choosing the number, form, size, shape, and distance of particles. Data was collected in the form of photographs, written explanations as well as ad hoc notes. Data from 64 students was analyzed using the three levels of analysis as presented by Hedegaard and framed within the theories of models. Results show that students’ choices gave rise to 34 variations of the atomic nuclei. The analysis provided two different categories: models with close resemblance to the teaching model and models with less resemblance to the teaching model. Results show the limitations of verbal and written communication and add to the discussion concerning students’ interpretations of the multitude of atomic models used in teaching. The method was indeed a beneficial tool both for students, who could explore the composition of atomic nuclei and isotopes, and for teachers, who could connect their teaching to students’ interpretations of scientific content since the method brings a new level of detail to discussions. Copyright © 2022 Adbo and AAkesson-Nilsson.
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8.
  • Borrie, Mats, et al. (författare)
  • The importance of stressful events during childhood on adult labour market outcome
  • 2011
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • This paper examines if stressful events during childhood impact the labour market position in adulthood within the Swedish 1973 birth cohort. Empirical analyses are based on individual, longitudinal register data from the ASTRID database covering the total Swedish population between 1960-2008. We will analyze the different ways in which three specific events; parental separation, death of parent(s) and/or frequent migration, affect labour market outcome in an OLS-regression, controlling for family background characteristics. These events can occur in isola- tion or they can be interrelated. It is of importance to examine the effect of one single event as well as the accumulated effect of several events. The 1973 cohort makes an interesting case, since they both have experienced change in the nuclear family system during their childhood, and a period of recession and youth unemployment as well as cutbacks in social policy programmes during their age of labour market entrance. Our study thus focuses on how stressful events in childhood affect children’s life courses in turbulent times.
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9.
  • Bortes, Cristian, et al. (författare)
  • Associations between children’s diagnosed mental disorders and educational achievements in Sweden
  • 2022
  • Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 50:8, s. 1140-1147
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Aims: To examine associations between multiple clinically diagnosed mental disorders among children in Sweden and educational achievements at the end of ninth grade.Methods: Data from Swedish administrative registers were utilised. Diagnoses of specific mental disorders (unipolar depression, mood, anxiety, obsessive compulsive, eating, attention deficit hyperactivity disorder) were used as exposure variables. Educational achievements were assessed in terms of teacher-assigned school grades and eligibility for upper secondary education. The sample comprised 266,664 individuals (49% females) born in 2000 to 2002 who were alive and resident in Sweden in 2017. Exposed and unexposed individuals were compared in terms of outcome variables by fitting linear and logistic regression models.Results: The results revealed negative associations between all the examined mental disorders and educational achievements, except for positive associations between eating disorders and grades among female students. Attention deficit hyperactivity disorder was the most strongly associated disorder in terms of non-successful completion of compulsory education, among both male and female students (odds ratio (OR): 3.58 (95% confidence interval (CI), 3.42 to 3.74) and 4.31 (95% CI, 4.07 to 4.57), respectively). This was followed by unipolar depression among males (OR: 2.92 (95% CI, 2.60 to 3.28)) and anxiety disorder among females (OR: 2.68 (95% CI, 2.49 to 2.88)). Obsessive compulsive disorder had the weakest negative association with educational achievements among both males (OR: 1.48 (95% CI, 1.01 to 2.17)) and females (OR: 1.38 (95% CI, 1.11 to 1.72)).Conclusions: Specific diagnosed mental disorders have varying, largely disadvantageous, associations with educational achievements of students in Sweden that differ between males and females.
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10.
  • Bortes, Cristian, et al. (författare)
  • Health problems during childhood and school achievement : Exploring associations between hospitalization exposures, gender, timing, and compulsory school grades
  • 2018
  • Ingår i: PLOS ONE. - San Fransisco, CA, USA : Public Library Science. - 1932-6203. ; 13:12, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To investigate while accounting for health at birth 1) associations between health problems during childhood, measured as hospitalizations, and school achievement in the final year of compulsory school, measured as overall grade points and eligibility for upper secondary education, 2) if and how gender moderates the association between health problems and school achievement, 3) if and how the timing of a health problem during childhood is associated with later school achievement. Methods Analyzes were performed on a population-based cohort (n = 115 196) born in 1990 in Sweden (51.3% boys, 48.7% girls) using data from several national registries. Multiple linear regression and logistic regression were used to analyze associations between study variables. Results Overall grade points and eligibility for continuation to upper secondary school were lower for individuals exposed to hospitalizations. Only the association between hospitalizations and overall grade points was moderated by gender and only for ages 13-16 years. Exposure close to actual grading had worst outcomes. Conclusions Health problems, measured through hospitalizations, was significantly associated with lower school achievements among Swedish children. Girls exposed to health problems requiring hospitalizations had relatively poorer school achievements as compared to boys. Health problems requiring hospitalization during junior high school had the greatest negative association with final achievement at compulsory school.
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