Overcoming Suppressive Tumor Microenvironment by Vaccines in Solid Tumor.

Conventional vaccines are widely used to boost human natural ability to defend against foreign invaders, such as bacteria and viruses. Recently, therapeutic cancer vaccines attracted the most attention for anti-cancer therapy. According to the main components, it can be divided into five types: cell, DNA, RNA, peptide, and virus-based vaccines. They mainly perform through two rationales: (1) it trains the host immune system to protect itself and effectively eradicate cancer cells; (2) these vaccines expose the immune system to molecules associated with cancer that enable the immune system to recognize and destroy cancer cells. In this review, we thoroughly summarized the potential strategies and technologies for developing cancer vaccines, which may provide critical achievements for overcoming the suppressive tumor microenvironment through vaccines in solid tumors.

[Evaluation of ecosystem cultural services of urban protected areas based on public participation GIS (PPGIS): A case study of Gongqing Forest Park in Shanghai, China]. / 基于参与式制图的城市保护地生态系统文化服务价值评价­­ä»¥ä¸Šæµ·å ±é’æ£®æž—å ¬å›­ä¸ºä¾‹.

Quantitative evaluation of ecosystem service value and its spatial mapping is an effective way to determine priority conservation areas of cultural ecosystem services (CES). We used a combination of questionnaires and structured interviews with public participatory GIS (PPGIS) in Gongqing Forest Park in Shanghai to connect non-monetary CES values with spatially explicit information. This method applied spatial indicators of abundance, diversity and rarity to quantitatively assess the value of CES and their spatial distribution, and identified priority CES areas. The results showed the value of CES varied among landscape types. Relatively open grassland, riverside, and shrub areas were associated with high aesthetic value. Riverside areas were associated with the CES category concerned with inspiration and supporting social relationships. High diversity values mainly distributed in riverside areas, while forest and grassland areas were associated with high rarity values. The areas with the highest values for the abundance, diversity, and rarity indices were overlaid with eight gradient thresholds, which indicated that defining the 25% of ecological areas with the highest overall rating as CES priority areas was an effective threshold for CES identification and management. The methodology in this study leveraged PPGIS to spatially refe-rence, quantify, and user perception to establish relationships between landscape attributes, space, and experience. These results could provide an important basis for identifying, planning for, and managing priority conservation areas in urban protected areas.

Food restriction alters villi morphology in obese rats: gut mechanism for weight regain?

Weight regain after a long-term weight-loss program is a greater problem in obesity treatment than is weight reduction. Hence, the gut may elevate the absorption rate and nutrient transportation remarkably during chronic food restriction. The extension of gut absorption may be one possible reason for weight regain. But there is little information about the mechanisms that regulate intestinal absorption during food restriction. In this study, we show that the surface absorptive areas of gut villi may be enlarged in the jejunum of rats maintained on a food restriction regimen compared with animals submitted to swimming or sedentary behavior. Our findings show that simply reducing the amount of food intake results in an increased appetite accompanied with obvious weight regain, and suggest that the resulting enlargement of villi surface areas plays a key role in the regain of weight reduction. These results bolster accumulating evidence that gut absorption may be a substantial mechanism for resistance of weight loss and enhancing the weight regain process.

Comparative analysis of ovine adenovirus 287 and human adenovirus 2 and 5 based on their codon usage.

Ovine adenovirus 287 (OAdV287) emerges as one of the most promising gene vectors resulting from its unique biological characteristics. To obtain a more detailed knowledge about the codon usage of OAdV287, a comparative study based on the codon usage of OAdV287 and the prototypes of human adenovirus serotypes 2 and 5 (HAdV2/5) was carried out. Some commonly used indices measuring the codon usage patterns, including effective number of codons, relative synonymous codon usage, and statistical methods, were adopted. Overall, OAdV287 had a more biased and conservative codon usage pattern than that of HAdV2/5. Both mutation pressure and natural selection played important roles in shaping the codon usage patterns of these three adenoviruses. All the preference codons of OAdV287 had A/U ends and were totally different from those of sheep and humans; however, the preference codons of HAdV2/5 mostly had G/C ends and were mostly coincident with those of sheep and humans. The codon usage analysis in this study supplies some clues for further comprehending the unique biological characteristics of OAdV287 as gene vectors.

Compare the differences of synonymous codon usage between the two species within cardiovirus.

BACKGROUND: Cardioviruses are positive-strand RNA viruses in the Picornaviridae family that can cause enteric infection in rodents and also been detected at lower frequencies in other mammals such as pigs and human beings. The Cardiovirus genus consists two distinct species: Encephalomyocarditis virus (EMCV) and Theilovirus (ThV). There are a lot differences between the two species. In this study, the differences of codon usage in EMCV and ThV were compared. RESULTS: The mean ENC values of EMCV and ThV are 54.86 and 51.08 respectively, higher than 40.And there are correlations between (C+G)12% and (C+G)3% for both EMCV and ThV (r = -0.736; r = 0.986, P < 0.01, repectively). For ThV the (C+G)12%, (C+G)3%, axis f'1 and axis f'2 had a significant correlations respectively but not for EMCV. According to the RSCU values, the EMCV species seemed to prefer U, G and C ending codon, while the ThV spice seemed to like using U and A ending codon. However, in both genus AGA for Arg, AUU for Ile, UCU for Ser, and GGA for Gly were chosen preferentially. Correspondence analysis detected one major trend in the first axis (f'1) which accounted for 22.89% of the total variation, and another major trend in the second axis (f'2) which accounted for 17.64% of the total variation. And the plots of the same serotype seemed at the same region at the coordinate. CONCLUSION: The overall extents of codon usage bias in both EMCV and ThV are low. The mutational pressure is the main factor that determines the codon usage bias, but the (C+G) content plays a more important role in codon usage bias for ThV than for EMCV. The synonymous codon usage pattern in both EMCV and ThV genes is gene function and geography specific, but not host specific. Maybe the serotype is one factor effected the codon bias for ThV, and location has no significant effect on the variations of synonymous codon usage in these virus genes.

Analysis of codon usage in type 1 and the new genotypes of duck hepatitis virus.

In this study, an abundant (A+U)% and low codon bias were revealed in duck hepatitis virus type 1 (DHV-1) and the new serotype strains isolated from Taiwan, South Korea and Mainland China (DHV-N). The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in these samples. By comparative analysis of the codon usage patterns of 40 ORFs of DHV, we found that all of DHV-1 strains grouped in genotype C; the DHV-N strains isolated in South Korea and China clustered into genotypes B; and the DHV-N strains isolated from Taiwan clustered into genotypes A. The findings revealed that more than one subtype of DHV-1 circulated in East Asia. Furthermore, the results of phylogenetic analyses based on RSCU values and Clustal W method indicated obvious phylogenetic congruities. This suggested that better genome consistency of DHV may exist in nature and phylogenetic analyses based on RSCU values maybe a good method in classifying genotypes of the virus. Our work might give some clues to the features and some evolutionary information of DHV.

Analysis of codon usage and nucleotide composition bias in polioviruses.

BACKGROUND: Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known. Analysis of codon usage can reveal much about the molecular evolution of the viruses. However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date. METHODS: The relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs) among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3. RESULTS: The result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40). The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes. Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses). No significant effect in gene length or vaccine derived polioviruses (DVPVs), wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes. The relative abundance of dinucleotide (CpG) in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1. CONCLUSION: The information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines.

Analysis of codon usage in Newcastle disease virus.

In this study, the relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents, and dinucleotide were used to investigate codon usage pattern of each protein-coding gene and genome among 31 Newcastle disease virus (NDV) isolates. The result shows that the overall extent of codon usage bias in NDV is low (mean ENC = 56.15 > 40). The good correlation between the (C + G)(12)% and (G + C)(3)% suggests that the mutational pressure, rather than natural selection, is the main factor that determines the codon usage bias and base component in NDV. It is observed that synonymous codon usage pattern in NDV genes is gene function and geography specific, but not host specific. By contrasting synonymous codon usage patterns of different NDV isolates, we suggest that more than one genotype of NDV circulates in waterfowl in USA; and gene length has no significant effect on the variations of synonymous codon usage in these virus genes. CpG under-represented is a characteristic for NDV to fit in its host. These results not only provide an insight into the variation of codon usage pattern among the genomes of NDV, but also may help in understanding the processes governing the evolution of NDV.

Analysis of codon usage in bovine viral diarrhea virus.

Bovine viral diarrhea virus (BVDV) is a widespread virus in beef and dairy herds. BVDV has been grouped into two genotypes, genotype 1 and genotype 2. In this study, the relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values and nucleotide content were investigated, and a comparative analysis of codon usage patterns for open reading frames (ORFs) of 22 BVDV genomes, including 14 of genotype 1 and 8 of genotype 2, was carried out. A high A+U content and low codon bias were found in BVDV genomes. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage between the two genotypes, and a geographic factor exists only in genotype-1 of BVDV. The RSCU data have a negative correlation with general average hydrophobicity (GRAVY), aromaticity and nucleotide content. Furthermore, the overall abundance of C and U has no effect on the synonymous codon usage patterns. In contrast, the A and G content showed a significant correlation with the nucleotide content at the third position. In addition, the codon usage patterns of BVDV are similar to those of 22 conserved genes of Bos taurus. Taken together, the genetic characteristics of BVDV possibly result from interactions between natural selection and mutation pressure.

Preparation and characterization of neutralizing monoclonal antibodies against FMDV serotype O with synthetic peptide antigen.

A short linear peptide was designed according to the antigenic site analysis of VP1 protein of foot-and-mouth virus (FMDV) serotype O and synthesized as the peptide immunogen. The peptide, which covers the region from amino acid 133 to 160 of VP1 of FMDV, was linked to the N-terminal cysteine and conjugated with the carrier protein of keyhole limpet hemocyanin (KLH). Normal 6- to 8-week-old BALB/c mice were immunized with the 20 µg dose conjugated peptide antigen four times. The splenocytes from the immunized mice were fused with SP2/0 mouse myeloma cells, and positive hybridomas were selected by indirect enzyme-linked immunosorbent assay (ELISA) and subcloned four times with limiting dilution. Five stable hybridoma cell lines, designated as 4F9, 1B11, 1E10, 1D4, and 4B8, were obtained. Isotyping of all obtained MAbs indicated that the MAbs of 4F9, 1E10, and 4B8 belonged to IgG2b; the 1B11 and 1D4 belonged to IgG1 and IgM, respectively. The micro-neutralization test indicated that the MAbs of 4F9, 4B8, and 1B11 were capable of neutralizing FMDV serotype O with neutralization indices ranging from 1.81 to 2.11. These results suggest that linear synthetic peptide conjugate can elicit antibodies against native FMDV virus and can be used as an alternative immunogen for production of MAbs with exact epitope.