| 1. |
- Krishna Vadivel, Chella, et al.
(author)
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Staphylococcus aureus induce drug resistance in cancer T cells in Sézary Syndrome
- 2024
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In: Blood. - 0006-4971 .- 1528-0020. ; 143:15, s. 1496-1512
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Journal article (peer-reviewed)abstract
- Key Points Enterotoxins from Staphylococcus aureus bacteria induce drug resistance in primary malignant T cells in Sézary syndrome. Targeting bacteria, their toxins, and downstream signaling pathways in malignant T cells abrogate the induction of drug resistance. Patients with Sézary syndrome (SS), a leukemic variant of cutaneous T cell lymphoma (CTCL), are prone to Staphylococcus aureus (S. aureus) infections and have a poor prognosis due to treatment-resistance. Here, we report that S. aureus and staphylococcal enterotoxins (SE) induce drug resistance in malignant T-cells against therapeutics commonly used in CTCL. Supernatant from patient-derived, SE-producing S. aureus and recombinant SE significantly inhibit cell death induced by HDAC inhibitor romidepsin in primary malignant T-cells from SS patients. Bacterial killing by engineered, bacteriophage-derived, S. aureus-specific endolysin (XZ.700) abrogates the effect of S. aureus supernatant. Likewise, mutations in MHC Class II binding sites of SE type-A (SEA) and anti-SEA antibody block induction of resistance. Importantly, SE also triggers resistance to other HDAC inhibitors (vorinostat and resminostat) and chemotherapeutic drugs (doxorubicin and etoposide). Multimodal single-cell sequencing indicates TCR, NFB, and JAK/STAT signaling pathways (previously associated with drug-resistance) as putative mediators of SE-induced drug resistance. In support, inhibition of TCR-signaling and Protein Kinase C (upstream of NFB) counteracts SE-induced rescue from drug-induced cell death. Inversely, SE cannot rescue from cell death induced by proteasome/NFB inhibitor bortezomib. Inhibition of JAK/STAT only blocks SE-induced rescue of malignant T-cells in some but not all patients, suggesting two distinct ways SE can induce drug resistance. In conclusion, we show that S. aureus enterotoxins induce drug-resistance in primary malignant T-cells. These findings suggest that S. aureus enterotoxins cause clinical treatment-resistance in SS patients and that anti-bacterial measures may improve the outcome of cancer-directed therapy in patients harboring S. aureus
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| 2. |
- Stenseke, Marie, et al.
(author)
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Kris i naturen – vår existens har blivit sårbar
- 2019
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In: Svenska Dagbladet, Stockholm. - 1101-2412.
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Journal article (pop. science, debate, etc.)abstract
- Fler arter än någonsin i mänsklighetens historia hotas av utrotning och den biologiska mångfalden lokalt har förändrats kraftigt i en stor del av världens ekosystem. Grundläggande förändringar behövs både i samhället och för individer, för att bromsa den negativa trenden, skriver en rad debattörer.
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| 3. |
- Bigdeli, Narmin, 1974, et al.
(author)
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Superior Osteogenic Capacity of Human Embryonic Stem Cells Adapted to Matrix-Free Growth Compared to Human Mesenchymal Stem Cells.
- 2010
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In: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:11, s. 3427-3440
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Journal article (peer-reviewed)abstract
- Human mesenchymal stem cells (hMSCs) represent a promising source of cells for bone tissue engineering. However, their low frequencies and limited proliferation restrict their clinical utility. An alternative is the use of human embryonic stem cells (hESCs), but labor-intensive expansion with the need for coating support limits their clinical use. We have previously derived a cell line from hESCs denoted matrix-free growth (MFG)-hESC that are independent of coating support for expansion, and we here compare its osteogenic capacity to that of hMSCs. Microarray analysis of hMSCs and MFG-hESCs revealed differential expression of genes involved in ossification. MFG-hESCs have significantly higher expression of secreted phosphoprotein 1 (SPP1) during osteogenic differentiation, whereas the opposite was true for alkaline phosphatase (ALPL), transforming growth factor, beta 1 (TGFB2), runt-related transcription factor 2 (RUNX2), and forkhead box C1 (FOXC1), as well as the activity of the ALPL enzyme, demonstrating that these two cell types differentiate into the osteogenic lineage using different signaling pathways. von Kossa staining, time-of-flight secondary ion mass spectrometry, and measurement of calcium and phosphate in the extracellular matrix demonstrated a superior ability of the MFG-hESCs to produce a mineralized matrix compared to hMSCs. The superior ability of the MFG-hESCs to form mineralized matrix compared to hMSCs demonstrates that MFG-hESCs are a promising alternative to the use of adult stem cells in future bone regenerative applications.
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| 4. |
- Bigdeli, Narmin, 1974, et al.
(author)
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Upregulation of adhesion molecules sustains matrix-free growth of human embryonic stem cells
- 2018
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In: Open Stem Cell Journal. - : Bentham Science Publishers Ltd.. - 1876-8938. ; 5:1, s. 14-30
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Journal article (peer-reviewed)abstract
- Background: Despite recent advances in culture techniques for undifferentiated human Embryonic Stem Cells (hESCs), further improvements are required to facilitate research and translation of these cells in clinical settings. We have previously derived hESC lines that can be cultured in their undifferentiated state on regular plastic culture dishes, without the need for feeder cells or other coating supports, denoted Matrix-Free Growth hESCs (MFG-hESCs). Objective: In this study, we further characterize and compare MFG-hESCs to hESCs in order to understand the molecular differences responsible for the unique ability of MFG-hESCs. Results: Microarray analysis demonstrated that MFG-hESCs highly resemble feeder-cultured hESCs in global gene expression profile. Two identified groups of genes with differential expression were those encoding for ribosomal proteins and attachment proteins, such as the RGD (Arg-Gly-Asp)-associated proteins. Real-time PCR and flow cytometry corroborated the microarray results. Culture of MFG-hESCs in the presence of RGD peptides resulted in decreased attachment ability compared to cells cultured in the presence of RGES (Arg-Gly-Asp-Ser) peptides. Conclusion: This study demonstrates that MFG-hESC lines overexpress cell attachment proteins but retain the typical characteristics of undifferentiated feeder-cultured hESCs. The ability to culture high-quality pluripotent stem cells in feeder-and matrix-free conditions creates a new opportunities for their large-scale manufacturing for experimental research and translational applications. © 2018 Bigdeli et al.
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| 5. |
- Bilén, Anna-Karin, et al.
(author)
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Miljökvalitetsmålen 2016 : Årlig uppföljning av miljökvalitetsmålen
- 2016
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Reports (other academic/artistic)abstract
- I Blekinge bedöms inte något miljökvalitetsmål vara möjligt att nå till år 2020. För att kunna lämna över ett hållbart samhälle till nästa generation krävs förebyggande arbete, ef?????????????????r. Ambitionerna måste öka och miljöfrågorna prioriteras högre på den politiska agendan.De mål som rör biologisk mångfald och bevarande av kulturmiljö följer enneutral eller negativ trend. I odlingslandskapet leder färre lantbrukare ochbrist på betesdjur till igenväxning av hagmarker. Livsmiljöer försvinner och????????????????????????????????????????,främst möte insekter.För att god ekologisk status ska uppnås i vattendragen behövs ny vattenlagstiftning och mer resurser för tillsyn. I Blekinges kustvatten är övergödning ett stort miljöproblem och det krävs kraftfulla åtgärder för att minska näringsläckaget. Arbetet med vattenförsörjningsplaner behöver fortsätta för att trygga framtida dricksvattenförsörjning. De senaste årens fynd av PFAS i dricksvatten visar på vikten av att skydda vattentäkter, genomföra riskbedömningar och undersöka förekomst av föroreningar.Obalans mellan den tätbefolkade kusten och den glesbyggda landsbygden är en utmaning i länet. Byggandet vid kusten ställer krav på en hänsynsfull bebyggelseutveckling som tydligt beaktar miljökvalitetsmålen.Internationella överenskommelser om kemikalier och minskade utsläpp till luft och vatten är nödvändigt för att uppnå uppsatta mål. Dessutom behövs en omställning till ett samhälle som baseras på förnybar energi. För att skapa en hållbar framtid måste vi förändra vår livsstil och vår attityd till konsumtion. Lokala och regionala åtgärder såsom arbete för en giftfri förskola och minskade utsläpp av mikroplaster är steg i rätt riktning.Minskad biologisk mångfald påverkar tillsammans med klimatförändringar, övergödning och miljögifter många av de ekosystemtjänster som vi är beroende av för mänsklig välfärd och en hållbar samhällsutveckling. Det pågår insatser som förbättrar tillståndet i miljön, men det går för långsamt. Det krävs mer resurser och modiga politiska beslut för att möjliggöra en hållbar framtid, den framtid som vi är skyldiga våra barn!
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| 6. |
- Bilén, Anna-Karin, et al.
(author)
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Miljökvalitetsmålen 2017 : Årlig uppföljning av miljömålen i Blekinge
- 2017
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Reports (other academic/artistic)abstract
- Trots miljöarbetet varit framgångsrikt inom många områden är nuvarande styrmedel och åtgärder inte tillräckliga. Inte något av de miljömål som bedöms på regional nivå kommer att uppnås till år 2020. För Frisk luft är utvecklingen i miljön positiv. För övriga mål bedöms utvecklingen vara neutral eller negativ. Minskad biologisk mångfald påverkar tillsammans med klimatförändringar, övergödning och miljögifter många av de ekosystemtjänster som vi är beroende av för mänsklig välfärd och en hållbar samhällsutveckling. Obalans mellan den tätbefolkade kusten och den glesbyggda landsbygden är en utmaning i länet. Byggandet vid kusten ställer krav på en hänsynsfull bebyggelseutveckling som tydligt beaktar miljökvalitetsmålen. De mål som rör biologisk mångfald och bevarande av kulturmiljö följer en neutral eller negativ trend. I odlingslandskapet leder färre lantbrukare och brist på betesdjur till igenväxning av hagmarker. Livsmiljöer försvinner och arter får det svårare att överleva. Lagring av flisvirke sommartid utgör ett hot, främst mot insekter. För att god ekologisk status ska uppnås i vattendragen behövs ny vattenlagstiftning och mer resurser för tillsyn. I Blekinges kustvatten är övergödning ett stort miljöproblem och det krävs kraftfulla åtgärder för att minska näringsläckaget. Arbetet med vattenförsörjningsplaner behöver fortsätta för att trygga framtida dricksvattenförsörjning. De senaste årens fynd av PFAS i dricksvatten visar på vikten av att skydda vattentäkter, genomföra riskbedömningar och undersöka förekomst av föroreningar. Internationella överenskommelser om kemikalier och minskade utsläpp till luft och vatten är nödvändigt för att uppnå uppsatta mål. Dessutom behövs en omställning till ett samhälle som baseras på förnybar energi. För att skapa en hållbar framtid måste vi förändra vår livsstil och vår attityd till konsumtion. Åtgärder såsom kommunala insatser för en giftfri förskola och att ställa miljökrav vid upphandling är steg i rätt riktning. Det pågår alltså insatser som förbättrar tillståndet i miljön, men det går för långsamt. Det krävs mer resurser och modiga politiska beslut för att möjliggöra en hållbar framtid, den framtid som vi är skyldiga våra barn!
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| 7. |
- Bodén, Stina, et al.
(author)
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Dietary inflammatory index and risk of first myocardial infarction : a prospective population-based study
- 2017
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In: Nutrition Journal. - : BioMed Central. - 1475-2891. ; 16
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Chronic, low-grade inflammation is an established risk factor for cardiovascular disease. The inflammatory impact of diet can be reflected by concentrations of inflammatory markers in the bloodstream and the inflammatory potential of diet can be estimated by the dietary inflammatory index (DII(TM)), which has been associated with cardiovascular disease risk in some previous studies. We aimed to examine the association between the DII and the risk of first myocardial infarction (MI) in a population-based study with long follow-up.METHOD: We conducted a prospective case-control study of 1389 verified cases of first MI and 5555 matched controls nested within the population-based cohorts of the Northern Sweden Health and Disease Study (NSHDS), of which the largest is the ongoing Västerbotten Intervention Programme (VIP) with nearly 100 000 participants during the study period. Median follow-up from recruitment to MI diagnosis was 6.4 years (6.2 for men and 7.2 for women). DII scores were derived from a validated food frequency questionnaire (FFQ) administered in 1986-2006. Multivariable conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using quartile 1 (most anti-inflammatory diet) as the reference category. For validation, general linear models were used to estimate the association between the DII scores and two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) in a subset (n = 605) of the study population.RESULTS: Male participants with the most pro-inflammatory DII scores had an increased risk of MI [ORQ4vsQ1 = 1.57 (95% CI 1.21-2.02) P trend = 0.02], which was essentially unchanged after adjustment for potential confounders, including cardiovascular risk factors [ORQ4vsQ1 = 1.50 (95% CI 1.14-1.99), P trend = 0.10]. No association was found between DII and MI in women. An increase of one DII score unit was associated with 9% higher hsCRP (95% CI 0.03-0.14) and 6% higher IL-6 (95% CI 0.02-0.11) in 605 controls with biomarker data available.CONCLUSION: A pro-inflammatory diet was associated with an elevated risk of first myocardial infarction in men; whereas for women the relationship was null. Consideration of the inflammatory impact of diet could improve prevention of cardiovascular disease.
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| 8. |
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| 9. |
- He, Qi, et al.
(author)
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The Cdh5-CreERT2 transgene causes conditional Shb gene deletion in hematopoietic cells with consequences for immune cell responses to tumors
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Journal article (peer-reviewed)abstract
- The tamoxifen-responsive conditional Cdh5-CreERT2 is commonly used for endothelial cell specific conditional deletion of loxP-flanked gene sequences. To address the role of endothelial cell Shb gene for B16F10 melanoma immune responses, tamoxifen-injected Cdh5-CreERT2/WT and Cdh5-CreERT2/Shbflox/flox mice received subcutaneous tumor cell injections. We observed a decrease of tumor myeloid cell Shb mRNA in the tamoxifen treated Cdh5-CreERT2/Shbflox/flox mice, which was not present when the mice had undergone a preceding bone marrow transplantation using wild type bone marrow. Differences in CD4+/FoxP3+ Tregs were similarly abolished by a preceding bone marrow transplantation. In ROSA26-mTmG mice, Cdh5-CreERT2 caused detectable floxing in certain bone marrow populations and in spleen cells. Floxing in bone marrow could be detected two months after tamoxifen treatment. In the spleen, however, floxing was undetectable two months after tamoxifen treatment, suggesting that Cdh5-CreERT2 is operating in a non-renewable population of hematopoietic cells in this organ. These data suggest that conditional gene deletion in hematopoietic cells is a potential confounder in experiments attempting to assess the role of endothelial specific effects. A cautious approach to achieve an endothelial-specific phenotype would be to adopt a strategy that includes a preceding bone marrow transplantation.
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| 10. |
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| 11. |
- Lindahl, Britt, et al.
(author)
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Socio-scientific Issues : A Way to Improve Students’ Interest and Learning?
- 2011
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In: US-China Education Review B. - New York : David Publishing Company. - 2161-6248 .- 1548-6613 .- 1930-1529. ; 8:9, s. 342-347
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Journal article (peer-reviewed)abstract
- According to many documents, there is a strong need to renew science education. One way could be to work with SSI (socio-scientific issues). This paper reports on both students' and teachers' experiences and learning when working with socio-scientific issues in science education in secondary school (aged from 13 to 16). The approach is multidimensional, as factors that influence cognition as well as motivation and the forming of attitudes are complex. Results suggest that SSI work forms are more important than personal factors for explaining outcomes. Relevant issues, autonomy and functioning group work seem to be important aspects of successful SSI work together with structure provided by the teacher, and information that challenges previous knowledge. In general, SSI seems to be most efficient for students, who believe that they learn from presenting and discussing their knowledge, focus on "the large picture", acknowledge own responsibility for learning, find school science personally relevant and are self-efficacious. It seems that the outcomes from SSI work are much in the hands of the teacher. This paper is a short summary of the first year and quantitative part of the project. Further results from the project will later be found in our homepage (http://www.sisc.se).
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| 12. |
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| 13. |
- Mattsson, Janet
(author)
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Uncovering pain and caring for children in the pediatric intensive care unit : nurses’ clinical approach and parent’s perspective
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- Background: The thesis has a standpoint in a synthesis of caring science and educationscience from a clinical perspective. Children in a Pediatric Intensive Care Unit (PICU) are in an exposed position, dependent on nurses to acknowledge their needs. The alleviation of children’s pain has been investigated from various perspectives, but undertreated pain remains a problem in the PICU. There is a preponderance of empirical evidence pointing toward the role of nurses in uncovering children’s pain and suffering. How nurses interpret the child’s expressions and judge the clinical situation influences their actions in the clinical care. In a PICU, the basis for nurses’ concerns and interpretation of what is meaningful in the nursing care situation are formed by professional concern, workplace culture, traditions, habits, and workplace structures. This influences how parents interpret the meaning of care as well. Patricia Benner’s theory on clinical judgment forms a reference framework for this thesis. The assumption is that children need to be approached from a holistic perspective in the caring situation in order to acknowledge their caring needs. A nurse’s clinical education and insights allow for the possibility to enhance the quality of care for children and parents in the PICU.Aim: To uncover clinical concerns, from caring and learning perspectives, in caring for children in the Pediatric Intensive Care Unit (PICU) from nurses and parents perspective.Methods: Qualitative methods were used in all studies to unfold and explore the phenomena in the nurses’ and parents’ everyday clinical life world. In Papers I and II, a phenomenographic method was adopted. In Papers III and IV, an interpretive phenomenological approach was adopted.Findings: Nurses that have a holistic view of the child and approach the child from a multidimensional perspective, with a focus on the individual child and his/her caring needs, develop a clinical “connoisseurship” and meet the parents’ expectations of the meaning of care. The nurses express that it is only when they focus on the child that subtle signs of pain are revealed. The meaning of nursing care, in the ideal case, is a holistic care where all aspects are integrated and the child as a person has first priority.Conclusion: The meaning of caring and children’s needs must become elucidated to improve the cultural influence of what can be seen as good nursing care within the PICU.
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| 14. |
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| 15. |
- Nilsson, Lena Maria, 1965-, et al.
(author)
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Consumption of filtered and boiled coffee and the risk of fist acute myocardial infarction : a nested case/referent study
- 2010
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In: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier. - 0939-4753 .- 1590-3729. ; 20:7, s. 527-535
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Journal article (peer-reviewed)abstract
- Background and aimIn northern Sweden, consumption of both filtered and boiled coffee is common. Boiled coffee, especially popular in rural areas, is known to raise blood lipids, a risk factor for acute myocardial infarction (MI). To our knowledge, only one epidemiological study, a case-control study from Sweden, has investigated boiled coffee in MI, noting an increased risk at high consumption levels in men, and no association in women. The aim of the present nested case-referent study was to relate consumption of filtered and boiled coffee to the risk of first MI.Methods and resultsThe study subjects were 375 cases (303 men, 72 women) and 1293 matched referents from the population-based Northern Sweden Health and Disease Study. Coffee consumption was assessed by food frequency questionnaire. Risk estimates were calculated by conditional logistic regression. A statistically significant positive association was found between consumption of filtered coffee and MI risk in men [odds ratio for consumption ≥4 times/day versus ≤1 time/day 1.73 (95% CI 1.05–2.84)]. In women, a similar association was observed, but for boiled coffee [odds ratio 2.51 (95% CI 1.08–5.86)]. After adjustment for current smoking, postsecondary education, hypertension, and sedentary lifestyle, the results for women were no longer statistically significant.ConclusionConsumption of filtered coffee was positively associated with the risk of a first MI in men. A similar tendency was observed for boiled coffee in women, but the result was not statistically significant in multivariate analysis. Further investigation in a larger study is warranted.
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| 16. |
- Näslund, Ulf, et al.
(author)
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Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) : a pragmatic, open-label, randomised controlled trial
- 2019
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 393:10167, s. 133-142
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Journal article (peer-reviewed)abstract
- BACKGROUND: Primary prevention of cardiovascular disease often fails because of poor adherence among practitioners and individuals to prevention guidelines. We aimed to investigate whether ultrasound-based pictorial information about subclinical carotid atherosclerosis, targeting both primary care physicians and individuals, improves prevention.METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a pragmatic, open-label, randomised controlled trial that was integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional risk factors were eligible to participate. Participants underwent clinical examination, blood sampling, and ultrasound assessment of carotid intima media wall thickness and plaque formation. Participants were randomly assigned 1:1 with a computer-generated randomisation list to an intervention group (pictorial representation of carotid ultrasound plus a nurse phone call to confirm understanding) or a control group (not informed). The primary outcomes, Framingham risk score (FRS) and European systematic coronary risk evaluation (SCORE), were assessed after 1 year among participants who were followed up. This study is registered with ClinicalTrials.gov, number NCT01849575.FINDINGS: 3532 individuals were enrolled between April 29, 2013, and June 7, 2016, of which 1783 were randomly assigned to the control group and 1749 were assigned to the intervention group. 3175 participants completed the 1-year follow-up. At the 1-year follow-up, FRS and SCORE differed significantly between groups (FRS 1·07 [95% CI 0·11 to 2·03, p=0·0017] and SCORE 0·16 [0·02 to 0·30, p=0·0010]). FRS decreased from baseline to the 1-year follow-up in the intervention group and increased in the control group (-0·58 [95% CI -0·86 to -0·30] vs 0·35 [0·08 to 0·63]). SCORE increased in both groups (0·13 [95% CI 0·09 to 0·18] vs 0·27 [0·23 to 0·30]).INTERPRETATION: This study provides evidence of the contributory role of pictorial presentation of silent atherosclerosis for prevention of cardiovascular disease. It supports further development of methods to reduce the major problem of low adherence to medication and lifestyle modification.
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| 17. |
- Sundqvist, Rasmus, et al.
(author)
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Kombinerad mobilitet - kundperspektiv på framtidens resande
- 2018
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In: Transportforum 2018, Linköping, Sweden, January 10-11, 2018.
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Conference paper (other academic/artistic)abstract
- I ett samverkansprojekt mellan Intermetra, Samtrafiken, Trafikverket, Västtrafik, Keolis och RISE Viktoria undersöker vi i en kvantitativ webbundersökning bland 1500 svenskar kunskap om, attityder till och förutsättningar för kombinerad mobilitet. Vi kartlägger också i en kvalitativ del den verklighet som kollektivresenärer, bilpendlare och cyklister möter i sitt dagliga resande, för att hitta svar på de frågor som är avgörande för hur vi kommer att resa i framtiden. Projektet slutrapporteras i december 2017 och vi önskar presentera de centrala insikterna vid Transportforum 2018.Det stora antalet privatägda bilar i samhället idag skapar problem med trängsel och påfrestningar på miljön. Kombinerad mobilitet öppnar möjligheter till att förändra detta och göra vårt resande smartare och mer hållbart. Utvecklingen mot kombinerad mobilitet drivs på av globala trender så som urbanisering, digitalisering och tjänstefiering, men också transportrelaterade trender som ökade kostnader för kollektivtrafiken och den framtida potentialen i självkörande fordon.Men kombinerad mobilitet är ingen mirakelkur. Många frågetecken kvarstår kring hur framtidens resande ska utformas. För att bli en lösning för det stora flertalet måste kombinerad mobilitet vara attraktivt på många olika plan. Det finns goda exempel att lära av; tjänster som Waze, Swish och Google Search har förändrat vårt beteende och blivit en del av vårt vardagsliv. Projektet syftar till att undersöka hur kombinerad mobilitet kan sälla sig till dessa, och vad som från ett kundperspektiv kan göra verklig skillnad för utvecklingen mot ett smartare och mer hållbart resande.
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| 18. |
- von Beek, Christopher, et al.
(author)
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A two-step activation mechanism enables mast cells to differentiate their response between extracellular and invasive enterobacterial infection
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- Mast cells localize to mucosal tissues and contribute to innate immune defense against infection. How mast cells sense, differentiate between, and respond to bacterial pathogens remains a topic of ongoing debate. Using the prototype enteropathogen Salmonella Typhimurium (S.Tm) and other related enterobacteria, here we show that mast cells can regulate their cytokine secretion response to distinguish between extracellular and invasive bacterial infection. Tissue-invasive S.Tm and mast cells colocalize in the mouse gut during acute Salmonella infection. Toll-like Receptor 4 (TLR4) sensing of extracellular S.Tm, or pure lipopolysaccharide, causes a modest induction of cytokine transcripts and proteins, including IL-6, IL-13, and TNF. By contrast, type-III-secretion-system-1 (TTSS-1)-dependent S.Tm invasion of both mouse and human mast cells triggers rapid and potent inflammatory gene expression and >100-fold elevated cytokine secretion. The S.Tm TTSS-1 effectors SopB, SopE, and SopE2 here elicit a second activation signal, including Akt phosphorylation downstream of effector translocation, which combines with TLR activation to drive the full-blown mast cell response. Supernatants from S.Tm-infected mast cells boost macrophage survival and maturation from bone-marrow progenitors. Taken together, this study shows that mast cells can differentiate between extracellular and host-cell invasive enterobacteria via a two-step activation mechanism and tune their inflammatory output accordingly.
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| 19. |
- von Beek, Christopher, et al.
(author)
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A two-step activation mechanism enables mast cells to differentiate their response between extracellular and invasive enterobacterial infection
- 2024
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Journal article (peer-reviewed)abstract
- Mast cells localize to mucosal tissues and contribute to innate immune defense against infection. How mast cells sense, differentiate between, and respond to bacterial pathogens remains a topic of ongoing debate. Using the prototype enteropathogen Salmonella Typhimurium (S.Tm) and other related enterobacteria, here we show that mast cells can regulate their cytokine secretion response to distinguish between extracellular and invasive bacterial infection. Tissue-invasive S.Tm and mast cells colocalize in the mouse gut during acute Salmonella infection. Toll-like Receptor 4 (TLR4) sensing of extracellular S.Tm, or pure lipopolysaccharide, causes a modest induction of cytokine transcripts and proteins, including IL-6, IL-13, and TNF. By contrast, type-III-secretion-system-1 (TTSS-1)-dependent S.Tm invasion of both mouse and human mast cells triggers rapid and potent inflammatory gene expression and >100-fold elevated cytokine secretion. The S.Tm TTSS-1 effectors SopB, SopE, and SopE2 here elicit a second activation signal, including Akt phosphorylation downstream of effector translocation, which combines with TLR activation to drive the full-blown mast cell response. Supernatants from S.Tm-infected mast cells boost macrophage survival and maturation from bone-marrow progenitors. Taken together, this study shows that mast cells can differentiate between extracellular and host-cell invasive enterobacteria via a two-step activation mechanism and tune their inflammatory output accordingly.
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| 20. |
- Ögmundsdóttir Michelsen, Halldóra, et al.
(author)
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The effect of audit and feedback and implementation support on guideline adherence and patient outcomes in cardiac rehabilitation : a study protocol for an open-label cluster-randomized effectiveness-implementation hybrid trial
- 2024
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In: Implementation Science. - : BioMed Central (BMC). - 1748-5908. ; 19:1
-
Journal article (peer-reviewed)abstract
- BackgroundProviding secondary prevention through structured and comprehensive cardiac rehabilitation programmes to patients after a myocardial infarction (MI) reduces mortality and morbidity and improves health-related quality of life. Cardiac rehabilitation has the highest recommendation in current guidelines. While treatment target attainment rates at Swedish cardiac rehabilitation centres is among the highest in Europe, there are considerable differences in service delivery and variations in patient-level outcomes between centres. In this trial, we aim to study whether centre-level guideline adherence and patient-level outcomes across Swedish cardiac rehabilitation centres can be improved through a) regular audit and feedback of cardiac rehabilitation structure and processes through a national quality registry and b) supporting cardiac rehabilitation centres in implementing guidelines on secondary prevention. Furthermore, we aim to evaluate the implementation process and costs.MethodsThe study is an open-label cluster-randomized effectiveness-implementation hybrid trial including all 78 cardiac rehabilitation centres (attending to approximately 10 000 MI patients/year) that report to the SWEDEHEART registry. The centres will be randomized 1:1:1 to three clusters: 1) reporting cardiac rehabilitation structure and process variables to SWEDEHEART every six months (audit intervention) and being offered implementation support to implement guidelines on secondary prevention (implementation support intervention); 2) audit intervention only; or 3) no intervention offered. Baseline cardiac rehabilitation structure and process variables will be collected. The primary outcome is an adherence score measuring centre-level adherence to secondary prevention guidelines. Secondary outcomes include patient-level secondary prevention risk factor goal attainment at one-year after MI and major adverse coronary outcomes for up to five-years post-MI. Implementation outcomes include barriers and facilitators to guideline adherence evaluated using semi-structured focus-group interviews and relevant questionnaires, as well as costs and cost-effectiveness assessed by a comparative health economic evaluation.DiscussionOptimizing cardiac rehabilitation centres’ delivery of services to meet standards set in guidelines may lead to improvement in cardiovascular risk factors, including lifestyle factors, and ultimately a decrease in morbidity and mortality after MI.
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| 21. |
- Abramsson, Alexandra, 1973, et al.
(author)
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Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development
- 2007
-
In: GENES & DEVELOPMENT. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 21:3, s. 316-331
-
Journal article (peer-reviewed)abstract
- During vascular development, endothelial platelet-derived growth factor B (PDGF-B) is critical for pericyte recruitment. Deletion of the conserved C-terminal heparin-binding motif impairs PDGF-BB retention and pericyte recruitment in vivo, suggesting a potential role for heparan sulfate (HS) in PDGF-BB function during vascular development. We studied the participation of HS chains in pericyte recruitment using two mouse models with altered HS biosynthesis. Reduction of N-sulfation due to deficiency in N-deacetylase/N-sulfotransferase-1 attenuated PDGF-BB binding in vitro, and led to pericyte detachment and delayed pericyte migration in vivo. Reduced N-sulfation also impaired PDGF-BB signaling and directed cell migration, but not proliferation. In contrast, HS from glucuronyl C5-epimerase mutants, which is extensively N- and 6-O-sulfated, but lacks 2-O-sulfated L-iduronic acid residues, retained PDGF-BB in vitro, and pericyte recruitment in vivo was only transiently delayed. These observations were supported by in vitro characterization of the structural features in HS important for PDGF-BB binding. We conclude that pericyte recruitment requires HS with sufficiently extended and appropriately spaced N-sulfated domains to retain PDGF-BB and activate PDGF receptor β (PDGFRβ) signaling, whereas the detailed sequence of monosaccharide and sulfate residues does not appear to be important for this interaction.
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| 22. |
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| 23. |
- Areskoug, Mats, et al.
(author)
-
Naturvetenskapens bärande idéer : för lärare F-6
- 2013
-
Book (other academic/artistic)abstract
- Att undervisa i de naturorienterande ämnena (NO) i de tidiga skolåren är ett utmanande, spännande och roligt uppdrag. Dessa ämnen spänner dock över stora innehållsområden och därför kan det vara svårt att få en överblick och välja ett innehåll som är lämpligt för åldersgruppen.Den här boken hjälper lärare att få grepp om det viktigaste innehållet i de naturvetenskapliga ämnena. Författarna beskriver naturvetenskaperna ur ett helhetsperspektiv och ger en övergripande struktur, som kompletteras med relevanta begrepp. Naturvetenskapens bärande idéer förklaras mer i detalj och utifrån en rad konkreta vardagliga exempel. Innehållet diskuteras i förhållande till Läroplan för grundskolan, förskoleklassen och fritidshemmet (Lgr 11).Boken kan användas både som kurslitteratur för blivande lärare och som ämnesfördjupning för verksamma lärare.
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| 24. |
- Areskoug, Mats, et al.
(author)
-
Naturvetenskapens bärande idéer : för lärare F-6
- 2020. - 3
-
Book (other academic/artistic)abstract
- Att undervisa i de naturvetenskapliga ämnena (NO) i de tidiga skolåren är ett utmanande, spännande och roligt uppdrag. Dessa ämnen spänner dock över stora innehållsområden och därför kan det vara svårt att få en överblick och välja ett innehåll som är lämpligt för åldersgruppen.Den här boken hjälper läraren att få grepp om det viktigaste innehållet i de naturvetenskapliga ämnena. Naturvetenskapens grundläggande och bärande idéer förklaras detaljerat och belyses med en rad konkreta och vardagliga exempel. Innehållet diskuteras i förhållande till Läroplan för grundskolan, förskoleklassen och fritidshemmet (Lgr 11).Boken kan, gärna i kombination med boken Naturvetenskapens bärande idéer i praktiken, användas både som kurslitteratur för blivande lärare och som ämnesfördjupning för verksamma lärare.Den 3:e upplagan har reviderats i förhållande till ändringarna i kursplanerna 2020.
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| 25. |
- Areskoug, Mats, et al.
(author)
-
Naturvetenskapens bärande idéer : för lärare F-6
- 2013
-
Book (other academic/artistic)abstract
- Att undervisa i de naturorienterande ämnena (NO) i de tidiga skolåren är ett utmanande, spännande och roligt uppdrag. Dessa ämnen spänner dock över stora innehållsområden och därför kan det vara svårt att få en överblick och välja ett innehåll som är lämpligt för åldersgruppen. Den här boken hjälper lärare att få grepp om det viktigaste innehållet i de naturvetenskapliga ämnena. Författarna beskriver naturvetenskaperna ur ett helhetsperspektiv och ger en övergripande struktur, som kompletteras med relevanta begrepp. Naturvetenskapens bärande idéer förklaras mer i detalj och utifrån en rad konkreta vardagliga exempel. Innehållet diskuteras i förhållande till Läroplan för grundskolan, förskoleklassen och fritidshemmet (Lgr 11). Boken kan användas både som kurslitteratur för blivande lärare och som ämnesfördjupning för verksamma lärare.
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| 26. |
- Areskoug, Mats, et al.
(author)
-
Naturvetenskapens bärande idéer : för lärare F-6
- 2020
-
Book (other academic/artistic)abstract
- Att undervisa i de naturvetenskapliga ämnena (NO) i de tidiga skolåren är ett utmanande, spännande och roligt uppdrag. Dessa ämnen spänner dock över stora innehållsområden och därför kan det vara svårt att få en överblick och välja ett innehåll som är lämpligt för åldersgruppen. Den här boken hjälper läraren att få grepp om det viktigaste innehållet i de naturvetenskapliga ämnena. Naturvetenskapens grundläggande och bärande idéer förklaras detaljerat och belyses med en rad konkreta och vardagliga exempel. Innehållet diskuteras i förhållande till Läroplan för grundskolan, förskoleklassen och fritidshemmet (Lgr 11). Boken kan, gärna i kombination med boken Naturvetenskapens bärande idéer i praktiken, användas både som kurslitteratur för blivande lärare och som ämnesfördjupning för verksamma lärare. Den 3:e upplagan har reviderats i förhållande till ändringarna i kursplanerna 2020.
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| 27. |
- Asp, Julia, 1973, et al.
(author)
-
Evaluation of p16 and Id1 status and endogenous reference genes in human chondrosarcoma by real-time PCR.
- 2005
-
In: International journal of oncology. - 1019-6439. ; 27:6, s. 1577-82
-
Journal article (peer-reviewed)abstract
- Both the tumour suppressor, p16, and the helix-loop-helix transcription factor, Id1, have been assigned roles in tumour growth in general and appear to be involved in chondrosarcoma. Id1 has further been found to repress the expression of p16. Therefore, the mRNA expression of these two genes was studied by real-time PCR in a search for prognostic markers in human chondrosarcoma. To get reliable quantitative data, however, the choice of endogenous reference gene for use in the assay is important. Therefore, eleven different endogenous reference genes were evaluated in chondrosarcoma cells and articular chondrocytes. 18S rRNA appeared to be the best choice to use as endogenous reference gene, since it was suitable for both kinds of cells. Several of the other reference genes tested showed variation between individuals or between normal chondrocytes and chondrosarcoma cells. This demonstrates the importance of using a correct endogenous reference gene to get reliable results from quantitative measurements. Both p16 and Id1 showed varied gene expression patterns among the samples and none of these genes could be significantly correlated to prognosis.
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| 28. |
- Barreto Henriksson, Helena, et al.
(author)
-
Identification of Cell Proliferation Zones, Progenitor Cells and a Potential Stem Cell Niche in the Intervertebral Disc Region: A Study in Four Species.
- 2009
-
In: SPINE. - 0362-2436. ; 34:21, s. 2278-2287
-
Journal article (peer-reviewed)abstract
- STUDY DESIGN.: Descriptive experimental study in 4 different mammals. OBJECTIVE.: To investigate cell proliferation/regeneration and localize stem cells/progenitor cells within the intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA.: Disc degeneration (DD) is believed to play a major role in patients with chronic lumbar pain. Lately, biologic treatment options for DD have gained increasing interest. Normal regeneration processes within the IVD and have previously been sparsely described and therefore it is of great interest to increase the knowledge about these processes. METHODS.: Detection of cell proliferations zones and label-retaining cells were done by in vivo 5-bromo-2-deoxyuridine (BrdU) labeling in 18 rabbits, killed after 4, 6, 10, 14, 28, or 56 days. Results were visualized with immunohistochemistry and fluorescence/confocal microscopy. Localization of progenitor cell were further investigated by immunohistochemistry using antibodies towards Notch1, Delta4, Jagged1, C-KIT, KI67, and Stro-1 in normal IVD from rabbits (n = 3), rats (n = 2), minipigs (n = 2), and in human degenerated IVD (n = 4). Further, flowcytometry analysis using progenitor markers were performed on additional human IVD cells (n = 3). RESULTS.: BrdU positive cells were found in comparable numbers at early and late time points in most regions of the anulus fibrosus (AF) and nucleus pulposus demonstrating slow ongoing cell proliferation. In the AF border to ligament zone (AFo) and the perichondriumregion (P) a stem cell niche-like pattern was determined (a high number of BrdU positive cells at early time points vs. only a few label retaining cells at later time points). In normal and DD tissue from the 4 investigated species progenitor cell markers were detected. CONCLUSION.: The IVD is a tissue with ongoing slow cell proliferation both in the AF and the nucleus pulposus. The stem cell niche pattern detected in AFo and P can be suggested to play a role for IVD morphology and function. These findings may be of importance for the development of biologic treatment strategies. PMID: 19755937 [PubMed - as supplied by publisher]
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| 29. |
- Berger, Karin, et al.
(author)
-
Xylooligosaccharides Increase Bifidobacteria and Lachnospiraceae in Mice on a High-Fat Diet, with a Concomitant Increase in Short-Chain Fatty Acids, Especially Butyric Acid
- 2021
-
In: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 69:12, s. 3617-3625
-
Journal article (peer-reviewed)abstract
- Effects of xylooligosaccharides (XOSs) as well as a mixture of XOS, inulin, oligofructose, and partially hydrolyzed guar gum (MIX) in mice fed a high-fat diet (HFD) were studied. Control groups were fed an HFD or a low-fat diet. Special attention was paid to the cecal composition of the gut microbiota and formation of short-chain fatty acids, but metabolic parameters were also documented. The XOS group had significantly higher cecum levels of acetic, propionic, and butyric acids than the HFD group, and the butyric acid content was higher in the XOS than in the MIX group. The cecum microbiota of the XOS group contained more Bifidobacteria, Lachnospiraceae, and S24-7 bacteria than the HFD group. A tendency of lower body weight gain was observed on comparing the XOS and HFD groups. In conclusion, the XOS was shown to be a promising prebiotic candidate. The fiber diversity in the MIX diet did not provide any advantages compared to the XOS diet.
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| 30. |
- Bergström, Petra, et al.
(author)
-
Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation
- 2016
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- Amyloid precursor protein (APP) and its cleavage product amyloid beta (A beta) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. alpha-Cleaved soluble APP (sAPP alpha) was secreted early during differentiation, from neuronal progenitors, while beta-cleaved soluble APP (sAPP beta) was first secreted after deep-layer neurons had formed. Short A beta peptides, including A beta 1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as A beta 1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by A beta 1-40/42, is associated with mature neuronal phenotypes.
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| 31. |
- Betsholtz, Christer, 1959, et al.
(author)
-
Role of platelet-derived growth factor in mesangium development and vasculopathies: lessons from platelet-derived growth factor and platelet-derived growth factor receptor mutations in mice.
- 2004
-
In: Current opinion in nephrology and hypertension. - 1062-4821. ; 13:1, s. 45-52
-
Journal article (peer-reviewed)abstract
- PURPOSE OF REVIEW: The phenotypic consequences of null mutations in the platelet-derived growth factor-B and the platelet-derived growth factor beta-receptor genes in mice have demonstrated that these proteins play pivotal roles in the development of the vascular smooth muscle cell lineage, including pericytes and mesangial cells. RECENT FINDINGS: The lethality of these mutants has precluded analysis of the physiological and pathophysiological consequences of platelet-derived growth factor-B and platelet-derived growth factor beta-receptor deficiency in adults. This review summarizes and discusses recent data from certain tissue-specific and subtle mutations in the platelet-derived growth factor-B and platelet-derived growth factor beta-receptor genes that are compatible with postnatal viability in spite of severe developmental deficits in pericyte and mesangial cell recruitment. In the postnatal period, the animals studied developed a characteristic set of pathological changes to small blood vessels of the retina and the kidney glomerulus, which sheds light on the importance of pericytes and mesangial cells for vascular integrity and function after birth. SUMMARY: These microvascular abnormalities and their consequences bear a resemblance to diabetic microangiopathy and nephropathy. The platelet-derived growth factor-B and platelet-derived growth factor beta-receptor mutant mouse models, therefore, might serve as valuable tools in the dissection of some of the pathogenic events in diabetic microangiopathy.
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| 32. |
- Bigdeli, Narmin, 1974, et al.
(author)
-
Adaptation of human embryonic stem cells to feeder-free and matrix-free culture conditions directly on plastic surfaces.
- 2008
-
In: Journal of biotechnology. - : Elsevier BV. - 0168-1656. ; 133:1, s. 146-53
-
Journal article (peer-reviewed)abstract
- Previous studies have shown that cultivation of undifferentiated human embryonic stem (hES) cells requires human fibroblasts (hF) or mouse embryonic fibroblast (mEF) feeders or a coating matrix such as laminin, fibronectin or Matrigeltrade mark in combination with mEF or hF conditioned medium. We here demonstrate a successful feeder-free and matrix-free culture system in which undifferentiated hES cells can be cultured directly on plastic surfaces without any supportive coating, in a hF conditioned medium. The hES cells cultured directly on plastic surfaces grow as colonies with morphology very similar to cells cultured on Matrigel(TM). Two hES cell lines SA167 and AS034.1 were adapted to matrix-free growth (MFG) and have so far been cultured up to 43 passages and cryopreserved successfully. The lines maintained a normal karyotype and expressed the expected marker profile of undifferentiated hES cells for Oct-4, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81 and SSEA-1. The hES cells formed teratomas in SCID mice and differentiated in vitro into derivates of all three germ layers. Thus, the MFG-adapted hES cells appear to retain pluripotency and to remain undifferentiated. The present culture system has a clear potential to be scaleable up to a manufacturing level and become the preferred culture system for various applications such as cell therapy and toxicity testing.
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| 33. |
- Bima, Paolo, et al.
(author)
-
Chest Pain in Cancer Patients Prevalence of Myocardial Infarction and Performance of High-Sensitivity Cardiac Troponins
- 2023
-
In: JACC: CARDIOONCOLOGY. - : Elsevier. - 2666-0873. ; 5:5, s. 591-609
-
Journal article (peer-reviewed)abstract
- BACKGROUND Little is known about patients with cancer presenting with acute chest discomfort to the emergency department (ED).OBJECTIVES The aim of this study was to assess the prevalence of acute myocardial infarction (AMI), outcomes, and the diagnostic utility of recommended diagnostic tools in this population.METHODS Patients presenting with chest pain to the ED were prospectively enrolled in an international multicenter diagnostic study with central adjudication. Cancer status was assessed prospectively and additional cancer details retrospectively. Findings were externally validated in an independent multicenter cohort.RESULTS Among 8,267 patients, 711 (8.6%) had cancer. Patients with cancer had a higher burden of cardiovascular risk factors and pre-existing cardiac disease. Total length of stay in the ED (5.2 hours vs 4.3 hours) and hospitalization rate (49.8% vs 34.3%) were both increased in patients with cancer (P < 0.001 for both). Among 8,093 patients eligible for the AMI analyses, those with cancer more often had final diagnoses of AMI (184 of 686 with cancer [26.8%] vs 1,561 of 7,407 without cancer [21.1%]; P < 0.001). In patients with cancer, high-sensitivity cardiac troponin T (hs-cTnT) but not high sensitivity cardiac troponin I (hs-cTnI) concentration had lower diagnostic accuracy for non-ST-segment elevation myocardial infarction (for hs-cTnT, area under the curve: 0.89 [95% CI: 0.86-0.92] vs 0.94 [95% CI: 0.93-0.94] [P < 0.001]; for hs-cTnI, area under the curve: 0.93 [95% CI: 0.91-0.95] vs 0.95 [95% CI: 0.94-0.95] [P 1/4 0.10]). In patients with cancer, the European Society of Cardiology 0/1-hour hs-cTnT and hs-cTnI algorithms maintained very high safety but had lower efficacy, with twice the number of patients remaining in the observe zone. Similar findings were obtained in the external validation cohort.CONCLUSIONS Patients with cancer have a substantially higher prevalence of AMI as the cause of chest pain. Length of ED stay and hospitalization rates are increased. The diagnostic performance of hs-cTnT and the efficacy of both the European Society of Cardiology 0/1-hour hs-cTnT and hs-cTnI algorithms is reduced. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587) (J Am Coll Cardiol CardioOnc 2023;5:591-609) (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 34. |
- Björntorp, Elisabeth, et al.
(author)
-
The helix-loop-helix transcription factor Id1 is highly expressed in psoriatic involved skin.
- 2003
-
In: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 83:6, s. 403-9
-
Journal article (peer-reviewed)abstract
- The helix-loop-helix transcription factor Id1 (inhibitor of differentiation/inhibitor of DNA binding) functions as an inhibitor of differentiation. We have examined Id1 gene expression in cultured keratinocytes in punch biopsies from psoriatic involved and uninvolved skin, and in skin specimens from normal individuals. Id1 mRNA expression was measured with an RNase protection assay and with Northern blot. Id1 immunoreactivity was determined in skin biopsies by immunofluorescence using a polyclonal antibody directed against the Id1 protein. In cultured keratinocytes, the expression of Id1 mRNA was strongest in small cells with high proliferative potential, whereas in large cells, which are terminally differentiated, the expression was low. Expression of the Id1 mRNA in psoriatic involved skin (n = 9) was significantly elevated compared to uninvolved skin from the same patient (n = 5) and to skin from normal controls (n = 9). Id1 immunoreactivity was intranuclear throughout all the layers in psoriatic involved epidermis, except in the stratum corneum, while no immunoreactivity was detected in uninvolved epidermis. In normal controls, cytoplasmatic Id1 immunoreactivity was detected in the basal layer in epidermis obtained from newborns, while no immunoreactivity was detected in epidermis obtained from the adults in the control group. We conclude that Id1 is expressed in cells with high proliferative potential, and is downregulated in cells that undergo terminal differentiation. Along with the overexpression of the Id1 gene in psoriatic involved skin, these observations suggest that Id1 is involved in the process of differentiation of keratinocytes seen in normal skin and that the Id1 pathway is activated in psoriasis.
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| 35. |
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| 36. |
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| 37. |
- Blumel, Edda, et al.
(author)
-
Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
- 2019
-
In: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 8:11
-
Journal article (peer-reviewed)abstract
- Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.
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| 38. |
- Boeddinghaus, Jasper, et al.
(author)
-
Impact of age on the performance of the ESC 0/1h-algorithms for early diagnosis of myocardial infarction
- 2018
-
In: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 39:42, s. 3780-3794
-
Journal article (peer-reviewed)abstract
- Aims We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific to older patients. Methods and results We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of and results acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), >= 55 to <70 years (middle-age), >= 70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.599.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P <0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P< 0.01), reduced overall efficacy for hs-cTnT (P <0.01), while maintaining efficacy for hs-cTnl. Findings were confirmed in two validation cohorts (n = 2767). Conclusion While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnl.
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| 39. |
- Boij, Roland, et al.
(author)
-
Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia
- 2012
-
In: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY. - : John Wiley and Sons. - 1046-7408 .- 8755-8920. ; 68:3, s. 258-270
-
Journal article (peer-reviewed)abstract
- Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.
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| 40. |
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| 41. |
- Boknäs, Niklas, et al.
(author)
-
Thrombin-induced platelet activation via PAR4 : pivotal role for exosite II
- 2014
-
In: Thrombosis and Haemostasis. - Stuttgart, Germany : Schattauer Gmbh. - 0340-6245 .- 2567-689X. ; 112:3, s. 558-565
-
Journal article (peer-reviewed)abstract
- Thrombin-induced platelet activation via PAR1 and PAR4 is an important event in haemostasis. Although the underlying mechanisms responsible for ensuring efficient PAR1 activation by thrombin have been extensively studied, the potential involvement of recognitions sites outside the active site of the protease in thrombin-induced PAR4 activation is largely unknown. In this study, we developed a new assay to assess the importance of exosite I and II for PAR4 activation with alpha- and gamma-thrombin. Surprisingly, we found that exosite II is critical for activation of PAR4. We also show that this dependency on exosite II likely represents a new mechanism, as it is unaffected by blockage of the previously known interaction between thrombin and glycoprotein Ib alpha.
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| 42. |
- Brambila-Macias, Sergio A., 1980-, et al.
(author)
-
State of the Art of Design Methods for Resource Efficient and Effective Solutions : Report from “Product and Service Design Methods for REES” Project of Mistra REES program
- 2017
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Reports (other academic/artistic)abstract
- This document reports on the results of work packages (WPs) 2.1 and 2.2 in Project 2 (Product and Service Design Methods for REES, i.e. resource efficient and effective solutions) of the Mistra REES program (www.mistrarees.se). WP 2.1 and WP 2.2 aim at documenting current use of design methods and deriving requirements for design methods, respectively. The document only covers results from the scientific literature review, while other reports to be developed will cover results, for instance, from the interview study and the design session with industry partners in the Mistra REES consortium. The results of the literature review will be a foundation for WP 2.3, which aims at developing new design methods. Note that methods here include frameworks, tools, and support for designers.The document describes current use (i.e., “as‐is” status) of product and service design methods when designing REES, as well as requirements for product and service design methods for REES (i.e., information soon‐to‐be). Both of these are results of analysis in different phases of an early phase of design for REES. Those phases consist of requirement specification, conceptual design, and analysis and evaluation, which can be ordered temporally along the design process.From the overall analysis, found is a lack of insights about methods for designing REES, although potentially useful methods are available. This means advancement of knowledge is insufficient for industry within the subject, which is relatively new. It may also mean the developed methods are not precisely according to the needs of companies. This shows a high potential of developing new methods in the rest of the project.More specifically, in the requirement specification, the literature shows that potentially useful methods include QFD (Quality Function Deployment), the Taguchi method, the Kano model, and data mining, among others. In the conceptual design, numerous methods exist, and most of them were developed in an older context, where REES was not as relevant as today. Those methods include DfX methods (X denotes cost, assembly, etc.), the functional block diagram, the checklist, morphological analysis, and the Fishbone Diagram. Only a few seem to be used widely in industry today. In the analysis and evaluation, available methods include Lifecycle Simulation, Lifecycle Costing, multi‐criteria decision making, and the Analytical Hierarchy Process. Most of the methods or tools available specialise in one area. This is a problem when developing an integrated offering of products and services, because designers need to have a holistic perspective for that.Regarding requirements for methods to be developed, the authors analysed literature as follows. In the requirement specification, requirements originating from multiple aspects and actors need to be taken into account. Since an enormous amount of data and information can be collected from products and by technologies implemented today, a huge opportunity is presented for enhancing requirement specification. Yet, there seems to be little insights to take this opportunity. In conceptual design, it is important to identify and involve relevant actors as well as their requirements according to a number of scientific reports. Especially, interaction between the relevant actors seems to be critical to be implemented. In analysis and evaluation, various pieces of earlier research works recommend different features to be implemented in methods. These features include visualization of information and information flows, graphical user interface, multiple users’ participation, and ability to handle environmental information, uncertainty and risk.
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| 43. |
- Brambila-Macias, Sergio A., 1980-, et al.
(author)
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Support for Designing Resource Efficient and Effective Solutions: Current Use and Requirements by Swedish Industry : Report from “Product and Service Design Support for REES” Project of Mistra REES program
- 2017
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Reports (other academic/artistic)abstract
- This document reports on the results of work packages (WPs) 2.1 and 2.2 in Project 2 (Product and Service Design Support for REES, i.e. resource efficient and effective solutions) of the Mistra REES program (www.mistrarees.se). WP 2.1 and WP 2.2 aim at documenting current use of design support and deriving requirements for design support, respectively. The document only covers results from interviews with companies, while the other reports will cover results, for instance, from scientific literature review (ISRN: LIU‐IEI‐RR‐‐17/00264—SE) and the design session with industry partners in the Mistra REES consortium. The results of this research into industrial practice will be a foundation for WP 2.3, which aims at developing new design support for designers.The document describes current use (i.e., “as‐is” status) of product and service design support when designing REES, as well as requirements for product and service design support for REES (i.e., information soon‐to‐be). Both of these are results of analysis in different phases of an early phase of design for REES. Those phases consist of requirement specification, conceptual design, and analysis and evaluation, which can be ordered temporally along the design process.Eight Sweden‐based companies that provide products and services in different sectors and work on resource efficiency participated in the interviews. They vary in terms of the size: from small to large. 24 individual interviews were conducted in total with the length being between 54 and 117 minutes (with two additional shorter follow up interviews via phone/skype). The 24 interviews were carried out all with face to face between May and July, 2016. The result from each company is described per section in this report, while cross‐company analysis will be made in a separate document.
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| 44. |
- Brittberg, Mats, 1953, et al.
(author)
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Clonal growth of human articular cartilage and the functional role of the periosteum in chondrogenesis.
- 2005
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In: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1063-4584. ; 13:2, s. 146-53
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Clinical cartilage repair with transplantation of cultured chondrocytes, the first described technique introduced in 1994, includes a periosteal membrane but today cells are also implanted without the periosteal combination. The aim of this study was to see if the periosteum had more than a biomechanical function and if the periosteum had a biological effect on the seeded cells tested in an agarose system in which the clonal growth in agarose and the external growth stimulation could be analysed. METHODS: Four different experiments were used to study the growth of human chondrocytes in agarose and the periosteal influence. Human chondrocytes were isolated and transferred to either primary or secondary agarose culture. After 4 weeks, the total number of clones >50 microm was counted. Cocultures of chondrocytes and periosteal tissue, cultures of chondrocytes with conditioned medium from chondrocytes, periosteal cells and fibroblast were used to study a potential stimulatory effect on growth and different cytokines and growth factors were analysed. RESULTS: It was found that the human chondrocytes had different growth properties in agarose with the formation of four different types of clones: a homogenous clone without matrix production, a homogenous clone with matrix production, a differentiated clone with matrix production and finally a differentiated clone without matrix production. The periosteum exerted a paracrine effect on cultured chondrocytes in agarose resulting in a higher degree of cloning. The chondrocytes produced significant amounts of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta. The periosteum produced significant amounts of IL-6, IL-8 and TGF-beta. Cocultures of chondrocytes and periosteum demonstrated a potentiation of IL-6 and IL-8 release but not of TGF-beta and GM-CSF. CONCLUSION: Articular chondrocytes are able to form clones of different properties in agarose and the periosteum has a capacity of stimulating chondrocyte clonal growth and differentiation and secretes significant amounts of IL-6, IL-8, GM-CSF and TGF-beta. It may be that the repair of cartilage defects with seeded chondrocytes could benefit from the combination with a periosteal graft. The production of TGF-beta by implanted chondrocytes could influence the chondrogenic cells in the periosteum to start a periosteal chondrogenesis and together with the matrix from implanted chondrocyte production, a repair of cartilaginous appearance may develop; a dual chondrogenic response is possible.
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| 45. |
- Buus, Terkild Brink, et al.
(author)
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Single-cell heterogeneity in Sézary syndrome
- 2018
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
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Journal article (peer-reviewed)abstract
- Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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| 46. |
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| 47. |
- Bäck, Maria, 1978, et al.
(author)
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The SWEDEHEART secondary prevention and cardiac rehabilitation registry (SWEDEHEART CR registry)
- 2021
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In: European Heart Journal-Quality of Care and Clinical Outcomes. - : Oxford University Press (OUP). - 2058-5225 .- 2058-1742. ; 7:5, s. 431-437
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Journal article (peer-reviewed)abstract
- Aims The quality registry SWEDEHEART covers data across the patient pathway after an acute myocardial infarction (MI), from hospital care to secondary prevention. Although cardiac rehabilitation (CR) is strongly recommended after an MI, there is still heterogeneity regarding standards, uptake, and adherence rates. The aim of the SWEDEHEART-CR registry is to provide continuous information on secondary prevention and CR performance to support the audit and development of evidence-based practice. To facilitate quality improvement and research initiatives, a description of the characteristics and development of the SWEDEHEART-CR registry is needed. Methods and results The SWEDEHEART-CR registry starts with data obtained during hospital care and then collects data at out-patient visits 2 months and 1-year after discharge, and at start and end of an exercise-based CR programme. The registry data covers comorbidities, biochemistry, blood pressure, anthropometric variables, medication, psychosocial- and lifestyle variables, readmissions, patient-reported outcome measures, attendance in CR-related programmes, and physical fitness variables. Over 100 000 patients with MI have been included in the SWEDEHEART-CR registry since its start in 2005. From initially covering 35 centres (47%) and 2200 patients annually (27%), SWEDEHEART-CR has developed to a nation-wide registry with 75 centres (100%) and 8800 patients annually (80%) in 2020. Conclusion The SWEDEHEART-CR registry includes a high proportion of the national MI population entering a CR programme and is a powerful tool for quality audit, improvement, and research. The registry provides insights into the characteristics, treatment, and outcomes of evidence-based secondary preventive practice, ultimately leading to better cardiovascular health.
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| 48. |
- Cederlöf, Elin, et al.
(author)
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Pregnancy Complications and Risk of Cardiovascular Disease Later in Life : A Nationwide Cohort Study
- 2022
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In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 11:2
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Journal article (peer-reviewed)abstract
- Background: The aim of this study was to investigate the associations between pregnancy complications and cardiovascular mortality and hospitalizations of cardiovascular disease (CVD) after adjustment for major confounding.Methods and Results: In a nationwide register‐based cohort study, women with singleton births between 1973 and 2014 were included from the Swedish Medical Birth Register. Outcomes of mortality and hospitalizations of CVD were collected from the Cause of Death Register and the National Inpatient Register. The cohort was followed from the date of the first delivery until death or end of follow‐up, whichever occurred first. The pregnancy complications studied were preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, small for gestational age, and stillbirth. Among the 2 134 239 women (mean age at first pregnancy, 27.0 [SD, 5.1] and mean parity 1.96 [SD, 0.9]), 19.1% (N=407 597) had 1 of the studied pregnancy complications. All pregnancy complications were associated with all‐cause and cardiovascular mortality and hospitalization for CVD (ischemic heart disease, ischemic stroke, and peripheral artery disease) after adjustment for major confounding in a Cox proportional hazard regression model. The adjusted hazard ratio for cardiovascular mortality was 1.84 (95% CI, 1.38–2.44) for preterm birth and 3.14 (95% CI, 1.81–5.44) for stillbirth.Conclusions: In this large cohort study, pregnancy complications were associated with all‐cause mortality, cardiovascular mortality, and hospitalizations for CVD, also after adjusting for confounding, including overweight, smoking, and comorbidities. The study highlights that less established pregnancy complications such as preterm birth and stillbirth are also associated with cardiovascular mortality and CVD.
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| 49. |
- Cheng, Kimberley, et al.
(author)
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tmRNA-SmpB complex mimics native aminoacyl-tRNAs in the A site of stalled ribosomes
- 2010
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In: Journal of Structural Biology. - : Elsevier BV. - 1047-8477 .- 1095-8657. ; 169:3, s. 342-348
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Journal article (peer-reviewed)abstract
- Bacterial ribosomes stalled on faulty, often truncated, mRNAs lacking stop codons are rescued by trans-translation. It relies on an RNA molecule (tmRNA) capable of replacing the faulty mRNA with its own open reading frame (ORF). Translation of tmRNA ORF results in the tagging of faulty protein for degradation and its release from the ribosome. We used single-particle cryo-electron microscopy to visualize tmRNA together with its helper protein SmpB on the 70S Escherichia coli ribosome in states subsequent to GTP hydrolysis on elongation factor Tu (EF-Tu). Three-dimensional reconstruction and heterogeneity analysis resulted in a 15 A resolution structure of the tmRNA-SmpB complex accommodated in the A site of the ribosome, which shows that SmpB mimics the anticodon- and D-stem of native tRNAs missing in the tRNA-like domain of tmRNA. We conclude that the tmRNA-SmpB complex accommodates in the ribosomal A site very much like an aminoacyl-tRNA during protein elongation.
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