Search

In this report, antibacterial peptides1-3 were prepared with a spiropyran fluorescence probe. The probe exhibits a change in fluorescence when isomerized from a colorless spiro-form (spiropyran, Sp) to a colored open-form (merocyanine, Mc) under different chemical environments, which can be used to study the mechanism of antimicrobial activity. Peptides 1-3 exhibit a marked decrease in antimicrobial activity with increasing alkyl chain length. This is likely due to the Sp-Mc isomers in different polar environments forming different aggregate sizes in TBS, as demonstrated by time-dependent dynamic light scattering (DLS). Moreover, peptides 1-3 exhibited low cytotoxicity and hemolytic activity. These probe-modified peptides may provide a novel approach to study the effect of structural changes on antibacterial activity, thus facilitating the design of new antimicrobial agents to combat bacterial infection. [ABSTRACT FROM AUTHOR]

The association between the rs6495309 polymorphism in CHRNA3 gene and lung cancer risk has been studied in Chinese by several number case-control control studies with small number of cases and controls, and these studies might be underpowered to reveal the true association. Thus we sought to investigate the association with the risk of lung cancer by performing a comprehensive meta-analysis on the polymorphism. Five case-control studies were extracted from 3 articles on the polymorphism involving 4608 lung cancer cases and 4617 controls. The results of meta-analysis showed that significant increased risk were found for the polymorphism with the risk of lung cancer in Chinese: OR51.47, 95%CI51.33-1.63, P <0.00001 for CC+TC vs. TT; OR=1.24, 95%CI=1.07-1.44,P =0.005 for CC vs. TT+TC; OR=1.62, 95%CI=1.32- 2.00, P < 0.00001 for CC vs. TT; OR = 1.42, 95%CI = 1.26-1.61, P < 0.00001 for CT vs. TT; OR 5 1.42, 95%CI51.26-1.61,P <0.00001. No significant publication bias was found for the five genetic models. Our findings demonstrated that CHRNA3 gene rs6495309 polymorphism might be a risk factor for the development of lung cancer in Chinese. [ABSTRACT FROM AUTHOR]

Microbial syntrophic metabolism has been well accepted as the heart of how methanogenic and other anaerobic microbial communities function. In this work, we applied a single-cell RT-qPCR approach to reveal gene-expression heterogeneity in a model syntrophic system of Desulfovibrio vulgaris and Methanosarcina barkeri, as compared with the D. vulgaris monoculture. Using the optimized primers and single-cell analytical protocol, we quantitatively determine gene-expression levels of 6 selected target genes in each of the 120 single cells of D. vulgaris isolated from its monoculture and dual-culture with M. barkeri. The results demonstrated very significant cell-to-cell gene-expression heterogeneity for the selected D. vulgaris genes in both the monoculture and the syntrophic dual-culture. Interestingly, no obvious increase in gene-expression heterogeneity for the selected genes was observed for the syntrophic dual-culture when compared with its monoculture, although the community structure and cell-cell interactions have become more complicated in the syntrophic dual-culture. In addition, the single-cell RT-qPCR analysis also provided further evidence that the gene cluster (DVU0148-DVU0150) may be involved syntrophic metabolism between D. vulgaris and M. barkeri. Finally, the study validated that single-cell RT-qPCR analysis could be a valuable tool in deciphering gene functions and metabolism in mixed-cultured microbial communities. [ABSTRACT FROM AUTHOR]

Selective inhibition of function-specific β-GlcNAcase has great potential in terms of drug design and biological research. The symmetrical bis-naphthalimide M-31850 was previously obtained by screening for specificity against human glycoconjugate-lytic β-GlcNAcase. Using protein-ligand co-crystallization and molecular docking, we designed an unsymmetrical dyad of naphthalimide and thiadiazole, Q2, that changes naphthalimide specificity from against a human glycoconjugate-lytic β-GlcNAcase to against insect and bacterial chitinolytic β-GlcNAcases. The crystallographic and in silico studies reveal that the naphthalimide ring can be utilized to bind different parts of these enzyme homologs, providing a new starting point to design specific inhibitors. Moreover, Q2-induced closure of the substrate binding pocket is the structural basis for its 13-fold increment in inhibitory potency. Q2 is the first non-carbohydrate inhibitor against chitinolytic β-GlcNAcases. This study provides a useful example of structure-based rationally designed inhibitors as potential pharmaceuticals or pesticides. [ABSTRACT FROM AUTHOR]