SummaryThe SWI/SNF complex plays an important role in mouse embryonic stem cells (mESCs), but it remains to be determined whether this complex is required for the pluripotency of human ESCs (hESCs). Using RNAi, we demonstrated that depletion of BRG1, the catalytic subunit of the SWI/SNF complex, led to impaired self-renewing ability and dysregulated lineage specification of hESCs. A unique composition of the BRG1-SWI/SNF complex in hESCs was further defined by the presence of BRG1, BAF250A, BAF170, BAF155, BAF53A, and BAF47. Genome-wide expression analyses revealed that BRG1 participated in a broad range of biological processes in hESCs through pathways different from those in mESCs. In addition, chromatin immunoprecipitation sequencing (ChIP-seq) demonstrated that BRG1 played a repressive role in transcriptional regulation by modulating the acetylation levels of H3K27 at the enhancers of lineage-specific genes. Our data thus provide valuable insights into molecular mechanisms by which transcriptional repression affects the self-renewal and differentiation of hESCs.

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The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate caspase-1 and drive the maturation of proinflammatory cytokines IL-1b and IL-18. NLRP3 inflammasome activity must be tightly controlled, as its overactivation is involved in the pathogenesis of inflammatory diseases. Here, we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances NLRP3 inflammasome activity both in the macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits the deubiquitinase CYLD to the centrosome for deubiquitination of polo-like kinase 4 (PLK4), the master regulator of centrosome duplication. Deubiquitination of PLK4 facilitates its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates NEK7 and NLRP3 interaction, which is required for NLRP3 inflammasome activation. Pharmacological or shRNA-mediated inhibition of PLK4, or mutation of the NEK7 Ser204 phosphorylation site, augments NEK7 interaction with NLRP3 and causes increased NLRP3 inflammasome activation. Our study unravels a novel centrosomal regulatory pathway of inflammasome activation and may provide new therapeutic targets for the treatment of NLRP3-associated inflammatory diseases.

Betweenness centrality is an indicator of a node’s centrality in a network. It is equal to the number of shortest paths from all vertices to all others that pass through that node. Most of real-world large networks display a hierarchical community structure, and their betweenness computation possesses rather high complexity. Here we propose a new hierarchical decomposition approach to speed up the betweenness computation of complex networks. The advantage of this new method is its effective utilization of the local structural information from the hierarchical community. The presented method can significantly speed up the betweenness calculation. This improvement is much more evident in those networks with numerous homogeneous communities. Furthermore, the proposed method features a parallel structure, which is very suitable for parallel computation. Moreover, only a small amount of additional computation is required by our method, when small changes in the network structure are restricted to some local communities. The effectiveness of the proposed method is validated via the examples of two real-world power grids and one artificial network, which demonstrates that the performance of the proposed method is superior to that of the traditional method.

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The integration of distributed generations (DGs) is transforming the traditional radial single-source distribution system into a complex multi-source one which requires its related protection is able to maintain proper coordination under bidirectional power flow conditions. Although the conventional backup protection methods are effective up to a certain level of DG penetration, they are incompetent for higher service demands such as high DG penetration and protective rapidity. To deal with such a problem, a fast and reliable backup protection strategy is presented on the basis of a proposed device detection method. In the proposed backup strategy, the device failure-related backup protection is started in advance to accelerate the fault isolation by locking the failed primary protection which can be predicted by the proposed device detection method. The presented strategy possesses an excellent performance on rapidity and stability. Particularly, the fault isolation area is only expanded to the upper level circuit breaker via our protection strategy. The performance of the proposed backup strategy has been validated by the realistic system and the real-time digital simulator (RTDS) system. INDEX TERMS Backup protection, differential protection, device detection, distribution networks.