Cbl negatively regulates nlrp3 inflammasome activation through glut1-dependent glycolysis inhibition

Activation of the nod-like receptor 3 (NLRP3) inflammasomes is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Cbl plays a pivotal role in suppressing NLRP3 inflammasome activation by inhibiting Pyk2-mediated apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. Here, we showed that Cbl dampened NLRP3 inflammasome activation by inhibiting glycolysis, as demonstrated with Cbl knockout cells and treatment with the Cbl inhibitor hydrocotarnine. We revealed that the inhibition of Cbl promoted caspase-1 cleavage and interleukin (IL)-1β secretion through a glycolysis-dependent mechanism. Inhibiting Cbl increased cellular glucose uptake, glycolytic capacity, and mitochondrial oxidative phosphorylation capacity. Upon NLRP3 inflammasome activation, inhibiting Cbl increased glycolysis-dependent activation of mitochondrial respiration and increased the production of reactive oxygen species, which contributes to NLRP3 inflammasome activation and IL-1β secretion. Mechanistically, inhibiting Cbl increased surface expression of glucose transporter 1 (GLUT1) protein through post-transcriptional regulation, which increased cellular glucose uptake and consequently raised glycolytic capacity, and in turn enhanced NLRP3 inflammasome activation. Together, our findings provide new insights into the role of Cbl in NLRP3 inflammasome regulation through GLUT1 downregulation. We also show that a novel Cbl inhibitor, hydrocortanine, increased NLRP3 inflammasome activity via its effect on glycolysis

Optoelectronic properties of poly(fluorene) co‐polymer light‐emitting devices on a plastic substrate *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92131/1/1.2150379.pd

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Synthesis of N -Heterocycles via Transition-Metal-Catalyzed Tandem Addition/Cyclization of a Nitrile

The diverse methodologies to synthesize N -heterocycles through transition-metal-catalyzed cascade addition/cyclization of a nitrile are discussed in this review. Aspects relating to three types of transition-metal-catalyzed addition of a nitrile with subsequent cyclization include (1) a transition-metal acting as a Lewis acid to accelerate the nucleophilic addition of a nitrile, (2) the late-transition-metal-catalyzed 1,2-insertion of a nitrile, and (3) an in situ generated radical by transition-metal catalysis to implement a radical addition/cyclization tandem reaction. Applications for the synthesis of natural alkaloids, their derivatives, and some bioactive compounds are also summarized herein. 1 Introduction 2 Nucleophilic Addition of a Nitrile Accelerated by a Lewis Acid 2.1 Late-Transition-Metal Catalysis 2.2 Early-Transition-Metal Catalysis 2.3 Lanthanide-Metal Catalysis 2.4 Cyclization from N -Arylnitriliums 3 Transition-Metal-Catalyzed Insertion of a Nitrile 4 Transition-Metal-Catalyzed Radical Addition of a Nitrile 5 Conclusions.This work was supported by the Ministry of Science and Technology, Taiwan (R.O.C.) (MOST 108-2113-M-032-001)

Evolution of chloroplast J proteins.

Hsp70 chaperones are involved in multiple biological processes and are recruited to specific processes by designated J domain-containing cochaperones, or J proteins. To understand the evolution and functions of chloroplast Hsp70s and J proteins, we identified the Arabidopsis chloroplast J protein constituency using a combination of genomic and proteomic database searches and individual protein import assays. We show that Arabidopsis chloroplasts have at least 19 J proteins, the highest number of confirmed J proteins for any organelle. These 19 J proteins are classified into 11 clades, for which cyanobacteria and glaucophytes only have homologs for one clade, green algae have an additional three clades, and all the other 7 clades are specific to land plants. Each clade also possesses a clade-specific novel motif that is likely used to interact with different client proteins. Gene expression analyses indicate that most land plant-specific J proteins show highly variable expression in different tissues and are down regulated by low temperatures. These results show that duplication of chloroplast Hsp70 in land plants is accompanied by more than doubling of the number of its J protein cochaperones through adding new J proteins with novel motifs, not through duplications within existing families. These new J proteins likely recruit chloroplast Hsp70 to perform tissue specific functions related to biosynthesis rather than to stress resistance

Tic21 Is an Essential Translocon Component for Protein Translocation across the Chloroplast Inner Envelope Membrane

An Arabidopsis thaliana mutant defective in chloroplast protein import was isolated and the mutant locus, cia5, identified by map-based cloning. CIA5 is a 21-kD integral membrane protein in the chloroplast inner envelope membrane with four predicted transmembrane domains, similar to another potential chloroplast inner membrane protein-conducting channel, At Tic20, and the mitochondrial inner membrane counterparts Tim17, Tim22, and Tim23. cia5 null mutants were albino and accumulated unprocessed precursor proteins. cia5 mutant chloroplasts were normal in targeting and binding of precursors to the chloroplast surface but were defective in protein translocation across the inner envelope membrane. Expression levels of CIA5 were comparable to those of major translocon components, such as At Tic110 and At Toc75, except during germination, at which stage At Tic20 was expressed at its highest level. A double mutant of cia5 At tic20-I had the same phenotype as the At tic20-I single mutant, suggesting that CIA5 and At Tic20 function similarly in chloroplast biogenesis, with At Tic20 functioning earlier in development. We renamed CIA5 as Arabidopsis Tic21 (At Tic21) and propose that it functions as part of the inner membrane protein-conducting channel and may be more important for later stages of leaf development

Copper-Catalyzed Dual Cyclization for the Synthesis of Quinindolines

[[abstract]]A synthetic approach to quinindoline derivatives by the Cu-catalyzed dual cyclization has been developed. This catalytic reaction is a practical method for the systematic synthesis of quinindoline core structure, which contains a limited-step synthetic strategy and can tolerant a wide variety of substituents. In addition, the mechanistic study reveals that the reaction initiates from a Lewis acid accelerated addition of aniline to nitrile and provides the indole substructure, and then the subsequent Cu-catalyzed C-N coupling reaction furnishes the quinoline subunit and affords the quinindoline structure.[[notice]]補正完

Putative chloroplast J proteins of Arabidopsis analyzed in this work.

a<p>Nomenclature according to Finka et al. (2011).</p>b<p>Molecular mass in kD.</p>c<p>Predicted subcellular localization listed in Miernyk (2001)/Rajan and D’Silva (2009)/Prasad et al. (2010)/Finka et al. (2011); progame used by Miernyk (2001): Psort, TargetP, Predotar and Mitoprot; by Rajan and D’Silva (2009): Mitoprot, ChloroP, SUBA, TargetP and Wolf psort; by Prasad et al. (2010): SUBA, iPSORT, MitoPred, Mitoprot II, MultiLoc, PeroxP, Predotar, SubLoc, TargetP and Wolf psort; by Finka et al. (2011): the Uniport database; c, cytosol; m, mitochondria; p, plastid; n, nucleus; s, secretory pathway; –, the gene is not yet annotated as a J protein in the publication.</p>d<p>PPDB database (<a href="http://ppdb.tc.cornell.edu/" target="_blank">http://ppdb.tc.cornell.edu/</a>)/plport database (<a href="http://www.plprot.ethz.ch/" target="_blank">http://www.plprot.ethz.ch/</a>)/AT_CHLORO database (<a href="http://www.grenoble.prabi.fr/at_chloro/" target="_blank">http://www.grenoble.prabi.fr/at_chloro/</a>).</p>e<p>Results from this work (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070384#pone-0070384-g001" target="_blank">Figure 1</a>).</p>f<p>Nomenclature according to Rajan and D’Silva (2009).</p>g<p>Nomenclature according to Miernyk (2001); commonly used AtJx naming system is also shown in parentheses.</p>h<p>TPR15 and TPR16 from Pradad et al. (2010); CRRJ from Yamamoto et al. (2011); NdhT from Ifuku et al. (2011).</p>i<p>PCJ1 from Schlicher and Soll (1997); CDJ1 from Willmund et al. (2008); CDJ2 from Liu et al. (2005); CDJ3 to CDJ5 from Dorn et al. (2010); CJD6 from GenBank (Accession number: EDO96593).</p>j<p>According to the incorrect old annotation (see text).</p>k<p>Newly named J protein in this study, suggested to be localized in plastids by TAIR.</p