Histone modification patterns and their combinatorial readout have emerged as a fundamental mechanism for epigenetic regulation. Here we characterized Spindlin1 as a histone effector that senses a cis-tail histone H3 methylation pattern involving trimethyllysine 4 (H3K4me3) and asymmetric dimethylarginine 8 (H3R8me2a) marks. Spindlin1 consists of triple tudor-like Spin/Ssty repeats. Cocrystal structure determination established concurrent recognition of H3K4me3 and H3R8me2a by Spin/Ssty repeats 2 and 1, respectively. Both H3K4me3 and H3R8me2a are recognized using an ''insertion cavity'' recognition mode, contributing to a methylation statespecific layer of regulation. In vivo functional studies suggest that Spindlin1 activates Wnt/b-catenin signaling downstream from protein arginine methyltransferase 2 (PRMT2) and the MLL complex, which together are capable of generating a specific H3 ''K4me3-R8me2a'' pattern. Mutagenesis of Spindlin1 reader pockets impairs activation of Wnt target genes. Taken together, our work connects a histone ''lysine-arginine'' methylation pattern readout by Spindlin1-to-Wnt signaling at the transcriptional level.

Human umbilical cord mesenchymal stem cells (huMSCs) can treat primary ovarian insufficiency (POI) related to ovarian granulosa cell (OGC) apoptosis caused by cisplatin chemotherapy. Exosomes are a class of membranous vesicles with diameters of 30–200 nm that are constitutively released by eukaryotic cells. Exosomes mediate local cell-to-cell communication by transferring microRNAs and proteins. In the present study, we demonstrated the effects of exosomes derived from huMSCs (huMSC-EXOs) on a cisplatin-induced OGC model in vitro and discussed the preliminary mechanisms involved in these effects. We successfully extracted huMSC-EXOs from huMSC culture supernatant and observed the effective uptake of exosomes by cells with fluorescent staining. Using flow cytometry (with annexin-V/PI labelling), we found that huMSC-EXOs increased the number of living cells. Western blotting showed that the expression of Bcl-2 and caspase-3 were upregulated, whilst the expression of Bax, cleaved caspase-3 and cleaved PARP were downregulated to protect OGCs. These results suggest that huMSC-EXOs can be used to prevent and treat chemotherapy-induced OGC apoptosis in vitro. Therefore, this work provides insight and further evidence of stem cell function and indicates that huMSC-EXOs protect OGCs from cisplatin-induced injury in vitro.

The ability to characterize the mitochondria in single living cells may provide a powerful tool in clinical applications. We have recently developed a 2D (both polar angle and azimuth angle dependences) light scattering cytometric technique which we apply here to assess experimental 2D light scattering patterns from single biological cells (yeast and human). We compare these patterns to those obtained from simulations using a 3D Finite-Difference Time-Domain (FDTD) method and demonstrate that microstructure (e.g., the cytoplasm and/or nucleus) of cells generates fringes of scattered light, while in the larger human cells the light scattered by the mitochondria dominates the scatter pattern, forming compact regions of high intensity that we term 'blobs'. These blobs provide information on the mitochondria within the cell and their analysis may ultimately be useful as a diagnostic technique.

This paper discusses the trend modeling for traffic time series. First, we recount two types of definitions for a long-term trend that appeared in previous studies and illustrate their intrinsic differences. We show that, by assuming an implicit temporal connection among the time series observed at different days/locations, the PCA trend brings several advantages to traffic time series analysis. We also describe and define the so-called short-term trend that cannot be characterized by existing definitions. Second, we sequentially review the role that trend modeling plays in four major problems in traffic time series analysis: abnormal data detection, data compression, missing data imputation, and traffic prediction. The relations between these problems are revealed, and the benefit of detrending is explained. For the first three problems, we summarize our findings in the last ten years and try to provide an integrated framework for future study. For traffic prediction problem, we present a new explanation on why prediction accuracy can be improved at data points representing the short-term trends if the traffic information from multiple sensors can be appropriately used. This finding indicates that the trend modeling is not only a technique to specify the temporal pattern but is also related to the spatial relation of traffic time series.

CypD stimulates mPTP excessive opening, subsequently causing endoplasmic reticulum stress through p38 mitogen-activated protein kinase activation, and results in enhanced sterol regulatory element-binding protein-1c transcription and hepatic steatosis. (Hepatology 2018;68:62-77).