Venn-diaNet : venn diagram based network propagation analysis framework for comparing multiple biological experiments

Background The main research topic in this paper is how to compare multiple biological experiments using transcriptome data, where each experiment is measured and designed to compare control and treated samples. Comparison of multiple biological experiments is usually performed in terms of the number of DEGs in an arbitrary combination of biological experiments. This process is usually facilitated with Venn diagram but there are several issues when Venn diagram is used to compare and analyze multiple experiments in terms of DEGs. First, current Venn diagram tools do not provide systematic analysis to prioritize genes. Because that current tools generally do not fully focus to prioritize genes, genes that are located in the segments in the Venn diagram (especially, intersection) is usually difficult to rank. Second, elucidating the phenotypic difference only with the lists of DEGs and expression values is challenging when the experimental designs have the combination of treatments. Experiment designs that aim to find the synergistic effect of the combination of treatments are very difficult to find without an informative system. Results We introduce Venn-diaNet, a Venn diagram based analysis framework that uses network propagation upon protein-protein interaction network to prioritizes genes from experiments that have multiple DEG lists. We suggest that the two issues can be effectively handled by ranking or prioritizing genes with segments of a Venn diagram. The user can easily compare multiple DEG lists with gene rankings, which is easy to understand and also can be coupled with additional analysis for their purposes. Our system provides a web-based interface to select seed genes in any of areas in a Venn diagram and then perform network propagation analysis to measure the influence of the selected seed genes in terms of ranked list of DEGs. Conclusions We suggest that our system can logically guide to select seed genes without additional prior knowledge that makes us free from the seed selection of network propagation issues. We showed that Venn-diaNet can reproduce the research findings reported in the original papers that have experiments that compare two, three and eight experiments. Venn-diaNet is freely available at: http://biohealth.snu.ac.kr/software/venndianetThis publication has been funded by (i) Next-Generation Information Computing Development Program through the National Research Foundation of Korea (NRF) the Ministry of Science ICT (MSIT) (No.NRF-2017M3C4A7065887), (ii) The Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF), the Ministry of Science and ICT (MSIT) (No.NRF2014M3C9A3063541), and (iii) a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) the Ministry of Health & Welfare, Republic of Korea (Grant number: HI15C3224)

SREBP1c-CRY1 signalling represses hepatic glucose production by promoting FOXO1 degradation during refeeding

SREBP1c is a key lipogenic transcription factor activated by insulin in the postprandial state. Although SREBP1c appears to be involved in suppression of hepatic gluconeogenesis, the molecular mechanism is not thoroughly understood. Here we show that CRY1 is activated by insulin-induced SREBP1c and decreases hepatic gluconeogenesis through FOXO1 degradation, at least, at specific circadian time points. SREBP1c−/− and CRY1−/− mice show higher blood glucose than wild-type (WT) mice in pyruvate tolerance tests, accompanied with enhanced expression of PEPCK and G6Pase genes. CRY1 promotes degradation of nuclear FOXO1 by promoting its binding to the ubiquitin E3 ligase MDM2. Although SREBP1c fails to upregulate CRY1 expression in db/db mice, overexpression of CRY1 attenuates hyperglycaemia through reduction of hepatic FOXO1 protein and gluconeogenic gene expression. These data suggest that insulin-activated SREBP1c downregulates gluconeogenesis through CRY1-mediated FOXO1 degradation and that dysregulation of hepatic SREBP1c-CRY1 signalling may contribute to hyperglycaemia in diabetic animals

Development of HTS Current Leads for the ITER Project

The HTS current leads for the ITER project will be the largest ever operated, with unprecedented currents, up to 68 kA and voltages, up to 14 kV. According to the ITER agreement they will be provided in-kind by China. After an extensive development program at the Hefei Institute of Plasma Physics (ASIPP), the ITER current leads were designed and qualified. The following discusses the main highlights of this development, with particular emphasis on the description of the design of the different types of ITER current leads and their final qualification in dedicated cold tests in nominal conditions

The newly synthesized 2-(3-hydroxy-5-methoxyphenyl)-6,7-methylenedioxyquinolin-4-one triggers cell apoptosis through induction of oxidative stress and upregulation of the p38 MAPK signaling pathway in HL-60 human leukemia cells

The aim of the present study was to discover the signaling pathways associated with 2-(3-hydroxy-5-methoxy-phenyl)-6,7-methylenedioxyquinolin-4-one (YYK1)-induced apoptosis in HL-60 human leukemia cells. YYK1 induced cytotoxic effects, cell morphological changes, decreased the cell number and increased reactive oxygen species (ROS) production and loss of mitochondrial membrane potential (ΔΨm) in HL-60 cells. YYK1-induced apoptosis was confirmed by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Results from colorimetric assays and western blot analysis indicated that activities of caspase-7/-3, caspase-8 and caspase-9 were increased in YYK1-treated HL-60 cells. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas/CD95, FasL and FADD), intrinsic related proteins (cytochrome c, Apaf-1, AIF and Endo G), the ratio of Bax/Bcl-2 and phosphorylated p38 MAPK were increased in HL-60 cells after YYK1 treatment. Cell apoptosis was significantly reduced after pre-treatment with N-acetylcysteine (NAC; a ROS scavenger) or diphenyleneiodonium chloride (DPI; a NADPH oxidase inhibitor). Blockage of p38 MAPK signaling by SB202190 abolished YYK1-induced Fas/CD95 upregulation and apoptosis in HL-60 cells. We conclude that YYK1 induces both of extrinsic and intrinsic apoptotic pathways via ROS-mediated activation of p38 MAPK signaling in HL-60 human leukemia cells in vitro

Novel Quinazolinone MJ-29 Triggers Endoplasmic Reticulum Stress and Intrinsic Apoptosis in Murine Leukemia WEHI-3 Cells and Inhibits Leukemic Mice

The present study was to explore the biological responses of the newly compound, MJ-29 in murine myelomonocytic leukemia WEHI-3 cells in vitro and in vivo fates. We focused on the in vitro effects of MJ-29 on ER stress and mitochondria-dependent apoptotic death in WEHI-3 cells, and to hypothesize that MJ-29 might fully impair the orthotopic leukemic mice. Our results indicated that a concentration-dependent decrease of cell viability was shown in MJ-29-treated cells. DNA content was examined utilizing flow cytometry, whereas apoptotic populations were determined using annexin V/PI, DAPI staining and TUNEL assay. Increasing vital factors of mitochondrial dysfunction by MJ-29 were further investigated. Thus, MJ-29-provaked apoptosis of WEHI-3 cells is mediated through the intrinsic pathway. Importantly, intracellular Ca2+ release and ER stress-associated signaling also contributed to MJ-29-triggered cell apoptosis. We found that MJ-29 stimulated the protein levels of calpain 1, CHOP and p-eIF2α pathways in WEHI-3 cells. In in vivo experiments, intraperitoneal administration of MJ-29 significantly improved the total survival rate, enhanced body weight and attenuated enlarged spleen and liver tissues in leukemic mice. The infiltration of immature myeloblastic cells into splenic red pulp was reduced in MJ-29-treated leukemic mice. Moreover, MJ-29 increased the differentiations of T and B cells but decreased that of macrophages and monocytes. Additionally, MJ-29-stimulated immune responses might be involved in anti-leukemic activity in vivo. Based on these observations, MJ-29 suppresses WEHI-3 cells in vitro and in vivo, and it is proposed that this potent and selective agent could be a new chemotherapeutic candidate for anti-leukemia in the future

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3, reports on three research projects and a list of publications.California Institute of Technology/Jet Propulsion Laboratory Contract 959548National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Grant Contract 958461U.S. Navy - Office of Naval Research Grant N00014-92-J-1616U.S. Navy - Office of Naval Research Grant N00014-92-J-4098Digital Equipment Corporation AGMT DTD 11/16/93Joint Services Electronics Program Contract DAAL03-92-C-0001Joint Services Electronics Program Grant DAAH04-95-1-0038MIT Lincoln Laboratory P.O. No. BX-5424U.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019DEMACO Agreement 11/15/93Federal Aviation Administration Grant 94-G-007U.S. Army Cold Regions Research and Engineering Laboratory Contract DACA89-93-K-000

Mineralogy and elasticity of the oceanic upper mantle: Origin of the low‐velocity zone

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94924/1/jgrb14078.pd

Development of HTS Current Leads for the ITER Project

The HTS current leads for the ITER project will be the largest ever operated, with unprecedented currents, up to 68 kA and voltages, up to 14 kV. According to the ITER agreement they will be provided in-kind by China. After an extensive development program at the Hefei Institute of Plasma Physics (ASIPP), the ITER current leads were designed and qualified. The following discusses the main highlights of this development, with particular emphasis on the description of the design of the different types of ITER current leads and their final qualification in dedicated cold tests in nominal conditions