| 1. |
- Balogh, Johanna, et al.
(författare)
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Deletion of a lectin gene does not affect the phenotype of the nematode-trapping fungus Arthrobotrys oligospora
- 2003
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Ingår i: Fungal Genetics and Biology. - 1087-1845. ; 39:2, s. 128-135
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Tidskriftsartikel (refereegranskat)abstract
- A number of filamentous fungi are known to produce high levels of saline-soluble and low-molecular-mass lectins. The function of these proteins are not clear but it has been proposed that they are involved in storage of nutrients, development, recognition of other organisms, and defense reactions. A gene encoding such a lectin (AOL) was deleted in the nematode-trapping fungus Arthrobotrys oligospora by homologous recombination. The deletion mutants did not express any hemagglutinating activity or protein cross-reacting with AOL antibodies. There were no significant differences between the DeltaAOL and wild-type strains in spore (conidia) germination, saprophytic growth, and pathogenicity. Furthermore, there was no significant difference in the growth and reproduction of collembolan feeding on the various strains of A. oligospora. Thus either the previous proposed functions of AOL are not correct, or the fungus can compensate for the absence of the lectin by expressing other proteins with similar function(s) as AOL. (C) 2003 Published by Elsevier Science (USA).
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| 2. |
- Balogh, Johanna, et al.
(författare)
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Desmin filaments influence myofilament spacing and lateral compliance of slow skeletal muscle fibres.
- 2005
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Ingår i: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 88:2, s. 1156-1165
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Tidskriftsartikel (refereegranskat)abstract
- Intermediate filaments composed of desmin interlink Z-disks and sarcolemma in skeletal muscle. Depletion of desmin results in lower active stress of smooth, cardiac, and skeletal muscles. Structural functions of intermediate filaments in fast (psoas) and slow (soleus) skeletal muscle were examined using x-ray diffraction on permeabilized muscle from desmin-deficient mice (Des–/–) and controls (Des+/+). To examine lateral compliance of sarcomeres and cells, filament distances and fiber width were measured during osmotic compression with dextran. Equatorial spacing (x-ray diffraction) of contractile filaments was wider in soleus Des–/– muscle compared to Des+/+, showing that desmin is important for maintaining lattice structure. Osmotic lattice compression was similar in Des–/– and Des+/+. In width measurements of single fibers and bundles, Des–/– soleus were more compressed by dextran compared to Des+/+, showing that intermediate filaments contribute to whole-cell compliance. For psoas fibers, both filament distance and cell compliance were similar in Des–/– and Des+/+. We conclude that desmin is important for stabilizing sarcomeres and maintaining cell compliance in slow skeletal muscle. Wider filament spacing in Des–/– soleus cannot, however, explain the lower active stress, but might influence resistance to stretch, possibly minimizing stretch-induced cell injury.
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| 3. |
- Balogh, Johanna, et al.
(författare)
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Hearts from mice lacking desmin have a myopathy with impaired active force generation and unaltered wall compliance.
- 2002
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Ingår i: Cardiovascular Research. - 1755-3245. ; 53:2, s. 439-450
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Desmin intermediate filaments are key structures in the cytoskeleton of cardiac muscle. Since they are associated with Z-discs and intercalated discs, they may have a role in sarcomere alignment or force transmission. We have explored the mechanical function of the desmin filaments in the cardiac wall by comparing desmin-deficient (Des-/-) and wild-type (Des+/+) mice. METHODS: The Langendorff technique was used to examine the contractility of the whole heart. Rate of force generation, Ca(2+)-sensitivity and force per cross-sectional area were measured in skinned ventricle muscle preparations. RESULTS: Des-/- mice have a cardiomyopathy with increased heart weight. Diastolic pressure was increased at all filling volumes in the Des-/- group. Since passive wall stress (i.e. force per area) was unchanged, the alteration in diastolic pressure is a consequence of the thicker ventricle wall. Developed pressure, rate of pressure increase and developed wall stress were significantly reduced, suggesting that active force generation of the contractile apparatus is reduced in Des-/-. Concentrations of actin and myosin in the ventricle were unaltered. Measurements in skinned muscle preparations showed a lower active force development with unaltered Ca(2+)-sensitivity and rate of tension development. CONCLUSION: It is suggested that the intermediate filaments have a role in active force generation of cardiac muscle, possibly by supporting sarcomere alignment or force transmission. The desmin filaments do not contribute the passive elasticity of the ventricle wall. Des-/- mice provide a model for genetic cardiomyopathy where the main factor contributing to altered cardiac performance is a decrease in active force generation, possibly in combination with a loss of functional contractile units.
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| 4. |
- Balogh, Johanna, et al.
(författare)
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Lower active force generation and improved fatigue resistance in skeletal muscle from desmin deficient mice.
- 2003
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Ingår i: Journal of Muscle Research and Cell Motility. - 0142-4319. ; 24:7, s. 453-459
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Tidskriftsartikel (refereegranskat)abstract
- The mechanical effects of the intermediate filament protein desmin was examined in desmin deficient mice (Des-/-) and their wild type control (Des+/+). Active force generation was determined in intact soleus muscles and in skinned single fibres from soleus and psoas. A decreased force generation of skinned muscle fibres from Des-/- mice and a tendency towards decreased active force in intact soleus muscle were detected. Concentrations of the contractile protein actin and myosin were not altered in Des-/- muscles. Ca(2+)-sensitivity of skinned single fibres in Des-/- muscles was unchanged compared to Des+/+. Using a protocol with repeated short tetani an increased fatigue resistance was found in the intact soleus muscles from Des-/- mice. In conclusion, desmin intermediate filaments are required for optimal generation or transmission of active force in skeletal muscle. Although other studies have shown that the desmin intermediate filaments appear to influence Ca(2+)-handling, the Ca(2+)-sensitivity of the contractile filaments is not altered in skeletal muscle of Des-/- mice. Previous studies have reported a switch towards slower myosin isoforms in slow skeletal muscle of Des-/- mice. The increased fatigue resistance show that this change is reflected in the physiological function of the muscle.
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| 5. |
- Balogh, Johanna, et al.
(författare)
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Phospholipase C and cAMP-dependent positive inotropic effects of ATP in mouse cardiomyocytes via P2Y(11)-like receptors.
- 2005
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 1095-8584 .- 0022-2828. ; 39:2, s. 223-230
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Tidskriftsartikel (refereegranskat)abstract
- ATP is released as a cotransmitter together with catecholamines from sympathetic nerves. In the heart ATP has been shown to cause a pronounced positive inotropic effect and may also act in synergy with β-adrenergic agonists to augment cardiomyocyte contractility. The aim of the present study was to investigate the inotropic effects mediated by purinergic P2 receptors using isolated mouse cardiomyocytes. Stable adenine nucleotide analogs were used and the agonist rank order for adenine nucleotide stimulation of the mouse cardiomyocytes was AR-C67085 > ATPγS > 2-MeSATP >>> 2-MeSADP = 0, that fits the agonist profile of the P2Y11 receptor. ATPγS induced a positive inotropic response in single mouse cardiomyocytes. The response was similar to that for the β1 receptor agonist isoproterenol. The most potent response was obtained using AR-C67085, a P2Y11 receptor agonist. This agonist also potentiated contractions in isolated trabecular preparations. The adenylyl cyclase blocker (SQ22563) and phospholipase C (PLC) blocker (U73122) demonstrated that both pathways were required for the inotropic response of AR-C67085. A cAMP enzyme immunoassay confirmed that AR-C67085 increased cAMP in the cardiomyocytes. These findings are in agreement with the P2Y11 receptor, coupled both to activation of IP3 and cAMP, being a major receptor for ATP induced inotropy. Analyzing cardiomyocytes from desmin deficient mice, Des–/–, with a congenital cardiomyopathy, we found a lower sensitivity to AR-C67085, suggesting a down-regulation of P2Y11 receptor function in heart failure. The prominent action of the P2Y11 receptor in controling cardiomyocyte contractility and possible alterations in its function during cardiomyopathy may suggest this receptor as a potential therapeutic target. It is possible that agonists for the P2Y11 receptor could be used to improve cardiac output in patients with circulatory shock and that P2Y11 receptor antagonist could be beneficial in patients with congestive heart failure (CHF).
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| 6. |
- Balogh, Johanna
(författare)
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Structure and function of the cytoskeleton in cardiac and skeletal muscle
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- We have examined the functional and structural roles of the cytoskeletal protein desmin in cardiac and skeletal muscles using a genetically modified mouse (Des-/-) with the desmin gene ablated. Desmin forms filaments at the Z-disks in the striated muscle sarcomere, have connections to the sarcolemma and most likely align sarcomeres and whole cells. We have shown a decreased contractile function of heart (study I) and skeletal muscle (study II) from Des-/- mice, indicating an important functional role of desmin transmitting the generated muscle force between cells or aligning sarcomeres. The Des-/- soleus skeletal muscle has an increased fatigue resistance (study II), which we interprete to be caused by a remodulation of the myosin isoform composition towards increased amount of the slow isoform. The filament lattice, examined with X-ray diffraction, is wider in Des-/- soleus muscles, which indicates that desmin has a structural role in anchoring the contractile filaments actin and myosin (study III). We have examined the role of a human desmin mutation (L345P) found in cardiomyopathy. The mutated desmin gene was expressed in a mouse model to study cardiac and skeletal muscle function (IV). We observed moderate signs of striated muscle myopathy. Knowledge about the intermediate filament functions is important for future treatment of desmin related myopathies. We have used the desmin deficient mouse model to examine how ATP receptor functions can be altered during cardiomyopathy. We report that a P2Y11-like receptor is involved in mediating the ATP induced inotropic responses of the mouse heart and that this receptor function might be down-regulated in desmin deficient cardiomyopathy (V). Modulation of this receptor function could be of possible therapeutic importance.
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| 7. |
- Jonsson, Johanna, et al.
(författare)
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Low-quality employment trajectories and risk of common mental disorders, substance use disorders and suicide attempt : a longitudinal study of the Swedish workforce
- 2021
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 47:7, s. 509-520
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Tidskriftsartikel (refereegranskat)abstract
- Objective High-quality longitudinal evidence exploring the mental health risk associated with low-quality employment trajectories is scarce. We therefore aimed to investigate the risk of being diagnosed with common mental disorders, substance use disorders, or suicide attempt according to low-quality employment trajectories.Methods A longitudinal register-study based on the working population of Sweden (N=2 743 764). Employment trajectories (2005–2009) characterized by employment quality and pattern (constancy, fluctuation, mobility) were created. Hazard ratios (HR) were estimated using Cox proportional hazards regression models for first incidence (2010–2017) diagnosis of common mental disorders, substance use disorders and suicide attempt as dependent on employment trajectories.Results We identified 21 employment trajectories, 10 of which were low quality (21%). With the exception of constant solo self-employment, there was an increased risk of common mental disorders (HR 1.07–1.62) and substance use disorders (HR 1.05–2.19) for all low-quality trajectories. Constant solo self-employment increased the risk for substance use disorders among women, while it reduced the risk of both disorders for men. Half of the low-quality trajectories were associated with a risk increase of suicide attempt (HR 1.08–1.76).Conclusions Low-quality employment trajectories represent risk factors for mental disorders and suicide attempt in Sweden, and there might be differential effects according to sex – especially in terms of self-employment. Policies ensuring and maintaining high-quality employment characteristics over time are imperative. Similar prospective studies are needed, also in other contexts, which cover the effects of the Covid-19 pandemic as well as the mechanisms linking employment trajectories with mental health.
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| 8. |
- Kostareva, Anna, et al.
(författare)
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Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria
- 2008
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Ingår i: Journal of Muscle Research and Cell Motility. - : Springer Science and Business Media LLC. - 0142-4319 .- 1573-2657. ; 29:1, s. 25-36
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Tidskriftsartikel (refereegranskat)abstract
- Desmin mutations underlie inherited myopathies/cardiomyopathies with varying severity and involvement of the skeletal and cardiac muscles. We developed a transgenic mouse model expressing low level of the L345P desmin mutation (DESMUT mice) in order to uncover changes in skeletal and cardiac muscles caused by this mutation. The most striking ultrastructural changes in muscle from DESMUT mice were mitochondrial swelling and vacuolization. The mitochondrial Ca2+ level was significantly increased in skeletal and cardiac myocytes from DESMUT mice compared to wild type cells during and after contractions. In isolated DESMUT soleus muscles, contractile function and recovery from fatigue were impaired. A SHIRPA screening test for neuromuscular performance demonstrated decreased motor function in DESMUT compared to WT mice. Echocardiographic changes in DESMUT mice included left ventricular wall hypertrophy and a decreased left ventricular chamber dimension. The results imply that low levels of L345P desmin acts, at least partially, by a dominant negative effect on mitochondria.
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| 9. |
- Lazar, Vladimir, et al.
(författare)
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Integrated molecular portrait of non-small cell lung cancers
- 2013
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Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 6:1, s. 53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods: Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC. Results: At DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of similar to 800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944. Conclusions: Integrated molecular characterization of AC and SCC helped identify clinically relevant markers and potential drivers, which are recurrent and stable changes at DNA level that have functional implications at RNA level and have strong association with histological subtypes.
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| 10. |
- Lindberg, Malin, Professor, 1978-, et al.
(författare)
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Co-Creative Place Innovation in an Arctic Town
- 2020
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Ingår i: Journal of Place Management and Development. - : Emerald Group Publishing Limited. - 1753-8335 .- 1753-8343. ; 13:4, s. 447-463
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – The purpose of the study is to shed light on co-creative approaches for place innovation in an Arctic town, based on the relocation of Kiruna’s city center in northern Sweden. Three cases of co-creative innovation processes in Kiruna are investigated and compared: an R&D project about local perceptions and visions of attractive urban environments, an R&D project about norm-creative design principles for inclusive and attractive urban design, and an R&D project about cross-industrial synergies for city center attractiveness.Design/methodology/approach – The study’s research design encompasses a comparative and participatory approach. The comparative approach implies investigation and comparison of three cases of co-creative innovation processes in Kiruna. The participatory approach implies joint development of new knowledge by researchers and local actors. The data consists of participatory observations of workshops and qualitative interviews with local actors.Findings – The study reveals that the studied processes have harnessed the city center relocation as an opportunity to make Kiruna more attractive to residents and visitors, by employing the co-creative approaches of Living Lab, Now-Wow-How and Norm-creative design. These approaches have enabled experts and local actors to jointly identify excluding patterns and norms in the relocation process, and to envision inclusive and attractive (re-)configurations and (re-)conceptualizations of the future Kiruna.Research implications – The results add to the academic strand of inclusive urban transformation, by providing insights into co-creative approaches for re-imagining an Arctic town in times of industrial and social change. New insights are provided regarding how the geographical, industrial and cultural identity of an Arctic town can be harnessed to envision new configuration, content and communication that is attractive and accessible for a diversity of residents and visitors. Practical implications – The results highlight the potential to harness Arctic and rural characteristics in the promotion of urban attractiveness and public wellbeing, especially when combined with co-creative identification and transformation of excluding norms and patterns.Originality/value – The results provide new insights into how co-creative approaches may facilitate innovative and inclusive renewal of towns and cities in the Arctic and beyond.
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| 11. |
- Lindberg, Malin, Professor, 1978-, et al.
(författare)
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Place Innovative Synergies for City Center Attractiveness : A Matter of Experiencing Retail and Retailing Experiences
- 2019
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Ingår i: Urban Planning. - : Cogitatio. - 2183-7635. ; 04:01, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- By investigating the occurrence of place innovative synergies between retail and tourism in a small-sized Swedish city, this article advances knowledge on how city center attractiveness can be enforced in a rural context with competing online shopping and suburban/out-of-town shopping centers. Previous studies of city center attractiveness, place innovation, and social innovation help distinguish innovative intertwinement of correlated trends of experiencing retail and retailing experiences, augmenting customer experiences through place-based characteristics. Interviews, workshops, and participatory observations with entrepreneurs, business promoters, and municipality representatives reveal three dimensions of place innovative synergies in city center attractiveness: 1) innovative variance in city center retail and tourism, 2) innovative interwovenness between the city center identity and its configuration, content, and communication, and 3) innovative interaction between retailers and tourism entrepreneurs in city center events. A key question is whether synergies in temporal events and everyday commerce are sufficiently combined, in order to engender encompassing renewal.
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| 12. |
- Lindberg, Malin, Professor, 1978-, et al.
(författare)
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Platsinnovativa stadskärnor : Genom nyskapande synergier
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Attraktivitet och innovativitet har hamnat högt upp på agendan för Sveriges stadskärnor, i strävan efter att locka och behålla besökare, invånare, företagare och investerare. Ett nytänkande samspel mellan en plats komponenter, processer och intressenter ses som centralt för att skapa platsunika upplevelser och kvaliteter, vilket här kallas för ”platsinnovativa synergier”. I projektet ”Attraktiv stadskärna genom platsinnovativa synergier” har sådana samspel studerats och stärkts i samarbete mellan forskare, företagare, företagsfrämjare, föreningar och kommuner. Dessa aktörer har involverats i workshops och intervjuer för att identifiera befintliga synergier och utveckla koncept för nya synergier, med särskilt fokus på samspelet mellan handel och besöksnäring. Parallellt har en trendspaning genomförts om platsinnovativa synergier i Sverige och internationellt. Projektet har drivits av Luleå tekniska universitet och Piteå Science Park under 2017-2019, i samarbete med Piteå kommun, Kiruna kommun, Destination Piteå, Företagarna Piteå, PiteåEntreprenörerna, Piteå Kvinnliga Företagare, Innovation Pite, Gallerian Piteå, Småstaden Piteå, BackCity Piteå, KUST Hotell & Spa, Pite Havsbad, m.fl. Projektet har finansierats inom programmet ”Framtidens fysiska mötesplats” som är ett samarbete mellan Handelsrådet och Besöksnäringens forsknings- och utvecklingsfond (BFUF), samt av Sparbanken Nord. Projektet bygger på erfarenheterna från ett tidigare projekt som Luleå tekniska universitet och Piteå Science Park drev under 2015-2017 om platsinnovationer i besöksnäringen, där Treehotel, Icehotel, Ice Music, Arctic Bath, Aurora Sky Station, Arthotel Tornedalen och andra exempel från Swedish Lapland studerades.
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| 13. |
- Lindberg, Malin, Professor, 1978-, et al.
(författare)
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Platsinnovativa synergier för attraktiva stadskärnor
- 2019
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Ingår i: Innovation och stadsutveckling. - Göteborg : RISE. - 9789189049086 ; , s. 189-200
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Bokkapitel (refereegranskat)abstract
- Ett annat perspektiv på hållbarhet är att synliggöra och ta vara på en plats befintliga och unika värden. Johanna Balogh, Kristina Johansson, Helena Karlberg, Malin Lindberg och Helena Karlberg utgår i kapitlet Platsinnovativa synergier för attraktiva stadskärnor från tidigare forskning om platsinnovation, som är ett begrepp och koncept för att förstå och planera nytänkande helhetsutveckling av attraktiva städer, besöksmål och andra sorters platser. Här är Kiruna och Piteå i fokus, och frågan hur kommuner, näringsliv och andra nyckelaktörer aktivt kan skapa upplevelser genom att väva samman stadens olika komponenter, processer och intressenter på ett nytänkande sätt.
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| 14. |
- Wihlborg, Anna-Karin, et al.
(författare)
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Positive inotropic effects by uridine triphosphate (UTP) and uridine diphosphate (UDP) via P2Y(2) and P2Y(6) receptors on cardiomyocytes and release of UTP in man during myocardial infarction
- 2006
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Ingår i: Circulation Research. - 0009-7330. ; 98:7, s. 970-976
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine a possible role for extracellular pyrimidines as inotropic factors for the heart. First, nucleotide plasma levels were measured to evaluate whether UTP is released in patients with coronary heart disease. Then, inotropic effects of pyrimidines were examined in isolated mouse cardiomyocytes. Finally, expression of pyrimidine-selective receptors ( a subgroup of the P2 receptors) was studied in human and mouse heart, using real time polymerase chain reaction, Western blot, and immunohistochemistry. Venous plasma levels of UTP were increased (57%) in patients with myocardial infarction. In electrically stimulated cardiomyocytes the stable P2Y(2/4) agonist UTP gamma S increased contraction by 52%, similar to beta(1)-adrenergic stimulation with isoproterenol (65%). The P2Y(6)-agonist UDP gamma S also increased cardiomyocyte contraction (35%), an effect abolished by the P2Y(6)-blocker MRS2578. The phospholipase C inhibitor U73122 inhibited both the UDP beta S and the UTP gamma S-induced inotropic effect, indicating an IP3-mediated effect via P2Y(6) receptors. The P2Y(14) agonist UDP-glucose was without effect. Quantification of mRNA with real time polymerase chain reaction revealed P2Y(2) as the most abundant pyrimidine receptor expressed in cardiomyocytes from man. Presence of P2Y(6) receptor mRNA was detected in both species and confirmed at protein level with Western blot and immunohistochemistry in man. In conclusion, UTP levels are increased in humans during myocardial infarction, giving the first evidence for UTP release in man. UTP is a cardiac inotropic factor most likely by activation of P2Y(2) receptors in man. For the first time we demonstrate inotropic effects of UDP, mediated by P2Y(6) receptors via an IP3-dependent pathway. Thus, the extracellular pyrimidines ( UTP and UDP) could be important inotropic factors involved in the development of cardiac disease.
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