| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
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| 3. |
- Botling, Johan, et al.
(författare)
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Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.
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| 4. |
- Burke, Derek G., et al.
(författare)
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Increased glucocerebrosidase (GBA) 2 activity in GBA1 deficient mice brains and in Gaucher leucocytes
- 2013
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 36:5, s. 869-872
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Tidskriftsartikel (refereegranskat)abstract
- Lysosomal glucocerebrosidase (GBA1) deficiency is causative for Gaucher disease. Not all individuals with GBA1 mutations develop neurological involvement raising the possibility that other factors may provide compensatory protection. One factor may be the activity of the non-lysosomal beta-glucosidase (GBA2) which exhibits catalytic activity towards glucosylceramide and is reported to be highly expressed in brain tissue. Here, we assessed brain GBA2 enzymatic activity in wild type, heterozygote and GBA1 deficient mice. Additionally, we determined activity in leucocytes obtained from 13 patients with Gaucher disease, 10 patients with enzymology consistent with heterozygote status and 19 controls. For wild type animals, GBA2 accounted for over 85 % of total brain GBA activity and was significantly elevated in GBA1 deficient mice when compared to heterozygote and wild types (GBA1 deficient; 92.4 +/- 5.6, heterozygote; 71.5 +/- 2.4, wild type 76.8 +/- 5.1 nmol/h/mg protein). For the patient samples, five Gaucher patients had GBA2 leucocyte activities markedly greater than controls. No difference in GBA2 activity was apparent between the control and carrier groups. Undetectable GBA2 activity was identified in four leucocyte preparations; one in the control group, two in the carrier group and one from the Gaucher disease group. Work is now required to ascertain whether GBA2 activity is a disease modifying factor in Gaucher disease and to identify the mechanism(s) responsible for triggering increased GBA2 activity in GBA1 deficiency states.
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| 5. |
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| 6. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 7. |
- Kim, HyeJin, et al.
(författare)
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Towards a better future for biodiversity and people : Modelling Nature Futures
- 2023
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Ingår i: Global Environmental Change. - 0959-3780 .- 1872-9495. ; 82
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Tidskriftsartikel (refereegranskat)abstract
- The Nature Futures Framework (NFF) is a heuristic tool for co-creating positive futures for nature and people. It seeks to open up a diversity of futures through mainly three value perspectives on nature - Nature for Nature, Nature for Society, and Nature as Culture. This paper describes how the NFF can be applied in modelling to support decision-making. First, we describe key considerations for the NFF in developing qualitative and quantitative scenarios: i) multiple value perspectives on nature as a state space where pathways improving nature toward a frontier can be represented, ii) mutually reinforcing key feedbacks of social-ecological systems that are important for nature conservation and human wellbeing, iii) indicators of multiple knowledge systems describing the evolution of complex social-ecological dynamics. We then present three approaches to modelling Nature Futures scenarios in the review, screening, and design phases of policy processes. This paper seeks to facilitate the integration of relational values of nature in models and strengthen modelled linkages across biodiversity, nature's contributions to people, and quality of life.
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| 8. |
- Massaro, Giulia, et al.
(författare)
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Fetal gene therapy for neurodegenerative disease of infants
- 2018
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 24:9, s. 1317-1323
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Tidskriftsartikel (refereegranskat)abstract
- For inherited genetic diseases, fetal gene therapy offers the potential of prophylaxis against early, irreversible and lethal pathological change. To explore this, we studied neuronopathic Gaucher disease (nGD), caused by mutations in GBA. In adult patients, the milder form presents with hepatomegaly, splenomegaly and occasional lung and bone disease; this is managed, symptomatically, by enzyme replacement therapy. The acute childhood lethal form of nGD is untreatable since enzyme cannot cross the blood–brain barrier. Patients with nGD exhibit signs consistent with hindbrain neurodegeneration, including neck hyperextension, strabismus and, often, fatal apnea1. We selected a mouse model of nGD carrying a loxP-flanked neomycin disruption of Gba plus Cre recombinase regulated by the keratinocyte-specific K14 promoter. Exclusive skin expression of Gba prevents fatal neonatal dehydration. Instead, mice develop fatal neurodegeneration within 15 days2. Using this model, fetal intracranial injection of adeno-associated virus (AAV) vector reconstituted neuronal glucocerebrosidase expression. Mice lived for up to at least 18 weeks, were fertile and fully mobile. Neurodegeneration was abolished and neuroinflammation ameliorated. Neonatal intervention also rescued mice but less effectively. As the next step to clinical translation, we also demonstrated the feasibility of ultrasound-guided global AAV gene transfer to fetal macaque brains.
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| 10. |
- Rhomberg-Kauert, Jan, et al.
(författare)
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Using adjusted local assortativity with Molecular Pixelation unveils colocalization of membrane proteins with immunological significance
- 2024
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Advances in spatial proteomics and protein colocalization are a driving force in the understanding of cellular mechanisms and their influence on biological processes. New methods in the field of spatial proteomics call for the development of algorithms and open up new avenues of research. The newly introduced Molecular Pixelation (MPX) provides spatial information on surface proteins and their relationship with each other in single cells. This allows for in silico representation of neighborhoods of membrane proteins as graphs. In order to analyze this new data modality, we adapted local assortativity in networks of MPX single-cell graphs and created a method that is able to capture detailed information on the spatial relationships of proteins. The introduced method can evaluate the pairwise colocalization of proteins and access higher-order similarity to investigate the colocalization of multiple proteins at the same time. We evaluated the method using publicly available MPX datasets where T cells were treated with a chemokine to study uropod formation. We demonstrate that adjusted local assortativity detects the effects of the stimuli at both single- and multiple-marker levels, which enhances our understanding of the uropod formation. We also applied our method to treating cancerous B-cell lines using a therapeutic antibody. With the adjusted local assortativity, we recapitulated the effect of rituximab on the polarity of CD20. Our computational method together with MPX improves our understanding of not only the formation of cell polarity and protein colocalization under stimuli but also advancing the overall insight into immune reaction and reorganization of cell surface proteins, which in turn allows the design of novel therapies. We foresee its applicability to other types of biological spatial data when represented as undirected graphs.
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