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- Akperov, M., et al.
(författare)
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Trends of intense cyclone activity in the Arctic from reanalyses data and regional climate models (Arctic-CORDEX)
- 2019. - 1
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Ingår i: Turbulence, Atmosphere and Climate Dynamics. - : IOP Publishing. - 1755-1307. ; 231
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Konferensbidrag (refereegranskat)abstract
- The ability of state-of-the-art regional climate models (RCMs) to simulate the trends of intense cyclone activity in the Arctic is assessed based on an ensemble of 13 simulations from 11 models from the Arctic-CORDEX initiative. Some models employ large-scale spectral nudging techniques. Cyclone characteristics simulated by the ensemble in winter and summer are compared with the results from four reanalyses (ERA-Interim, NCEP-CFSR, NASA-MERRA2 and JMA-JRA55) in winter and summer for 1981-2010 period.
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- Bum-Erdene, Khuchtumur, et al.
(författare)
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Investigation into the Feasibility of Thioditaloside as a Novel Scaffold for Galectin-3-Specific Inhibitors
- 2013
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227. ; 14:11, s. 1331-1342
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-3 is extensively involved in metabolic and disease processes, such as cancer metastasis, thus giving impetus for the design of specific inhibitors targeting this -galactose-binding protein. Thiodigalactoside (TDG) presents a scaffold for construction of galectin inhibitors, and its inhibition of galectin-1 has already demonstrated beneficial effects as an adjuvant with vaccine immunotherapy, thereby improving the survival outcome of tumour-challenged mice. A novel approachreplacing galactose with its C2 epimer, taloseoffers an alternative framework, as extensions at C2 permit exploitation of a galectin-3-specific binding groove, thereby facilitating the design of selective inhibitors. We report the synthesis of thioditaloside (TDT) and crystal structures of the galectin-3 carbohydrate recognition domain in complexes with TDT and TDG. The different abilities of galactose and talose to anchor to the protein correlate with molecular dynamics studies, likely explaining the relative disaccharide binding affinities. The feasibility of a TDT scaffold to enable access to a particular galectin-3 binding groove and the need for modifications to optimise such a scaffold for use in the design of potent and selective inhibitors are assessed.
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- Chinh, Bkrong, et al.
(författare)
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Whole blood gene expression in adolescent chronic fatigue syndrome : an exploratory cross-sectional study suggesting altered B cell differentiation and survival
- 2017
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group.MethodsCFS patients (12-18 years old) were recruited nation-wide to a single referral center as part of the Nor-CAPITAL project. A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/ relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings.ResultsA total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated.ConclusionAdolescent CFS is characterized by differential gene expression pattern in whole blood suggestive of impaired B cell differentiation and survival, and enhanced innate antiviral responses and inflammation. This expression pattern is associated with neuroendocrine markers of altered HPA axis and autonomic nervous activity, and with symptoms of post-exertional malaise.
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