| 1. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 2. |
- Björkman, Per, et al.
(författare)
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Common Interactions between S100A4 and S100A9 Defined by a Novel Chemical Probe.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- S100A4 and S100A9 proteins have been described as playing roles in the control of tumor growth and metastasis. We show here that a chemical probe, oxyclozanide (OX), selected for inhibiting the interaction between S100A9 and the receptor for advanced glycation end-products (RAGE) interacts with both S100A9 and S100A4. Furthermore, we show that S100A9 and S100A4 interact with RAGE and TLR4; interactions that can be inhibited by OX. Hence, S100A4 and S100A9 display similar functional elements despite their primary sequence diversity. This was further confirmed by showing that S100A4 and S100A9 dimerize both in vitro and in vivo. All of these interactions required levels of Zn(++) that are found in the extracellular space but not intracellularly. Interestingly, S100A4 and S100A9 are expressed by distinct CD11b(+) subpopulations both in healthy animals and in animals with either inflammatory disease or tumor burden. The functions of S100A9 and S100A4 described in this paper, including heterodimerization, may therefore reflect S100A9 and S100A4 that are released into the extra-cellular milieu.
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| 3. |
- Källberg, Eva, et al.
(författare)
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CD11b(+)Ly6C(++)Ly6G(-) cells show distinct function in mice with chronic inflammation or tumor burden
- 2012
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Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: S100A9 has been shown to be important for the function of so called Myeloid Derived Suppressor Cells (MDSC). Cells with a similar phenotype are also involved in pro-inflammatory processes, and we therefore wanted to investigate the gene expression and function of these cells in animals that were either subjected to chronic inflammation, or inoculated with tumors. Methods: CD11b(+)Ly6C(++) and Ly6G(+) cells were isolated from spleen, tumor tissue or inflammatory granulomas. S100A9, Arginase 1 and iNOS gene expression in the various CD11b(+) cell populations was analyzed using Q-PCR. The suppressive activity of the CD11b(+) cell populations from different donors was studied in co-culture experiments. Results: S100A9 was shown to be expressed mainly in splenic CD11b(+)Ly6C(+)G(+) cells both at the RNA and protein level. Arginase I and iNOS expression could be detected in both CD11b(+)Ly6C(+)Ly6G(+) and CD11b(+)Ly6C(+)G(-)/C(++)G(-) derived from tumors or a site of chronic inflammation, but was very low in the same cell populations isolated from the spleen. CD11b(+) cells isolated from mice with peritoneal chronic inflammation were able to stimulate T lymphocytes, while CD11b(+) cells from mice with peritoneal tumors suppressed T cell growth. Conclusion: An identical CD11b(+)Ly6C(++)G(-) cell population appears to have the ability to adopt immune stimulatory or immune suppressive functions dependent on the presence of a local inflammatory or tumor microenvironment. Thus, there is a functional plasticity in the CD11b(+)Ly6C(++)G(-) cell population that cannot be distinguished with the current molecular markers.
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| 4. |
- Källberg, Eva, et al.
(författare)
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S100A9 Interaction with TLR4 Promotes Tumor Growth
- 2012
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 7:3, s. e34207-
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Tidskriftsartikel (refereegranskat)abstract
- By breeding TRAMP mice with S100A9 knock-out (S100A9(-/-)) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+) S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+) macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/-) and TLR4(-/-), but not in RAGE(-/-) animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGF beta expression in splenic CD11b(+) cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies.
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