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- Adrianto, Indra, et al.
(författare)
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Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:3, s. 253-258
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 x 10(-8), odds ratio = 1.70) and Korean (P = 8.33 x 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-kappa B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
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| 2. |
- Chen, Xiaolong, et al.
(författare)
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Nontrivial resource requirement in the early stage for containment of epidemics
- 2019
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Ingår i: Physical review. E. - 2470-0045 .- 2470-0053. ; 100:3
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Tidskriftsartikel (refereegranskat)abstract
- During epidemic control, containment of the disease is usually achieved through increasing a devoted resource to reduce the infectiousness. However, the impact of this resource expenditure has not been studied quantitatively. For disease spread, the recovery rate can be positively correlated with the average amount of resource devoted to infected individuals. By incorporating this relation we build a novel model and find that insufficient resource leads to an abrupt increase in the infected population size, which is in marked contrast with the continuous phase transitions believed previously. Counterintuitively, this abrupt phase transition is more pronounced in less contagious diseases. Furthermore, we find that even for a single infection source, the public resource needs to be available in a significant amount, which is proportional to the total population size, to ensure epidemic containment. Our findings provide a theoretical foundation for efficient epidemic containment strategies in the early stage.
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| 3. |
- Wimsatt, Jeffrey, et al.
(författare)
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Oral perfluorooctane sulfonate (PFOS) lessens tumor development in the APC(min) mouse model of spontaneous familial adenomatous polyposis
- 2016
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Ingår i: BMC Cancer. - London, United Kingdom : BioMed Central. - 1471-2407 .- 1471-2407. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer is the second most common cause of cancer deaths for both men and women, and the third most common cause of cancer in the U.S. Toxicity of current chemotherapeutic agents for colorectal cancer, and emergence of drug resistance underscore the need to develop new, potentially less toxic alternatives. Our recent cross-sectional study in a large Appalachian population, showed a strong, inverse, dose-response association of serum perfluorooctane sulfonate (PFOS) levels to prevalent colorectal cancer, suggesting PFOS may have therapeutic potential in the prevention and/or treatment of colorectal cancer. In these preliminary studies using a mouse model of familial colorectal cancer, the APC(min) mouse, and exposures comparable to those reported in human populations, we assess the efficacy of PFOS for reducing tumor burden, and evaluate potential dose-response effects.Methods: At 5-6 weeks of age, APC(min) mice were randomized to receive 0, 20, 250 mg PFOS/kg (females) or 0, 10, 50 and 200 mg PFOS/kg (males) via their drinking water. At 15 weeks of age, gastrointestinal tumors were counted and scored and blood PFOS levels measured.Results: PFOS exposure was associated with a significant, dose-response reduction in total tumor number in both male and female mice. This inverse dose-response effect of PFOS exposure was particularly pronounced for larger tumors (r(2) for linear trend = 0.44 for males, p's <0.001).Conclusions: The current study in a mouse model of familial adenomatous polyposis offers the first experimental evidence that chronic exposure to PFOS in drinking water can reduce formation of gastrointestinal tumors, and that these reductions are both significant and dose-dependent. If confirmed in further studies, these promising findings could lead to new therapeutic strategies for familial colorectal cancer, and suggest that PFOS testing in both preventive and therapeutic models for human colorectal cancer is warranted.
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