S100A8 and S100A9 (also known as MRP8 and MRP14, respectively) are Ca2+ binding proteins belonging to the S100 family. They often exist in the form of heterodimer, while homodimer exists very little because of the stability. S100A8/A9 is constitutively expressed in neutrophils and monocytes as a Ca2+ sensor, participating in cytoskeleton rearrangement and arachidonic acid metabolism. During inflammation, S100A8/A9 is released actively and exerts a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion. S100A8/A9 serves as a candidate biomarker for diagnosis and follow-up as well as a predictive indicator of therapeutic responses to inflammation-associated diseases. As blockade of S100A8/A9 activity using small-molecule inhibitors or antibodies improves pathological conditions in murine models, the heterodimer has potential as a therapeutic target. In this review, we provide a comprehensive and detailed overview of the distribution and biological functions of S100A8/A9 and highlight its application as a diagnostic and therapeutic target in inflammation-associated diseases.
The Visual Object Tracking challenge VOT2018 is the sixth annual tracker benchmarking activity organized by the VOT initiative. Results of over eighty trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis and a "real-time" experiment simulating a situation where a tracker processes images as if provided by a continuously running sensor. A long-term tracking subchallenge has been introduced to the set of standard VOT sub-challenges. The new subchallenge focuses on long-term tracking properties, namely coping with target disappearance and reappearance. A new dataset has been compiled and a performance evaluation methodology that focuses on long-term tracking capabilities has been adopted. The VOT toolkit has been updated to support both standard short-term and the new longterm tracking subchallenges. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website 60 .
Summary Long non-coding (lnc)RNAs, once thought to merely represent noise from imprecise transcription initiation, have now emerged as major regulatory entities in all eukaryotes. In contrast to the rapidly expanding identification of individual lncRNAs, mechanistic characterization has lagged behind. Here we provide evidence that the GAL lncRNAs in the budding yeast S. cerevisiae promote transcriptional induction in trans by formation of lncRNA-DNA hybrids or R-loops. The evolutionarily conserved RNA helicase Dbp2 regulates formation of these R-loops as genomic deletion or nuclear depletion results in accumulation of these structures across the GAL cluster gene promoters and coding regions. Enhanced transcriptional induction is manifested by lncRNA-dependent displacement of the Cyc8 co-repressor and subsequent gene looping, suggesting that these lncRNAs promote induction by altering chromatin architecture. Moreover, the GAL lncRNAs confer a competitive fitness advantage to yeast cells as expression of these non-coding molecules correlates with faster adaptation in response to an environmental switch.
Herein, we demonstrate the design and fabrication of a well dispersed triplex Ag@SiO2@TiO2 core-shell photocatalyst, which shows enhanced visible light photocatalytic activity due to the plasmonic field of the inner Ag core. The SiO2 interlayer is coated on the Ag core by a sol-gel process to prevent oxidation of Ag and adjusting the plasmonic field. The Ag@SiO2@TiO2 nanoparticles with systematic variation of the SiO2 interlayer thickness of 2, 4, 8, 20 nm and TiO2 shell thickness of 2, 10, 20, 40 nm are prepared. The enhancement of the photocatalytic efficiency increases with decreased SiO2 thickness. Nanoparticles with a 2 nm SiO2 interlayer and a 20 nm TiO2 shell exhibited the best photocatalytic performance, ca. 31 times larger in photocatalytic activity and ca. 38 times larger in photocurrent density than P25 under visible light. A brief mechanism relating the plasmon resonance energy transfer from Ag to TiO2 and scattering is proposed. Such an intriguing photocatalyst may find significant applications in various fields.
A novel strategy is provided to construct alkali-stable poly(phenylene oxide) based anion exchange membranes to alleviate cation-induced degradation.
The association between chronic inflammation and cancer has long been recognized. The inflammatory bowel disease ulcerative colitis frequently progresses to colon cancer; however, the underlying mechanism is still unclear. S100a9 has been emerged as an important pro-inflammatory mediator in acute and chronic inflammation, and the aberrant expression of S100a9 also contributes to tumorigenic processes such as cell proliferation, angiogenesis, metastasis, and immune evasion. We previously revealed that S100a8 and S100a9 are highly activated and play an important role in the process of colitis-associated carcinogenesis, which suggests an attractive therapeutic target for ulcerative colitis and related colon cancer. Here, we report that administration of a neutralizing anti-S100a9 antibody significantly ameliorated dextran sulfate sodium (DSS)-induced colitis and accompanied by diminished cellular infiltrate of innate immunity cells (macrophages, neutrophils, and dendritic cells) and production of pro-inflammatory cytokines (Tnfα, Il1β, Ifnγ, Il6, Il17a, Il23a, Il4, and Il12a). The protective effect of anti-S100a9 antibody treatment was also observed in azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) mouse model. The inflammatory response, tumor cell proliferation, and immune cells infiltration in the colon tissues were suppressed by anti-S100a9 antibody. Gene expression profiling showed that key pathways known to be involved in CAC development, such as Wnt signaling pathway, PI3K–Akt signaling pathway, cytokine–cytokine receptor interaction, and ECM–receptor interaction pathway, were suppressed after treatment with anti-S100a9 antibody in CAC mice. In view of the protective effect of neutralizing anti-S100a9 antibody against DSS-induced colitis and AOM/DSS-induced CAC in mouse model, this study suggests that anti-S100a9 antibody may provide a novel therapeutic approach to treat ulcerative colitis and may decrease the risk for developing CAC.
The GAL cluster-associated long non-coding RNAs (lncRNAs) promote rapid induction of GAL genes in budding yeast, thereby promoting a faster switch in transcriptional programs when needed.
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