| 31. |
- Dalmo, Erika, et al.
(författare)
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Growth-Inhibitory Activity of Bone Morphogenetic Protein 4 in Human Glioblastoma Cell Lines Is Heterogeneous and Dependent on Reduced SOX2 Expression
- 2020
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Ingår i: Molecular Cancer Research. - 1541-7786 .- 1557-3125. ; 18:7, s. 981-991
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme continues to have a dismal prognosis. Even though detailed information on the genetic aberrations in cell signaling and cell-cycle checkpoint control is available, no effective targeted treatment has been developed. Despite the advanced molecular defects, glioblastoma cells may have remnants of normal growth-inhibitory pathways, such as the bone morphogenetic protein (BMP) signaling pathway. We have evaluated the growth-inhibitory effect of BMP4 across a broad spectrum of patient samples, using a panel of 40 human glioblastoma initiating cell (GIC) cultures. A wide range of responsiveness was observed. BMP4 sensitivity was positively correlated with a proneural mRNA expression profile, high SOX2 activity, and BMP4-dependent upregulation of genes associated with inhibition of the MAPK pathway, as demonstrated by gene set enrichment analysis. BMP4 response in sensitive cells was mediated by the canonical BMP receptor pathway involving SMAD1/5/9 phosphorylation and SMAD4 expression. SOX2 was consistently downregulated in BMP4-treated cells. Forced expression of SOX2 attenuated the BMP4 sensitivity including a reduced upregulation of MAPK-inhibitory genes, implying a functional relationship between SOX2 downregulation and sensitivity. The results show an extensive heterogeneity in BMP4 responsiveness among GICs and identify a BMP4-sensitive subgroup, in which SOX2 is a mediator of the response.
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| 32. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 33. |
- Deb, Siddhartha, et al.
(författare)
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Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer
- 2014
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 27:9, s. 1223-1230
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Tidskriftsartikel (refereegranskat)abstract
- Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1 alpha (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.
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| 34. |
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| 35. |
- Duprez, Ida Rasmusson, et al.
(författare)
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Preparatory studies of composite mesenchymal stem cell islets for application in intraportal islet transplantation
- 2011
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 116:1, s. 8-17
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background. Low engraftment and adverse immune reactions hamper the success rate of clinical islet transplantation. In this study, we investigated the capacity of human mesenchymal stem cells (MSCs) to adhere to human islets of Langerhans and their effects in immune modulation and during blood interactions in vitro. Methods. Composite MSC-islets were formed by suspension co-culture, and the phenotype was evaluated by confocal microscopy. Islet function was assessed by dynamic insulin release in response to glucose in vitro. Mixed lymphocyte-islet reactions (MLIR) and the tubing blood loop model were utilized as in vitro tools to analyse the effect of MSCs on the innate and adaptive immune reactions triggered by the islets. Results. MSCs rapidly adhered to islets and spread out to cover the islet surface. Insulin expression and secretion were sustained with the MSC coating. MSC-coated islets showed unaffected reactions with blood in vitro in comparison to control islets. Furthermore, MSCs suppressed lymphocyte proliferation induced by islet cells in MLIR. Conclusion. We conclude that it is possible to create composite MSC-islets to enable delivery of the MSCs by utilizing the adhesive capacity of the MSCs. This could have beneficial immunosuppressive effects in optimizing pancreatic islet transplantation.
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| 36. |
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| 37. |
- Envall, Ida, et al.
(författare)
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Existing evidence related to soil retention of phosphorus from on-site wastewater treatment systems in boreal and temperate climate zones : a systematic map
- 2023
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Ingår i: Environmental Evidence. - : Springer Nature. - 2047-2382. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In Sweden there are nearly one million soil-based on-site wastewater treatment systems (OWTSs). OWTSs may contribute to eutrophication of surface waters, due to the discharge of phosphorus (P). Hence, in certain cases, a high P removal rate (up to 90%) of OWTSs is required by Swedish authorities. Since these requirements may have costly consequences to property owners, it is debated whether they are too strict. In this debate, it is often claimed that the soil retention of P occurring in the natural environments may be underestimated by authorities. Soil retention is the inhibition of the transport of P through the ground, due to different chemical, physical and biological processes occurring there. These processes make the P transport slower, which may reduce the unwanted impact on receiving water bodies. However, the efficiency of soil retention of P remains unclear. The objective of this systematic map was to collect, code, organise and elucidate the relevant evidence related to the topic, to be able to guide stakeholders through the evidence base, and to support future research synthesising, commissioning, and funding. The systematic map was carried out in response to needs declared by the Swedish Agency for Marine and Water Management but the conclusions should be valid for a wider range of countries across boreo-temperate regions.Methods: Searches were made for peer-reviewed and grey literature using bibliographic databases, search engines, specialist websites, and stakeholder contacts. The references were screened for relevance according to a predefined set of eligibility criteria. A detailed database of the relevant studies was compiled. Data and metadata that enable evaluation and discussion of the character and quality of the evidence base were extracted and coded. Special focus was placed on assessing if existing evidence could contribute to policy and practice decision making. Descriptive information about the evidence base was presented in tables and figures. An interactive evidence atlas and a choropleth were created, displaying the locations of all studies.Review findings: 234 articles out of 10,797 screened records fulfilled the eligibility criteria. These articles contain 256 studies, performed in the field or in the laboratory. Six different study types were identified, based on where the measurements were conducted. Most studies, including laboratory studies, lack replicates. Most field studies are observational case studies.Conclusions: It is not possible to derive valid generic measures of the efficiency of soil retention of P occurring in the natural soil environment from available research. Neither does the evidence base allow for answering the question of the magnitude of the potential impact of OWTSs on the P concentration in recipients on a general basis, or under what conditions OWTSs generally have such an impact. A compilation of groundwater studies may provide examples of how far the P may reach in x years, but the number of groundwater studies is insufficient to draw any general conclusions, given the complexity and variability of the systems. Future research should strive for replicated study designs, more elaborate reporting, and the establishment of a reporting standard.
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| 38. |
- Envall, Ida, et al.
(författare)
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What evidence exists related to soil retention of phosphorus from on-site wastewater treatment systems in boreal and temperate climate zones? : A systematic map protocol
- 2020
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Ingår i: Environmental Evidence. - : BMC. - 2047-2382. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Soil-based on-site wastewater treatment systems (OWSs) are suspected to contribute to eutrophication of surface waters, due to the discharge of phosphorus (P). However, along the flow path between the facilities and surface waters, different processes contribute to delay the transport of phosphorus through the ground. This may reduce the unwanted impact on receiving water bodies. However, the strength and significance of this so-called soil retention remains unclear. In Sweden, there are nearly one million OWSs. To protect surface waters, a high P removal rate (up to 90%) is often required by the local municipalities. However, since these requirements may have costly consequences to property owners, it is debated as to whether they are too strict. In this debate, it is often claimed that the retention of P occurring in natural environments may be underestimated by authorities. Accordingly, there is a need for a scrutiny of the available evidence related to soil retention of phosphorus from OWSs. This is the objective of the planned systematic map. Focus will be on boreal and temperate climate zones. Methods Searches will be made for peer-reviewed articles and grey literature using bibliographic databases, search engines, specialist websites and stakeholder contacts. The references will be screened for relevance according to a predefined set of eligibility criteria. At stage one, after testing and clarifying the eligibility criteria, the references will be single-screened based on title and abstract. At stage two, potentially relevant references will be screened in full-text independently by two reviewers. We will compile a detailed database of the relevant studies. Moreover, a narrative report will be produced, describing the research landscape in general terms. This will be carried out with a conceptual model, describing the processes involved in P retention in natural environments, as a foundation. It will be discussed where the respective studies/study types fit into the conceptual model, and also evaluated how each study/study type can be related to the overarching question of eutrophication. Moreover, we will describe identified knowledge gaps that warrant further primary research effort, as well as identified knowledge clusters that could be suitable for systematic reviews.
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| 39. |
- Ericsson, Olle, et al.
(författare)
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Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
- 2019
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Ingår i: Prenatal diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 39:11, s. 1011-1015
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
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| 40. |
- Eriksson K., Susanna, et al.
(författare)
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Geometrical and energetical structural changes in organic dyes for dye-sensitized solar cells probed using photoelectron spectroscopy and DFT
- 2016
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 18:1, s. 252-260
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Tidskriftsartikel (refereegranskat)abstract
- The effects of alkoxy chain length in triarylamine based donor acceptor organic dyes are investigated with respect to the electronic and molecular surface structures on the performance of solar cells and the electron lifetime. The dyes were investigated when adsorbed on TiO2 in a configuration that can be used for dye sensitized solar cells (DSCs). Specifically, the two dyes D35 and D45 were compared using photoelectron spectroscopy (PES) and density functional theory (DFT) calculations. The differences in solar cell characteristics when longer alkoxy chains are introduced in the dye donor unit are attributed to geometrical changes in dye packing while only minor differences were observed in the electronic structure. A higher dye load was observed for D45 on TiO2. However, D35 based solar cells result in higher photocurrent although the dye load is lower. This is explained by different geometrical structures of the dyes on the surface.
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