Understanding and predicting synthetic lethal genetic interactions in Saccharomyces cerevisiae using domain genetic interactions

Genetic interactions have been widely used to define functional relationships between proteins and pathways. In this study, we demonstrated that yeast synthetic lethal genetic interactions can be explained by the genetic interactions between domains of those proteins. The domain genetic interactions rarely overlap with the domain physical interactions from iPfam database and provide a complementary view about domain relationships. Moreover, we found that domains in multidomain yeast proteins contribute to their genetic interactions differently. The domain genetic interactions help more precisely define the function related to the synthetic lethal genetic interactions, and then help understand how domains contribute to different functionalities of multidomain proteins. Using the probabilities of domain genetic interactions, we were able to predict novel yeast synthetic lethal genetic interactions. Furthermore, we had also identified novel compensatory pathways from the predicted synthetic lethal genetic interactions. Our study significantly improved the understanding of yeast mulitdomain proteins, the synthetic lethal genetic interactions and the functional relationships between proteins and pathways.Comment: 36 page, 4 figure

Wnt1-Cre-mediated deletion of AP-2α causes multiple neural crest-related defects

AbstractThe AP-2α transcription factor is required for multiple aspects of vertebrate development and mice lacking the AP-2α gene (tcfap2a) die at birth from severe defects affecting the head and trunk. Several of the defects associated with the tcfap2a-null mutation affect neural crest cell (NCC) derivatives including the craniofacial skeleton, cranial ganglia, and heart outflow tract. Consequently, there is considerable interest in the role of AP-2α in neural crest cell function in development and evolution. In addition, the expression of the AP-2α gene is utilized as a marker for premigratory and migratory neural crest cells in many vertebrate species. Here, we have specifically addressed how the presence of AP-2α in neural crest cells affects development by creating a conditional (floxed) version of tcfap2a which has subsequently been intercrossed with mice expressing Cre recombinase under the control of Wnt1 cis-regulatory sequences. Neural crest-specific disruption of tcfap2a results in frequent perinatal lethality associated with neural tube closure defects and cleft secondary palate. A small but significant fraction of mutant mice can survive into adulthood, but have retarded craniofacial growth, abnormal middle ear development, and defects in pigmentation. The phenotypes obtained confirm that AP-2α directs important aspects of neural crest cell function. At the same time, we did not observe several neurocristopathies affecting the head and heart that might be expected based on the phenotype of the AP-2α-null mouse. These results have important implications for the evolution and function of the AP-2 gene family in both the neural crest and the vertebrate embryo

Alterations of dendritic cell subsets in the peripheral circulation of patients with cervical carcinoma

Patients with cervical carcinoma (CC) are frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting cells. Using multicolor flow cytometry, the percentages of CD11c+ (DC1) and CD123+ (DC2) subsets, were determined in the peripheral blood of 37 patients with cervical carcinoma (CC), 54 patients with CIN, and 62 healthy individuals. A substantial reduction of circulating dendritic cells and accordingly immunodepression may be associated with increased IL-6 and TGF-β in serum. These findings could give expression to the immunosuppression of circulating dendritic cells in patients with CC and CIN, thus, may indicate novel aspects of cervical carcinoma immune evasion

Green synthesis and antibacterial/fungal studies of two new Schiff base derived from 4-(imidazol-1-yl)benzaldehyde

298-304This study synthesizes two new Schiff bases, (E)-1-(4-1H-imidazol-1-yl)phenyl)-N-(o-tolyl)methanimine and (E)-1-(4-(1Himidazol- 1-yl)phenyl)-N-(m-tolyl)methanimine through condensation reaction between 4-(imidazol-1-yl)benzaldehyde and 2-toluidine/o-toluidine, respectively. FT-IR, X-ray diffraction and 1H NMR spectroscopy have been carried out to characterize the structure of the products. Through antibacterial/ antifungal activity tests performed using 8 kinds of bacteria/fungus, it is found that the both of the two Schiff bases can suppress the growth of Staphylococcus, Bacillus subtilis and Salmonella, showing good potential as antibacterial drug

Unraveling the diversity of sedimentary sulfate-reducing prokaryotes (SRP) across Tibetan saline lakes using epicPCR

Sulfate reduction is an important biogeochemical process in the ecosphere; however, the major taxa of sulfate reducers have not been fully identified. Here, we used epicPCR (Emulsion, Paired Isolation, and Concatenation PCR) technology to identify the phylogeny of sulfate-reducing prokaryotes (SRP) in sediments from Tibetan Plateau saline lakes. A total of 12,519 OTUs and 883 SRP-OTUs were detected in ten lakes by sequencing of 16S rRNA gene PCR amplicons and epicPCR products of fused 16S rRNA plus dsrB gene, respectively, with Proteobacteria, Firmicutes, and Bacteroidetes being the dominant phyla in both datasets. The 120 highly abundant SRP-OTUs (>1% in at least one sample) were affiliated with 17 described phyla, only 7 of which are widely recognized as SRP phyla. The majority of OTUs from both the whole microbial communities and the SRPs were not detected in more than one specific lake, suggesting high levels of endemism. The -diversity of the entire microbial community and SRP sub-community showed significant positive correlations. The pH value and mean water temperature of the month prior to sampling were the environmental determinants for the whole microbial community, while the mean water temperature and total nitrogen were the major environmental drivers for the SRP sub-community. This study revealed there are still many undocumented SRP in Tibetan saline lakes, many of which could be endemic and adapted to specific environmental conditions.Peer reviewe

The expression and antigenicity of a truncated spike-nucleocapsid fusion protein of severe acute respiratory syndrome-associated coronavirus

<p>Abstract</p> <p>Background</p> <p>In the absence of effective drugs, controlling SARS relies on the rapid identification of cases and appropriate management of the close contacts, or effective vaccines for SARS. Therefore, developing specific and sensitive laboratory tests for SARS as well as effective vaccines are necessary for national authorities.</p> <p>Results</p> <p>Genes encoding truncated nucleocapsid (N) and spike (S) proteins of <it>SARSCoV </it>were cloned into the expression vector <it>pQE30 </it>and fusionally expressed in <it>Escherichia coli </it>M15. The fusion protein was analyzed for reactivity with SARS patients' sera and with anti-sera against the two human coronaviruses <it>HCoV </it>229E and <it>HCoV </it>OC43 by ELISA, IFA and immunoblot assays. Furthermore, to evaluate the antigen-specific humoral antibody and T-cell responses in mice, the fusion protein was injected into 6-week-old BALB/c mice and a neutralization test as well as a T-cell analysis was performed. To evaluate the antiviral efficacy of immunization, BALB/c mice were challenged intranasally with <it>SARSCoV </it>at day 33 post injection and viral loads were determined by fluorescent quantitative RT-PCR. Serological results showed that the diagnostic sensitivity and specificity of the truncated S-N fusion protein derived the SARS virus were > 99% (457/460) and 100.00% (650/650), respectively. Furthermore there was no cross-reactivity with other two human coronaviruses. High titers of antibodies to <it>SRASCoV </it>appeared in the immunized mice and the neutralization test showed that antibodies to the fusion protein could inhibit <it>SARSCoV</it>. The T cell proliferation showed that the fusion protein could induce an antigen-specific T-cell response. Fluorescent quantitative RT-PCR showed that BALB/c mice challenged intranasally with <it>SARSCoV </it>at day 33 post injection were completely protected from virus replication.</p> <p>Conclusion</p> <p>The truncated S-N fusion protein is a suitable immunodiagnostic antigen and vaccine candidate.</p