| 11. |
- Andreasson, K. I., et al.
(författare)
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Targeting innate immunity for neurodegenerative disorders of the central nervous system
- 2016
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; , s. 653-693
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7–9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. (Figure presented.) Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7–9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. © 2016 International Society for Neurochemistry
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| 12. |
- Wu, X. N., et al.
(författare)
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Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy
- 2019
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Ingår i: Prostate. - : Wiley. - 0270-4137. ; 79:10, s. 1079-1089
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Tidskriftsartikel (refereegranskat)abstract
- Background Enhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance. Methods EZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative intent. Associations between EZH2 expression in malignant and benign tissue in prostate biopsy cores and outcomes were investigated using univariate and multivariate Cox regression analyses. LNCaP and PC3 cell radiosensitivity was investigated using colony formation and gamma H2AX assays following UNC1999 chemical probe-mediated EZH2 inhibition. Results While there was no significant association between EZH2 expression and biochemical recurrence following radiotherapy, univariate analysis revealed that prostate cancer cytoplasmic and total EZH2 expression were significantly associated with metastasis development postradiotherapy (P = 0.034 and P = 0.003, respectively). On multivariate analysis, the prostate cancer total EZH2 expression score remained statistically significant (P = 0.003), while cytoplasmic EZH2 expression did not reach statistical significance (P = 0.053). No association was observed between normal adjacent prostate EZH2 expression and biochemical recurrence or metastasis. LNCaP and PC3 cell treatment with UNC1999 reduced histone H3 lysine 27 tri-methylation levels. Irradiation of LNCaP or PC3 cells with a single 2 Gy fraction with UNC1999-mediated EZH2 inhibition resulted in a statistically significant, though modest, reduction in cell colony number for both cell lines. Increased gamma H2AX foci were observed 24 hours after ionizing irradiation in LNCaP cells, but not in PC3, following UNC1999-mediated EZH2 inhibition vs controls. Conclusions Taken together, these results reveal that high pretreatment EZH2 expression in prostate cancer in diagnostic biopsies is associated with an increased risk of postradiotherapy metastatic disease recurrence, but EZH2 function may only at most play a modest role in promoting prostate cancer cell radioresistance.
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| 13. |
- Acosta-Herrera, M, et al.
(författare)
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Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:3, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.
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| 14. |
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| 15. |
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| 16. |
- Eyles, R. A. J., et al.
(författare)
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An unusual transient following the short GRB 071227
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 489:1, s. 13-27
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Tidskriftsartikel (refereegranskat)abstract
- We present X-ray and optical observations of the short duration gamma-ray burst GRB 071227 and its host at z= 0.381, obtained using Swift, Gemini South, and theVery Large Telescope. We identify a short-lived and moderately bright optical transient, with flux significantly in excess of that expected from a simple extrapolation of the X-ray spectrum at 0.2-0.3 d after burst. We fit the SED with afterglow models allowing for high extinction and thermal emission models that approximate a kilonova to assess the excess' origins. While some kilonova contribution is plausible, it is not favoured due to the low temperature and high luminosity required, implying superluminal expansion and a large ejectamass of similar to 0.1 M-circle dot. We find, instead, that the transient is broadly consistent with power-law spectra with additional dust extinction of E(B - V) similar to 0.4 mag, although a possibly thermal excess remains in the z band. We investigate the host, a spiral galaxy with an edge-on orientation, resolving its spectrum along its major axis to construct the galaxy rotation curve and analyse the star formation and chemical properties. The integrated host emission shows evidence for high extinction, consistent with the afterglow findings. The metallicity and extinction are consistent with previous studies of this host and indicate the galaxy is a typical, but dusty, late-type SGRB host.
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| 17. |
- Lamb, Alastair D, et al.
(författare)
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Aiming for a holistic integrated service for men diagnosed with prostate cancer – Definitions of standards and skill sets for nurses and allied healthcare professionals
- 2017
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Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889. ; 29, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To establish a comprehensive set of recommendations for the service structure and skill set of nurses and allied healthcare professionals in prostate cancer care. Methods Using components of formal consensus methodology, a 30-member multidisciplinary panel produced 53 items for discussion relating to the provision of care for prostate cancer patients by specialist nurses and allied healthcare professionals. Items were developed by two rounds of email correspondence in which, first, items were generated and, second, items refined to form the basis of a consensus meeting which constituted the third round of review. The fourth and final round was an email review of the consensus output. Results The panel agreed on 33 items that were appropriate for recommendations to be made. These items were grouped under categories of “Environment” and “Patient Pathway” and included comments on training, leadership, communication and quality assessment as well as specific items related to prostate diagnosis clinics, radical treatment clinics and follow-up survivor groups. Conclusions Specialist nurses and allied healthcare professionals play a vital role alongside urologists and oncologists to provide care to men with prostate cancer and their families. We present a set of standards and consensus recommendations for the roles and skill-set required for these practitioners to provide gold-standard prostate cancer care. These recommendations could form the basis for development of comprehensive integrated prostate cancer pathways in prostate cancer centres as well as providing guidance for any units treating men with prostate cancer.
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| 20. |
- Lamb, M., et al.
(författare)
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Using the multi-object adaptive optics demonstrator RAVEN to observe metal-poor stars in and towards the Galactic Centre
- 2017
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 465:3, s. 3536-3557
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Tidskriftsartikel (refereegranskat)abstract
- The chemical abundances for five metal-poor stars in and towards the Galactic bulge have been determined from the H-band infrared spectroscopy taken with the RAVEN multi-object adaptive optics science demonstrator and the Infrared Camera and Spectrograph at the Subaru 8.2-m telescope. Three of these stars are in the Galactic bulge and have metallicities between -2.1<[Fe/H] < -1.5, and high [α/Fe]~+0.3, typical of Galactic disc and bulge stars in this metallicity range; [Al/Fe] and [N/Fe] are also high, whereas [C/Fe] < +0.3. An examination of their orbits suggests that two of these stars may be confined to the Galactic bulge and one is a halo trespasser, though proper motion values used to calculate orbits are quite uncertain. An additional two stars in the globular cluster M22 show [Fe/H] values consistent to within 1σ, although one of these two stars has [Fe/H] = -2.01 ± 0.09, which is on the low end for this cluster. The [α/Fe] and [Ni/Fe] values differ by 2σ, with the most metal-poor star showing significantly higher values for these elements. M22 is known to show element abundance variations, consistent with a multipopulation scenario though our results cannot discriminate this clearly given our abundance uncertainties. This is the first science demonstration of multiobject adaptive optics with high-resolution infrared spectroscopy, and we also discuss the feasibility of this technique for use in the upcoming era of 30-m class telescope facilities.
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