| 1. |
- Conze, Tim, 1977-, et al.
(författare)
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MUC2 mucin is a major carrier of the cancer-associated sialyl-Tn antigen in intestinal metaplasia and gastric carcinomas
- 2010
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 20:2, s. 199-206
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Tidskriftsartikel (refereegranskat)abstract
- Changes in mucin protein expression and in glycosylation are common features in pre-neoplastic lesions and cancer and are therefore used as cancer-associated markers. De novo expression of intestinal mucin MUC2 and cancer-associated sialyl-Tn antigen are frequently observed in intestinal metaplasia (IM) and gastric cancer. However, despite that these antigens often co-localize, MUC2 has not been demonstrated to be a carrier of sialyl-Tn. By using the in situ proximity ligation assay (in situ PLA), we herein could show that MUC2 is a major carrier of the sialyl-Tn antigen in all IM cases and in most gastric carcinoma cases. The requirement by in situ PLA for the presence of both antigens in close proximity increases the selectivity compared to measurement of co-localization, as determined by immunohistochemistry. Identification of the mucin which is the carrier of a carbohydrate structure offers unique advantages for future development of more accurate diagnostic and prognostic markers.
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| 2. |
- Metcalfe, Daniel B., et al.
(författare)
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Impacts of experimentally imposed drought on leaf respiration and morphology in an Amazon rain forest
- 2010
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Ingår i: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 24:3, s. 524-533
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Tidskriftsartikel (refereegranskat)abstract
- P>1. The Amazon region may experience increasing moisture limitation over this century. Leaf dark respiration (R) is a key component of the Amazon rain forest carbon (C) cycle, but relatively little is known about its sensitivity to drought. 2. Here, we present measurements of R standardized to 25 degrees C and leaf morphology from different canopy heights over 5 years at a rain forest subject to a large-scale through-fall reduction (TFR) experiment, and nearby, unmodified Control forest, at the Caxiuana reserve in the eastern Amazon. 3. In all five post-treatment measurement campaigns, mean R at 25 degrees C was elevated in the TFR forest compared to the Control forest experiencing normal rainfall. After 5 years of the TFR treatment, R per unit leaf area and mass had increased by 65% and 42%, respectively, relative to pre-treatment means. In contrast, leaf area index (L) in the TFR forest was consistently lower than the Control, falling by 23% compared to the pre-treatment mean, largely because of a decline in specific leaf area (S). 4. The consistent and significant effects of the TFR treatment on R, L and S suggest that severe drought events in the Amazon, of the kind that may occur more frequently in future, could cause a substantial increase in canopy carbon dioxide emissions from this ecosystem to the atmosphere.
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| 3. |
- Pinto, Rita, et al.
(författare)
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Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
- 2012
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Ingår i: Journal of Cellular and Molecular Medicine (Print). - : Wiley. - 1582-1838 .- 1582-4934. ; 16:7, s. 1474-1484
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Tidskriftsartikel (refereegranskat)abstract
- Mucin glycoproteins are major secreted or membrane-bound molecules that, in cancer, show modifications in both the mucin proteins expression and in the O-glycosylation profile, generating some of the most relevant tumour markers in clinical use for decades. Thus far, the identification of these biomarkers has been based on the detection of either the protein or the O-glycan modifications. We therefore aimed to identify the combined mucin and O-glycan features, i.e. specific glycoforms, in an attempt to increase specificity of these cancer biomarkers. Using in situ proximity ligation assays (PLA) based on existing monoclonal antibodies directed to MUC1, MUC2, MUC5AC and MUC6 mucins and to cancer-associated carbohydrate antigens Tn, Sialyl-Tn (STn), T, Sialyl-Lea (SLea) and Sialyl-Lex (SLex) we screened a series of 28 mucinous adenocarcinomas from different locations (stomach, ampulla of Vater, colon, lung, breast and ovary) to detect specific mucin glycoforms. We detected Tn/STn/SLea/SLex-MUC1 and STn/SLea/SLex-MUC2 glycoforms in ≥50% of the cases, with a variable distribution among organs. Some new glycoforms – T/SLea-MUC2, STn/T/SLea/SLex-MUC5AC and STn/T/SLea/SLex-MUC6 – were identified for the first time in the present study in a variable percentage of cases from different organs. In conclusion, application of the PLA technique allowed sensitive detection of specific aberrant mucin glycoforms in cancer, increasing specificity to the use of antibodies either to the mucin protein backbone or the O-glycan haptens alone.
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| 4. |
- Sadio, Ana, et al.
(författare)
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Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Development of effective non-viral vectors is of crucial importance in the implementation of RNA interference in clinical routine. The localized delivery of siRNAs to the gastrointestinal mucosa is highly desired but faces specific problems such as the stability in gastric acidity conditions and the presence of the mucus barrier. CDX2 is a transcription factor critical for intestinal differentiation being involved in the initiation and maintenance of gastrointestinal diseases. Specifically, it is the trigger of gastric intestinal metaplasia which is a precursor lesion of gastric cancer. Its expression is also altered in colorectal cancer, where it may constitute a lineage-survival oncogene. Our main objective was to develop a nanoparticle-delivery system of siRNA targeting CDX2 using modified chitosan as a vector. CDX2 expression was assessed in gastric carcinoma cell lines and nanoparticles behaviour in gastrointestinal mucus was tested in mouse explants. We show that imidazole-modified chitosan and trimethylchitosan/siRNA nanoparticles are able to downregulate CDX2 expression and overpass the gastric mucus layer but not colonic mucus. This system might constitute a potential therapeutic approach to treat CDX2-dependent gastric lesions.
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| 5. |
- 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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