| 5231. |
- Månsson, Robert, et al.
(författare)
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Pearson correlation analysis of microarray data allows for the identification of genetic targets for early B-cell factor
- 2004
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 279:17, s. 17905-17913
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Tidskriftsartikel (refereegranskat)abstract
- B lymphocyte development is a complex biological process critically dependent on the transcription factor early B cell factor (EBF). To deepen understanding of the roles for EBF in this process, we have used Pearson correlation analysis to evaluate microarray data from a set of mouse B lymphoid cell lines representing different stages of development. Comparing the expression pattern of EBF to that of the other genes in the data set revealed that VpreB1, mb-1, and lambda5, all known target genes, presented high correlation values to EBF. High correlations were also seen for the VpreB3 and CD19 genes and biochemical as well as functional data supported that they are target genes for EBF even though the expression of CD19 was critically dependent of Pax-5. We also obtained evidence for extensive collaborative actions of EBF and E47 even though microarray analysis of hematopoetic progenitor cells ectopically expressing these proteins suggested that they activated only a subset of pre-B cell restricted genes.
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| 5232. |
- Månsson, Robert
(författare)
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To be or not to be, unraveling molecular mechanisms for lineage decisions in developing blood cells
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- All hematopoietic cells originate from hematopoietic stem cells (HSC) residing in the BM. The process of differentiation, through which HSCs generate progenitors and subsequently mature blood cells has been extensively studied but many of the regulatory mechanisms involved remains elusive. The classical model for hematopoiesis has been established based on the identification of common myeloid precursors and common lymphoid precursors, suggesting that the first lineage commitment step results in the strict separation between the lymphoid and myeloid lineages. However, by subfractionation of the LIN-SCA1+KIT+ bone marrow population, containing all HSCs in the mouse, based on expression of CD34 and FLT3, three functionally distinct populations were identified. CD34- cells contained the HSCs, CD34+FLT3- short term repopulating cells and CD34+ FLT3+/hi cells with combined lymhpoid and GM potential but, only a small fraction (3%) displaying MkE potential in vitro. In agreement with this MkE associated genes (Gata1, Epor, Vwf etc) were found to be down-regulated in CD34+FLT3hi cells while lymphoid associated genes (Il7r, Rag1, Tdt, sterile IgH transcripts) were found to be up-regulated both at the population and single cell level. Based on this we proposed a new model for hematopoietic development were the first restriction point involves the separation of MkE and lymphoid potential while retaining GM potential. In order to investigate the continued development of B-lymphoid cells we investigated the functional role of the transcription factor EBF1, known to be of critical importance for B cell development. By means of comparativ and correlativ analysis of microarray data from cell-lines we, in addition to the previously known EBF1 target genes, identified Vpreb3, CD19, Ceacam1 and CD53 as EBF1 target genes. Furthermore, by transplantations of EBF1 deficient fetal liver cells, we were able to show EBF1 to be dispensable for the generation of CLPs but that lack of EBF1 expression resulted in diminished IgH DJ recombination and reduced expression of B-lineage associated genes already at this early stage of development. Using a hCD25 lambda5-promoter transgene as a marker for EBF1 activity a small CLP subpopulation (~6%) could be identified. This population demonstrated diminished T-cell potential, increased B-cell potential, as well as up-regulation of Vpreb, lambda5, B29, Mb1 and importantly Pax5. Taken together this suggest that B-lineage commitment occurs already at the level of the CLP.
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| 5233. |
- Mårtensson, Carina, et al.
(författare)
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Factors behind change in knowledge after a mass media campaign targeting periodontitis
- 2006
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Ingår i: International Journal of Dental Hygiene. - 1601-5029 .- 1601-5037. ; 4:1, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate changes in knowledge before and after a mass media campaign, in relation to social attributes, care system attributes and oral health aspects. The study was based on a questionnaire in a cohort design, sent out to 900 randomly sampled people aged 50–75 in Sweden. The response rate to the questionnaire before and after the campaign was 70% and 65% respectively. Sixty-four percent answered both questionnaires. Two questions addressed knowledge, while 10 questions aimed to measure social attributes, care system attributes and oral health aspects. Data were analysed for bivariate relations as to change in knowledge and social attributes, care system attributes and oral health aspects. Data were also analysed in multiple regression analysis with knowledge before, knowledge after and knowledge differences as dependent variables. The results showed that there were a number of independent variables with influence on the dependent variables. Of the social attributes, secondary education gave almost 10% (P < 0.001) better knowledge both before and after the campaign. Among care system attributes, high care utilization was related to knowledge both before and after the campaign. The most important factors for knowledge about periodontitis were education, care utilization and perceived importance of oral health. In conclusion, this study demonstrates that mass media might increase knowledge about periodontitis as a health promotion strategy.
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| 5234. |
- Mårtensson, Carina, et al.
(författare)
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Factors behind change in knowledge after a mass media campaign targeting periodontitis
- 2006
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Ingår i: International Journal of Dental Hygiene. - : Wiley. - 1601-5029 .- 1601-5037. ; 4:1, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate changes in knowledge before and after a mass media campaign, in relation to social attributes, care system attributes and oral health aspects. The study was based on a questionnaire in a cohort design, sent out to 900 randomly sampled people aged 50–75 in Sweden. The response rate to the questionnaire before and after the campaign was 70% and 65% respectively. Sixty-four percent answered both questionnaires. Two questions addressed knowledge, while 10 questions aimed to measure social attributes, care system attributes and oral health aspects. Data were analysed for bivariate relations as to change in knowledge and social attributes, care system attributes and oral health aspects. Data were also analysed in multiple regression analysis with knowledge before, knowledge after and knowledge differences as dependent variables. The results showed that there were a number of independent variables with influence on the dependent variables. Of the social attributes, secondary education gave almost 10% (P< 0.001) better knowledge both before and after the campaign. Among care system attributes, high care utilization was related to knowledge both before and after the campaign. The most important factors for knowledge about periodontitis were education, care utilization and perceived importance of oral health. In conclusion, this study demonstrates that mass media might increase knowledge about periodontitis as a health promotion strategy.
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| 5235. |
- Mårtensson, Carina, et al.
(författare)
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Knowledge on periodontal disease before and after a mass media campaign
- 2004
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Ingår i: Swedish Dental Journal. - : Swedish Dental Association. - 0347-9994. ; 28:4, s. 165-171
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to evaluate if a mass media campaign regarding periodontal disease could increase the knowledge in the general population of diagnoses, symptoms and treatment options of periodontal disease. More specifically, the aim was to investigate the number of correct answers to knowledge questions before and after the campaign. The Swedish Association of Periodontology conducted the campaign through brochures, newspapers, radio and TV. The effect of the campaign was evaluated by a pre- and post campaign questionnaire with a cohort design. From a national population register of 50-75 year olds in Sweden, 900 persons were randomly sampled for the study. A total of 64% of the sample answered both questionnaires. The result of the study showed an improvement among the respondents. There was a significant increase in the number of correct answers regarding diagnoses, symptoms and treatments of periodontitis. In the questionnaire, correct answers regarding "Mobile teeth" increased from 57% to 65% (p=0.003) and "careful dental hygiene" from 65% to 73% (p=0.001). Kappa value's were calculated for consistency in the reply and all kappa values were low especially for the questions "X-ray" (0.36) and "Cleaning between the teeth" (0.38). It was concluded that the campaign probably was successful from a public health knowledge standpoint.
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| 5236. |
- Mårtensson, Jonas, et al.
(författare)
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Neutrophil priming that turns natural FFA2R agonists into potent activators of the superoxide generating NADPH-oxidase
- 2018
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Ingår i: Journal of leukocyte biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 104:6, s. 1117-1132
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Tidskriftsartikel (refereegranskat)abstract
- Acetate, an agonist for the free fatty acid receptor 2 (FFA2R/GPR43), triggers an increase in the cytosolic concentration of free Ca2+ in neutrophils without any assembly of the superoxide generating NADPH-oxidase. We show that the phenylacetamide compound 58 (Cmp 58; (S)-2-(4-chlorophenyl)-3,3-dimethyl-N-(5-phenylthiazol-2-yl)butanamide), lacking a direct activating effect on neutrophils, acts as a positive FFA2R modulator that turns acetate into a potent activating agonist that triggers an assembly of the NADPH-oxidase. The NADPH-oxidase activity could be further increased in neutrophils treated with the pro-inflammatory cytokine TNF-alpha. Many neutrophil chemoattractant receptors are stored in secretory organelles but no FFA2R mobilization was induced in neutrophils treated with TNF-alpha. The receptor selectivity was demonstrated through the inhibition of the neutrophil response induced by the combined action of acetate and Cmp 58 by the FFA2R antagonist CATPB. Receptor modulators that positively co-operate with natural FFA2R agonists and prime neutrophils in their response to such agonists, may serve as good tools for further unraveling the physiological functions of FFA2R and its involvement in various diseases. In this study, we show that neutrophils primed with a presumed allosteric FFA2R modulator produce increased amounts of reactive oxygen species when activated by receptor specific agonists.
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| 5237. |
- Mäe, Maarja Andaloussi, et al.
(författare)
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Single-Cell Analysis of Blood-Brain Barrier Response to Pericyte Loss
- 2021
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Ingår i: Circulation Research. - : Lippincott Williams & Wilkins. - 0009-7330 .- 1524-4571. ; 128:4, s. E46-E62
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Pericytes are capillary mural cells playing a role in stabilizing newly formed blood vessels during development and tissue repair. Loss of pericytes has been described in several brain disorders, and genetically induced pericyte deficiency in the brain leads to increased macromolecular leakage across the blood-brain barrier (BBB). However, the molecular details of the endothelial response to pericyte deficiency remain elusive.Objective: To map the transcriptional changes in brain endothelial cells resulting from lack of pericyte contact at single-cell level and to correlate them with regional heterogeneities in BBB function and vascular phenotype.Methods and Results: We reveal transcriptional, morphological, and functional consequences of pericyte absence for brain endothelial cells using a combination of methodologies, including single-cell RNA sequencing, tracer analyses, and immunofluorescent detection of protein expression in pericyte-deficient adult Pdgfb(ret/ret) mice. We find that endothelial cells without pericyte contact retain a general BBB-specific gene expression profile, however, they acquire a venous-shifted molecular pattern and become transformed regarding the expression of numerous growth factors and regulatory proteins. Adult Pdgfb(ret/ret) brains display ongoing angiogenic sprouting without concomitant cell proliferation providing unique insights into the endothelial tip cell transcriptome. We also reveal heterogeneous modes of pericyte-deficient BBB impairment, where hotspot leakage sites display arteriolar-shifted identity and pinpoint putative BBB regulators. By testing the causal involvement of some of these using reverse genetics, we uncover a reinforcing role for angiopoietin 2 at the BBB.Conclusions: By elucidating the complexity of endothelial response to pericyte deficiency at cellular resolution, our study provides insight into the importance of brain pericytes for endothelial arterio-venous zonation, angiogenic quiescence, and a limited set of BBB functions. The BBB-reinforcing role of ANGPT2 (angiopoietin 2) is paradoxical given its wider role as TIE2 (TEK receptor tyrosine kinase) receptor antagonist and may suggest a unique and context-dependent function of ANGPT2 in the brain.
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| 5238. |
- Mäkelä, Olli, et al.
(författare)
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Effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate on adult equine cartilage.
- 2004
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 31:2, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate (166Ho-FHMA) on articular cartilage in 6 adult horses.METHODS: Arthritic changes and mechanical properties of articular cartilage were evaluated with arthroscopy and postmortem microscopic analyses. Glycosaminoglycan content was measured by safranin-O staining combined with digital densitometry, uronic acid analyses, and dimethylene blue binding assay. 35S-sulfate labeling and autoradiography were used to localize proteoglycan synthesis and to characterize proteoglycan structures using SDS-agarose gel electrophoresis. Northern hybridizations were performed to measure the mRNA levels for aggrecan and pro-a1(II) collagen in cartilage samples.RESULTS: Histological signs of degeneration were present in the articular cartilage of both control and radiosynovectomized equine joints. Radiosynovectomy did not aggravate degenerative changes or significantly alter the matrix glycosaminoglycan content. A slightly decreased size of proteoglycan monomers was observed 2 months after 166Ho-FHMA radiosynovectomy. Tissue analysis of extracted proteoglycans revealed lower 35S incorporation after radiosynovectomy, but corresponding changes could not be observed in aggrecan mRNA levels. Transient downregulation of pro-a1(II) collagen mRNA transcription was observed 5 days after 166Ho-FHMA radiosynovectomy.CONCLUSION: 166Ho-FHMA treatment did not markedly affect the composition or morphology of adult articular cartilage showing mild degeneration. However, minor degradation of proteoglycan monomers and transient downregulation of pro-a1(II) collagen mRNA were observed.
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| 5239. |
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| 5240. |
- Möller, Christine, 1975-
(författare)
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Regulation of Mast Cell Survival
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mast cells are long-lived effector cells of importance for both acute and chronic inflammations. Mast cells can be activated in many different ways, leading to the release of inflammatory mediators. In contrast to most other inflammatory cells, activated mast cells have the capacity to recover, regranulate and thereby be activated again. In this thesis I have investigated the mechanisms involved in regulating activation-induced mast cell survival. We have found that cross-linking of FcεRI-bound IgE with an antigen (IgER-CL) induces a survival program in mast cells. Upon IgER-CL, mouse and human mast cells upregulate the pro-survival Bcl-2 family gene A1/Bfl-1. A1-/- mast cells degranulate upon FcεRI activation but they cannot recover most likely due to the lack of A1. Sensitized and provoked A1-/- mice exhibit lower amounts of mast cells compared to littermate controls. In contrast to mast cells, no Bfl-1 expression or survival promotion can be detected in basophils after IgER-CL. Another mast cell secretagogue, an adenosine receptor agonist, neither promoted upregulation of A1 nor survival.Although it is well established that mast cell survival is dependent on stem cell factor (SCF), it has not been described how this process is regulated. We have found that SCF promotes survival through Akt-mediated inhibition of the forkhead transcription factor FOXO3a and its transcriptional target Bim, a BH3-only pro-apoptotic protein. SCF-treatment prevents upregulation of Bim protein expression and leads to an upregulation of Bim phosphorylation through PI3-kinase and MEK-dependent pathways. Overexpression of FOXO3a causes an upregulation of Bim and induces mast cell apoptosis, even in the presence of SCF. Taken together, the work in this thesis demonstrates that A1/Bfl-1 and Bim play key roles in mast cell survival. These findings might be of importance in understanding the mechanisms of mast cell longevity and hence for possible new therapeutics used for mast cell-associated inflammations.
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