| 1. |
- Kottyan, Leah C., et al.
(författare)
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The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
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Tidskriftsartikel (refereegranskat)abstract
- Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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| 2. |
- Liu, Caifeng, et al.
(författare)
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A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated Cancer Metastasis
- 2017
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 23:16, s. 4769-4779
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cancer metastasis can occur at the early stage of tumor development when a primary tumor is at the microscopic size. In particular, the interaction of malignant cells with other cell types including cancer-associated fibroblasts (CAF) in promoting metastasis at the early stage of tumor development remains largely unknown. Here, we investigated the role of CAFs in facilitating the initial events of cancer metastasis when primary tumors were at microscopic sizes. Experimental Design: Multicolor-coded cancer cells and CAFs were coimplanted into the transparent zebrafish body and metastasis at a single-cell level was monitored in living animals. Healthy fibroblasts, tumor factor-educated fibroblasts, and CAFs isolated from various tumors were tested for their ability to facilitate metastasis. Results: We showed that CAFs promoted cancer cell metastasis at the very early stage during primary tumor development. When a primary tumor was at the microscopic size consisting of a few hundred cells, CAFs were able to hijack cancer cells for dissemination from the primary site. Surprisingly, a majority of metastatic cancer cells remained in tight association with CAFs in the circulation. Furthermore, stimulation of non-metastasis-promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to acquisition of their metastatic capacity. Conclusions: Cancer metastasis occurs at the very early stage of tumor formation consisting of only a few hundred cells. CAFs are the key cellular determinant for metastasis. Our findings provide novel mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs for cancer therapy should be aimed at the early stage during cancer development. (C) 2017 AACR.
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| 3. |
- Lu, Y., et al.
(författare)
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Fuzzy hegselmann-krause opinion dynamics with opinion leaders
- 2019
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Ingår i: 2019 Chinese Control Conference (CCC). ; , s. 6019-6024
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Konferensbidrag (refereegranskat)abstract
- In this paper, from the perspective of opinion dynamics theory, we investigate the intrinsic interaction principles of a group of autonomous agents and develop a fuzzy opinion dynamics model with leaders. First, this paper divides group agents into three subgroups: opinion followers, positive opinion leaders, and negative opinion leaders according to the opinion's update manner and influence. Then, we consider the uncertainty of the agents' opinion gaps and apply the Fuzzy Inference Machine to the effects of the leaders' opinions on a certain follower's opinion. The innovation of this paper is that the weight is distributed from 0 to 1 in accordance with the closeness among the opinion leaders and followers, which is closer to real life. Finally, the simulation results show that the proposed model can effectively explain the opinion interaction and evolution and conforms with the existing theoretical results in the field of opinion dynamics.
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| 4. |
- Sun, Xiaoming, et al.
(författare)
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Adjustable hardness of hydrogel for promoting vascularization and maintaining sternness of stem cells in skin flap regeneration
- 2018
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Ingår i: Applied Materials Today. - : Elsevier. - 2352-9407. ; 13, s. 54-63
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Tidskriftsartikel (refereegranskat)abstract
- The matrix mechanical stiffness of biomaterials plays an important role in the pluripotency and biological function of stem cells in the microenvironment. It is a key step to adjust the stiffness of biomaterials for inducing stem cells to promote vascularization in order to promote damaged tissue repair. In this study, we transplant adipose derived stem cells (ADSCs) within an in situ forming dextran hydrogel with controllable mechanical strength formed by cross-linking glycidyl methacrylate derivatized dextran and dithiothreitol, which can regulate the stemness and biological functions of stem cells. We show that softer dextran hydrogel can better maintain stemness markers expression of ADSCs, and significantly stimulate ADSCs to secrete angiogenic factors. The ADSCs-encapsulated hydrogel distinctly promote the skin flap survival compared to direct cell injection. Bioluminescence imaging analysis shows that in situ forming dextran hydrogel can improve cells retention, and postmortem analysis reveals that the transplanted ADSCs with hydrogel can promote vascularization. These results support the use of injectable dextran hydrogel for skin ischemia tissue regeneration. (C) 2018 Elsevier Ltd. All rights reserved.
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| 5. |
- Zhang, Hanzhi, et al.
(författare)
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Quantitative estimation of the contribution of dustsources to Chinese loess using detrital zircon U-Pbage patterns
- 2016
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Ingår i: Journal of Geophysical Research - Earth Surface. - 2169-9003 .- 2169-9011. ; 121:11, s. 2085-2099
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Tidskriftsartikel (refereegranskat)abstract
- The origin and provenance of the loess deposits of the Chinese Loess Plateau (CLP) are stilldebated. In order to pinpoint the dust sources, surface samples from the piedmont of the NortheasternTibetan Plateau, the Gobi Altai Mountains, and modern eolian dunes from the Tengger desert and Mu Ussand field were analyzed by using the detrital zircon dating technique. In order to quantitatively discriminatethe content of different potential sources, zircon grains of different ages were grouped according to theirtectonic origin. Zircon grains aged from 1300 to 550 Ma were assigned to the Northeastern Tibetan Plateau,and grains aged from 550 to 0 Ma to the Northeastern Tibetan Plateau or the Gobi Altai Mountains, or to acombination of the two. Zircon ages of around 2.8 Ga to 1.3 Ga may be a mixture of sources from theNortheastern Tibetan Plateau, Gobi Altai Mountains, or North China Craton. Sediments from the Tenggerdesert and Mu Us sand field consist of a mixture of the three sources and exhibit a high degree of spatialvariability in terms of their source. In the northern part of the two deserts, 43–83% of the sediments arederived from the Gobi Altai Mountains, while in the south, material from the Northeastern Tibetan Plateaucomprises 51–98% of the sediments. Loess deposits from the CLP also comprise a mixture of the threedifferent sources, with material from the Northeastern Tibetan Plateau making the dominant contribution(65–100%), with material from the North China Craton and the Gobi Altai Mountains comprising 0–35% and0–40% of the loess deposits, respectively. The contributions from the three sources to the loess deposits onCLP vary spatially. Application of the novel statistical method of provenance group analysis demonstratesthat the loess deposits comprise a mixture of material from a broad region of northern China and that theNortheastern Tibetan Plateau material makes the dominant contribution.
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