OncomiRs: the discovery and progress of microRNAs in cancers

microRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about 22 nucleotides in length that function as posttranscriptional gene regulators. They are deemed to play a crucial role in the initiation and progression of human cancer, and those with a role in cancer are designated as oncogenic miRNAs (oncomiRs). For example, miR-15 and miR-16 induce apoptosis by targeting Bcl2. miRNAs from the miR-17-92 cluster modulate tumor formation and function as oncogenes by influencing the translation of E2F1 mRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10-dependent activation of PI 3-kinase signaling. miR-34a acts as a suppressor of neuroblastoma tumorigenesis by targeting the mRNA encoding E2F3 and reducing E2F3 protein levels. The chromosomal translocations associating with human tumors disrupt the repression of High mobility group A2 by let-7 miRNA. In addition, the oncomiRs expression profiling of human malignancies has also identified a number of diagnostic and prognostic cancer signatures. This article introduces the roles of oncomiRs in neoplasm development, progression, diagnosis, prognostication, as well as their mechanism of actions on target mRNAs and the functional outcomes of their actions on mRNAs. The paper ends with a brief perspective to the future of oncomiRs

Contribution of oncoproteomics to cancer biomarker discovery

Oncoproteomics is the study of proteins and their interactions in a cancer cell by proteomic technologies. Proteomic research first came to the fore with the introduction of two-dimensional gel electrophoresis. At the turn of the century, proteomics has been increasingly applied to cancer research with the wide-spread introduction of mass spectrometry and proteinchip. There is an intense interest in applying proteomics to foster an improved understanding of cancer pathogenesis, develop new tumor biomarkers for diagnosis, and early detection using proteomic portrait of samples. Oncoproteomics has the potential to revolutionize clinical practice, including cancer diagnosis and screening based on proteomic platforms as a complement to histopathology, individualized selection of therapeutic combinations that target the entire cancer-specific protein network, real-time assessment of therapeutic efficacy and toxicity, and rational modulation of therapy based on changes in the cancer protein network associated with prognosis and drug resistance. Besides, oncoproteomics is also applied to the discovery of new therapeutic targets and to the study of drug effects. In pace with the successful completion of the Human Genome Project, the wave of proteomics has raised the curtain on the postgenome era. The study of oncoproteomics provides mankind with a better understanding of neoplasia. In this article, the discovery of cancer biomarkers in recent years is reviewed. The challenges ahead and perspectives of oncoproteomics for biomarkers development are also addressed. With a wealth of information that can be applied to a broad spectrum of biomarker research projects, this review serves as a reference for biomarker researchers, scientists working in proteomics and bioinformatics, oncologists, pharmaceutical scientists, biochemists, biologists, and chemists

EFFECT ON 105KW NORTH WALL DUE TO ADDITION OF FILTRATION SYSTEM

CHPRC D&D Projects is adding three filtration system on two 1-ft concrete pads adjacent to the north side of existing KW Basin building. This analysis is prepared to provide qualitative assessment based on the review of design information available for 105KW basin substructure. In the proposed heating, ventilation and air conditioning (HVAC) filtration pad designs a 2 ft gap will be maintained between the pads and the north end of the existing 1 05KW -Basin building. Filtration Skids No.2 and No.3 share one pad. It is conservative to evaluate the No.2 and No.3 skid pad for the wall assessment. Figure 1 shows the plan layout of the 105KW basin site and the location of the pads for the filtration system or HVAC skids. Figure 2 shows the cross-section elevation view of the pad. The concrete pad Drawing H-1-91482 directs the replacement of the existing 8-inch concrete pad with two new 1-ft think pads. The existing 8-inch pad is separated from the 105KW basin superstructure by an expansion joint of only half an inch. The concrete pad Drawing H-1-91482 shows the gap between the new proposed pads and the north wall and any overflow pits and sumps is 2-ft. Following analysis demonstrates that the newly added filtration units and their pads do not exceed the structural capacity of existing wall. The calculation shows that the total bending moment on the north wall due to newly added filtration units and pads including seismic load is 82.636 ft-kip/ft and is within the capacity of wall which is 139.0ft-kip/ft

The N-terminal methionine of cellular proteins as a degradation signal

The Arg/N-end rule pathway targets for degradation proteins that bear specific unacetylated N-terminal residues while the Ac/N-end rule pathway targets proteins through their N-infinity-terminally acetylated (Nt-acetylated) residues. Here, we show that Ubr1, the ubiquitin ligase of the Arg/N-end rule pathway, recognizes unacetylated N-terminal methionine if it is followed by a hydrophobic residue. This capability of Ubr1 expands the range of substrates that can be targeted for degradation by the Arg/N-end rule pathway because virtually all nascent cellular proteins bear N-terminal methionine. We identified Msn4, Sry1, Arl3, and Pre5 as examples of normal or misfolded proteins that can be destroyed through the recognition of their unacetylated N-terminal methionine. Inasmuch as proteins bearing the Nt-acetylated N-terminal methionine residue are substrates of the Ac/N-end rule pathway, the resulting complementarity of the Arg/N-end rule and Ac/N-end rule pathways enables the elimination of protein substrates regardless of acetylation state of N-terminal methionine in these substrates.X117863Ysciescopu

Crystal Structure of the Rad3/XPD regulatory domain of Ssl1/p44

The Ssl1/p44 subunit is a core component of the yeast/mammalian general transcription factor TFIIH, which is involved in transcription and DNA repair. Ssl1/p44 binds to and stimulates the Rad3/XPD helicase activity of TFIIH. To understand the helicase stimulatory mechanism of Ssl1/p44, we determined the crystal structure of the N-terminal regulatory domain of Ssl1 from Saccharomyces cerevisiae. Ssl1 forms a von Willebrand factor A fold in which a central six-stranded beta-sheet is sandwiched between three alpha helices on both sides. Structural and biochemical analyses of Ssl1/p44 revealed that the beta 4-alpha 5 loop, which is frequently found at the interface between von Willebrand factor A family proteins and cellular counterparts, is critical for the stimulation of Rad3/XPD. Yeast genetics analyses showed that double mutation of Leu-239 and Ser-240 in the beta 4-alpha 5 loop of Ssl1 leads to lethality of a yeast strain, demonstrating the importance of the Rad3-Ssl1 interactions to cell viability. Here, we provide a structural model for the Rad3/XPD-Ssl1/p44 complex and insights into how the binding of Ssl1/p44 contributes to the helicase activity of Rad3/XPD and cell viability.X1165Ysciescopu

Effect of surfactant concentration variation on the thermoelectric properties of mesoporous ZnO

The electrical and thermal conductivities and the Seebeck coefficient of mesoporous ZnO thin films were investigated to determine the change of their thermoelectric properties by controlling surfactant concentration in the mesoporous ZnO films, because the thermoelectric properties of mesoporous ZnO films can be influenced by the porosity of the mesoporous structures, which is primarily determined by surfactant concentration in the films. Mesoporous ZnO thin films were successfully synthesized by using sol-gel and evaporation-induced self-assembly processes. Zinc acetate dihydrate and Brij-76 were used as the starting material and pore structure-forming template, respectively. The porosity of mesoporous ZnO thin films increased from 29% to 40% with increasing surfactant molar ratio. Porosity can be easily altered by controlling the molar ratio of surfactant/precursor. The electrical and thermal conductivity and Seebeck coefficients showed a close correlation with the porosity of the films, indicating that the thermoelectric properties of thin films can be changed by altering their porosity. Mesoporous ZnO thin films with the highest porosity had the best thermoelectric properties (the lowest thermal conductivity and the highest Seebeck coefficient) of the films examined. © 2013 Min-Hee Hong et al

High-throughput amplicon sequencing reveals distinct communities within a corroding concrete sewer system

This study investigated the variation in microbially induced concrete corrosion communities at different circumferential locations of a real sewer pipe and the effects of a wastewater flooding event on the community. Three distinct microbial community groups were found in different corrosion samples. The physico-chemical properties of the corrosion layers and the microbial communities were distinct for the cross-sectional positions within the pipe, ie ceiling, wall and tidal zones. The microbial communities detected from the same positions in the pipe were consistent over the length of the pipe, as well as being consistent between the replicate pipes. The dominating ceiling communities were members of the bacterial orders Rhodospirillales, Acidithiobacillales, Actinomycetales, Xanthomonadales and Acidobacteriales. The wall communities were composed of members of the Xanthomonadales, Hydrogenophilales, Chromatiales and Sphingobacteriales. The tidal zones were dominated by eight bacterial and one archaeal order, with the common physiological trait of anaerobic metabolism. Sewage flooding within the sewer system did not change the tidal and wall communities, although the corrosion communities in ceiling samples were notably different, becoming more similar to the wall and tidal samples. This suggests that sewage flooding has a significant impact on the corrosion community in sewers

Placental Growth Factor-1 and -2 Induce Hyperplasia and Invasiveness of Primary Rheumatoid Synoviocytes

Inflammation-mediated oncogenesis has been implicated in a variety of cancer types. Rheumatoid synovial tissues can be viewed as a tumor-like mass, consisting of hyperplastic fibroblast-like synoviocytes (FLSs). FLSs of rheumatoid arthritis (RA) patients have promigratory and invasive characteristics, which may be caused by chronic exposure to genotoxic stimuli, including hypoxia and growth factors. We tested whether a transformed phenotype of RA-FLSs is associated with placental growth factor (PlGF), a representative angiogenic growth factor induced by hypoxia. In this study, we identified PlGF-1 and PlGF-2 as the major PlGF isoforms in RA-FLSs. Global gene expression profiling revealed that cell proliferation, apoptosis, angiogenesis, and cell migration were mainly represented by differentially expressed genes in RA-FLSs transfected with small interfering RNA for PlGF. Indeed, PlGF-deficient RA-FLSs showed a decrease in cell proliferation, migration, and invasion, but an increase in apoptotic death in vitro. PlGF gene overexpression resulted in the opposite effects. Moreover, exogeneous PlGF-1 and PlGF-2 increased survival, migration, and invasiveness of RA-FLSs by binding their receptors, Flt-1 and neuropilin-1, and upregulating the expression of antiapoptotic molecules, pErk and Bcl2. Knockdown of PlGF transcripts reduced RA-FLS proliferation in a xenotransplantation model. Collectively, in addition to their role for neovascularization, PlGF-1 and -2 promote proliferation, survival, migration, and invasion of RA-FLSs in an autocrine and paracrine manner. These results demonstrated how primary cells of mesenchymal origin acquired an aggressive and transformed phenotype. PlGF and its receptors thus offer new targets for anti-FLS therapy.1177Ysciescopu