SH3 interactome conserves general function over specific form

Src homology 3 (SH3) domains bind peptides to mediate protein–protein interactions that assemble and regulate dynamic biological processes. We surveyed the repertoire of SH3 binding specificity using peptide phage display in a metazoan, the worm Caenorhabditis elegans, and discovered that it structurally mirrors that of the budding yeast Saccharomyces cerevisiae. We then mapped the worm SH3 interactome using stringent yeast two-hybrid and compared it with the equivalent map for yeast. We found that the worm SH3 interactome resembles the analogous yeast network because it is significantly enriched for proteins with roles in endocytosis. Nevertheless, orthologous SH3 domain-mediated interactions are highly rewired. Our results suggest a model of network evolution where general function of the SH3 domain network is conserved over its specific form

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

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. </jats:sec

MRI and clinical features of maple syrup urine disease: preliminary results in 10 cases

PURPOSE:We aimed to evaluate the magnetic resonance imaging (MRI) and clinical features of maple syrup urine disease (MSUD).METHODS:This retrospective study consisted of 10 MSUD patients confirmed by genetic testing. All patients underwent brain MRI. Phenotype, genotype, and areas of brain injury on MRI were retrospectively reviewed.RESULTS:Six patients (60%) had the classic form of MSUD with BCKDHB mutation, three patients (30%) had the intermittent form (two with BCKDHA mutations and one with DBT mutation), and one patient (10%) had the thiamine-responsive form with DBT mutation. On diffusion-weighted imaging, nine cases presented restricted diffusion in myelinated areas, and one intermittent case with DBT mutation was normal. The classic form of MSUD involved the basal ganglia in six cases; the cerebellum, mesencephalon, pons, and supratentorial area in five cases; and the thalamus in four cases, respectively. The intermittent form involved the cerebellum, pons, and supratentorial area in two cases. The thiamine-responsive form involved the basal ganglia and supratentorial area.CONCLUSION:Our preliminary results indicate that patients with MSUD presented more commonly in classic form with BCKDHB mutation and displayed extensive brain injury on MRI

Line identification of extreme ultraviolet spectra from aluminum ions in EAST Tokamak plasmas

Extreme ultraviolet (EUV) spectra emitted from aluminum in the 5-340 A wavelength range were observed in Experimental Advanced Superconducting Tokamak (EAST) discharges. Several spectral lines from aluminum ions with different degrees of ionization were successfully observed with sufficient spectral intensities and resolutions using three fast-time-response EUV spectrometers. The line identification uses three independent state-of-art computational codes for the atomic structure calculations, which provide the wavelengths and radiative transition probabilities rate coefficients. These programs are HULLAC (Hebrew University - Lawrence Livermore Atomic Code), AUTOSTRUCTURE, and FAC (Flexible Atomic Code). Using three different codes allows us to resolve some ambiguities in identifying certain spectral lines and assess the validity of the theoretical predictions