Arginyltransferase, Its Specificity, Putative Substrates, Bidirectional Promoter, and Splicing-derived Isoforms

Substrates of the N-end rule pathway include proteins with destabilizing N-terminal residues. Three of them, Asp, Glu, and (oxidized) Cys, function through their conjugation to Arg, one of destabilizing N-terminal residues that are recognized directly by the pathway's ubiquitin ligases. The conjugation of Arg is mediated by arginyltransferase, encoded by ATE1. Through its regulated degradation of specific proteins, the arginylation branch of the N-end rule pathway mediates, in particular, the cardiovascular development, the fidelity of chromosome segregation, and the control of signaling by nitric oxide. We show that mouse ATE1 specifies at least six mRNA isoforms, which are produced through alternative splicing, encode enzymatically active arginyltransferases, and are expressed at varying levels in mouse tissues. We also show that the ATE1 promoter is bidirectional, mediating the expression of both ATE1 and an oppositely oriented, previously uncharacterized gene. In addition, we identified GRP78 (glucose-regulated protein 78) and protein-disulfide isomerase as putative physiological substrates of arginyltransferase. Purified isoforms of arginyltransferase that contain the alternative first exons differentially arginylate these proteins in extract from ATE1-/- embryos, suggesting that specific isoforms may have distinct functions. Although the N-end rule pathway is apparently confined to the cytosol and the nucleus, and although GRP78 and protein-disulfide isomerase are located largely in the endoplasmic reticulum, recent evidence suggests that these proteins are also present in the cytosol and other compartments in vivo, where they may become N-end rule substrates

Make Caffeine Visible: a Fluorescent Caffeine "Traffic Light" Detector

Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy indicate that ??-stacking and hydrogen-bonding contribute to their interactions while dynamic light scattering and transmission electron microscopy experiments demonstrate the change of Caffeine Orange ambient environment induces its fluorescence emission. To utilize this probe in real life, we developed a non-toxic caffeine detection kit and tested it for caffeine quantification in various beverages. Naked-eye sensing of various caffeine concentrations was possible based on color changes upon irradiation with a laser pointer. Lastly, we performed the whole system on a microfluidic device to make caffeine detection quick, sensitive and automated.open5

Testing a priority-based queue model with Linux command histories

We study human dynamics by analyzing Linux history files. The goodness-of-fit test shows that most of the collected datasets belong to the universality class suggested in the literature by a variable-length queueing process based on priority. In order to check the validity of this model, we design two tests based on mutual information between time intervals and a mathematical relationship known as the arcsine law. Since the previously suggested queueing process fails to pass these tests, the result suggests that the modelling of human dynamics should properly consider the statistical dependency in the temporal dimension.Comment: 17 pages, 17 figure

High-efficiency in vitro and in vivo detection of Zn2+ by dye-assembled upconversion nanoparticles

10.1021/ja5115248Journal of the American Chemical Society13762336-234

Elm tree bark extract inhibits HepG2 hepatic cancer cell growth via pro-apoptotic activity

Control of inflammation is widely accepted as an important strategy for cancer chemoprevention. Anti-inflammatory effects of bark extracts of elm tree (BEE) have been amply reported. Therefore, BEE may be a good candidate cancer chemopreventive agent. Considering the high incidence of hepatic cancer and limited therapeutic approaches for treating this disease, it is important to develop liver cancer-specific chemopreventive agents. To evaluate the chemopreventive potential of BEE, we investigated the growth inhibition effect of BEE on the HepG2 human hepatocellular carcinoma cell line. We performed a cell counting kit-8 assay to determine cell viability, and 4,6-diamino-2-phenylindole staining and flow cytometry to measure apoptotic cell death. Finally, the expression levels of pro- and anti-apoptotic proteins were measured. BEE inhibited the growth of HepG2 cells and induced apoptosis in a dose-dependent manner. Pro-apoptotic activity was promoted via the mitochondrial pathway of apoptosis, as demonstrated by the activation of pro-apoptotic proteins Bax, caspase-9, caspase-3, and poly (ADP-ribose) polymerase as well as the down-regulation of the anti-apoptotic protein Bcl-2. These results suggest that BEE may have potential use in hepatic cancer chemoprevention by suppressing cancer cell growth via pro-apoptotic activity

Tailoring the surface of perovskite through in situ growth of Ru/RuO2 nanoparticles as robust symmetrical electrodes for reversible solid oxide cells

Although numerous perovskite oxides can enhance the electrochemical activity via exsolved metallic nanoparticles on the surface, most of them can only be applied as catalysts in a reducing atmosphere. These nanoparticles cause serious performance degradation in oxidizing conditions due to the formation of low-conductive metal oxides. This poses a big challenge to the design of highly active catalysts of electrochemical devices, especially for symmetrical solid oxide cells. Herein, based on the strategy of exsolved metallic nanoparticles in A-site deficient perovskite, a unique and simple method is demonstrated for the synthesis of Ru/RuO2 nanoparticles on the surface of perovskite oxide via in situ growth. The electrode material (La0.75Sr0.25)0.9Cr0.5Mn0.45Ru0.05O3−δ (LSCMR) is designed through careful choice of composition and the core idea is to make use of the exsolved nanoparticles concept applied for the first time at both hydrogen electrode and oxygen electrode for symmetrical solid oxide cells. Inspired by exsolved Ru and RuO2, the surface-decorated LSCMR exhibits significantly enhanced electrochemical activity for both H2 and O2, respectively, accompanied by high redox long-term stability. Moreover, simple, low-cost, and environmental-friendly synthesis of Ru/RuO2 nanoparticles on the substrate of typical perovskites is realized with this in situ growth approach

Immunoglobulin A Nephropathy Associated with Plasmodium falciparum Malaria

Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time. A 49-yr old male who had been to East Africa was diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria along with acute kidney injury developed during the course of the disease. Kidney biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial inflammation. Laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function. Our findings suggest that malaria infection might be associated with IgA nephropathy

Integration of Brassinosteroid Signal Transduction with the Transcription Network for Plant Growth Regulation in Arabidopsis

SummaryBrassinosteroids (BRs) regulate a wide range of developmental and physiological processes in plants through a receptor-kinase signaling pathway that controls the BZR transcription factors. Here, we use transcript profiling and chromatin-immunoprecipitation microarray (ChIP-chip) experiments to identify 953 BR-regulated BZR1 target (BRBT) genes. Functional studies of selected BRBTs further demonstrate roles in BR promotion of cell elongation. The BRBT genes reveal numerous molecular links between the BR-signaling pathway and downstream components involved in developmental and physiological processes. Furthermore, the results reveal extensive crosstalk between BR and other hormonal and light-signaling pathways at multiple levels. For example, BZR1 not only controls the expression of many signaling components of other hormonal and light pathways but also coregulates common target genes with light-signaling transcription factors. Our results provide a genomic map of steroid hormone actions in plants that reveals a regulatory network that integrates hormonal and light-signaling pathways for plant growth regulation