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- Alexius, Susanna, 1976-, et al.
(författare)
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Market Means to Political Mission Ends : Scrutinizing the Social Meaning of Moneyin the Swedish Federation for Sexual Education (RFSU)
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In the nonprofit debate, there is an assumption that market means lead to market ends, oftentimes with grim consequences for nonprofit organizations. By drawing on a theoretical framework related to the social meaning of money in hybrid organizations, and by applying the framework to a longitudinal mixedmethod single case study ofmoneymanagement in the Swedish Federation for Sexual Education (RFSU), we argue in this paper instead that management of market means may also promote political mission ends. Empirical findings suggest that there are different social currencies at play that help explain why some money (income of a lower perceived social status) may be used by the organization simply as a means to get access to higher status money (and the legitimacy that comes with it). Hence, contrary to common assumptions of mission-drift as a consequence of market means, in this case study, business dividends and royalties commercially generated in fully owned subsidiaries have been informally and formally earmarked as lower status money and then used as means to secure higher status political mission ends.
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- Alexius, Susanna, et al.
(författare)
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Vad har ni för värden på kontot?
- 2017
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Ingår i: Kurage. - Stockholm : Idealistas förlag. - 2001-175X. ; :23
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Tidskriftsartikel (populärvet., debatt m.m.)
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- Alexius, Susanna, et al.
(författare)
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Vad har ni för värden på kontot?
- 2017
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Ingår i: Kurage. - 2001-175X.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Kan en organisations olika intäkter användas till samma saker? Eller är det skillnad på en medlemsavgift och ett testamente? Eller ett offentligt bidrag? Ledare i organisationer verkar värdera olika intäkter på olika sätt och frågan är om en krona alltid är en krona. Forskarna Susanna Alexius och Ola Segnestam Larsson funderar på om pengar har olika värden.
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- Andersson, Anna-Maria, 1990-
(författare)
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Mycobacterium tuberculosis and HIV coinfection : Effects on innate immunity and strategies to boost the immune response
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis (TB) still remains a big threat today, being the leading cause of death by a single infectious agent. The TB epidemic is fueled by HIV along with the increasing drug-resistance which prolongs the already long treatment duration and decreases the success rate for curing TB. In most cases an infection results in latency but HIV patients have a 20-30 times higher risk of developing active TB. There are around 36.9 million people living with HIV globally, with the highest burden in Africa. Although there are effective treatments against the disease, there is no cure for AIDS and the availability of the lifelong treatment is limited in low-income countries were the burden is highest. HIV infection causes an immunodeficiency characterized by the progressive loss of CD4 T cells which increases the risk of opportunistic infections, and infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB. Mtb spreads through aerosols from one person with active tuberculosis to a healthy person. Upon inhalation the bacteria are phagocytosed by alveolar macrophages that secrete cytokines and chemokines to recruit more cells, such as dendritic cells, macrophages and lymphocytes, leading to the formation of a granuloma. During a single TB infection the bacteria are usually contained within the granuloma, but HIV can disrupt the stable granuloma, causing a rupture and dissemination of Mtb. This inflammatory site is also beneficial to HIV since it promotes replication of the virus within infected cells. HIV and Mtb are two successful intracellular pathogens able to avoid immune defense mechanisms both of the innate and adaptive immunity in order to persist and replicate. Their virulence factors can manipulate or inhibit cell signaling, phagosome maturation, autophagy, ROS production, apoptosis and antigen presentation, to promote survival. Boosting of immune defenses with host-directed therapies (HDT) has been proposed as a treatment strategy against TB, either alone or adjunctive to the current regimen.In this thesis, ways to boost the innate immune responses in Mtb and HIV coinfected macrophages were investigated, along with studies of the effect of HIV on Mtb antigen presentation in coinfected dendritic cells. The initial hypothesis was that autophagy induction through inhibition of mammalian target of rapamycin (mTOR) could suppress Mtb growth in HIV coinfected macrophages. However, during a low grade infection, autophagy induction increased Mtb replication due to a decreased autophagic flux and acidification of Mtb phagosomes. A general autophagic flux was induced, although not localized to the Mtb phagosomes, thus not inducing a xenophagy (autophagy of intracellular pathogens). Other ways of inducing autophagy or boosting the response in coinfected macrophages might be more beneficial and therefore the effect of efferocytosis was investigated. Uptake of apoptotic neutrophils by coinfected macrophages did not induce autophagy but enhanced the control of Mtb by other means. Upon efferocytosis, the macrophages acquired active myeloperoxidase (MPO) from the neutrophils that suppressed Mtb growth. The coinfected macrophages also produced more ROS after efferocytosis. The inhibition of Mtb growth could thus be mediated by MPO and the increased ROS production either directly or indirectly.The possibility to boost the innate immunity could prove to be important during an HIV coinfection, when the adaptive immunity is deficient. In addition to the well-known decline in CD4 T cells during the course of HIV progression, we found that HIV infection of dendritic cells inhibited antigen presentation by suppressing the expression of HLA-DR and co-stimulatory molecules on coinfected dendritic cells. Furthermore, HIV reduced secretion of pro-inflammatory cytokines and suppressed antigen processing through inhibition of autophagy. This impaired antigen presentation in coinfected dendritic cells resulted in a decreased activation and response of Mtb-specific CD4 T cells.In conclusion, this thesis shows how HIV can manipulate antigen presentation in Mtb coinfected dendritic cells and subsequently inhibit the adaptive immune response. It also contributes to insights on how efferocytosis of apoptotic neutrophils can boost the innate immune responses during coinfection. Lastly, autophagy induction through mTOR inhibition does not enhance protection against TB. Induction of autophagy should therefore be handled with care, particularly during HIV coinfection.
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- Andrade, Pedro Amarante, et al.
(författare)
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The Flow and Pressure Relationships in Different Tubes Commonly Used for Semi-occluded Vocal Tract Exercises
- 2016
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Ingår i: Journal of Voice. - : Mosby-Elsevier. - 0892-1997 .- 1873-4588. ; 30:1, s. 36-41
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Tidskriftsartikel (refereegranskat)abstract
- This experimental study investigated the back pressure (Pback) versus flow (U) relationship for 10 different tubes commonly used for semi-occluded vocal tract exercises, that is, eight straws of different lengths and diameters, a resonance tube, and a silicone tube similar to a Lax Vox tube. All tubes were assessed with the free end in air. The resonance tube and silicone tube were further assessed with the free end under water at the depths from 1 to 7 cm in steps of 1 cm. The results showed that relative changes in the diameter of straws affect Pback considerably more compared with the same amount of relative change in length. Additionally, once tubes are submerged into water, Pback needs to overcome the pressure generated by the water depth before flow can start. Under this condition, only a small increase in Pback was observed as the flow was increased. Therefore, the wider tubes submerged into water produced an almost constant Pback determined by the water depth, whereas the thinner straws in air produced relatively large changes to Pback as flow was changed. These differences may be taken advantage of when customizing exercises for different users and diagnoses and optimizing the therapy outcome.
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- Asplund, Annika, 1979-, et al.
(författare)
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One Standardized Differentiation Procedure Robustly Generates Homogenous Hepatocyte Cultures Displaying Metabolic Diversity from a Large Panel of Human Pluripotent Stem Cells
- 2016
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Ingår i: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 1550-8943 .- 1558-6804. ; 12:1, s. 90-104
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Tidskriftsartikel (refereegranskat)abstract
- Human hepatocytes display substantial functional inter-individual variation regarding drug metabolizing functions. In order to investigate if this diversity is mirrored in hepatocytes derived from different human pluripotent stem cell (hPSC) lines, we evaluated 25 hPSC lines originating from 24 different donors for hepatic differentiation and functionality. Homogenous hepatocyte cultures could be derived from all hPSC lines using one standardized differentiation procedure. To the best of our knowledge this is the first report of a standardized hepatic differentiation procedure that is generally applicable across a large panel of hPSC lines without any adaptations to individual lines. Importantly, with regard to functional aspects, such as Cytochrome P450 activities, we observed that hepatocytes derived from different hPSC lines displayed inter-individual variation characteristic for primary hepatocytes obtained from different donors, while these activities were highly reproducible between repeated experiments using the same line. Taken together, these data demonstrate the emerging possibility to compile panels of hPSC-derived hepatocytes of particular phenotypes/genotypes relevant for drug metabolism and toxicity studies. Moreover, these findings are of significance for applications within the regenerative medicine field, since our stringent differentiation procedure allows the derivation of homogenous hepatocyte cultures from multiple donors which is a prerequisite for the realization of future personalized stem cell based therapies.
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| 10. |
- Bahram, Fuad, et al.
(författare)
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Interferon-γ-induced p27KIP1 binds to and targets MYC for proteasome-mediated degradation.
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:3, s. 2837-2854
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Tidskriftsartikel (refereegranskat)abstract
- The Myc oncoprotein is tightly regulated at multiple levels including ubiquitin-mediated protein turnover. We recently demonstrated that inhibition of Cdk2-mediated phosphorylation of Myc at Ser-62 pharmacologically or through interferon (IFN)-γ-induced expression of p27Kip1 (p27) repressed Myc's activity to suppress cellular senescence and differentiation. In this study we identified an additional activity of p27 to interfere with Myc independent of Ser-62 phosphorylation. p27 is required and sufficient for IFN-γ-induced turnover of Myc. p27 interacted with Myc in the nucleus involving the C-termini of the two proteins, including Myc box 4 of Myc. The C-terminus but not the Cdk2 binding fragment of p27 was sufficient for inducing Myc degradation. Protein expression data of The Cancer Genome Atlas breast invasive carcinoma set revealed significantly lower Myc protein levels in tumors with highly expressed p27 lacking phosphorylation at Thr-157 - a marker for active p27 localized in the nucleus. Further, these conditions correlated with favorable tumor stage and patient outcome. This novel regulation of Myc by IFN-γ/p27KIP1 potentially offers new possibilities for therapeutic intervention in tumors with deregulated Myc.
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