Merkel cell polyomavirus and its etiological relationship with skin tumors

Abstract Viruses have been frequently identified in several human neoplasms, but the etiological role of these viruses in some tumors is still a matter of controversy. Polyomaviruses stand out among the main viruses with oncogenic capacity, specifically the Merkel cell polyomavirus (MCPyV). Recent revisions in the taxonomy of polyomaviruses have divided the Polyomaviridae family into six genera, including 117 species, with a total of 14 currently known human-infecting species. Although the oncogenicity of polyomaviruses has been widely reported in the literature since 1950, the first description of a polyomavirus as an etiological agent of a neoplasm in humans was made only in 2008 with the description of MCPyV, present in approximately 80% of cases of Merkel cell carcinoma (MCC), with the integration of its genome to that of the tumor cells and tumor-specific mutations, and it is considered the etiological agent of this neoplasm since then. MCPyV has also been detected in keratinocyte carcinomas, such as basal cell carcinoma and squamous cell carcinoma of the skin in individuals with and without immunosuppression. Data on the occurrence of oncogenic viruses potentially involved in oncogenesis, which cause persistence and tissue injury, related to the Merkel cell polyomavirus are still scarce, and the hypothesis that the Merkel cell polyomavirus may play a relevant role in the genesis of other cutaneous carcinomas in addition to MCC remains debatable. Therefore, the present study proposes to explore the current knowledge about the presence of MCPyV in keratinocyte carcinomas.

The role and action mechanism of signaling proteins in the occurrence and development of neuroblastoma / 国际药学研究杂志

Neuroblastoma(NB)is the most common extracranial solid tumor derived from the sympathetic ner- vous system in childhood. The location of NB is variable, the pathogenesis is complex and the clinical manifestations vary greatly. The prognosis is good in low or medium risk NB patients but bad in high risk NB patients. Recent studies have shown that the occurrence, growth, proliferation, migration and invasion of NB as well as the prognosis of NB pa- tients are associated with the abnormal expression of signaling proteins in NB, including the transcriptional regulators, kinases, and receptors, etc.. This article reviews the role and action mechanism of different signaling proteins in the oc- currence and development of NB.

Characterization of Cd(II)/Pb(II) transcriptional regulator Alcaligenes faecalis SF-S1-60

Aims@#Metal transcriptional regulators controlled the regulation of metal ion homeostasis in bacteria genera. Cd(II)/Pb(II) transcriptional regulator is one of the member of MerR family found in Alcaligenes faecalis SF-S1-60 (PbrT-AF). @*Methodology and results@#The PbrT-AF gene with 432 bp open reading frame was successfully isolated from genomic DNA of A. faecalis using polymerase chain reaction (PCR) analysis. This gene was phylogenetically grouped with A. alcaligenes species using PHYLIP version 3.69 by the neighbor-joining method with 1000 bootstrap replicates. Phylogeny analysis shows that these proteins have distinct amino acids compared to Cd(II)/Pb(II) regulators from different species. The structure of PbrT-AF shows similar conformation with other members of MerR family using MODELLERv9.17. We also demonstrated that the expression of Pbrt-AF in Escherichia coli BL21 were able to increase the bacteria tolerance towards Pb up to 1000 ppm. @*Conclusion, significance and impact of study@#This result suggests that PbrT-AF promotes cell adaptation and tolerance towards Pb toxicity.

Improvement of clavulanic acid production in Streptomyces clavuligerus F613-1 by using a claR-neo reporter strategy

Background: Streptomyces clavuligerus was the producer of clavulanic acid, claR, a pathway-specific transcriptional regulator in S. clavuligerus, positively regulates clavulanic acid biosynthesis. In this study, the promoter-less kanamycin resistance gene neo was fused with claR to obtain strain NEO from S. clavuligerus F613-1. The claR-neo fusion strain NEO was mutated using physical and chemical mutagens and then screened under high concentrations of kanamycin for high-yield producers of clavulanic acid. Results: The reporter gene neo was fused downstream of claR and used as an indicator for expression levels of claR in strain NEO. After three rounds of continuous treatment and screening, the high-yield clavulanic acid-producing strain M3-19 was obtained. In the shaking flask model, the clavulanic acid titer of M3-19 reached 4.33 g/L, which is an increase of 33% over the titer of 3.26 g/L for the starting strains S. clavuligerus F613-1 and NEO. Conclusions: Our results indicate that neo can be effectively used as a reporter for the expression of late-stage biosynthetic genes when screening for high-yield strains and that this approach has strong potential for improving Streptomyces strains of industrial value.

Prokaryotic expression of Rex transcription regulator in Streptococcus suis 2 and in vitro binding assay / 中国人兽共患病学报

We cloned and prokaryoticly expressed the gene encoding Redox regulator(Rex)of Streptococcus suis serotype 2 and analyzed biological information and in vitro binding activity.The encoding Rex gene of SS2-1 strain was amplified by PCR with the designed primers,and then cloned into prokaryotic expression plasmid pET28a.The recombinant plasmid pET28a-Rex was transformed into E.coli BL21.After induced expression by IPTG,the Rex protein was obtained.The binding activity of Rex protein and DNA was analyzed by gel mobility shift assay (EMSA) in vitro.Purification of recombinant protein Rex was successfully expressed.The presence of NAD+ did not have major effect on mobility shift,but addition of NADH almost abolished such a binding activity.By in vitro binding assay,Rex was found to regulate the expression of Prex in response to NADH/NAD+ equilibrium.

Development of transcriptional regulators of Streptococcus mutans in cariogenic virulence / 华西口腔医学杂志

Some transcriptional regulators contribute to the expression of Streptococcus mutans (S. mutans) cariogenic virulence factors. Although the target sequence transcriptional regulators anchored on the cell wall and the molecular mechanism of the regulation of S. mutans are yet to be clarified, certain global regulators potentially associated with the cariogenicity of S. mutans have been identified. This review is about these related transcriptional regulators, their function, and possible mechanisms.

The correlation between the central carbon metabolic flux distribution and the number of shared enzyme regulators in Saccharomyces cerevisiae

The central carbon metabolic system is the upstream energy source for microbial fermentation. In addition, it is a master switch for increasing the production of metabolites and an important part of the microbial metabolic network. Investigation into the relationship between genes, environmental factors, and metabolic networks is a main focus of systems biology, which significantly impacts research in biochemistry, metabolic engineering, and synthetic biology. To this end, the central carbon metabolic flux under a variety of growth conditions or using strains with various genetic modifications was previously measured in Saccharomyces cerevisiae using 13C tracer technology. However, the measured values were not integrated and investigated further. In this study, we collected and analyzed the metabolic flux rates of the central carbon metabolic system in S. cerevisiae measured in recent studies. We carried out preliminary analyses of flux values of each pathway, performed regression analyses on relationship between different fluxes, and extracted principal component factors of the flux variables. Based on the results, the general characteristics of pathway flux distribution were clustered and explored, and the effects of environmental and genetic factors on the flux distribution were analyzed. Furthermore, this study explored the relationship between similarity in the enzyme's transcriptional regulation and the correlations in the enzyme's reaction flux. Our results provide a foundation for further studies on the control of the central carbon metabolic flux and facilitate the search for targets in metabolic engineering research.

The Streptococcus mutans GlnR protein exhibits an increased affinity for the glnRA operon promoter when bound to GlnK

The control of nitrogen metabolism in pathogenic Gram-positive bacteria has been studied in a variety of species and is involved with the expression of virulence factors. To date, no data have been reported regarding nitrogen metabolism in the odontopathogenic species Streptococcus mutans. GlnR, which controls nitrogen assimilation in the related bacterial species, Bacillus subtilis, was assessed in S. mutans for its DNA and protein binding activity. Electrophoretic mobility shift assay of the S. mutans GlnR protein indicated that GlnR binds to promoter regions of the glnRA and amtB-glnK operons. Cross-linking and pull-down assays demonstrated that GlnR interacts with GlnK, a signal transduction protein that coordinates the regulation of nitrogen metabolism. Upon formation of this stable complex, GlnK enhances the affinity of GlnR for the glnRA operon promoter. These results support an involvement of GlnR in transcriptional regulation of nitrogen metabolism-related genes and indicate that GlnK relays information regarding ammonium availability to GlnR.