A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis

A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-κB signaling in response to specific proinflammatory stimuli in different cell types and has been suggested as a susceptibility gene for rheumatoid arthritis. To define the contribution of A20 to rheumatoid arthritis pathology, we generated myeloid-specific A20-deficient mice and show that specific ablation of Tnfaip3 in myeloid cells results in spontaneous development of a severe destructive polyarthritis with many features of rheumatoid arthritis. Myeloid-A20-deficient mice have high levels of inflammatory cytokines in their serum, consistent with a sustained NF-κB activation and higher TNF production by macrophages. Destructive polyarthritis in myeloid A20 knockout mice was TLR4-MyD88 and IL-6 dependent but was TNF independent. Myeloid A20 deficiency also promoted osteoclastogenesis in mice. Together, these observations indicate a critical and cell-specific function for A20 in the etiology of rheumatoid arthritis, supporting the idea of developing A20 modulatory drugs as cell-targeted therapies.     

Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm

Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β-mediated vasculopathies.     

从随机和到随机和过程

随机和的概念是早就有的,但利用随机和的形式构造随机过程尚未见先例。本文首先引进随机和过程的概念,对过程的一些性质进行了探讨,并举例说明了随机和过程的应用。我们利用本文的结论对布朗运动问题给出了简单的解法,得出的结果与求解朗之万随机微分方程的结果是相合的。本文提出了随机耗散系统的概念,这种系统是广泛存在的,发现随机和过程是描述这种系统机制的有效工具。     

电力系统振荡时负荷点频率的振荡规律

本文对电力系统发生振荡或异步运行时负荷点的频率的变化规律进行了研究,并从两机系统出发导出了瞬时频率和平均频率的计算公式.     

半序集的内禀拓扑(Ⅱ)

在这篇文章中我们讨论了一个半序集的内禀拓扑的紧性和连通性,以及内禀拓扑与其在子集中的导出拓扑之间的关系,主要结果有:1.格L的区间拓扑是紧的,当且仅当L是备的;2.局部有限散度半序集P的区间拓扑是连通的,当且仅当P是稠的且条件备;3.格L中设M=[←,p],则M的区间拓扑(开区间拓扑)和L的区间拓扑(开区间拓扑)在M的导出拓扑等价.