The well-coordinated linkage between acidogenicity and aciduricity via insoluble glucans on the surface of Streptococcus mutans.

Streptococcus mutans is considered the principal cariogenic bacterium for dental caries. Despite the recognition of their importance for cariogenesis, the possible coordination among S. mutans' main virulence factors, including glucan production, acidogenicity and aciduricity, has been less well studied. In the present study, using S. mutans strains with surface-displayed pH-sensitive pHluorin, we revealed sucrose availability- and Gtf functionality-dependent proton accumulation on S. mutans surface. Consistent with this, using a pH-sensitive dye, we demonstrated that both in vivo cell-produced and in vitro enzymatically synthesized insoluble glucans displayed proton-concentrating ability. Global transcriptomics revealed proton accumulation triggers the up-regulation of genes encoding functions involved in acid tolerance response in a glucan-dependent manner. Our data suggested that this proton enrichment around S. mutans could pre-condition the bacterium for acid-stress. Consistent with this hypothesis, we found S. mutans strains defective in glucan production were more acid sensitive. Our study revealed for the first time that insoluble glucans is likely an essential factor linking acidogenicity with aciduricity. The coordination of these key virulence factors could provide new insights on how S. mutans may have become a major cariogenic pathogen

Larval Hemolymph Proteins and Physiological Role of Prophenoloxidases in Anopheles Gambiae

The African mosquito Anopheles gambiae is one of the major vectors for human malaria. Understanding its immune system may provide new means for disrupting the disease transmission. While the Drosophila melanogaster and Manduca sexta immune systems are well studied, most components ofthe mosquito system remain to be examined. Insect hemolymph contains important factors for humoral and cellular defense responses as well as immune signal transduction, including pattern recognition receptors, serine proteases, serpins, antimicrobial peptides. In the present study, we collected hemolymph samples from water- and E. coli-pricked A. gambiae larvae. The samples were separated on SDS-PAGE and subjected to LC-MS/MS analysis. The detected peptides were searched against A. gambiae proteins from VectorBase. We have identified a total of 1,756 proteins.Most of the abundant proteins contain putative signal peptides. Twenty-five most abundant proteins represent over half of the total protein amount, 109 proteins are up-regulated, 49 are down-regulated, and 235 are considered to be defense-related. After examining the protein distribution in the gel slices, we found that more abundant proteins tend to exist in more of the slices. We also obtained evidence for proteolysis, post-translational modification, serpin-protease complex formation, and high Mr immune complex formation based on the distribution data. In addition to the proteomic study, we generated monoclonal antibodies against prophenoloxidases PPO2 and PPO7 and found that PPO2 is presented in the adult hemolymph. Lastly, we tried to knockdown PPO gene expression in female adults by injecting double-stranded RNA and examined their survival following an E. coli challenge. No significant difference was observed between the test and control groups.Entomology & Plant Pathology (MS

Prognostic Outcomes and Risk Factors for Patients with Renal Cell Carcinoma and Venous Tumor Thrombus after Radical Nephrectomy and Thrombectomy: The Prognostic Significance of Venous Tumor Thrombus Level.

IntroductionTo evaluate the prognostic outcomes and risk factors for renal cell carcinoma (RCC) patients with venous tumor thrombus in China.Materials and methodsWe reviewed the clinical information of 169 patients who underwent radical nephrectomy and thrombectomy. Overall and cancer-specific survival rates were analyzed. Univariate and multivariate analyses were used to investigate the potential prognostic factors.ResultsThe median survival time was 63 months. The five-year overall survival and cancer-specific survival rate were 53.6% and 54.4% for all patients. For all patients, significant survival difference was only observed between early (below hepatic vein) and advanced (above hepatic vein) tumor thrombus. However, significant differences existed between both RV/IVC and early/advanced tumor thrombus groups in N0M0 patients. Multivariate analysis demonstrated that higher tumor thrombus level (p = 0.016, RR = 1.58), N (p = 0.013, RR = 2.60), and M (p < 0.001, RR = 4.14) stages and adrenal gland invasion (p = 0.001, RR = 4.91) were the most significant negative prognostic predictors.ConclusionsIn this study, we reported most cases of RCC patients with venous extension in China. We proved that patients with RCC and venous tumor thrombus may have relative promising long-term survival rate, especially those with early tumor thrombus

Mapping the tail fiber as the receptor binding protein responsible for differential host specificity of Pseudomonas aeruginosa bacteriophages PaP1 and JG004.

The first step in bacteriophage infection is recognition and binding to the host receptor, which is mediated by the phage receptor binding protein (RBP). Different RBPs can lead to differential host specificity. In many bacteriophages, such as Escherichia coli and Lactococcal phages, RBPs have been identified as the tail fiber or protruding baseplate proteins. However, the tail fiber-dependent host specificity in Pseudomonas aeruginosa phages has not been well studied. This study aimed to identify and investigate the binding specificity of the RBP of P. aeruginosa phages PaP1 and JG004. These two phages share high DNA sequence homology but exhibit different host specificities. A spontaneous mutant phage was isolated and exhibited broader host range compared with the parental phage JG004. Sequencing of its putative tail fiber and baseplate region indicated a single point mutation in ORF84 (a putative tail fiber gene), which resulted in the replacement of a positively charged lysine (K) by an uncharged asparagine (N). We further demonstrated that the replacement of the tail fiber gene (ORF69) of PaP1 with the corresponding gene from phage JG004 resulted in a recombinant phage that displayed altered host specificity. Our study revealed the tail fiber-dependent host specificity in P. aeruginosa phages and provided an effective tool for its alteration. These contributions may have potential value in phage therapy

Managing Denture Biofilm Related Diseases

The oral cavity harbors more than 700 microbial species and is one of the most complex ecosystems ever described. While the majority of these microbes are considered commensal, some of them are responsible for oral infectious diseases such as dental caries, periodontitis, halitosis and stomatitis. The advancement of modern science has greatly furthered our understanding of oral microbes and their roles in host health and disease. It has also led to the development of new tools for early detection, effective treatment, and prevention of oral microbial infections. This perspective provides a general understanding of oral microbiology, and its clinical relationship to oral infectious diseases, with a specific focus on denture-related microbial infections. The perspective also discusses the potential for developing innovative interventions for managing denture-related disease based on recent advances in our understanding of oral microbiology and denture-associated biofilms