Human-derived IgG level as an indicator for EBV-associated lymphoma model in Hu-PBL/SCID chimeras

<p>Abstract</p> <p>Background</p> <p>Epstein-Barr virus (EBV) has a close association with various types of human lymphomas. Animal models are essential to elucidate the pathogenesis of human EBV-associated lymphomas. The aim of the present study is to evaluate the association between human IgG concentration and EBV-associated lymphoma development in huPBL/SCID mice.</p> <p>Methods</p> <p>Human peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were inoculated intraperitoneally into SCID mouse. Immunohistochemical staining was used to examine differentiated antigens of tumor cells. EBV infection of the induced tumors was detected by <it>in situ </it>hybridization. IgG concentrations in the serums of 12 SCID mice were measured by unidirectional immunodiffusion assay.</p> <p>Results</p> <p>21 out of 29 mice developed tumors in their body. Immunohistochemical staining showed that all induced tumors were LCA (leukocyte common antigen) positive, B-cell markers (CD20, CD79a) positive, and T-cell markers (both CD3 and CD45RO) negative. The tumors can be diagnosed as human B-cell lymphomas by these morphological and immunohistochemical features. In situ hybridization exhibited resultant tumor cells had EBV encoded small RNA-1 (EBER-1). Human-derived IgG could be found in the serum from SCID mice on the 15^thday following hu-PBL transplantation, and IgG levels increased with the tumor development in 6 hu-PBL/SCID chimeras.</p> <p>Conclusions</p> <p>Intraperitoneal transfer of hu-PBLs from EBV+ donors to SCID mice leads to high human IgG levels in mouse serum and B cell lymphomas. Our findings suggest that increasing levels of human-derived IgG in peripheral blood from hu-PBL/SCID mice could be used to monitor EBV-related human B-cell lymphoma development in experimental animals.</p

Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis.</p> <p>Methods</p> <p>To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453.</p> <p>Results</p> <p>20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them.</p> <p>Conclusion</p> <p>This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.</p

Description of three new species of the genus Cicurina Menge, 1871 from Guangdong, China (Araneae, Hahniidae)

Liao, Rongrong, Yin, Haiqiang, He, Ailan, Xu, Xiang (2022): Description of three new species of the genus Cicurina Menge, 1871 from Guangdong, China (Araneae, Hahniidae). Zootaxa 5188 (5): 477-488, DOI: https://doi.org/10.11646/zootaxa.5188.5.

Description of three new species of spider genus Leptonetela Kratochvíl, 1978 from caves of Hunan Province, China (Araneae, Leptonetidae)

He, Ailan, Liu, Jinxin, Xu, Xiang, Yin, Haiqiang, Peng, Xianjin (2019): Description of three new species of spider genus Leptonetela Kratochvíl, 1978 from caves of Hunan Province, China (Araneae, Leptonetidae). Zootaxa 4554 (2): 584-600, DOI: https://doi.org/10.11646/zootaxa.4554.2.1

The complete mitochondrial genome of Atypus karschi (Araneae, Atypidae) with phylogenetic consideration

The complete mitochondrial genome sequence of Atypus karschi has a circular genome of 14,149 bp, comprised of 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and a control region. The nucleotide composition is 35.82% of T, 35.13% of A, 17.19% of G, and 9.16% of C. Most genes are encoded on the heavy strand except seven tRNA genes (Leu, Phe, His, Pro, Leu, Ile, Gln), four protein-coding genes (nad5, nad4, nad4l, nad1), and 16S-rRNA on the light strand. Most protein-coding genes start with TTG, ATT or ATA initiation codon except cox1, cox1’s start codon cannot be determined, and three types of inferred termination codons are TAA, TAG, and an incomplete stop codon. There are four intergenic spacers and 25 gene overlaps. The phylogenetic analysis shows that A. karschi has closer genetic relationship with Cyriopagopus schmidti (von Wirth, 1991) and Phyxioschema suthepium (Raven & Schwendinger, 1898) with high bootstrap support

Screening and functional analysis of differentially expressed genes in EBV-transformed lymphoblasts

Abstract Background Epstain-Barr virus (EBV) can transform human B lymphocytes making them immortalized and inducing tumorigenic ability in vitro, but the molecular mechanisms remain unclear. The aim of the present study is to detect and analyze differentially expressed genes in two types of host cells, normal human lymphocytes and coupled EBV-transformed lymphoblasts in vitro using gene chips, and to screen the key regulatory genes of lymphocyte transformation induced by EB virus. Methods Fresh peripheral blood samples from seven healthy donors were collected. EBV was used to transform lymphocytes in vitro. Total RNA was extracted from 7 cases of the normal lymphocytes and transformed lymphoblasts respectively, marked with dihydroxyfluorane after reverse transcription, then hybridized with 4 × 44 K Agilent human whole genome microarray. LIMMA, String, Cytoscape and other softwares were used to screen and analyze differentially expressed genes. Real-time PCR was applied to verify the result of gene expression microarrays. Results There were 1745 differentially expressed genes that had been screened, including 917 up-regulated genes and 828 down-regulated genes. According to the results of Generank, String and Cytoscape analyses, 38 genes may be key controlled genes related to EBV-transformed lymphocytes, including 22 up-regulated genes(PLK1, E2F1, AURKB, CDK2, PLCG2, CD80, PIK3R3, CDC20, CDC6, AURKA, CENPA, BUB1B, NUP37, MAD2L1, BIRC5, CDC25A, CCNB1, RPA3, HJURP, KIF2C, CDK1, CDCA8) and 16 down-regulated genes(FYN, CD3D, CD4, CD3G, ZAP70, FOS, HCK, CD247, PRKCQ, ITK, LCP2, CXCL1, CD8A, ITGB5, VAV3, CXCR4), which primarily control biological processes such as cell cycle, mitosis, cytokine-cytokine pathway, immunity response and so on. Conclusions Human lymphocyte transformation induced by EB virus is a complicated process, involving multiple-genes and –pathways in virus-host interactions. Global gene expression profile analysis showed that EBV may transform human B lymphocytes by promoting cell cycle and mitosis, inhibiting cell apoptosis, hindering host immune function and secretion of cytokines.</p