MACC1 Down-Regulation Inhibits Proliferation and Tumourigenicity of Nasopharyngeal Carcinoma Cells through Akt/β-Catenin Signaling Pathway

The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.     

Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes

Chronic inflammation is closely associated with metabolic disorders such as obesity and type 2 diabetes, however, the underlying mechanism is unclear. Toll-like receptors (TLRs) play a key role in innate immune response as well as inflammatory signals. Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes.     

Structure-activity relationship of 5'-substituted fluoro-neplanocin a analogues as potent inhibitors of S-adenosylhomocysteine hydrolase

Four 5'-substituted fluoro-neplanocin A analogues la-d were designed and synthesized, and the inhibitory activity against SAH was in the following order: NH2 > SH > F, N3, indicating a hydrogen bonding donor is essential for inhibitory activity.     

Are chlorella viruses a rich source of ion channel genes?

Plaque-forming dsDNA (>330 kb) viruses that infect certain unicellular, eukaryotic chlorella-like green algae contain approximately 375 protein-encoding genes. These proteins include a 94 amino acid K+ channel protein, called Kcv, as well as two putative ligand-gated ion channels. The viruses also encode other proteins that could be involved in the assembly and/or function of ion channels, including protein kinases and a phosphatase, polyamine biosynthetic enzymes and histamine decarboxylase.     

Grassland ecosystems in China: review of current knowledge and research advancement

Grasslands are the dominant landscape in China, accounting for 40% of the national land area. Research concerning China's grassland ecosystems can be chronologically summarized into four periods: (i) pre-1950s, preliminary research and survey of grassland vegetation and plant species by Russians, Japanese and Western Europeans, (ii) 1950-1975, exploration and survey of vegetation, soils and topography as part of natural resource inventory programmes by regional and national institutions mainly led by the Chinese Academy of Sciences, (iii) 1976-1995, establishment of field stations for long-term ecological monitoring and studies of ecosystem processes, (iv) 1996-present, comprehensive studies of community dynamics and ecosystem function integrating multi-scale and multidisciplinary approaches and experimental manipulations.Major findings of scientific significance in China's grassland ecosystem research include: (i) improved knowledge on succession and biogeochemistry of the semi-arid and temperate grassland ecosystems, (ii) elucidation of life-history strategies and diapause characteristics of the native grasshopper species as one of the key grassland pests, and (iii) development of effective management strategies for controlling rodent pests in grassland ecosystems. Opportunities exist for using the natural grasslands in northern China as a model system to test ecosystem theories that so far have proven a challenge to ecologists worldwide.     

The involvement of the Arabidopsis CRT1 ATPase family in disease resistance protein-mediated signaling

Resistance (R) gene-mediated immunity provides plants with rapid and strain-specific protection against pathogen infection. Our recent study using the genetically tractable Arabidopsis and turnip crinkle virus (TCV) pathosystem revealed a novel component, named CRT1 (compromised for recognition of the TCV CP), that is involved in general R gene-mediated signaling, including that mediated by HRT, an R gene against TCV. The Arabidopsis CRT1 gene family contains six additional members, of which two share high homology to CRT1 (75 and 81% a.a. identity); either CRT1 or its closest homolog restore the cell death phenotype suppressed by crt1. Analysis of single knock-out mutants for CRT1 and its closest homologs suggest that each may have unique and redundant functions. Here, we provide insight into the screening conditions that enabled identification of a mutant gene despite the presence of functionally redundant family members. We also discuss a potential mechanism that may regulate the interaction between CRT1 and R proteins.Key words: resistance gene, ATPase, suppressor screening, Arabidopsis, turnip crinkle virusPlant resistance (R) proteins activate defense signaling pathways following detection of a specific pathogen-encoded effector, or perception that a host factor has been altered by a pathogen effector. The vast majority of R proteins contain nucleotide binding site (NBS) and leucine-rich repeat (LRR) domains. These R proteins can be further divided into two subgroups, TIR-NBS-LRR and CC-NBS-LRR, depending on whether the N terminus consists of a Toll-interleukin 1 receptor (TIR) or a coiled-coiled (CC) domain, respectively.¹ Subsequent to pathogen perception, the signal(s) generated by various R proteins likely converge into a limited set of pathways, with CC-NBS-LRR proteins usually utilizing NDR1 and TIR-NBS-LRR proteins generally requiring EDS1.² However, the molecular mechanism(s) through which R proteins recognize a pathogen(s) and initiate a defense signal(s) remains unclear.To gain insights into this elusive signaling process, several groups have performed genetic screens to isolate mutants whose R gene-mediated resistance responses are suppressed following either pathogen infection or expression of a transgene-encoded bacterial effector protein. Several proteins, including HSP90, SGT1 and RAR1, were shown to be required for resistance triggered by a variety of R proteins, suggesting their universal function in R protein-mediated resistance.^3–7 However, while some R protein-mediated signaling pathways required both RAR1 and SGT1, others needed only one or neither protein. Thus, the requirement for RAR1 and SGT1 appears to be specific to each pathway.⁸ Further studies revealed that SGT1, RAR1 and HSP90 regulate the stability/accumulation of various R proteins,^8–11 raising the possibility that they serve as (co)chaperones for assembling an active R protein complex.The Arabidopsis R protein HRT was previously shown to recognize the coat protein (CP) of turnip crinkle virus (TCV) and trigger necrotic lesion formation in the inoculated leaf, as well as local and systemic defense responses.¹² To identify components of the HRT-mediated signaling pathway, a line containing HRT and an inducible CP transgene was constructed and screened for suppressors of CP-induced cell death.¹³ One mutant, named crt1 (compromised for recognition of the TCV CP), was identified; it contains a mutation in a GHKL (Gyrase, Hsp90, histidine kinase, MutL) ATPase.¹³ Interestingly, HSP90 also belongs to this recently recognized ATPase superfamily, although sequence homology between HSP90 and CRT1 is limited to the ATPase domain.¹⁴ Either wt CRT1 or its closest homolog, CRT1-h1 (81% a.a. identity to CRT1; 13 suggesting that CRT1 and CRT1-h1 are functionally redundant.

Table 1

Amino-acid sequence identity between CRTI family members in Arabidopsis

Electron paramagnetic and electron nuclear double resonance of the hydrogen peroxide compound of cytochrome c peroxidase

We have collected electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) spectra from the hydrogen peroxide compound of yeast cytochrome c peroxidase, termed ES, employing EPR microwave frequencies of 9.6 and 11.6 GHz. We have measured and analyzed the temperature dependence of the spin-lattice relaxation rate (1/T1) of the paramagnetic center of ES over the temperature range 1.9 to 4 K. In addition, an upper bound to exchange coupling between the ferryl heme and EPR-visible centers of ES has been calculated and expressions for the dipolar interaction between a ferryl heme and a free radical have been derived. These results all confirm that the EPR signal of ES is not associated with an aromatic amino acid radical, and in particular not with a tryptophanyl radical. This conclusion has led us to consider an explanation of the EPR signal in terms of a nucleophilically stabilized methionyl radical.