Om jag saknar något? Ja, facit.

Syftet med uppsatsen är att bidra med kunskap om framväxten av en hållbarhetsstrategi. Vi gör detta genom att studera meningsskapandets roll i strategiarbetet. Slutsatsen i denna uppsats visar på meningsskapandets centrala roll vid framväxandet av en avsedd hållbarhetsstrategi gällande att omformulera en omständighet till en gripbar situation. Meningsskapande leder till tolkning vilket blir handlingar som skapar kunskap och erfarenhet. Handlingarna syftar till att uppnå strategins målsättningar och förkroppsligas således i hela organisationen genom den avsiktliga strategin i kombination med den framväxande strategin vilket blir den realiserade strategin. Interaktionen mellan meningsskapande och meningsgivande påvisas även som central genom att ge och skapa mening bevaras verklighetsförankringen och därmed rimligheten vid framväxandet av en hållbarhetsstrategi

Effects of experimental rewilding on butterflies, bumblebees and grasshoppers

Grassland ecosystems are species-rich habitats that are rapidly declining globally posing serious concerns for biodiversity conservation. This situation is particularly relevant in agricultural areas in Europe. As traditional management practices and livestock grazing regimes ceased, rewilding could be a potential avenue to tackle current biodiversity declines. To test this hypothesis, we set up a 3-year experiment where 12 horses were introduced in three 10-hectare enclosure replicates (four horses per enclosure). Horses were kept without supplementary feeding to mimic ecosystem functions of wild horses. We applied Generalized Linear Mixed Effects Models and a backward stepwise model selection procedure to elucidate factors that modulate insect richness induced by grazing. Our results show that plant species richness, the proportion of flowers and plant height play a significant role for butterfly and bumblebee richness, while the opposite effect was detected for grasshoppers. However, the effect on grasshoppers was counterbalanced by increased grasshopper species richness in habitats adjacent to horse latrines. Implications for insect conservation Rewilding with horses may offset current biodiversity declines by maintaining important functional links between plants and pollinators in grassland ecosystems. Horse grazing can however have different effects on diverse functional groups of insects. Application of integrative landscape scale approaches may be needed to elucidate the effects of rewilding for certain functional groups such as grasshoppers. With current biodiversity declines, up-scaling rewilding research and practice might be crucial to mitigate the pervasive effects on insects as their services and functions are critical for our existence

Inhibition of STAT3 prevents bone metastatic progression of prostate cancer in vivo

Background: Prostate cancer (PC) metastasizes to the skeleton forming predominantly sclerotic lesions, and there is currently no cure for bone metastatic disease. The transcription factor signal transducer and activator of transcription 3 (STAT3) is implicated as a metastatic driver, but its potential as therapeutic target in bone metastasis has not been investigated. In this study, we evaluated for the first time a STAT3 inhibitor, Napabucasin, as a therapeutic option for bone metastatic PC.Methods: Effects of STAT3 inhibitors, Stattic and Napabucasin, on metastatic potential in PC cells were studied in vitro by assessment of migration capacity, self-renewal potential, and tumorsphere formation. For evaluation of the role of STAT3 in initial skeletal establishment of PC cells as well as in progressed castration-resistant PC (CRPC) in bone, human VCaP prostate cancer cells were inoculated in the tibia of mice which subsequently were treated with the STAT3 inhibitor Napabucasin. Bone specimens were analyzed using computed tomography (CT), immunohistochemistry, and quantitative polymerase chain reaction.Results: The small molecule STAT3 inhibitors Stattic and Napabucasin both effectively impaired metastatic potential of PC cells in vitro. Furthermore, treatment with Napabucasin prevented metastatic establishment in tibial bones in vivo and thereby also the tumor-induced sclerotic bone response seen in vehicle-treated VCaP xenografts. In addition, treatment with Napabucasin of established bone CRPC significantly decreased both tumor burden and tumor-induced trabecular bone volume compared with effects seen in vehicle-treated animals. Anti-mitotic effects were confirmed by decreased Ki67 staining in Napabucasin-treated xenografts compared with vehicle-treated xenografts. Alterations of gene expression in the femoral bone marrow (BM) niche toward the maintenance of hematopoietic stem cells and the myeloid lineage were demonstrated by quantitative real-time polymerase chain reaction and were further reflected by a substantial increase in the number of erythrocytes in BM of Napabucasin-treated mice. Furthermore, a unique pattern of STAT3 phosphorylation in osteoblasts/stromal cells surrounding the areas of tumor cells was demonstrated immunohistochemically in bone xenograft models using several different PC cell lines.Conclusion: Inhibition of STAT3 activity disrupts the bone metastatic niche and targets both the skeletal establishment of PC and advanced bone metastatic CRPC in mice, suggesting STAT3 as a candidate for molecular targeted therapies of skeletal metastatic disease.</div

Enhanced Platelet Activation Mediates the Accelerated Angiogenic Switch in Mice Lacking Histidine-Rich Glycoprotein

BACKGROUND: The heparin-binding plasma protein histidine-rich glycoprotein (HRG; alternatively, HRGP/HPRG) can suppress tumor angiogenesis and growth in vitro and in vivo. Mice lacking the HRG gene are viable and fertile, but have an enhanced coagulation resulting in decreased bleeding times. In addition, the angiogenic switch is significantly enhanced in HRG-deficient mice. METHODOLOGY/PRINCIPAL FINDINGS: To address whether HRG deficiency affects tumor development, we have crossed HRG knockout mice with the RIP1-Tag2 mouse, a well established orthotopic model of multistage carcinogenesis. RIP1-Tag2 HRG(-/-) mice display significantly larger tumor volume compared to their RIP1-Tag2 HRG(+/+) littermates, supporting a role for HRG as an endogenous regulator of tumor growth. In the present study we also demonstrate that platelet activation is increased in mice lacking HRG. To address whether this elevated platelet activation contributes to the increased pathological angiogenesis in HRG-deficient mice, they were rendered thrombocytopenic before the onset of the angiogenic switch by injection of the anti-platelet antibody GP1bα. Interestingly, this treatment suppressed the increase in angiogenic neoplasias seen in HRG knockout mice. However, if GP1bα treatment was initiated at a later stage, after the onset of the angiogenic switch, no suppression of tumor growth was detected in HRG-deficient mice. CONCLUSIONS: Our data show that increased platelet activation mediates the accelerated angiogenic switch in HRG-deficient mice. Moreover, we conclude that platelets play a crucial role in the early stages of tumor development but are of less significance for tumor growth once angiogenesis has been initiated

Bacterial Phenotype Variants in Group B Streptococcal Toxic Shock Syndrome1

Variants with markedly different expression of virulence factors can arise in invasive infection in humans

Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection

BACKGROUND: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells. METHODS AND FINDINGS: We characterized in vivo interactions between group A streptococci (GAS) and cells involved in innate immune responses, using human biopsies (n = 70) collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria. CONCLUSIONS: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections highlights a need for alternative therapeutic strategies

Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease

Peer reviewe