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Sökning: WFRF:(Dahl Sara)

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1.
  • Dahl, Sara, et al. (författare)
  • The host defense peptide LL-37 triggers release of nucleic acids from human mast cells
  • 2018
  • Ingår i: Peptides. - Elsevier. - 0196-9781. ; 109, s. 39-45
  • Tidskriftsartikel (refereegranskat)abstract
    • The human host defense peptide LL-37 possesses antimicrobial activity but also affects host cell function and viability. Mast cells are involved in innate immunity but no data have been presented on effects of LL-37 on human mast cell viability and export of nucleic acids. Here, we demonstrated by immunofluorescence microscopy that synthesized LL-37 was internalized by human LAD2 mast cells and detected both in cytoplasm and nucleus. Treatment with high (4 and 10 μM) but not low (1 μM) concentrations of LL-37 for 4 h reduced cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Stimulation with 10 μM LL-37 for 4 h enhanced export of nucleic acids, total protein and lactate dehydrogenase (LDH), suggesting that both nuclear and plasma membranes are permeabilized by LL-37. Although LL-37 triggered release of nucleic acids, no extracellular trap-like structures were observed by laser scanning confocal microscopy of cells incubated with the plasma membrane impermeable nucleic acid fluorophore SYTOX-Green, indicating that LL-37 promotes export of nucleic acids but not formation of extracellular traps. On the other hand, phorbol-12-myristate-13-acetate (PMA), which is a well-known inducer of extracellular traps, stimulated export of nucleic acids and also formation of extracellular trap-like structures. However, PMA had no effect on export of either total protein or LDH. Hence, LL-37 and PMA seem to stimulate export of nucleic acids from LAD2 mast cells through different pathways. In conclusion, we demonstrate that LL-37 triggers release of nucleic acids from human mast cells but not the formation of extracellular trap-like structures.
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2.
  • Kee, Nigel, et al. (författare)
  • Single-Cell Analysis Reveals a Close Relationship between Differentiating Dopamine and Subthalamic Nucleus Neuronal Lineages
  • 2017
  • Ingår i: Cell Stem Cell. - Cell Press. - 1934-5909. ; 20:1, s. 29-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons, while also highlighting a distinct transcription factor set that can distinguish between them. While previous hESC mesDA differentiation protocols have relied on markers that are shared between the two lineages, we found that application of these highlighted markers can help to refine current stem cell engineering protocols, increasing the proportion of appropriately patterned mesDA progenitors. Our results, therefore, have important implications for cell replacement therapy in PD.
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3.
  • Ahlstedt, Sara, 1977- (författare)
  • The Feeling of Migration Narratives of Queer Intimacies and Partner Migration
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Avhandlingen analyserar narrativ om queer partnermigration, dvs en familjebandsmigration i vilken en av de två personerna i ett parförhållande migrerar för att de två ska kunna leva i samma land och i vilken de två individerna queerar migrationen på så sätt att de har en icke-normativ sexualitet och/eller könsidentitet. Syftet med studien är att undersöka hur queera partnermigranter och deras svenska partners upplever migrationsprocessen – vilken pågår även efter att den administrativa processen är avslutad – genom att analysera de känslor som uppstår i processen. Studien är ett bidrag till forskning om så väl privilegierad migration som intim migration.</p><p>I fokus står det queera partnermigrationsförhållandet och vad känslor ”gör” med detta förhållande, men också hur känslor strukturerar migrationsprocessen på olika sätt. Studien analyserar det arbete tre olika känslor – kärlek, förlust och tillhörighet – gör i migrationsprocessen och hur detta arbete beskrivs i deltagarnas narrativ. Migrantdeltagarna i studien kommer från olika delar av världen (Afrika, Europa, Latinamerika och Nordamerika), vilket gör det möjligt att analysera vad känslor gör i den här specifika migrationsprocessen utifrån nationalitet, och specifikt närhet till västerländskhet, ras och språkbakgrund samt hur privilegier kopplade till dessa positioner spelar in i processen.</p><p>Avhandlingen är en etnografisk intervjustudie där både migranter och svenska partners har intervjuats. Intervjumaterialet består av en blandning av parintervjuer och enskilda intervjuer.</p><p>Genom att använda affektteorier och queer fenomenologi visar avhandlingen hur det arbete känslor utför i migrationsprocesser är kopplat till könsidentitet, sexuell identitet, ras och vithet, nationalitet, upplevd närhet till västerländskhet, klass, språk och det migrationsnarrativ den migrerande partnern är inskriven i (eller inte) genom det land den migrerat från. Detta analyseras i relation till de teoretiska ramverken trassel (<em>entanglement</em>), homonationalism och intimt medborgarskap.</p><p>I analysen framkommer att känslor strukturerar migrationsprocessen för både mer privilegierade och mindre privilegierade migranter men på olika sätt. Förståelsen av vem som ”är” en migrant och beredskapen för de känslor som uppstår i migrationsprocessen är till stor del kopplade till de positioner som nämns ovan samt de privilegier migranten har tillgång till genom dessa. Genom att fokusera på känslor och vad dessa gör visar studien också att migrationsprocessen påverkar den icke-migrerande partnern genom att denna förutsätts utföra känsloarbete för att ”göra” den migrerande partnern ”svensk.” Samtidigt blir den icke-migrerande partnern själv, genom sin migrerande partner, riktad på ett sätt som gör den lite mindre ”svensk”, vilket bidrar till att också den icke-migrerande partnerns liv ”stoppas” på sätt den vanligtvis inte tidigare upplevt. Studien visar vidare på hur migrationsprocesser producerar ojämlikhet och de svårigheter som då uppstår när paren försöker leva upp till det jämlika svenska idealförhållandet.</p><p>Intervjuerna är analyserade som narrativ och både narrativ och berättande är genomgående viktiga i avhandlingen, inte bara som metod utan också som avhandlingens form och en slags struktur som organiserar texten. Skrivande (att skriva tillgängligt och intressant) och läsande (att skriva på ett sätt som inbjuder till öppet och aktivt läsande) är viktiga aspekter i avhandlingen.</p>
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4.
  • Aidoukovitch, Alexandra, et al. (författare)
  • Antimicrobial peptide LL-37 and its pro-form, hCAP18, in desquamated epithelial cells of human whole saliva
  • ????
  • Ingår i: European Journal of Oral Sciences. - Wiley-Blackwell. - 0909-8836.
  • Tidskriftsartikel (refereegranskat)abstract
    • The antimicrobial peptide LL-37 is active against oral bacteria and has been demonstrated to be present in human saliva, but its distribution in different fractions of saliva is not known. LL-37 is formed from its intracellular pro-form, hCAP18, in an extracellular enzymatic reaction catalyzed by proteinase 3 and kallikrein 5. Here, we prepared cell-containing and cell-free fractions of unstimulated human whole saliva by centrifugation after depolymerization of mucins with dithiothreitol, and measured the levels of hCAP18/LL-37 in these fractions using ELISA. Cellular expression of hCAP18/LL-37 was determined by western blotting and immunocytochemistry. The ELISA analyses demonstrated that both cells and cell-free saliva contained hCAP18/LL-37. Western blot analysis of cell-pellet homogenates showed a strong band corresponding to hCAP18 at the correct molecular weight and a weak band corresponding to LL-37. Phase-contrast and light microscopy revealed that the cells consisted of desquamated epithelial cells. These cells expressed cytoplasmic immunoreactivity for hCAP18/LL-37. The peripheral part of the cytoplasm, corresponding to the plasma membrane, was particularly rich in hCAP18/LL-37 immunoreactivity. No immunoreactivity was observed after omission of the primary antibody. We conclude that desquamated epithelial cells of human whole saliva contain antimicrobial hCAP18/LL-37, suggesting that these cells may take part in the innate immune system by harboring and releasing these peptides.
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5.
  • Aidoukovitch, Alexandra, et al. (författare)
  • The host defense peptide LL-37 is internalized by human periodontal ligament cells and prevents LPS-induced MCP-1 production
  • 2019
  • Ingår i: Journal of Periodontal Research. - Wiley-Blackwell. - 0022-3484. ; 54:6, s. 662-670
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The human host defense peptide LL-37 both shows antimicrobial effects and modulates host cell properties. Here, we assess the effects of synthesized LL-37 on lipopolysaccharide (LPS)-induced inflammation in human periodontal ligament (PDL) cells and investigates underlying mechanisms. Background: LL-37 has been detected in the periodontal tissues, but its functional importance for PDL cell innate immune responses is not known. Methods: Human PDL cells were obtained from premolars extracted on orthodontic indications. Cellular pro-inflammatory monocyte chemoattractant protein-1 (MCP-1) mRNA expression was determined using quantitative real-time RT-PCR. MCP-1 protein production was assessed by western blot and ELISA. Internalization of LL-37 by PDL cells was visualized by immunocytochemistry. Nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activity was assessed by western blot of phosphorylated p65, phosphorylated p105, and IκBα proteins. Binding of LL-37 to PDL cell DNA was determined by isolation and purification of DNA and dot blot for LL-37 immunoreactivity. Results: Treatment with LL-37 (1 µmol/L) for 24 hours prevented LPS-induced stimulation of MCP-1 expression analyzed both on transcript and on protein levels. Stimulation with LL-37 (1 µmol/L) for 24 hours had no effect on toll-like receptor (TLR)2 and TLR4 transcript expression, suggesting that LL-37 acts downstream of the TLRs. Preincubation with LL-37 for 60 minutes followed by stimulation with LPS for 24 hours in the absence of LL-37 completely prevented LPS-evoked MCP-1 transcript expression, implying that LL-37 acts intracellularly and not via binding and neutralization of LPS. In PDL cells stimulated with LL-37 for 60 minutes, the peptide was internalized as demonstrated by immunocytochemistry, suggesting an intracellular mechanism of action. LL-37 immunoreactivity was observed both in the cytosol and in the nucleus. Downregulation of LPS-induced MCP-1 by LL-37 was not mediated by reduction in NF-κB activity as shown by unaltered expression of phosphorylated p65, phosphorylated p105, and IκBα NF-κB proteins in the presence of LL-37. Immunoreactivity for LL-37 was observed in PDL cell DNA treated with but not without 0.1 and 1 µmol/L LL-37 for 60 minutes in vitro. Conclusion: LL-37 abolishes LPS-induced MCP-1 production in human PDL cells through an intracellular, NF-κB-independent mechanism which probably involves direct interaction between LL-37 and DNA.
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6.
  • Anders, Emma, et al. (författare)
  • LL-37-induced human osteoblast cytotoxicity and permeability occurs independently of cellular LL-37 uptake through clathrin-mediated endocytosis
  • 2018
  • Ingår i: Biochemical and Biophysical Research Communications. - Elsevier. - 0006-291X. ; 501:1, s. 280-285
  • Tidskriftsartikel (refereegranskat)abstract
    • The host defense peptide LL-37 is cytotoxic for bacteria but it has also been reported to reduce host cell viability through an intracellular mechanism. LL-37-evoked cytotoxicity may be involved in the loss of bone tissue in periodontitis which is an inflammatory disease characterized by high concentrations of LL-37 observed locally in the periodontal tissue at the inflammation process. Here, we showed that LL-37 reduced human osteoblast-like MG63 cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and increased plasma membrane permeability determined by measuring intracellular Ca2+ levels and lactate dehydrogenase (LDH) release. Treatment with chlorpromazine, a well-recognized inhibitor of clathrin-mediated endocytosis, reduced cellular uptake of synthesized LL-37 b y about 30% assessed by Western blotting and ELISA, while filipin, an inhibitor of caveolin-mediated endocytosis, had no effect. The chlorpromazine-induced attenuation of LL-37 uptake was not associated with modulation of LL-37-induced cytotoxicity and LL-37-evoked plasma membrane permeability. Clathrin heavy chain 2 is a major protein of the polyhedral coat of coated pits and vesicles encoded by clathrin heavy chain like 1 gene. Down-regulation of clathrin heavy chain like 1 gene activity by siRNA reduced uptake of LL-37 but did not affect LL-37-induced cytotoxicity and permeability. Thus, we show, using both a pharmacological approach and knockdown of clathrin heavy chain like 1 expression, that LL-37-induced MG63 cell cytotoxicity and permeability occurs independently of LL-37 uptake via clathrin-mediated endocytosis.
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7.
  • Azawi, Nessn H., et al. (författare)
  • Incidence and Associated Risk Factors of Venous Thromboembolism After Open and Laparoscopic Nephrectomy in Patients Administered Short-period Thromboprophylaxis : A Danish Nationwide Population-based Cohort Study
  • ????
  • Ingår i: Urology. - Elsevier. - 0090-4295.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To report the incidence of venous thromboembolism (VTE) after nephrectomy in Denmark and explore associated risk factors. Materials and Methods: A nationwide population-based retrospective cohort study was performed. All nephrectomies from January 2010 to August 2018 were assessed for postoperative VTE events. Univariable and multivariable analyses were used to evaluate the odds ratio (OR) of clinical variables’ effect on postoperative VTEs, within 4 weeks and 4 months after nephrectomy. Results: In 5213 nephrectomized patients, postoperative VTE incidence was 1% and 2% within 4 weeks and 4 months, respectively. Multivariable analyses revealed that predictors of postoperative VTE within 4 months were: open nephrectomy (OR 2.5, P =.001), history of VTE (OR 13.3, P <.001), length of hospital stay (OR 0.98, P =.02), and lymph node dissection (OR 2.0, P =.04). Limitations included the retrospective and registry-based study design and absence of individual patient data on patient body mass index and length of surgery. CONCLUSION: For nephrectomy, postoperative VTE is rare. Open nephrectomy, history of VTE, length of hospital stay, and lymph node dissection are important risk factors which should be evaluated when tailoring VTE prophylaxis regimens.
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8.
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9.
  • Dahl, Sara, et al. (författare)
  • Can sense of coherence be a predictor for treatment outcome in patients with TMD-pain?
  • 2011
  • Ingår i: Svenska tandläkaresällskapets 47:e odontologisk riksstämma 2011. - Svenska tandläkaresällskapet. ; s. 110-110
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • <p>Aims. To investigate whether SOC (sense of coherence) changed after twelve months of treatment of TMD-pain, and if any such change could be correlated with treatment outcome. Another objective was to examine whether SOC was correlated with grade of depression and somatisation. Materials and Methods. 73 patients participated in the double-blind randomized controlled trial. The TMD-treatment was active for at least ten weeks and consisted of either a resilient or a non-occluding control appliance. Patients were diagnosed according to RDC/TMD and completed the SOC-29 at baseline and after twelve months. Treatment outcome was evaluated as a reduction of pain registered as characteristic pain intensity. No difference was found between the resilient appliance and the control appliance in reducing pain at the 12-months follow-up. Therefore the material was pooled together. Results. Of the 73 participating TMD-pain patients, a total of 44 patients filled in the SOC-29 at both baseline and after twelve months, and 42 of them also stated values for depression and somatisation. There was no correlation between high SOC and treatment outcome. No differences were found in the mean value of SOC for patients younger and older than 30 respectively 40 years. Significant correlations were found between mean differences of SOC and grade of depression, and between mean differences of grade of depression and somatisation. Conclusion. Our results showed that SOC was not a predictor for treatment outcome in TMD-pain patients previously treated with an appliance. SOC seems to be correlated to grade of depression.</p>
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10.
  • Dahl, Sara, et al. (författare)
  • Children with optic nerve hypoplasia face a high risk of neurodevelopmental disorders
  • 2018
  • Ingår i: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 107:3, s. 484-489
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Aim</strong>: Optic nerve hypoplasia (ONH) is a congenital ocular malformation that has been associated with neurodevelopmental disorders, but the prevalence in unilateral disease and less severe visual impairment is unknown. We studied intellectual disability and autism spectrum disorders (ASDs) in patients with ONH.</p><p><strong>Methods</strong>: This was a population-based cross-sectional cohort study of 65 patients (33 female) with ONH below 20 years of age, living in Stockholm in December 2009, with data analysed in January 2016. Of these 35 were bilateral and 30 were unilateral. Neurodevelopmental disorders were diagnosed or confirmed by neurological assessments, the Five to Fifteen parent questionnaire and reviewing previous neuropsychological investigations or conducting neuropsychological tests.</p><p><strong>Results</strong>: Bilateral ONH patients had lower mean full scale intelligence quotient scores than unilateral patients (84.4 and 99.4, respectively, p = 0.049). We assessed intellectual disability in 55 eligible patients, and it was more common in patients with bilateral ONH (18 of 32, 56%) than unilateral ONH (two of 23, 9%, p &lt; 0.001). ASDs were diagnosed in seven of 42 (17%) patients.</p><p><strong>Conclusion</strong>: Children with bilateral ONH had a high risk of neurodevelopmental disorders, especially intellectual disability. The risk was lower in unilateral ONH, but the levels of neurodevelopmental disorders warrant screening of both groups.</p>
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