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Construction of bridged and fused bicyclic skeletons via intramolecular addition of nucleophiles to (.eta.4-diene)Fe(CO)3 iron complexes bearing functionalized side chains
No full text[[abstract]]Reaction of lithium diisopropylamide (LDA) with (η^4-l ,3-cyclohexadiene)Fe(C0)3 complexes bearing functionalized side chains at C-5, under an atmosphere of carbon monoxide, gives bridged bicyclo[3.2.l]octene and bicyclo[3.3. llnonene systems after electrophilic quenching, whereas larger rings cannot be obtained in this series. Under the same reaction conditions, intramolecular cyclization of acyclic (η^4-l ,3-butadiene)Fe(CO)3 complexes with functionalized side chains at the terminal position of the diene ligands furnishes fused bicyclo[3.3.0]octanone and bicyclo[4.3.0]nonanone derivatives after acid quenching. The iron-mediated intramolecular nucleophilic addition allows for the direct stereocontrol of four stereogenic centers of these fused bicyclic skeletons.[[fileno]]2050119010008[[department]]生科
A Novel Cell-Penetrating Peptide Derived from Human Eosinophil Cationic Protein
No full text[[abstract]]Cell-penetrating peptides (CPPs) are short peptides which can carry various types of molecules into cells; however, although most CPPs rapidly penetrate cells in vitro, their in vivo tissue-targeting specificities are low. Herein, we describe cell-binding, internalization, and targeting characteristics of a newly identified 10-residue CPP, denoted ECP^32-41, derived from the core heparin-binding motif of human eosinophil cationic protein (ECP). Besides traditional emphasis on positively charged residues, the presence of cysteine and tryptophan residues was demonstrated to be essential for internalization. ECP^32-41 entered Beas-2B and wild-type CHO-K1 cells, but not CHO cells lacking of cell-surface glycosaminoglycans (GAGs), indicating that binding of ECP^32-41 to cell-surface GAGs was required for internalization. When cells were cultured with GAGs or pre-treated with GAG-digesting enzymes, significant decreases in ECP^32-41 internalization were observed, suggesting that cell-surface GAGs, especially heparan sulfate proteoglycans were necessary for ECP^32-41 attachment and penetration. Furthermore, treatment with pharmacological agents identified two forms of energy-dependent endocytosis, lipid-raft endocytosis and macropinocytosis, as the major ECP^32-41 internalization routes. ECP^32-41 was demonstrated to transport various cargoes including fluorescent chemical, fluorescent protein, and peptidomimetic drug into cultured Beas-2B cells in vitro, and targeted broncho-epithelial and intestinal villi tissues in vivo. Hence this CPP has the potential to serve as a novel vehicle for intracellular delivery of biomolecules or medicines, especially for the treatment of pulmonary or gastrointestinal diseases.[[fileno]]2050119010019[[department]]生科
Helicobacter pylori neutrophil-activating protein: From molecular pathogenesis to clinical applications
No full text[[abstract]]Helicobacter pylori (H. pylori ) neutrophil-activating protein (HP-NAP) was originally identified as a virulence factor of H. pylori for its ability to activate neutrophils to generate respiratory burst by releasing reactive oxygen species. Later on, HP-NAP was also found to be involved in the protection of H. pylori from DNA damage, supporting the survival of H. pylori under oxidative stress. This protein is highly conserved and expressed by virtually all clinical isolates of H. pylori . The majority of patients infected with H. pylori produced antibodies specific for HP-NAP, suggesting its important role in immunity. In addition to acting as a pathogenic factor by activating the innate immunity through a wide range of human leukocytes, including neutrophils, monocytes, and mast cells, HP-NAP also mediates adaptive immunity through the induction of T helper cell type Ⅰ responses. The pro-inflammatory and immunomodulatory properties of HP-NAP not only make it play an important role in disease pathogenesis but also make it a potential candidate for clinical use. Even though there is no convincing evidence to link HP-NAP to a disease outcome, recent findings supporting the pathogenic role of HP-NAP will be reviewed. In WJG 20th Anniversary Special Issues (6): Helicobacter pylori TOPIC HIGHLIGHT addition, the potential clinical applications of HP-NAP in vaccine development, clinical diagnosis, and drug development will be discussed.[[fileno]]2050119010021[[department]]生科
Electrical stimulation promotes nerve growth factor-induced neurite outgrowth and signaling
Get PDF[[abstract]]Background
Neurotrophins are important regulators for neural development and regeneration. Nerve growth factor (NGF) therapy has been tested in various models of neural injury and degeneration. However, whether NGF can reach target tissues and maintain effective concentration for a certain period of time remains uncertain. To facilitate neural regeneration, we investigate the possibility of combining NGF and electrical stimulation (ES) in promoting neurite outgrowth, an essential process during neural regeneration.
Methods
PC12 cells were seeded on collagen and indium tin oxide (ITO)-coated area on the transparent conductive devices. Cells were then subjected to the combination of ES and NGF treatment. Neurite outgrowth was compared.
Results
Our findings suggest that ES of 100 mV/mm together with NGF provides optimal effect on neurite outgrowth of PC12 cells. ES increases NGF-induced neurite length but reduces neurite branching, indicative of its primary effect on neurite elongation instead of initiation. One mechanism that ES enhances neurite outgrowth is through increasing NGF-induced phosphorylation of ERK1/2 (pERK1/2) and expression of Egr1 gene. ES has previously been demonstrated to increase the activity of protein kinase C (PKC). Our result indicates that activating PKC further increases NGF-induced pERK1/2 and thus neurite outgrowth.
Conclusion
It is likely that ES promotes NGF-induced neurite outgrowth through modulating the activity of ERK1/2.
General significance
Findings from this study suggest that combining ES and NGF provides a promising strategy for promoting neurite outgrowth.[[fileno]]2050132010013[[department]]生命科學
國立清華大學簡訊第847期
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Toward Automated Validation of Computer Programs
No full text[[fileno]]2030201010077[[department]]資訊工程學
Automated Techniques for Static Software Validation
No full text[[fileno]]2032021030069[[department]]資訊工程學
A Complete Parallel Prolog System on Tree-Structured System
No full text[[fileno]]2032021030080[[department]]資訊工程學
Design of a Parallel Theorem Prover for First Order Logic
No full text[[fileno]]2032021030113[[department]]資訊工程學