Human PI15 blocking peptide

Molecular identification of protein molecules surrounding nanoparticles (NPs) may provide useful information that influences NP clearance, biodistribution, and toxicity. Hence, nanoproteomics provides specific information about the environment that NPs interact with and can therefore report on the changes in protein distribution that occurs during tumorigenesis. Therefore, we hypothesized that characterization and identification of protein molecules that interact with 20 nm AuNPs from cancer and noncancer cells may provide mechanistic insights into the biology of tumor growth and metastasis and identify new therapeutic targets in ovarian cancer. Hence, in the present study, we systematically examined the interaction of the protein molecules with 20 nm AuNPs from cancer and noncancerous cell lysates. Time-resolved proteomic profiles of NP-protein complexes demonstrated electrostatic interaction to be the governing factor in the initial time-points which are dominated by further stabilization interaction at longer time-points as determined by ultraviolet visible spectroscopy (UV-vis), dynamic light scattering (DLS), measurements, transmission electron microscopy (TEM), and tandem mass spectrometry (MS/MS). Reduction in size, charge, and number of bound proteins were observed as the protein-NP complex stabilized over time. Interestingly, proteins related to mRNA processing were overwhelmingly represented on the NP-protein complex at all times. More importantly, comparative proteomic analyses revealed enrichment of a number of cancer-specific proteins on the AuNP surface. Network analyses of these proteins highlighted important hub nodes that could potentially be targeted for maximal therapeutic advantage in the treatment of ovarian cancer. The importance of this methodology and the biological significance of the network proteins were validated by a functional study of three hubs that exhibited variable connectivity, namely, PPA1, SMNDC1, and PI15. Western blot analysis revealed overexpression of these proteins in ovarian cancer cells when compared to normal cells. Silencing of PPA1, SMNDC1, and PI15 by the siRNA approach significantly inhibited proliferation of ovarian cancer cells and the effect correlated with the connectivity pattern obtained from our network analyses.

Rice blast, caused by the fungus Magnaporthe oryzae, is the most devastating fungal disease of rice. Mowanggu, a local japonica cultivar in Yunnan Province, China, confers broad-spectrum resistance to this pathogen. To identify the resistance gene(s) in Mowanggu, we obtained an F-2 population and 280 F-8 recombinant inbred lines (RILs) from a cross between Mowanggu and CO39, a highly susceptible indica cultivar. A linkage map with 145 simple sequence repeat (SSR) and single feature polymorphism markers over 12 chromosomes was constructed using the 280 RILs. The resistance evaluation of the F-2 and F-8 populations in both the growth chamber and in a natural rice blast nursery showed that a single dominant gene controls blast resistance in Mowanggu. Moreover, nine quantitative trait loci, which were responsible for different partial resistance components, were mapped on chromosomes 2, 3, 6, 8, 9, and 12, making contributions to the phenotypic variation ranging from 3.03 to 6.18 %. The dominant resistance gene, designated Pi49, was mapped on chromosome 11 with genetic distance of 1.01 and 1.89 cM from SSR markers K10 and K134, respectively. The physical distance between K10 and K134 is about 181 kb in the Nipponbare genome. The Pi49 gene accounted for the major phenotypic variation of disease severity in the growth chamber (where plants were inoculated with single blast isolates) and also accounted for most of the phenotypic variance of disease severity, lesion number, diseased leaf area, and lesion size in the blast nursery. Our study not only identified tightly linked markers for introgression of Pi49 into elite rice cultivars via marker-aided selection but also provides a starting point for map-based cloning of the new resistance gene.