Publikationer från Umeå universitet
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Bacterial extracellular vesicles exploit filopodial surfing and retraction mechanisms to reach the host cell body in an actin-dependent manner
No full textExtracellular vesicles derived from gram-negative bacteria are nano-sized particles of different size and origin released by these microbes and are collectively called bacterial extracellular vesicles (BEVs). These BEVs may serve as vehicles for delivering bacterial molecules to eukaryotic host cells. Depending on the bacterial species, BEVs elicit various host cellular and immunomodulatory responses, often aiding bacterial survival and communication. Early events in the initial interaction between BEVs and the host cell, as well as how BEVs reach the cell body, remain unexplored. In this study, we describe the interaction of BEVs with actin-rich cellular extensions, including filopodia and retraction fibres, which extend from the host cell surface. Using microscopy-based tracking at the single cell level, BEVs were shown to exploit cellular extensions at the cell periphery to reach the main cell body, either by hijacking retracted extensions or by surfing along these extensions in an actin-dependent manner. BEVs bind to the outer surface of the extensions, but no internalization occurs at this stage. Instead, they serve as transport for BEVs to the main cell body, where endocytosis takes place. Importantly, this process appears to be a general phenomenon for BEVs across different bacterial species and cell origins
Exploring teaching practices in an innovative learning environment : a pragmatic view on the student-centred ideal in future classrooms
No full textThis study explores teaching practices in an Innovative Learning Environment (ILE) with the attempt to examine the student-centred ideal emphasised in these kinds of postdigital classrooms. Rather than treating student-centredness as a self-evident pedagogical aim, we explore it through entanglements of human and non-human actors in one lesson analysed iteratively using explanatory sequential research design. Building on Bernstein’s concepts of classification and framing, the first step of analysis investigated how power and control were negotiated within the ILE classroom, where spatial and material flexibility challenged traditional practices. Thereafter, a sociomaterial analysis targeted how humans and material intra-acted attributing agency in shaping postdigital classroom entanglements. The findings show how social, spatial, and material boundaries shape power dynamics and agency. It emphasises the complex, shifting interplay of teacher-student roles in postdigital pedagogy advocating a pragmatic rather than idealised student-centred use of ILEs. Spatial competence involves understanding how boundaries—whether physical or symbolic—can empower or exclude. Teachers play a key role in scaffolding students towards spatial co-regulation, enabling autonomy and response-ability. By extending sociomaterial and postdigital perspectives, the study reveals how agency and authority develop within ILE classrooms, including ongoing safety concerns. The study contributes to discussions on the implications of ILEs for power relations, agency, and student-centred learning in the postdigital era
On Ramsey theory, van der Waerden’s theorem and Positional Games
No full textThis essay aims to outline some key theorems in Ramsey theory, with a focus on van der Waerden’s theorem. We then cover some basic game theory regarding positional games specifically van der Waerden games. Lastly we introduce a new variation of the van der Waerden game which we call Sibling-Sibling.Denna uppsats har som avsikt att beskriva några av nyckelsatserna i Ramsey-teorin, med fokus på van der Waerdens sats. Vi täcker sedan lite grundläggande spelteori angående positionsspel, speciellt van der Waerden-spel. Till sist introducerar vi en ny variant av van der Waerden-spelet som vi kallar Sibling-Sibling
Dissecting FAP+ Cell Diversity in Pancreatic Cancer Uncovers an Interferon-Response Subtype of Cancer-Associated Fibroblasts with Tumor-Restraining Properties
No full textWithin the stroma of pancreatic ductal adenocarcinoma (PDAC), mesenchymal cells differentiate into cancer-associated fibroblast (CAF) subtypes that differentially mediate disease progression. Defining the regulatory mechanism and diversity of CAF subtypes could identify potential therapeutic strategies to harness the tumor-suppressive activities of CAFs. To address this, we utilized single-cell RNA sequencing to profile fibroblast activation protein-α (FAP)–expressing mesenchymal cells in human PDAC. The mesenchymal subpopulations in PDAC reflected mesenchymal cell heterogeneity found in the normal developing pancreas. In addition to characterizing inflammatory CAF and myofibroblastic CAF subpopulations in detail, the analysis uncovered a previously undescribed interferon-response CAF (ifCAF) subtype. Tumor-derived signals induced specific CAF subtypes from pancreatic stellate cells in an organoid-based coculture model, and time-course experiments revealed regulatory mechanisms that govern subtype formation. STING agonists promoted an ifCAF phenotype in vivo and in vitro. Importantly, induction of an ifCAF phenotype suppressed tumor cell invasiveness and induced an antitumor phenotype in tumor-associated neutrophils. Together, this study resolves FAP+ stromal cell heterogeneity in PDAC and identifies an ifCAF subtype that can be induced to suppress protumorigenic features of PDAC. Significance: Characterization of FAP+ mesenchymal cell heterogeneity in pancreatic cancer identifies a tumor-suppressive interferon-response cancer-associated fibroblast subtype that can be induced by stimulating type I interferon signaling using STING agonists
Survival and quality of life after isolated hepatic perfusion with melphalan as a treatment for uveal melanoma liver metastases : final results from the phase III randomized controlled trial SCANDIUM
No full textObjective: To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care for patients with uveal melanoma liver metastases. Background: Approximately half of the patients with uveal melanoma develop metastatic disease, most commonly in the liver, and systemic treatment options are limited. IHP is a locoregional therapy with high response rates but with an unclear effect on OS. Methods: In this phase III randomized controlled multicenter trial (the SCANDIUM trial), patients with previously untreated isolated uveal melanoma liver metastases were included between 2013 and 2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or best alternative care. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months. Results: The intention-to-treat population included 87 patients randomized to the IHP group [43 patients; 41 (89%) received IHP] or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the intention-to-treat population, the median progression-free survival was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group (P=0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group. Conclusions: For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in progression-free survival including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met
Factors that make school leaders leave : developing a model of school leader turnover
No full textSchool leader turnover affects school stability, staff cohesion, and student outcomes. While stress and workload are well-documented factors, fewer studies examine school-specific conditions influencing leaders’ decisions to leave. Through qualitative interviews with former school leaders, this study identifies two key themes: fragmentation and pressure, encompassing institutional and organizational conditions, as well as operational and leadership demands. These dimensions contribute to long-term disengagement or acute challenges, ultimately leading to attrition. The study offers a conceptual model that clarifies turnover mechanisms, providing insights for policymakers and educational leaders aiming to foster leadership retention and school stability
Forskolin enhances urokinase plasminogen activator secretion and angiogenic activity of xeno-free cultures of human adipose tissue-derived stem cells
No full textAdipose tissue-derived stem cells (ASCs) hold significant potential for treating various clinical conditions. To enhance their regenerative properties, ASCs can be chemically stimulated using various in vitro protocols. However, unsatisfactory results persist, partly due to the relatively costly long-term methods. Furthermore, current culturing techniques often rely on the use of xenogenic fetal bovine serum that can be immunogenic, limiting clinical translations. To facilitate clinical translation of ASCs-derived therapeutics, the effect of different stimulation protocols on human ASCs cultured in a xeno-free medium (PRIME-XV MSC Expansion XSFM) is investigated. The xeno-free medium was supplemented with stimulants (forskolin (FSK), basic fibroblast growth factor, platelet-derived growth factor-AA, neuregulin-1) in combinations or individually. Stimulation for 72 h in FSK alone, or together with the growth factors, enhanced the production of urokinase plasminogen activator (uPA), a serine protease involved in tissue remodeling processes. Conditioned medium derived from stimulated ASCs enhanced in vitro angiogenesis and endothelial cells migration. This study shows that pro-angiogenic responses in human ASCs can be enhanced with a defined short stimulation protocol using a xeno-free medium. The protocol, using readily available manufacturing cell therapy grade molecules, may boost the regenerative properties of ASCs secretome which could enhance their efficacy in clinical treatments
Prediagnostic serum immune marker levels and multiple myeloma : a prospective longitudinal study using samples from the Janus serum bank in Norway
No full textMultiple myeloma is preceded by monoclonal gammopathy of undetermined significance (MGUS). Only a minority of patients with MGUS will develop multiple myeloma, but precise prediction of progression is impossible using routine clinical biomarkers. Changes in the levels of blood immune markers can help predict disease progression. Data remain inconsistent for some markers of interest such as monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1α), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), fractalkine, and transforming growth factor-alpha (TGF-α). We aimed to investigate the associations between the prediagnostic serum levels of these candidate biomarkers and future multiple myeloma risk, as well as to assess marker changes over time. We performed a nested case-control study using prospective samples from the Janus Serum Bank in Norway to investigate associations between multiple myeloma risk and prediagnostic serum levels of MCP-3, MIP-1α, FGF-2, VEGF, fractalkine, and TGF-α. The study included 293 future multiple myeloma cases with serum samples collected 20 years (median) before multiple myeloma diagnosis and 293 matched cancer-free controls. Patients with multiple myeloma had an additional prediagnostic sample collected up to 42 years before diagnosis to identify marker changes over time. Markers with >60% detection rate (MIP-1α, VEGF, and TGF-α) were included in the statistical analysis. We observed no statistically significant associations between multiple myeloma risk and serum levels of MIP-1α, VEGF, or TGF-α in samples collected 20 years before diagnosis. However, TGF-α levels decreased significantly closer to the diagnosis in patients with multiple myeloma (P < 0.001). The decrease in TGF-α levels may reflect subtle microenvironmental changes related to multiple myeloma progression. PREVENTION RELEVANCE: This study observed a decline in TGF-α serum levels closer to multiple myeloma diagnosis, which may aid in predicting multiple myeloma progression and early detection, although validation in other longitudinal cohorts is needed
Human traces in Arctic soils : geoarchaeological evidence from 19th-century herders and farmers
No full textThis study examines how human activities influenced soil development at two contrasting Arctic sites: Maiva, a 19th-century farmstead, and Snuvrejohka, a seasonal Sámi reindeer herding settlement in the Lake Torneträsk region, northern Sweden. Using geochemical and geophysical soil analyses, we explore the spatial distribution and vertical development of anthropogenic signals in the soil. At Maiva, prolonged agricultural use and earthworm bioturbation have led to extensive soil mixing and altered soil horizons, resulting in elevated phosphate, lead, and organic matter concentrations in Ap and Ah horizons. In contrast, Snuvrejohka displays more stratified profiles with localized chemical enrichment around hearths, primarily within E horizons. These results highlight how different land-use practices leave distinct geochemical fingerprints in Arctic soils and emphasize the need for sampling strategies adapted to site-specific soil formation processes. Our findings demonstrate that even short-term or seasonal human activities can leave distinct and detectable signatures in Arctic soils. Through an integrated approach combining soil science, geoarchaeological methods, and historical data, this study provides new insights into the reconstruction of past land-use practices and highlights the vulnerability of archaeological soil records in Arctic environments facing rapid climate-driven change
Feasibility and potential efficacy of radically open dialectical behavior therapy for anorexia nervosa
No full textAnorexia nervosa (AN) is a serious health condition with insufficient treatment options. Radically Open Dialectical Behavior Therapy (RO-DBT) offers a new treatment approach targeting maladaptive overcontrol, a proposed underlying mechanism in AN. This study evaluated the feasibility, acceptability, and the preliminary efficacy of a 32-week standard RO-DBT intervention for individuals with AN in an outpatient setting. Twenty-three participants with AN (median age 20 years; median illness duration 5 years; 95.7% female) were included. Feasibility was demonstrated by a high retention rate (83%) and satisfactory completion of outcome measures, while acceptability was demonstrated by high treatment satisfaction. Participation in RO-DBT was associated with significant reductions in eating disorder psychopathology (95% CI: 0.34–1.45, Cohen’s d = 0.90), significant increase in BMI (95% CI: 0.22–1.24, Cohen’s d = 0.74), and increased use of the emotion regulation strategy cognitive reappraisal (95% CI: 0.19–1.20, Cohen’s d = 0.70). These findings suggest that RO-DBT is a feasible, acceptable, and potentially effective treatment for AN