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Sökning: WFRF:(Hansson EM)

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  • Hermansson, A, et al. (författare)
  • Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis
  • 2010
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 207:5, s. 1081-1093
  • Tidskriftsartikel (refereegranskat)abstract
    • Immune responses to oxidized low-density lipoprotein (oxLDL) are proposed to be important in atherosclerosis. To identify the mechanisms of recognition that govern T cell responses to LDL particles, we generated T cell hybridomas from human ApoB100 transgenic (huB100tg) mice that were immunized with human oxLDL. Surprisingly, none of the hybridomas responded to oxidized LDL, only to native LDL and the purified LDL apolipoprotein ApoB100. However, sera from immunized mice contained IgG antibodies to oxLDL, suggesting that T cell responses to native ApoB100 help B cells making antibodies to oxLDL. ApoB100 responding CD4+ T cell hybridomas were MHC class II–restricted and expressed a single T cell receptor (TCR) variable (V) β chain, TRBV31, with different Vα chains. Immunization of huB100tgxLdlr−/− mice with a TRBV31-derived peptide induced anti-TRBV31 antibodies that blocked T cell recognition of ApoB100. This treatment significantly reduced atherosclerosis by 65%, with a concomitant reduction of macrophage infiltration and MHC class II expression in lesions. In conclusion, CD4+ T cells recognize epitopes on native ApoB100 protein, this response is associated with a limited set of clonotypic TCRs, and blocking TCR-dependent antigen recognition by these T cells protects against atherosclerosis.
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  • Went, M, et al. (författare)
  • Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
  • Tidskriftsartikel (refereegranskat)abstract
    • The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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  • Niemi, MEK, et al. (författare)
  • 2021
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  • Kanai, M, et al. (författare)
  • 2023
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  • Duffy, DL, et al. (författare)
  • Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 299-
  • Tidskriftsartikel (refereegranskat)abstract
    • The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
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  • Hansson, Anneli, 1958- (författare)
  • Arbete med skolutveckling - En potentiell gränszon mellan verksamheter? : Ett verksamhetsteoretiskt perspektiv på en svensk skolas arbete över tid med att verksamhetsintegrera IT
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • I en skola som historiskt präglats av en differentierad arbetsorganisation och autonoma traditioner kan ett skolövergripande arbete med att verksamhetsintegrera informations­teknik antas ställa aktörerna inför en rad utmaningar som involverar både omskapande och nyskapande processer. Föreliggande studie utgör ett bidrag till att med en holistisk och verksamhetsteoretisk ansats utforska arbete med förändring, i detta fall ett arbete med att verksamhetsintegrera modern teknik, i skärningspunkten mellan en skolas arbete med att sprida och utveckla teknikbruk över skolan samt dess lärares arbete med pedagogisk praxisförändring. Studiens övergripande fråga löd: Hur kan arbete med skol­utveckling förstås och förklaras i det potentiella spänningsfältet mellan arbete med skolförändring och lärares arbete med eller motstånd mot pedagogisk praxisförändring? Syftet var att utforska den förändringsprocess som uppstod när en skola satte i sikte att utveckla ”digitala” kompetenser och IT-stödd undervisning inom dess verksamhets­område liksom att över tid följa lärare, IT-pedagoger och skolledare i detta arbete. Studien genomfördes över tre år mellan hösten 2008 och våren 2011 som en etnografiskt orien­terad fallstudie vid en 7–9 skola i en mellan­stor svensk stad. Data­produktionen skedde genom närvaro vid skolan och på nätet genom deltagande och ickedeltagande observationer, genom informella samtal, semistrukturerade intervjuer, dokument­insamling samt genom en enkät. Resultatet visar framför allt hur verksamhets­integreringen av IT, bland de lärare som utforskar informationstekniken, i hög utsträckning motiveras av undervisningsrelaterade och elevutvecklande behov, medan arbetet med att leda skolans arbete med verksam­hetsintegrering av IT i högre utsträckning motiveras av organisations­relaterade behov, samt att dessa skilda motiv framträder på olika och systemiskt inkonsekvent sätt inom skolan. Utifrån studiens resultat formuleras tre interrelaterade utmaningar för skolut­veckling. Dessa rör (a) praxis- och objektsförståelse, vilket uppfattas ha betydelse för möjligheter att åstad­komma gemensam riktning i ett kollektivt och flerstämmigt arbete, samt (b) förutsättningar för gränsöver­skridande lärprocesser inom skolan mellan lärare sinsemellan liksom mellan lärare och skolledning jämte (c) processledarskap och dess förutsättningar.
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  • Hansson, EM, et al. (författare)
  • Control of Notch-ligand endocytosis by ligand-receptor interaction
  • 2010
  • Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 123:17Pt 17, s. 2931-2942
  • Tidskriftsartikel (refereegranskat)abstract
    • In Notch signaling, cell-bound ligands activate Notch receptors on juxtaposed cells, but the relationship between ligand endocytosis, ubiquitylation and ligand-receptor interaction remains poorly understood. To study the specific role of ligand-receptor interaction, we identified a missense mutant of the Notch ligand Jagged1 (Nodder, Ndr) that failed to interact with Notch receptors, but retained a cellular distribution that was similar to wild-type Jagged1 (Jagged1WT) in the absence of active Notch signaling. Both Jagged1WT and Jagged1Ndr interacted with the E3 ubiquitin ligase Mind bomb, but only Jagged1WT showed enhanced ubiquitylation after co-culture with cells expressing Notch receptor. Cells expressing Jagged1WT, but not Jagged1Ndr, trans-endocytosed the Notch extracellular domain (NECD) into the ligand-expressing cell, and NECD colocalized with Jagged1WT in early endosomes, multivesicular bodies and lysosomes, suggesting that NECD is routed through the endocytic degradation pathway. When coexpressed in the same cell, Jagged1Ndr did not exert a dominant-negative effect over Jagged1WT in terms of receptor activation. Finally, in Jag1Ndr/Ndr mice, the ligand was largely accumulated at the cell surface, indicating that engagement of the Notch receptor is important for ligand internalization in vivo. In conclusion, the interaction-dead Jagged1Ndr ligand provides new insights into the specific role of receptor-ligand interaction in the intracellular trafficking of Notch ligands.
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  • Hansson, EM, et al. (författare)
  • Recording Notch signaling in real time
  • 2006
  • Ingår i: Developmental neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 28:1-2, s. 118-127
  • Tidskriftsartikel (refereegranskat)abstract
    • Notch signaling is a highly conserved signaling pathway, which is critical for many cell fate decisions. Ligand activation of Notch leads to cleavage of the Notch receptor and liberation of the Notch intracellular domain (ICD) from the membrane-tethered receptor. After translocation to the nucleus, the Notch ICD interacts with the DNA-binding protein CSL to activate gene transcription. To better understand the temporal and spatial aspects of Notch signaling, we here describe a fluorescent protein-based reporter assay that allows Notch activation to be followed in real time in individual cells. We have generated a reporter construct composed of 12 CSL-binding motifs linked to fluorescent proteins with different half-lives: a stabler red fluorescent protein (DsRedExpressDR) and a destabilized form of green fluorescent protein (d1EGFP). The fluorescent reporters reflect the activation status of Notch signaling with single-cell resolution. The reporters rapidly respond to various forms of Notch activation, including ligand activation of full-length Notch receptors. Finally, we use this assay to gain insights into the level of Notch signaling in CNS progenitor cells in culture and in vivo.
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  • Hansson, Per, seniorprofessor em. 1944- (författare)
  • Befogenhetsprövningar i Svenska kyrkan : Ett spel för galleriet?
  • 2021
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • Befogenhetsprövning inom Svenska kyrkan ska enligt kyrkoordningen skydda präster och diakoner från arbetsrättsliga åtgärder från arbetsgivaren som grundar sig på läran, utövandet av vigningstjänsten eller efterlevnaden av vigningslöftena. Sådana ärenden handhas av domkapitlet. Utifrån ett professionsteoretiskt perspektiv kan befogenhetsprövningen antas vara tänkt som ett skydd för professionen.I denna studie har 89 ansökningar om befogenhetsprövning för präster under tiden 2001 – 2019 analyserats. Enligt anvisningar från Överklagandenämnden skall domkapitlen ta arbetsgivarnas uppgifter för goda. Det blir därmed i praktiken arbetsgivaren som beslutar om befogenhetsprövningen skall godkännas.Det finns inga statistiskt säkerställda skillnader i utfall av ansökningar mellan män och kvinnor eller mellan kyrkoherdar och komministrar. För kyrkoherdar handlar klagomålen i stor utsträckning om deras ledarskap medan komministrar anses brista i samarbete.  Över 66% av alla ansökningar bifalls. Nästan samtliga korrekta ansökningar bifalls. Prästernas yttranden har inte visats påverka domkapitlens beslut, huvudsakligen för att prästerna argumenterar i sak. Endast i undantagsfall argumenterar prästerna för att klagomålen har att göra med deras vigningslöften och efterlevnaden av dem. Vissa ärenden avvisas eller upphävs av domkapitlet. Detta förefaller inte påverka församlingarna, utan de går vidare enligt sin planering. Domkapitlens roll är snarast att legitimera församlingarnas beslut, inte att granska dem. De kan därför sägas vara en tillsynesmyndighet och inte en tillsynsmyndighet.Om bestämmelsen om befogenhetsprövning skall vara ett verksamt skydd för professionen behöver regelverket ses över.
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  • Hansson, Per, seniorprofessor em. 1944- (författare)
  • Hur gick det sen? : En studie av karriär för präster inom Svenska kyrkan som tilldelats erinran eller prövotid
  • 2023
  • Ingår i: Scandinavian Journal for Leadership & Theology. - : Ansgar University College. - 1894-7875. ; 10, s. 15-35
  • Tidskriftsartikel (refereegranskat)abstract
    • What happened after? A study of the careers of priests within the Church of Sweden who have been assigned a rebuke or probationary period.The purpose of this study is to examine whether a rebuke or probationary time affects the careers of priests within the Church of Sweden. It is the diocesan chapter that decides on such measures. The reason may be a breach of consecration vows or that the priest has damaged the esteem of ordained ministry to a great extent. The purpose is primarily to protect the congregations from unsuitable priests.The career of a study group of 35 priests who received a rebuke or probationary period was compared with a control group of 42 priests, who were reported to the diocesan chapter but where the case did not lead to any action. Data were collected for every three years 2004–2019. The priests have been followed through a register­­ study for up to 10 years or until retirement.The careers of priests in the study group are negatively affected. For five years they have an average lower position. The year after the decision, about 25% are without employment in the church. After five years, the careers of these priests are on a par with the careers of the control group.The results indicate that priests in the study group have a worse career than the priests in the control group. This is particularly obvious in the first five years after the decision. The purpose of the disciplinary decisions is partly fulfilled by the fact that these priests for a period do not work within the church.This study is one of the few, which examines the careers of professionals who have received some form of reprimand. It thus constitutes a new contribution to the research on professionals.
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  • Marklund, U, et al. (författare)
  • Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression
  • 2010
  • Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 137:3, s. 437-445
  • Tidskriftsartikel (refereegranskat)abstract
    • Homeodomain (HD) transcription factors and components of the Notch pathway [Delta1 (Dll1), Jagged1 (Jag1) and the Fringe (Fng) proteins] are expressed in distinct progenitor domains along the dorsoventral (DV) axis of the developing spinal cord. However, the internal relationship between these two regulatory pathways has not been established. In this report we show that HD proteins act upstream of Notch signalling. Thus, HD proteins control the spatial distribution of Notch ligands and Fng proteins, whereas perturbation of the Notch pathway does not affect the regional expression of HD proteins. Loss of Dll1 or Jag1 leads to a domain-specific increase of neuronal differentiation but does not affect the establishment of progenitor domain boundaries. Moreover, gain-of-function experiments indicate that the ability of Dll1 and Jag1 to activate Notch is limited to progenitors endogenously expressing the respective ligand. Fng proteins enhance Dll1-activated Notch signalling and block Notch activation mediated by Jag1. This finding, combined with the overlapping expression of Fng with Dll1 but not with Jag1, is likely to explain the domain-specific activity of the Notch ligands. This outcome is opposite to the local regulation of Notch activity in most other systems, including the Drosophila wing, where Fng co-localizes with Jagged/Serrate rather than Dll/Delta, which facilitates Notch signalling at regional boundaries instead of within domains. The regulation of Notch activation in the spinal cord therefore appears to endow specific progenitor populations with a domain-wide autonomy in the control of neurogenesis and prevents any inadequate activation of Notch across progenitor domain boundaries.
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  • Moss, B, et al. (författare)
  • The determination of ecological status in shallow lakes - a tested system (ECOFRAME) for implementation of the European Water Framework Directive
  • 2003
  • Ingår i: Aquatic Conservation: Marine and Freshwater Ecosystems. - : Wiley. - 1052-7613. ; 13:6, s. 507-549
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The European Water Framework Directive requires the determination of ecological status in European fresh and saline waters. This is to be through the establishment of a typology of surface water bodies, the determination of reference (high status) conditions in each element (ecotype) of the typology and of lower grades of status (good, moderate, poor and bad) for each ecotype. It then requires classification of the status of the water bodies and their restoration to at least 'good status' in a specified period. 2. Though there are many methods for assessing water quality, none has the scope of that defined in the Directive. The provisions of the Directive require a wide range of variables to be measured and give only general guidance as to how systems of classification should be established. This raises issues of comparability across States and of the costs of making the determinations. 3. Using expert workshops and subsequent field testing, a practicable pan-European typology and classification system has been developed for shallow lakes, which can easily be extended to all lakes. It is parsimonious in its choice of determinands, but based on current limnological understanding and therefore as cost-effective as possible. 4. A core typology is described, which can be expanded easily in particular States to meet local conditions. The core includes 48 ecotypes across the entire European climate gradient and incorporates climate, lake area, geology of the catchment and conductivity. 5. The classification system is founded on a liberal interpretation of Annexes in the Directive and uses variables that are inexpensive to measure and ecologically relevant. The need for taxonomic expertise is minimized. 6. The scheme has been through eight iterations, two of which were tested in the field on tranches of 66 lakes. The final version, Version 8, is offered for operational testing and further refinement by statutory authorities.
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  • Noges, P, et al. (författare)
  • Factors controlling hydrochemical and trophic state variables in 86 shallow lakes in Europe
  • 2003
  • Ingår i: Hydrobiologia. - 1573-5117 .- 0018-8158. ; 506:1-3, s. 51-58
  • Konferensbidrag (refereegranskat)abstract
    • In order to disentangle the causes of variations in water chemistry among European shallow lakes, we performed standardised sampling programs in 86 lakes along a latitudinal gradient from southern Spain to northern Sweden. Lakes with an area of 0.1 to 27000 ha and mean depth of 0.4-5.6 m located in low to high altitudes were investigated within the EC project ECOFRAME 1-4 times during June-October 2000-2001. Several variables like conductivity, alkalinity, abundance of submerged plants, concentrations of suspended solids, total nitrogen and phosphorus were latitude-dependent decreasing from south to north. Secchi depth, concentrations of total nitrogen, total phosphorus, suspended solids, and chlorophyll a correlated strongly with the presumed quality classes of the lakes. We came to the conclusion that the variability of shallow lakes in Europe is still mostly dependent on natural differences. Variables connected to lake morphometry, seasonality, basin geology and climate explained altogether nearly half of the total variability of lakes. The trophic state factor, describing mostly the human influence on lakes, was the strongest single factor responsible for nearly a quarter of the total variability of the studied European lakes.
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  • Rodin, S, et al. (författare)
  • Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment
  • 2014
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3195-
  • Tidskriftsartikel (refereegranskat)abstract
    • Lack of robust methods for establishment and expansion of pluripotent human embryonic stem (hES) cells still hampers development of cell therapy. Laminins (LN) are a family of highly cell-type specific basement membrane proteins important for cell adhesion, differentiation, migration and phenotype stability. Here we produce and isolate a human recombinant LN-521 isoform and develop a cell culture matrix containing LN-521 and E-cadherin, which both localize to stem cell niches in vivo. This matrix allows clonal derivation, clonal survival and long-term self-renewal of hES cells under completely chemically defined and xeno-free conditions without ROCK inhibitors. Neither LN-521 nor E-cadherin alone enable clonal survival of hES cells. The LN-521/E-cadherin matrix allows hES cell line derivation from blastocyst inner cell mass and single blastomere cells without a need to destroy the embryo. This method can facilitate the generation of hES cell lines for development of different cell types for regenerative medicine purposes.
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  • Spater, D, et al. (författare)
  • How to make a cardiomyocyte
  • 2014
  • Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 141:23, s. 4418-4431
  • Tidskriftsartikel (refereegranskat)abstract
    • During development, cardiogenesis is orchestrated by a family of heart progenitors that build distinct regions of the heart. Each region contains diverse cell types that assemble to form the complex structures of the individual cardiac compartments. Cardiomyocytes are the main cell type found in the heart and ensure contraction of the chambers and efficient blood flow throughout the body. Injury to the cardiac muscle often leads to heart failure due to the loss of a large number of cardiomyocytes and its limited intrinsic capacity to regenerate the damaged tissue, making it one of the leading causes of morbidity and mortality worldwide. In this Primer we discuss how insights into the molecular and cellular framework underlying cardiac development can be used to guide the in vitro specification of cardiomyocytes, whether by directed differentiation of pluripotent stem cells or via direct lineage conversion. Additional strategies to generate cardiomyocytes in situ, such as reactivation of endogenous cardiac progenitors and induction of cardiomyocyte proliferation, will also be discussed.
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  • Werley, CA, et al. (författare)
  • Multiplexed Optical Sensors in Arrayed Islands of Cells for multimodal recordings of cellular physiology
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3881-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cells typically respond to chemical or physical perturbations via complex signaling cascades which can simultaneously affect multiple physiological parameters, such as membrane voltage, calcium, pH, and redox potential. Protein-based fluorescent sensors can report many of these parameters, but spectral overlap prevents more than ~4 modalities from being recorded in parallel. Here we introduce the technique, MOSAIC, Multiplexed Optical Sensors in Arrayed Islands of Cells, where patterning of fluorescent sensor-encoding lentiviral vectors with a microarray printer enables parallel recording of multiple modalities. We demonstrate simultaneous recordings from 20 sensors in parallel in human embryonic kidney (HEK293) cells and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and we describe responses to metabolic and pharmacological perturbations. Together, these results show that MOSAIC can provide rich multi-modal data on complex physiological responses in multiple cell types.
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  • Wisse, Laura EM, et al. (författare)
  • Tau pathology mediates age effects on medial temporal lobe structure
  • 2022
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 109, s. 135-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Hippocampal atrophy is endemic in ‘normal aging’ but it is unclear what factors drive age-related changes in medial temporal lobe (MTL) structural measures. We investigated cross-sectional (n = 191) and longitudinal (n = 164) MTL atrophy patterns in cognitively normal older adults from ADNI-GO/2 with no to low cerebral β-amyloid and assessed whether white matter hyperintensities (WMHs) and cerebrospinal fluid (CSF) phospho tau (p-tau) levels can explain age-related changes in the MTL. Age was significantly associated with hippocampal volumes and Brodmann Area (BA) 35 thickness, regions affected early by neurofibrillary tangle pathology, in the cross-sectional analysis and with anterior and/or posterior hippocampus, entorhinal cortex and BA35 in the longitudinal analysis. CSF p-tau was significantly associated with hippocampal volumes and atrophy rates. Mediation analyses showed that CSF p-tau levels partially mediated age effects on hippocampal atrophy rates. No significant associations were observed for WMHs. These findings point toward a role of tau pathology, potentially reflecting Primary Age-Related Tauopathy, in age-related MTL structural changes and suggests a potential role for tau-targeted interventions in age-associated neurodegeneration and memory decline.
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  • Wuestefeld, Anika, et al. (författare)
  • Medial temporal lobe atrophy patterns in early- versus late-onset amnestic Alzheimer's disease
  • 2024
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • BACKGROUND: The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer's disease (EOAD). Yet, detailed examination of MTL subfield volumes and drivers of atrophy in amnestic EOAD is lacking.METHODS: BioFINDER-2 participants with memory impairment, abnormal amyloid-β status and tau-PET were included. Forty-one EOAD individuals aged ≤65 years and, as comparison, late-onset AD (LOAD, ≥70 years, n=154) and Aβ-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured.RESULTS: AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups, although LOAD showed thinner entorhinal cortices compared to EOAD. EOAD showed lower WMH compared to LOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity was found.CONCLUSIONS: We found in vivo evidence for MTL atrophy in amnestic EOAD and overall similar levels to LOAD of MTL tau pathology and co-pathologies.
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