[Show abstract][Hide abstract] ABSTRACT: Mutations in SMARCAL1 cause Schimke Immuno-Osseous Dysplasia (SIOD), an autosomal recessive multisystem developmental disease characterized by growth retardation, T-cell deficiency, bone marrow failure, anemia and renal failure. SMARCAL1 encodes an ATP-driven annealing helicase. However, the biological function of SMARCAL1 and the molecular basis of SIOD remain largely unclear. In this work, we cloned the zebrafish homologue of the human SMARCAL1 gene and found that smarcal1 regulated cell cycle progression. Morpholino knockdown of smarcal1 in zebrafish recapitulated developmental abnormalities in SIOD patients, including growth retardation, craniofacial abnormality, and haematopoietic and vascular defects. Lack of smarcal1 caused G0/G1 cell cycle arrest and induced cell apoptosis. Furthermore, using Electrophoretic Mobility Shift Assay and reporter assay, we found that SMARCAL1 was transcriptionally inhibited by E2F6, an important cell cycle regulator. Over-expression of E2F6 in zebrafish embryos reduced the expression of smarcal1 mRNA and induced developmental defects similar to those in smarcal1 morphants. These results suggest that SIOD may be caused by defects in cell cycle regulation. Our study provides a model of SIOD and reveals its cellular and molecular bases.
[Show abstract][Hide abstract] ABSTRACT: Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia-Pacific region. We assembled more than 43,700 S. japonicum expressed sequence tags and conducted comparative genomic analyses between S. japonicum and its human host. Some schistosome genes showed exceptionally high similarity in nucleotide sequence to their human homologues, of which five exhibited anomalous phylogeny and human codon usage bias. The most plausible explanation for their presence is horizontal gene transfer from host to parasite. Functional evidence suggests that S. japonicum might exploit host endocrine and immune signals for cell development and maturation via these host-like genes.
[Show abstract][Hide abstract] ABSTRACT: Conidia are considered to be the primary cause of infections by Trichophyton rubrum.
We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD). A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions.
Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum.
[Show abstract][Hide abstract] ABSTRACT: Schistosomes cause schistosomiasis disease which severely threatens human health. Little is known about the functions of EF-hand
domain containing schistosomes tegument proteins other than as antigens. More possible functions of these tegument proteins
were investigated with in silico analyses including protein-protein functional interaction, site-specific variation and glycosylation modification. The analysis
results suggested that schistosomes could actively modulate host immune responses for its own favor through functional interactions
with host proteins with immunomodulatory function, and passively regulate host immune responses through sequence variation
under positive selection and glycosylating the recognition sites of host immune attack. In addition, the analysis of the C-terminal
domain of these tegument proteins indicated that they could assist schistosomes in escaping host immune attacks through inhibiting
chemotaxis and non-complement fixing antibody (IgG4) responses. In summary, our results suggested that these tegument antigen
proteins could assist schistosomes in escaping and modulating host immune responses for self-protection during the process
of host-parasite interaction.
Chinese Science Bulletin 01/2007; 52(15):2100-2107. · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: At present, little is known about signal transduction mechanisms in schistosomes, which cause the disease of schistosomiasis. The mitogen-activated protein kinase (MAPK) signaling pathways, which are evolutionarily conserved from yeast to Homo sapiens, play key roles in multiple cellular processes. Here, we reconstructed the hypothetical MAPK signaling pathways in Schistosoma japonicum and compared the schistosome pathways with those of model eukaryote species. We identified 60 homologous components in the S. japonciumMAPK signaling pathways. Among these, 27 were predicted to be full-length sequences. Phylogenetic analysis of these proteins confirmed the evolutionary conservation of the MAPK signaling pathways. Remarkably, we identified S. japonicum homologues of GTP-binding protein beta and alpha-I subunits in the yeast mating pathway, which might be involved in the regulation of different life stages and female sexual maturation processes as well in schistosomes. In addition, several pathway member genes, including ERK, JNK, Sja-DSP, MRAS and RAS, were determined through quantitative PCR analysis to be expressed in a stage-specific manner, with ERK, JNK and their inhibitor Sja-DSP markedly upregulated in adult female schistosomes.
[Show abstract][Hide abstract] ABSTRACT: Dermatophytes are the primary causative agent of dermatophytoses, a disease that affects billions of individuals worldwide. Trichophyton rubrum is the most common of the superficial fungi. Although T. rubrum is a recognized pathogen for humans, little is known about how its transcriptional pattern is related to development of the fungus and establishment of disease. It is therefore necessary to identify genes whose expression is relevant to growth, metabolism and virulence of T. rubrum.
We generated 10 cDNA libraries covering nearly the entire growth phase and used them to isolate 11,085 unique expressed sequence tags (ESTs), including 3,816 contigs and 7,269 singletons. Comparisons with the GenBank non-redundant (NR) protein database revealed putative functions or matched homologs from other organisms for 7,764 (70%) of the ESTs. The remaining 3,321 (30%) of ESTs were only weakly similar or not similar to known sequences, suggesting that these ESTs represent novel genes.
The present data provide a comprehensive view of fungal physiological processes including metabolism, sexual and asexual growth cycles, signal transduction and pathogenic mechanisms.