| 1. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 2. |
- Lindgren, David, et al.
(författare)
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Isolation and characterization of progenitor-like cells from human renal proximal tubules.
- 2011
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 178:2, s. 828-837
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Tidskriftsartikel (refereegranskat)abstract
- The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDH(high) and ALDH(low) cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population scattered through the proximal tubules (PTs). These cells expressed CD24 and CD133, previously described markers for renal progenitors of Bowman's capsule. Furthermore, we show that the PT cells, and the glomerular progenitors, are positive for KRT7, KRT19, BCL2, and vimentin. In addition, tubular epithelium regenerating on acute tubular necrosis displayed long stretches of CD133(+)/VIM(+) cells, further substantiating that these cells may represent a progenitor cell population. Furthermore, a potential association of these progenitor cells with papillary renal cell carcinoma was discovered. Taken together, our data demonstrate the presence of a previously unappreciated subset of the PT cells that may be endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules.
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| 3. |
- Bayani, Jane, et al.
(författare)
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Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
- 2021
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Ingår i: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.
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| 4. |
- Belle, Simon, et al.
(författare)
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Use of sedimentary algal pigment analyses to infer past lake-water total phosphorus concentrations
- 2022
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Ingår i: Journal of Paleolimnology. - : Springer Science and Business Media LLC. - 0921-2728 .- 1573-0417. ; 68, s. 415-426
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Tidskriftsartikel (refereegranskat)abstract
- We tested the feasibility of using sedimentary algal pigment analyses by spectral deconvolution to infer past lake-water total phosphorus concentrations. We established equations that link lake-water nutrient concentrations and sediment pigment concentrations, using a combination of calibration in both space and time, with a training set of 31 Swedish lakes. The calibration dataset yielded a significant positive relationship between total carotenoid concentrations and lake-water total phosphorus concentrations. We also compared sediment-pigment-based nutrient inferences with time series of water column monitoring data to evaluate whether temporal changes in total phosphorus concentrations are well captured by analysis of sedimentary pigments. We found that changes in pigment preservation through time can alter the relationship between concentrations of lake-water nutrients and sedimentary pigments, thus limiting the reliability of historical ecological conditions inferred from pigments in the sediment. Our data suggested that ratios of Chlorophyll derivatives to total carotenoids (CD/TC ratio) and Chlorophyll a to Chlorophyll derivatives (CPI) can be used as proxies for pigment preservation. Using our approach, inferred temporal changes in water-column total phosphorus concentrations in lakes are promising, but require further development, specifically with respect to the influence of pigment degradation in both the water column and sediments, as well as the factors that control such degradation.
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| 5. |
- Bjartell, Anders, et al.
(författare)
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Time-resolved fluorescence in immunocytochemical detection of prostate-specific antigen in prostatic tissue sections
- 1999
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Ingår i: Histochemical Journal. - 0018-2214. ; 31:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Chelates with fluorescent lanthanides such as europium and terbium are widely used in immunofluorometric assays, e.g. for the measurement of different molecular forms of prostate-specific antigen (PSA) in serum for detection and monitoring of prostate cancer. These chelates have also been introduced as non-radioactive labels in immunocytochemistry and in situ hybridization. In the present study, sections of non-malignant prostate were investigated using monoclonal IgGs against PSA. Detection of specific immunostaining employing time-resolved fluorescence with europium-labeled streptavidin was compared with conventional detection by streptavidin conjugated to horse-radish peroxidase. The high PSA concentration in the tissue produced high intensity, specific time-resolved fluorescence signals in the epithelial cells of the prostate gland without disturbance from non-specific tissue autofluorescence. This allowed short exposure times to be used which resulted in insignificant photobleaching. Two of the three europium-chelates evaluated yielded high signal intensities. Counterstaining was found to be optimal with Gill No. 1-Haematoxylin solution and Merckoglas(TM) was the best mounting medium for the europium chelates tested. In conclusion, time-resolved fluorescence imaging is an attractive alternative to conventional detection of streptavidin conjugated to horse-radish peroxidase, as it provides linear, high intensity, specific signals subsequent to the decay of non-specific tissue autofluorescence.
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| 6. |
- Boström, Anna-Karin, et al.
(författare)
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Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition.
- 2012
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Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 43, s. 708-719
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma.
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| 7. |
- Clark, Charlotte, et al.
(författare)
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Psychological restoration, coping strategies and children’s cognitive performance in the RANCH study
- 2006
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Ingår i: Proceedings of Inter-Noise 2006, Honolulu, Hawaii, USA, 3-6 December, 2006, Paper no in06_090 (Available on CD). ; :Paper no in06_090
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Konferensbidrag (refereegranskat)abstract
- The RANCH study found a linear exposure effect association between chronic aircraft noise exposure at primary school and the impairment of children’s reading comprehension, in the Netherlands, Spain and the United Kingdom. This paper presents multilevel modelling analyses, exploring psychological mechanisms, which may moderate the effect of aircraft noise on children’s cognition. Psychological restoration – the process whereby places which afford tranquility and relaxation are utilized to reduce stress and promote well being – has been shown to reduce the adverse effect of noise on children’s annoyance responses. This paper examines whether having places for psychological restoration at home, moderates the adverse effects of chronic aircraft noise exposure at school on children’s cognition. In addition, the effectiveness of coping strategies in relation to noise exposure at school are examined – are specific coping strategies associated with less impairment of cognition? Multi-level models examining the role of psychological restoration and coping strategies, as part of a broader model of environmental risk and protective factors for children’s cognition are presented. The implication of the findings for interventions for children attending noise exposed schools are discussed.
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| 8. |
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| 9. |
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| 10. |
- Ehlén, Åsa, et al.
(författare)
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Tumors with non-functional RB1 are killed by reduced gamma-tubulin levels.
- 2012
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 287:21, s. 17241-17247
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Tidskriftsartikel (refereegranskat)abstract
- In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway. Here, we describe that RB1 and γ tubulin proteins moderate each other's expression by binding to their respective gene promoters. Simultaneous reduction of RB1 and γ tubulin protein levels result in an E2F1-dependent upregulation of apoptotic genes such as caspase 3. We report that in various tumors types, there is an inverse correlation between the expression levels of γ tubulin and RB1 and that in tumor cell lines with a non-functioning RB1, reduction of γ tubulin protein levels leads to induction of apoptosis. Thus, the RB1/γ tubulin signal network can be considered as a new target for cancer treatment.
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