Upregulation of Src homology phosphotyrosyl phosphatase 2 (Shp2) expression in oral cancer and knockdown of Shp2 expression inhibit tumor cell viability and invasion in vitro

ObjectiveThis study investigated the clinical significance of Shp2 protein expression in oral squamous cell carcinoma (OSCC) and elucidated its biologic significance in OSCC cells.Study DesignA total of 88 OSCC cases were used to assess Shp2 expression, out of which 70 were for immunohistochemistry and 18 paired tumors vs normal tissues were for Western blot of Shp2 expression. OSCC cells were used to assess the effects of Shp2 knockdown for cell viability, apoptosis, invasion, and protein expressions.ResultsExpression of Shp2 protein was significantly upregulated in OSCC tissues compared with the normal tissues, and Shp2 overexpression was associated with advanced tumor clinical stages and lymph node metastasis ex vivo. Knockdown of Shp2 expression in vitro inhibited OSCC cell viability and invasion but induced apoptosis by regulating expression of the apoptosis-related proteins.ConclusionsThe data indicated that Shp2 may play an important role in OSCC progression. Further studies will investigate whether a target of Shp2 expression could be a novel therapeutic strategy for clinical control of OSCC

The paleoclimatic footprint in the soil carbon stock of the Tibetan permafrost region

Data and code availability The authors declare that the majority of the data supporting the findings of this study are available through the links given in the paper. The unpublished data are available from the corresponding author upon request. The new estimate of Tibetan soil carbon stock and R code are available in a persistent repository (https://figshare.com/s/4374f28d880f366eff6d). Acknowledgements This study was supported by the Strategic Priority Research Program (A) of the Chinese Academy of Sciences (XDA20050101), the National Natural Science Foundation of China (41871104), Key Research and Development Programs for Global Change and Adaptation (2017YFA0603604), International Partnership Program of the Chinese Academy of Sciences (131C11KYSB20160061) and the Thousand Youth Talents Plan project in China. Jinzhi Ding acknowledges the General (2017M620922) and the Special Grade (2018T110144) of the Financial Grant from the China Postdoctoral Science Foundation.Peer reviewedPublisher PD

The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis

The long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) maintains the integrity of the intestinal epithelial barrier and regulates local inflammation. However, its influences on intestinal microbial communities and tissue susceptibility to cancer development remain unexplored. Here, we report that MALAT1 regulates host anti-microbial response gene expression and the composition of mucosal-associated microbial communities in a region-specific manner. In the APC mutant mouse model of intestine tumorigenesis, knocking out MALAT1 results in higher polyp counts in the small intestine and colon. Interestingly, intestine polyps that developed in the absence of MALAT1 were smaller in size. These findings highlight the unexpected bivalent role of MALAT1 in restricting and promoting cancer progression at different disease stages. Among the 30 MALAT1-targets shared by both the small intestine and colon, ZNF638 and SENP8 levels are predictive of colon adenoma patient overall survival and disease-free survival. Genomic assays further revealed that MALAT1 modulates intestinal target expression and splicing through both direct and indirect mechanisms. This study expands the role of lncRNAs in regulating intestine homeostasis, microbial communities, and cancer pathogenesis

State-machine replication for planet-scale systems

Online applications now routinely replicate their data at multiple sites around the world. In this paper we present Atlas, the first state-machine replication protocol tailored for such planet-scale systems. Atlas does not rely on a distinguished leader, so clients enjoy the same quality of service independently of their geographical locations. Furthermore, client-perceived latency improves as we add sites closer to clients. To achieve this, Atlas minimizes the size of its quorums using an observation that concurrent data center failures are rare. It also processes a high percentage of accesses in a single round trip, even when these conflict. We experimentally demonstrate that Atlas consistently outperforms state-of-The-Art protocols in planet-scale scenarios. In particular, Atlas is up to two times faster than Flexible Paxos with identical failure assumptions, and more than doubles the performance of Egalitarian Paxos in the YCSB benchmark.H2020 - Horizon 2020 Framework Programme(825184

SVIP Induces Localization of p97/VCP to the Plasma and Lysosomal Membranes and Regulates Autophagy

The small p97/VCP-interacting protein (SVIP) functions as an inhibitor of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. Here we show that overexpression of SVIP in HeLa cells leads to localization of p97/VCP at the plasma membrane, intracellular foci and juxtanuclear vacuoles. The p97/VCP-positive vacuolar structures colocalized or associated with LC3 and lamp1, suggesting that SVIP may regulate autophagy. In support of this possibility, knockdown of SVIP diminished, whereas overexpression of SVIP enhanced LC3 lipidation. Surprisingly, knockdown of SVIP reduced the levels of p62 protein at least partially through downregulation of its mRNA, which was accompanied by a decrease in starvation-induced formation of p62 bodies. Overexpression of SVIP, on the other hand, increased the levels of p62 protein and enhanced starvation-activated autophagy as well as promoted sequestration of polyubiquitinated proteins and p62 in autophagosomes. These results suggest that SVIP plays a regulatory role in p97 subcellular localization and is a novel regulator of autophagy