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Sample records for hgps cells exhibited

  1. Discordant gene expression signatures and related phenotypic differences in lamin A- and A/C-related Hutchinson-Gilford progeria syndrome (HGPS.

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    Martina Plasilova

    Full Text Available Hutchinson-Gilford progeria syndrome (HGPS is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N, we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic and lamin A and C-related (hereditary HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657 in sporadic and hereditary HGPS, with 83.3% (75/90 concordant and 16.7% (15/90 discordant transcriptional changes. Among the concordant ones we observed down-regulation of TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat and dermal appendages, and loss of expression in dermal fibroblasts and periadnexial cells from a LMNA(K542N/K542N patient further confirming its pivotal role in skin development. Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS. Finally, this study correlates reduced TWIST2 and OPG expression with increased osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis in hereditary HGPS.

  2. Unique Preservation of Neural Cells in Hutchinson- Gilford Progeria Syndrome Is Due to the Expression of the Neural-Specific miR-9 MicroRNA

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    Xavier Nissan

    2012-07-01

    Full Text Available One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS, who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage.

  3. Exhibition

    CERN Document Server

    Staff Association

    2017-01-01

    A Look of Hope Islam Mahmoud Sweity From 19 to 30 June 2017 CERN Meyrin, Main Building Islam Mahmoud Sweity Islam Mahmoud Sweity was born in 1997 at Beit Awwa, Palestine. She is currently following a course to get an Art diploma of Painting at the college of Fine Arts at An-Najah National University under the supervision of Esmat Al As'aad. Her portraits, landscapes and still life paintings are full of life and shining colours. Charged of emotional empathy they catch the attention of the viewer and are reminding us that life is beautiful and worth living in spite of all difficulties we have to go through. She participated in many exhibitions and has exposed her drawings in 2015 at CERN and in France in the framework of the exhibition "The Origin“, and in 2017 in the Former Yugoslav Republic of Macedonia, Palestina and Jordan. In this exhibition the oil paintings made in the past year will be presented. For more information : staff.association@cern.ch | T&eacu...

  4. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    Encounters Hanne Blitz From February 1st to 12th 2016 CERN Meyrin, Main Building What is our reaction to a first encounter with a tourist attraction? Contemporary Dutch painter Hanne Blitz captures visitors' responses to art and architecture, sweeping vistas and symbolic memorials. Encounters, a series of oil paintings curated specially for this CERN exhibition, depicts tourists visiting cultural highlights around the world. A thought-provoking journey not to be missed, and a tip of the hat to CERN's large Hadron Collider.

  5. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Sintropie Flavio Pellegrini From 13 to 24 March 2017 CERN Meyrin, Main Building Energia imprigionata - Flavio Pellegrini. The exhibition is composed by eleven wood artworks with the expression of movement as theme. The artworks are the result of harmonics math applied to sculpture. The powerful black colour is dominated by the light source, generating reflexes and modulations. The result is a continuous variation of perspective visions. The works generate, at a first approach, an emotion of mystery and incomprehension, only a deeper contemplation lets one discover entangling and mutative details, evidencing the elegance of the lines and letting the meaning emerge. For more information : staff.association@cern.ch | Tél: 022 766 37 38

  6. Abnormal nuclear morphology is independent of longevity in a zmpste24-deficient fish model of Hutchinson-Gilford progeria syndrome (HGPS).

    Science.gov (United States)

    Tonoyama, Yasuhiro; Shinya, Minori; Toyoda, Atsushi; Kitano, Takeshi; Oga, Atsunori; Nishimaki, Toshiyuki; Katsumura, Takafumi; Oota, Hiroki; Wan, Miles T; Yip, Bill W P; Helen, Mok O L; Chisada, Shinichi; Deguchi, Tomonori; Au, Doris W T; Naruse, Kiyoshi; Kamei, Yasuhiro; Taniguchi, Yoshihito

    2018-07-01

    Lamin is an intermediate protein underlying the nuclear envelope and it plays a key role in maintaining the integrity of the nucleus. A defect in the processing of its precursor by a metalloprotease, ZMPSTE24, results in the accumulation of farnesylated prelamin in the nucleus and causes various diseases, including Hutchinson-Gilford progeria syndrome (HGPS). However, the role of lamin processing is unclear in fish species. Here, we generated zmpste24-deficient medaka and evaluated their phenotype. Unlike humans and mice, homozygous mutants did not show growth defects or lifespan shortening, despite lamin precursor accumulation. Gonadosomatic indices, blood glucose levels, and regenerative capacity of fins were similar in 1-year-old mutants and their wild-type (WT) siblings. Histological examination showed that the muscles, subcutaneous fat tissues, and gonads were normal in the mutants at the age of 1 year. However, the mutants showed hypersensitivity to X-ray irradiation, although p53target genes, p21 and mdm2, were induced 6 h after irradiation. Immunostaining of primary cultured cells from caudal fins and visualization of nuclei using H2B-GFP fusion proteins revealed an abnormal nuclear shape in the mutants both in vitro and in vivo. The telomere lengths were significantly shorter in the mutants compared to WT. Taken together, these results suggest that zmpste24-deficient medaka phenocopied HGPS only partially and that abnormal nuclear morphology and lifespan shortening are two independent events in vertebrates. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

    Science.gov (United States)

    Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

    2017-09-01

    Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

  8. Hepatoma SK Hep-1 cells exhibit characteristics of oncogenic mesenchymal stem cells with highly metastatic capacity.

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    Jong Ryeol Eun

    Full Text Available SK Hep-1 cells (SK cells derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity.We found that classical mesenchymal stem cell (MSC markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC and bone marrow-derived MSC (BM-MSC do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC, and that their derivatives also function as CSCs.Our findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a novel mechanism of tumor initiation, development and

  9. Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors.

    Science.gov (United States)

    Cannon, C M; Pozniak, J; Scott, M C; Ito, D; Gorden, B H; Graef, A J; Modiano, J F

    2015-03-01

    We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cells. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human leukaemia and canine lymphoma cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not because of failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate that canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted. © 2013 Blackwell Publishing Ltd.

  10. Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation

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    Brahmbhatt, Meera; Gundala, Sushma R.; Asif, Ghazia; Shamsi, Shahab A; Aneja, Ritu

    2014-01-01

    Dietary phytochemicals offer non-toxic therapeutic management as well as chemopreventive intervention for slow-growing prostate cancers. However, the limited success of several single-agent clinical trials suggest a paradigm shift that the health benefits of fruits and vegetables are not ascribable due to individual phytochemicals rather may be ascribed to but to synergistic interactions among them. We recently reported growth-inhibiting and apoptosis-inducing properties of ginger extract (GE) in in vitro and in vivo prostate cancer models. Nevertheless, the nature of interactions among the constituent ginger biophenolics, viz. 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogoal, remains elusive. Here we show antiproliferative efficacy of the most-active GE biophenolics as single-agents and in binary combinations, and investigate the nature of their interactions using the Chou-Talalay combination-index (CI) method. Our data demonstrate that binary combinations of ginger phytochemicals synergistically inhibit proliferation of PC-3 cells with CI values ranging from 0.03-0.88. To appreciate synergy among phytochemicals present in GE, the natural abundance of ginger biophenolics was quantitated using LC-UV/MS. Interestingly, combining GE with its constituents (in particular, 6-gingerol) resulted in significant augmentation of GE’s antiproliferative activity. These data generate compelling grounds for further preclinical evaluation of GE alone and in combination with individual ginger biophenols for prostate cancer management. PMID:23441614

  11. Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

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    Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

  12. Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

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    Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Tabibzadeh, Siamak, E-mail: fbs@bioscience.org [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Dept of Oncologic Radiology, University of California, Irvine, CA (United States)

    2014-06-13

    Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.

  13. Juglans mandshurica Maxim extracts exhibit antitumor activity on HeLa cells in vitro.

    Science.gov (United States)

    Xin, Nian; Hasan, Murtaza; Li, Wei; Li, Yan

    2014-04-01

    The present study examined the potential application of Juglans mandshurica Maxim extracts (HT) for cancer therapy by assessing their anti‑proliferative activity, reduction of telomerase activity, induction of apoptosis and cell cycle arrest in S phase in HeLa cells. From the perspective of using HT as a herbal medicine, photomicroscopy and florescent microscopy techniques were utilized to characterize the effect of the extracts on telomerase activity and cell morphology. Flow cytometry was employed to study apoptosis and cell cycle of HeLa cells, and DNA laddering was performed. The results showed that HT inhibited cell proliferation and telomerase activity, induced apoptosis and caused S phase arrest of HeLa cells in vitro. HT inhibited HeLa cell proliferation significantly, and the highest inhibition rate was 83.7%. A trap‑silver staining assay showed that HT was capable of markedly decreasing telomerase activity of HeLa cells and this inhibition was enhanced in a time‑ and dose‑dependent manner. Results of a Hoechst 33258 staining assay showed that HeLa cells treated by HT induced cell death. Through DNA agarose gel electrophoresis, DNA ladders of HeLa cells treated with HT were observed, indicating apoptosis. In conclusion, the present study demonstrated that HT exhibited anti‑tumor effects comprising the inhibition of growth and telomerase activity as well as apoptosis and cell cycle arrest in HeLa cells.

  14. A cationic amphiphilic peptide ABP-CM4 exhibits selective cytotoxicity against leukemia cells.

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    Chen, Yu Qing; Min, Cui; Sang, Ming; Han, Yang Yang; Ma, Xiao; Xue, Xiao Qing; Zhang, Shuang Quan

    2010-08-01

    Some cationic antibacterial peptides exhibit a broad spectrum of cytotoxic activity against cancer cells, which could provide a new class of anticancer drugs. In the present study, the anticancer activity of ABP-CM4, an antibacterial peptide from Bombyx mori, against leukemic cell lines THP-1, K562 and U937 was evaluated, and the cytotoxicity compared with the effects on non-cancerous mammalian cells, including peripheral blood mononuclear cells (PBMCs), HEK-293 and erythrocytes. ABP-CM4 reduced the number of viable cells of the leukemic cell lines after exposure for 24h. The reduction was concentration dependent, and the IC50 values ranged from 14 to 18 microM. Conversely, ABP-CM4, even at 120 microM, exhibited no cytotoxicity toward HEK-293 or PBMCs, indicating that there was no significant effect on these two types of non-cancer cells. ABP-CM4 at a concentration of 200 microM had no hemolytic activity on mammalian erythrocytes. Together, these results suggested a selective cytotoxicity in leukemia cells. Flow cytometry demonstrated that the binding activity of ABP-CM4 to leukemia cells was much higher than that to HEK-293 or PBMCs, and there was almost no binding to erythrocytes. FITC-labeled ABP-CM4 molecules were examined under a confocal microscope and found to be concentrated at the surface of leukemia cells and changes of the cell membrane were determined by a cell permeability assay, which led us to the conclusion that ABP-CM4 could act at the cell membrane for its anticancer activity on leukemia cells. Collectively, our results indicated that ABP-CM4 has the potential for development as a novel antileukemic agent. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

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    Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

    2017-08-02

    The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

  16. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    International Nuclear Information System (INIS)

    López, Jacqueline; Poitevin, Adela; Mendoza-Martínez, Veverly; Pérez-Plasencia, Carlos; García-Carrancá, Alejandro

    2012-01-01

    Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 10 3 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 10 5 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, Si

  17. Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines.

    Science.gov (United States)

    Adalsteinsson, Viktor A; Tahirova, Narmin; Tallapragada, Naren; Yao, Xiaosai; Campion, Liam; Angelini, Alessandro; Douce, Thomas B; Huang, Cindy; Bowman, Brittany; Williamson, Christina A; Kwon, Douglas S; Wittrup, K Dane; Love, J Christopher

    2013-10-01

    Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine our understanding of the clonotypic heterogeneity within tumors, the complex interplay between genetic variations and non-genetic factors ultimately affects therapeutic outcome. Much has been learned through bulk studies of secreted factors in the tumor microenvironment, but the secretory behavior of single cells has been largely uncharacterized. Here we directly profiled the secretions of ELR+ CXC chemokines from thousands of single colorectal tumor and stromal cells, using an array of subnanoliter wells and a technique called microengraving to characterize both the rates of secretion of several factors at once and the numbers of cells secreting each chemokine. The ELR+ CXC chemokines are highly redundant, pro-angiogenic cytokines that signal via the CXCR1 and CXCR2 receptors, influencing tumor growth and progression. We find that human primary colorectal tumor and stromal cells exhibit polyfunctional heterogeneity in the combinations and magnitudes of secretions for these chemokines. In cell lines, we observe similar variance: phenotypes observed in bulk can be largely absent among the majority of single cells, and discordances exist between secretory states measured and gene expression for these chemokines among single cells. Together, these measures suggest secretory states among tumor cells are complex and can evolve dynamically. Most importantly, this study reveals new insight into the intratumoral phenotypic heterogeneity of human primary tumors.

  18. Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection.

    Science.gov (United States)

    Raué, Hans-Peter; Slifka, Mark K

    2007-05-01

    Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.

  19. New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells

    International Nuclear Information System (INIS)

    Cen, Ling; Hutzen, Brian; Ball, Sarah; DeAngelis, Stephanie; Chen, Chun-Liang; Fuchs, James R; Li, Chenglong; Li, Pui-Kai; Lin, Jiayuh

    2009-01-01

    Colorectal carcinoma is one of the major causes of morbidity and mortality in the Western World. Novel therapeutic approaches are needed for colorectal carcinoma. Curcumin, the active component and yellow pigment of turmeric, has been reported to have several anti-cancer activities including anti-proliferation, anti-invasion, and anti-angiogenesis. Clinical trials have suggested that curcumin may serve as a potential preventive or therapeutic agent for colorectal cancer. We compared the inhibitory effects of curcumin and novel structural analogues, GO-Y030, FLLL-11, and FLLL-12, in three independent human colorectal cancer cell lines, SW480, HT-29, and HCT116. MTT cell viability assay was used to examine the cell viability/proliferation and western blots were used to determine the level of PARP cleavages. Half-Maximal inhibitory concentrations (IC 50 ) were calculated using Sigma Plot 9.0 software. Curcumin inhibited cell viability in all three of the human colorectal cancer cell lines studied with IC 50 values ranging between 10.26 μM and 13.31 μM. GO-Y030, FLLL-11, and FLLL-12 were more potent than curcumin in the inhibition of cell viability in these three human colorectal cancer cell lines with IC 50 values ranging between 0.51 μM and 4.48 μM. In addition, FLLL-11 and FLLL-12 exhibit low toxicity to WI-38 normal human lung fibroblasts with an IC-50 value greater than 1,000 μM. GO-Y030, FLLL-11, and FLLL-12 are also more potent than curcumin in the induction of apoptosis, as evidenced by cleaved PARP and cleaved caspase-3 in all three human colorectal cancer cell lines studied. The results indicate that the three curcumin analogues studied exhibit more potent inhibitory activity than curcumin in human colorectal cancer cells. Thus, they may have translational potential as chemopreventive or therapeutic agents for colorectal carcinoma

  20. Fibroblasts Cultured on Nanowires Exhibit Low Motility, Impaired Cell Division, and DNA Damage

    DEFF Research Database (Denmark)

    Persson, H.; Købler, Carsten; Mølhave, Kristian

    2013-01-01

    beam milling and scanning electron microscopy, highly curved but intact nuclear membranes are observed, showing no direct contact between the nanowires and the DNA. The nanowires possibly induce cellular stress and high respiration rates, which trigger the formation of ROS, which in turn results in DNA......Nanowires are commonly used as tools for interfacing living cells, acting as biomolecule-delivery vectors or electrodes. It is generally assumed that the small size of the nanowires ensures a minimal cellular perturbation, yet the effects of nanowires on cell migration and proliferation remain...... largely unknown. Fibroblast behaviour on vertical nanowire arrays is investigated, and it is shown that cell motility and proliferation rate are reduced on nanowires. Fibroblasts cultured on long nanowires exhibit failed cell division, DNA damage, increased ROS content and respiration. Using focused ion...

  1. Human dental pulp cells exhibit bone cell-like responsiveness to fluid shear stress

    NARCIS (Netherlands)

    Kraft, D.C.E.; Bindslev, D.A.; Melsen, B.; Klein-Nulend, J.

    2011-01-01

    Background aims. For engineering bone tissue to restore, for example, maxillofacial defects, mechanosensitive cells are needed that are able to conduct bone cell-specific functions, such as bone remodelling. Mechanical loading affects local bone mass and architecture in vivo by initiating a cellular

  2. Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Long Zheng

    2017-12-01

    Full Text Available T cells expressing chimeric antigen receptors (CARs recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo. Human T cells from healthy donors were transduced to express a Lym-1 CAR, and assessed for epitope-driven function in culture and towards Raji xenografts in NOD-scidIL2Rgammanull (NSG mice. Lym-1 CAR T cells exhibited epitope-driven activation and lytic function against human B-cell lymphoma cell lines in culture and mediated complete regression of Raji/Luciferase-Green fluorescent protein (Raji/Luc-GFP in NSG mice with similar or better reactivity than CD19 CAR T cells. Lym-1 CAR transduction of T cells is a promising immunotherapy for patients with Lym-1 epitope positive B-cell malignancies.

  3. Induced pluripotent stem cells derived from rabbits exhibit some characteristics of naïve pluripotency

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    Pierre Osteil

    2013-05-01

    Not much is known about the molecular and functional features of pluripotent stem cells (PSCs in rabbits. To address this, we derived and characterized 2 types of rabbit PSCs from the same breed of New Zealand White rabbits: 4 lines of embryonic stem cells (rbESCs, and 3 lines of induced PSCs (rbiPSCs that were obtained by reprogramming adult skin fibroblasts. All cell lines required fibroblast growth factor 2 for their growth and proliferation. All rbESC lines showed molecular and functional properties typically associated with primed pluripotency. The cell cycle of rbESCs had a prolonged G1 phase and a DNA damage checkpoint before entry into the S phase, which are the 2 features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naïve pluripotency, including resistance to single-cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naïve pluripotency-specific genes, as defined in rodents. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass (ICM than rbESCs. Furthermore, rbiPSCs were capable of colonizing the ICM after aggregation with morulas. Therefore, we propose that rbiPSCs self-renew in an intermediate state between naïve and primed pluripotency, which represents a key step toward the generation of bona fide naïve PSC lines in rabbits.

  4. Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells

    Directory of Open Access Journals (Sweden)

    Li Qianqian

    2010-10-01

    Full Text Available Abstract Background Spontaneous immortalisation of cultured mammary epithelial cells (MECs is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs and the changes in gene expression associated with BME65Cs cells. Results BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line. In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a. Conclusions Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and

  5. Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance

    Science.gov (United States)

    Hsu, Alan Yi-Hui; Wu, Shang-Rung; Tsai, Jih-Jin; Chen, Po-Lin; Chen, Ya-Ping; Chen, Tsai-Yun; Lo, Yu-Chih; Ho, Tzu-Chuan; Lee, Meed; Chen, Min-Ting; Chiu, Yen-Chi; Perng, Guey Chuen

    2015-01-01

    The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a “sunny-side up egg” appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development. PMID:26657027

  6. Human dental pulp cells exhibit bone cell-like responsiveness to fluid shear stress.

    Science.gov (United States)

    Kraft, David Christian Evar; Bindslev, Dorth Arenholt; Melsen, Birte; Klein-Nulend, Jenneke

    2011-02-01

    For engineering bone tissue to restore, for example, maxillofacial defects, mechanosensitive cells are needed that are able to conduct bone cell-specific functions, such as bone remodelling. Mechanical loading affects local bone mass and architecture in vivo by initiating a cellular response via loading-induced flow of interstitial fluid. After surgical removal of ectopically impacted third molars, human dental pulp tissue is an easily accessible and interesting source of cells for mineralized tissue engineering. The aim of this study was to determine whether human dental pulp-derived cells (DPC) are responsive to mechanical loading by pulsating fluid flow (PFF) upon stimulation of mineralization in vitro. Human DPC were incubated with or without mineralization medium containing differentiation factors for 3 weeks. Cells were subjected to 1-h PFF (0.7 ± 0.3 Pa, 5 Hz) and the response was quantified by measuring nitric oxide (NO) and prostaglandin E₂ (PGE₂) production, and gene expression of cyclooxygenase (COX)-1 and COX-2. We found that DPC are intrinsically mechanosensitive and, like osteogenic cells, respond to PFF-induced fluid shear stress. PFF stimulated NO and PGE₂ production, and up-regulated COX-2 but not COX-1 gene expression. In DPC cultured under mineralizing conditions, the PFF-induced NO, but not PGE₂, production was significantly enhanced. These data suggest that human DPC, like osteogenic cells, acquire responsiveness to pulsating fluid shear stress in mineralizing conditions. Thus DPC might be able to perform bone-like functions during mineralized tissue remodeling in vivo, and therefore provide a promising new tool for mineralized tissue engineering to restore, for example, maxillofacial defects.

  7. Vaccinium corymbosum L. (blueberry) extracts exhibit protective action against cadmium toxicity in Saccharomyces cerevisiae cells.

    Science.gov (United States)

    Oprea, Eliza; Ruta, Lavinia L; Nicolau, Ioana; Popa, Claudia V; Neagoe, Aurora D; Farcasanu, Ileana C

    2014-01-01

    Blueberries (Vaccinium corymbosum L.) are a rich source of antioxidants and their consumption is believed to contribute to food-related protection against oxidative stress. In the present study, the chemoprotective action of blueberry extracts against cadmium toxicity was investigated using a cadmium-hypersensitive strain of Saccharomyces cerevisiae. Four varieties of blueberries were used in the study, and it was found that the extracts with high content of total anthocyanidins exhibited significant protective effect against the toxicity of cadmium and H2O2. Both the blueberry extracts and pure cyanidin exhibited protective effects against cadmium in a dose-dependent manner, but without significantly interfering with the cadmium accumulation by the yeast cells. The results imply that the blueberry extracts might be a potentially valuable food supplement for individuals exposed to high cadmium. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns

    International Nuclear Information System (INIS)

    Altman, R.; Harrich, D.; Garcia, J.A.; Gaynor, R.B.

    1988-01-01

    Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, the authors performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses

  9. Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

    Science.gov (United States)

    Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

    2005-03-01

    Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

  10. Ligase-deficient yeast cells exhibit defective DNA rejoining and enhanced gamma ray sensitivity

    International Nuclear Information System (INIS)

    Moore, C.W.

    1982-01-01

    Yeast cells deficient in DNA ligase were also deficient in their capacity to rejoin single-strand scissions in prelabeled nuclear DNA. After high-dose-rate gamma irradiation (10 and 25 krads), cdc9-9 mutant cells failed to rejoin single-strand scissions at the restrictive temperature of 37 0 C. In contrast, parental (CDC9) cells (incubated with mutant cells both during and after irradiation) exhibited rapid medium-independent DNA rejoining after 10 min of post-irradiation incubation and slower rates of rejoining after longer incubation. Parental cells were also more resistant than mutant cells to killing by gamma irradiation. Approximately 2.5 +- 0.07 and 5.7 +- 0.6 single-strand breaks per 10 8 daltons were detected in DNAs from either CDC9 or cdc9-9 cells converted to spheroplasts immediately after 10 and 25 krads of irradiation, respectively. At the permissive temperature of 23 0 C, the cdc9-9 cells contained 2 to 3 times the number of DNA single-strand breaks as parental cells after 10 min to 4 h of incubation after 10 krads of irradiation, and two- to eightfold more breaks after 10 min to 2.5 h of incubation after 25 krads of irradiation. Rejoining of single-strand scissions was faster in medium. After only 10 min in buffered growth medium after 10 krads of irradiation, the number of DNA single-strand breaks was reduced to 0.32 +- 0.3 (at 23 0 C) or 0.21 +- 0.05 (at 37 0 C) per 10 8 daltons in parental cells, but remained at 2.1 +- 0.06 (at 23 0 C) or 2.3 +- 0.07 (at 37 0 C) per 10 8 daltons in mutant cells. After 10 or 25 krads of irradiation plus 1 h of incubation in medium at 37 0 C, only DNA from CDC9 cells was rejoined to the size of DNA from unirradiated cells, whereas at 23 0 C, DNAs in both strains were completely rejoined

  11. Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.

    Science.gov (United States)

    Allende, Maria L; Cook, Emily K; Larman, Bridget C; Nugent, Adrienne; Brady, Jacqueline M; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J; Proia, Richard L

    2018-03-01

    Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB -corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB -corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB -corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses.

  12. Cyclometalated Ruthenium(II) Anthraquinone Complexes Exhibit Strong Anticancer Activity in Hypoxic Tumor Cells.

    Science.gov (United States)

    Zeng, Leli; Chen, Yu; Huang, Huaiyi; Wang, Jinquan; Zhao, Donglei; Ji, Liangnian; Chao, Hui

    2015-10-19

    Hypoxia is the critical feature of the tumor microenvironment that is known to lead to resistance to many chemotherapeutic drugs. Six novel ruthenium(II) anthraquinone complexes were designed and synthesized; they exhibit similar or superior cytotoxicity compared to cisplatin in hypoxic HeLa, A549, and multidrug-resistant (A549R) tumor cell lines. Their anticancer activities are related to their lipophilicity and cellular uptake; therefore, these physicochemical properties of the complexes can be changed by modifying the ligands to obtain better anticancer candidates. Complex 1, the most potent member of the series, is highly active against hypoxic HeLa cancer cells (IC50 =0.53 μM). This complex likely has 46-fold better activity than cisplatin (IC50 =24.62 μM) in HeLa cells. This complex tends to accumulate in the mitochondria and the nucleus of hypoxic HeLa cells. Further mechanistic studies show that complex 1 induced cell apoptosis during hypoxia through multiple pathways, including those of DNA damage, mitochondrial dysfunction, and the inhibition of DNA replication and HIF-1α expression, making it an outstanding candidate for further in vivo studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Induced pluripotent stem cells derived from rabbits exhibit some characteristics of naïve pluripotency

    Science.gov (United States)

    Osteil, Pierre; Tapponnier, Yann; Markossian, Suzy; Godet, Murielle; Schmaltz-Panneau, Barbara; Jouneau, Luc; Cabau, Cédric; Joly, Thierry; Blachère, Thierry; Gócza, Elen; Bernat, Agnieszka; Yerle, Martine; Acloque, Hervé; Hidot, Sullivan; Bosze, Zsuzsanna; Duranthon, Véronique; Savatier, Pierre; Afanassieff, Marielle

    2013-01-01

    Summary Not much is known about the molecular and functional features of pluripotent stem cells (PSCs) in rabbits. To address this, we derived and characterized 2 types of rabbit PSCs from the same breed of New Zealand White rabbits: 4 lines of embryonic stem cells (rbESCs), and 3 lines of induced PSCs (rbiPSCs) that were obtained by reprogramming adult skin fibroblasts. All cell lines required fibroblast growth factor 2 for their growth and proliferation. All rbESC lines showed molecular and functional properties typically associated with primed pluripotency. The cell cycle of rbESCs had a prolonged G1 phase and a DNA damage checkpoint before entry into the S phase, which are the 2 features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naïve pluripotency, including resistance to single-cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naïve pluripotency-specific genes, as defined in rodents. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass (ICM) than rbESCs. Furthermore, rbiPSCs were capable of colonizing the ICM after aggregation with morulas. Therefore, we propose that rbiPSCs self-renew in an intermediate state between naïve and primed pluripotency, which represents a key step toward the generation of bona fide naïve PSC lines in rabbits. PMID:23789112

  14. Vascular smooth muscle cells exhibit a progressive loss of rigidity with serial culture passaging.

    Science.gov (United States)

    Dinardo, Carla Luana; Venturini, Gabriela; Omae, Samantha Vieira; Zhou, Enhua H; da Motta-Leal-Filho, Joaquim Maurício; Dariolli, Rafael; Krieger, José Eduardo; Alencar, Adriano Mesquita; Costa Pereira, Alexandre

    2012-01-01

    One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.

  15. A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Víctor A. Solarte

    2015-01-01

    Full Text Available Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20–254, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90% in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC.

  16. A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines.

    Science.gov (United States)

    Solarte, Víctor A; Rosas, Jaiver E; Rivera, Zuly J; Arango-Rodríguez, Martha L; García, Javier E; Vernot, Jean-Paul

    2015-01-01

    Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20-25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC.

  17. Human mammary epithelial cells exhibit a bimodal correlated random walk pattern.

    Science.gov (United States)

    Potdar, Alka A; Jeon, Junhwan; Weaver, Alissa M; Quaranta, Vito; Cummings, Peter T

    2010-03-10

    Organisms, at scales ranging from unicellular to mammals, have been known to exhibit foraging behavior described by random walks whose segments confirm to Lévy or exponential distributions. For the first time, we present evidence that single cells (mammary epithelial cells) that exist in multi-cellular organisms (humans) follow a bimodal correlated random walk (BCRW). Cellular tracks of MCF-10A pBabe, neuN and neuT random migration on 2-D plastic substrates, analyzed using bimodal analysis, were found to reveal the BCRW pattern. We find two types of exponentially distributed correlated flights (corresponding to what we refer to as the directional and re-orientation phases) each having its own correlation between move step-lengths within flights. The exponential distribution of flight lengths was confirmed using different analysis methods (logarithmic binning with normalization, survival frequency plots and maximum likelihood estimation). Because of the presence of non-uniform turn angle distribution of move step-lengths within a flight and two different types of flights, we propose that the epithelial random walk is a BCRW comprising of two alternating modes with varying degree of correlations, rather than a simple persistent random walk. A BCRW model rather than a simple persistent random walk correctly matches the super-diffusivity in the cell migration paths as indicated by simulations based on the BCRW model.

  18. Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling.

    Science.gov (United States)

    Hirata, Shinji; Takayama, Naoya; Jono-Ohnishi, Ryoko; Endo, Hiroshi; Nakamura, Sou; Dohda, Takeaki; Nishi, Masanori; Hamazaki, Yuhei; Ishii, Ei-ichi; Kaneko, Shin; Otsu, Makoto; Nakauchi, Hiromitsu; Kunishima, Shinji; Eto, Koji

    2013-09-01

    Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor-mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl(-/-) mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC-derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT.

  19. Human mammary epithelial cells exhibit a bimodal correlated random walk pattern.

    Directory of Open Access Journals (Sweden)

    Alka A Potdar

    2010-03-01

    Full Text Available Organisms, at scales ranging from unicellular to mammals, have been known to exhibit foraging behavior described by random walks whose segments confirm to Lévy or exponential distributions. For the first time, we present evidence that single cells (mammary epithelial cells that exist in multi-cellular organisms (humans follow a bimodal correlated random walk (BCRW.Cellular tracks of MCF-10A pBabe, neuN and neuT random migration on 2-D plastic substrates, analyzed using bimodal analysis, were found to reveal the BCRW pattern. We find two types of exponentially distributed correlated flights (corresponding to what we refer to as the directional and re-orientation phases each having its own correlation between move step-lengths within flights. The exponential distribution of flight lengths was confirmed using different analysis methods (logarithmic binning with normalization, survival frequency plots and maximum likelihood estimation.Because of the presence of non-uniform turn angle distribution of move step-lengths within a flight and two different types of flights, we propose that the epithelial random walk is a BCRW comprising of two alternating modes with varying degree of correlations, rather than a simple persistent random walk. A BCRW model rather than a simple persistent random walk correctly matches the super-diffusivity in the cell migration paths as indicated by simulations based on the BCRW model.

  20. Group 2 Innate Lymphoid Cells Exhibit a Dynamic Phenotype in Allergic Airway Inflammation

    Science.gov (United States)

    Li, Bobby W. S.; Stadhouders, Ralph; de Bruijn, Marjolein J. W.; Lukkes, Melanie; Beerens, Dior M. J. M.; Brem, Maarten D.; KleinJan, Alex; Bergen, Ingrid; Vroman, Heleen; Kool, Mirjam; van IJcken, Wilfred F. J.; Rao, Tata Nageswara; Fehling, Hans Jörg; Hendriks, Rudi W.

    2017-01-01

    Group 2 innate lymphoid cells (ILC2) are implicated in allergic asthma as an early innate source of the type 2 cytokines IL-5 and IL-13. However, their induction in house dust mite (HDM)-mediated airway inflammation additionally requires T cell activation. It is currently unknown whether phenotypic differences exist between ILC2s that are activated in a T cell-dependent or T cell-independent fashion. Here, we compared ILC2s in IL-33- and HDM-driven airway inflammation. Using flow cytometry, we found that surface expression levels of various markers frequently used to identify ILC2s were dependent on their mode of activation, highly variable over time, and differed between tissue compartments, including bronchoalveolar lavage (BAL) fluid, lung, draining lymph nodes, and spleen. Whereas in vivo IL-33-activated BAL fluid ILC2s exhibited an almost uniform CD25+CD127+T1/ST2+ICOS+KLRG1+ phenotype, at a comparable time point after HDM exposure BAL fluid ILC2s had a very heterogeneous surface marker phenotype. A major fraction of HDM-activated ILC2s were CD25lowCD127+T1/ST2low ICOSlowKLRG1low, but nevertheless had the capacity to produce large amounts of type 2 cytokines. HDM-activated CD25low ILC2s in BAL fluid and lung rapidly reverted to CD25high ILC2s upon in vivo stimulation with IL-33. Genome-wide transcriptional profiling of BAL ILC2s revealed ~1,600 differentially expressed genes: HDM-stimulated ILC2s specifically expressed genes involved in the regulation of adaptive immunity through B and T cell interactions, whereas IL-33-stimulated ILC2s expressed high levels of proliferation-related and cytokine genes. In both airway inflammation models ILC2s were present in the lung submucosa close to epithelial cells, as identified by confocal microscopy. In chronic HDM-driven airway inflammation ILC2s were also found inside organized cellular infiltrates near T cells. Collectively, our findings show that ILC2s are phenotypically more heterogeneous than previously thought

  1. Group 2 Innate Lymphoid Cells Exhibit a Dynamic Phenotype in Allergic Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Bobby W. S. Li

    2017-12-01

    Full Text Available Group 2 innate lymphoid cells (ILC2 are implicated in allergic asthma as an early innate source of the type 2 cytokines IL-5 and IL-13. However, their induction in house dust mite (HDM-mediated airway inflammation additionally requires T cell activation. It is currently unknown whether phenotypic differences exist between ILC2s that are activated in a T cell-dependent or T cell-independent fashion. Here, we compared ILC2s in IL-33- and HDM-driven airway inflammation. Using flow cytometry, we found that surface expression levels of various markers frequently used to identify ILC2s were dependent on their mode of activation, highly variable over time, and differed between tissue compartments, including bronchoalveolar lavage (BAL fluid, lung, draining lymph nodes, and spleen. Whereas in vivo IL-33-activated BAL fluid ILC2s exhibited an almost uniform CD25+CD127+T1/ST2+ICOS+KLRG1+ phenotype, at a comparable time point after HDM exposure BAL fluid ILC2s had a very heterogeneous surface marker phenotype. A major fraction of HDM-activated ILC2s were CD25lowCD127+T1/ST2low ICOSlowKLRG1low, but nevertheless had the capacity to produce large amounts of type 2 cytokines. HDM-activated CD25low ILC2s in BAL fluid and lung rapidly reverted to CD25high ILC2s upon in vivo stimulation with IL-33. Genome-wide transcriptional profiling of BAL ILC2s revealed ~1,600 differentially expressed genes: HDM-stimulated ILC2s specifically expressed genes involved in the regulation of adaptive immunity through B and T cell interactions, whereas IL-33-stimulated ILC2s expressed high levels of proliferation-related and cytokine genes. In both airway inflammation models ILC2s were present in the lung submucosa close to epithelial cells, as identified by confocal microscopy. In chronic HDM-driven airway inflammation ILC2s were also found inside organized cellular infiltrates near T cells. Collectively, our findings show that ILC2s are phenotypically more heterogeneous than

  2. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  3. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

    Science.gov (United States)

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

    2018-01-01

    Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo . © FASEB.

  4. Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration.

    Science.gov (United States)

    Li, P; Tian, H; Li, Z; Wang, L; Gao, F; Ou, Q; Lian, C; Li, W; Jin, C; Zhang, J; Xu, J-Y; Wang, J; Zhang, J; Wang, F; Lu, L; Xu, G-T

    2016-01-01

    Bone marrow mesenchymal stem cells (BMSCs) have a therapeutic role in retinal degeneration (RD). However, heterogeneity of BMSCs may be associated with differential therapeutic effects in RD. In order to confirm this hypothesis, two subsets of rat BMSCs, termed rBMSC1 and rBMSC2, were obtained, characterized and functionally evaluated in the treatment of RD of Royal College of Surgeons (RCS) rats. Both subpopulations expressed mesenchymal stem cells (MSC) markers CD29 and CD90, but were negative for hemacyte antigen CD11b and CD45 expression. In comparison with rBMSC2, rBMSC1 showed higher rate of proliferation, stronger colony formation, and increased adipogenic potential, whereas rBMSC2 exhibited higher osteogenic potential. Microarray analysis showed differential gene expression patterns between rBMSC1 and rBMSC2, including functions related to proliferation, differentiation, immunoregulation, stem cell maintenance and division, survival and antiapoptosis. After subretinal transplantation in RCS rats, rBMSC1 showed stronger rescue effect than rBMSC2, including increased b-wave amplitude, restored retinal nuclear layer thickness, and decreased number of apoptotic photoreceptors, whereas the rescue function of rBMSC2 was essentially not better than the control. Histological analysis also demonstrated that rBMSC1 possessed a higher survival rate than rBMSC2 in subretinal space. In addition, treatment of basic fibroblast growth factor, an accompanying event in subretinal injection, triggered more robust increase in secretion of growth factors by rBMSC1 as compared to rBMSC2. Taken together, these results have suggested that the different therapeutic functions of BMSC subpopulations are attributed to their distinct survival capabilities and paracrine functions. The underlying mechanisms responsible for the different functions of BMSC subpopulation may lead to a new strategy for the treatment of RD.

  5. NKp46+CD3+ cells - a novel non-conventional T-cell subset in cattle exhibiting both NK cell and T-cell features

    Science.gov (United States)

    Connelley, Timothy K.; Longhi, Cassandra; Burrells, Alison; Degnan, Kathryn; Hope, Jayne; Allan, Alasdair; Hammond, John A.; Storset, Anne K.; Morrison, W. Ivan

    2014-01-01

    The NKp46 receptor demonstrates a high degree of lineage-specificity, being expressed almost exclusively in natural killer cells. Previous studies have demonstrated NKp46 expression by T-cells, but NKp46+CD3+ cells are rare and almost universally associated with NKp46 acquisition by T-cells following stimulation. In this study we demonstrate the existence of a population of NKp46+CD3+ cells resident in normal bovine PBMC which include cells of both the αβ TCR+ and γδ TCR+ lineages and is present at a frequency of 0.1-1.7%. NKp46+CD3+ cells express transcripts for a broad repertoire of both natural killer (NKR) and T-cell receptors (TCR) and also the CD3ζ, DAP10 and FcεR1γ but not DAP12 adaptor proteins. In vitro functional analysis of NKp46+CD3+ cells confirm that NKp46, CD16 and CD3 signalling pathways are all functionally competent and capable of mediating-re-direct cytolysis. However, only CD3 cross-ligation elicits IFN-γ release. NKp46+CD3+ cells exhibit cytotoxic activity against autologous Theileria parva infected cells in vitro and during in vivo challenge with this parasite an expansion of NKp46+CD3+ cells was observed in some animals, indicating the cells have the potential to act as an anti-pathogen effector population. The results presented herein identifies and describes a novel non-conventional NKp46+CD3+ T-cell subset that is phenotypically and functionally distinct from conventional NK and T-cells. The ability to exploit both NKR and TCR suggests these cells may fill a functional niche at the interface of innate and adaptive immune responses. PMID:24639352

  6. Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma.

    Science.gov (United States)

    Starrett, Gabriel J; Marcelus, Christina; Cantalupo, Paul G; Katz, Joshua P; Cheng, Jingwei; Akagi, Keiko; Thakuria, Manisha; Rabinowits, Guilherme; Wang, Linda C; Symer, David E; Pipas, James M; Harris, Reuben S; DeCaprio, James A

    2017-01-03

    Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tumors. Our study reveals that virus-associated tumors have minimally altered genomes compared to non-virus-associated tumors, which are dominated by UV-mediated mutations. Although virus-associated tumors contain relatively small mutation burdens, they exhibit a distinct mutation signature with observable transcriptionally biased kataegic events. In addition, viral integration sites overlap focal genome amplifications in virus-associated tumors, suggesting a potential mechanism for these events. Collectively, our studies indicate that Merkel cell polyomavirus is capable of hijacking cellular processes and driving tumorigenesis to the same severity as tens of thousands of somatic genome alterations. A variety of mutagenic processes that shape the evolution of tumors are critical determinants of disease outcome. Here, we sequenced the entire genome of virus-positive and virus-negative primary Merkel cell carcinomas (MCCs), revealing distinct mutation spectra and corresponding expression profiles. Our studies highlight the strong effect that Merkel cell polyomavirus has on the divergent development of viral MCC compared to the somatic alterations that typically drive nonviral tumorigenesis. A more comprehensive understanding of the distinct mutagenic processes operative in viral and nonviral MCCs has implications for the effective treatment of these tumors. Copyright © 2017 Starrett et al.

  7. Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

    Directory of Open Access Journals (Sweden)

    Nicole Purrier

    Full Text Available Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods. Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

  8. Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells.

    Science.gov (United States)

    Topoluk, Natasha; Hawkins, Richard; Tokish, John; Mercuri, Jeremy

    2017-09-01

    Therapeutic efficacy of various mesenchymal stromal cell (MSC) types for orthopaedic applications is currently being investigated. While the concept of MSC therapy is well grounded in the basic science of healing and regeneration, little is known about individual MSC populations in terms of their propensity to promote the repair and/or regeneration of specific musculoskeletal tissues. Two promising MSC sources, adipose and amnion, have each demonstrated differentiation and extracellular matrix (ECM) production in the setting of musculoskeletal tissue regeneration. However, no study to date has directly compared the differentiation potential of these 2 MSC populations. To compare the ability of human adipose- and amnion-derived MSCs to undergo osteogenic and chondrogenic differentiation. Controlled laboratory study. MSC populations from the human term amnion were quantified and characterized via cell counting, histologic assessment, and flow cytometry. Differentiation of these cells in comparison to commercially purchased human adipose-derived mesenchymal stromal cells (hADSCs) in the presence and absence of differentiation media was evaluated via reverse transcription polymerase chain reaction (PCR) for bone and cartilage gene transcript markers and histology/immunohistochemistry to examine ECM production. Analysis of variance and paired t tests were performed to compare results across all cell groups investigated. The authors confirmed that the human term amnion contains 2 primary cell types demonstrating MSC characteristics-(1) human amniotic epithelial cells (hAECs) and (2) human amniotic mesenchymal stromal cells (hAMSCs)-and each exhibited more than 90% staining for MSC surface markers (CD90, CD105, CD73). Average viable hAEC and hAMSC yields at harvest were 2.3 × 10 6 ± 3.7 × 10 5 and 1.6 × 10 6 ± 4.7 × 10 5 per milliliter of amnion, respectively. As well, hAECs and hAMSCs demonstrated significantly greater osteocalcin ( P = .025), aggrecan ( P

  9. Fibroblasts Cultured on Nanowires Exhibit Low Motility, Impaired Cell Division, and DNA Damage

    DEFF Research Database (Denmark)

    Persson, H.; Købler, Carsten; Mølhave, Kristian

    2013-01-01

    Mouse fibroblasts cultured on 7-μm-long vertical nanowires are reported on page 4006 by C. N. Prinz and co-workers. Culturing cells on this kind of substrate interferes greatly with cell function, causing the cells to develop into widely different morphologies. The cells' division is impaired...

  10. Recombinant Nox4 cytosolic domain produced by a cell or cell-free base systems exhibits constitutive diaphorase activity

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Minh Vu Chuong, E-mail: mvchuong@yahoo.fr [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Zhang, Leilei [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Lhomme, Stanislas; Mouz, Nicolas [PX' Therapeutics, MINATEC/Batiment de Haute Technologie, Grenoble (France); Lenormand, Jean-Luc [HumProTher Laboratory, TheReX/TIMC-IMAG UMR 5525 CNRS UJF, Universite Joseph Fourier, UFR de Medecine, Domaine de la Merci, 38706 La Tronche (France); Lardy, Bernard; Morel, Francoise [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer A comparison of two bacterial cell and cell-free protein expression systems is presented. Black-Right-Pointing-Pointer Soluble and active truncated Nox4 proteins are produced. Black-Right-Pointing-Pointer Nox4 has a constitutive diaphorase activity which is independent of cytosolic factors. Black-Right-Pointing-Pointer Isoform Nox4B is unable to initiate the first electronic transfer step. Black-Right-Pointing-Pointer Findings contribute to the understanding of the mechanism of Nox4 oxidase activity. -- Abstract: The membrane protein NADPH (nicotinamide adenine dinucleotide phosphate) oxidase Nox4 constitutively generates reactive oxygen species differing from other NADPH oxidases activity, particularly in Nox2 which needs a stimulus to be active. Although the precise mechanism of production of reactive oxygen species by Nox2 is well characterized, the electronic transfer throughout Nox4 remains unclear. Our study aims to investigate the initial electronic transfer step (diaphorase activity) of the cytosolic tail of Nox4. For this purpose, we developed two different approaches to produce soluble and active truncated Nox4 proteins. We synthesized soluble recombinant proteins either by in vitro translation or by bacteria induction. While proteins obtained by bacteria induction demonstrate an activity of 4.4 {+-} 1.7 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 20.5 {+-} 2.8 nmol/min/nmol with cytochrome c, the soluble proteins produced by cell-free expression system exhibit a diaphorase activity with a turn-over of 26 {+-} 2.6 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 48 {+-} 20.2 nmol/min/nmol with cytochrome c. Furthermore, the activity of the soluble proteins is constitutive and does not need any stimulus. We also show that the cytosolic tail of the isoform Nox4B lacking the first NADPH binding site is unable to demonstrate any diaphorase activity pointing out the

  11. Cell lines generated from a chronic lymphocytic leukemia mouse model exhibit constitutive Btk and Akt signaling

    NARCIS (Netherlands)

    Singh, Simar Pal; Pillai, Saravanan Y.; de Bruijn, Marjolein J. W.; Stadhouders, Ralph; Corneth, Odilia B. J.; van den Ham, Henk Jan; Muggen, Alice; van Ijcken, Wilfred; Slinger, Erik; Kuil, Annemieke; Spaargaren, Marcel; Kater, Arnon P.; Langerak, Anton W.; Hendriks, Rudi W.

    2017-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5(+) B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6,

  12. Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells.

    Science.gov (United States)

    Huang, Szu-Han; Ren, Yanqin; Thomas, Allison S; Chan, Dora; Mueller, Stefanie; Ward, Adam R; Patel, Shabnum; Bollard, Catherine M; Cruz, Conrad Russell; Karandish, Sara; Truong, Ronald; Macedo, Amanda B; Bosque, Alberto; Kovacs, Colin; Benko, Erika; Piechocka-Trocha, Alicja; Wong, Hing; Jeng, Emily; Nixon, Douglas F; Ho, Ya-Chi; Siliciano, Robert F; Walker, Bruce D; Jones, R Brad

    2018-02-01

    The presence of persistent, latent HIV reservoirs in CD4+ T cells obstructs current efforts to cure infection. The so-called kick-and-kill paradigm proposes to purge these reservoirs by combining latency-reversing agents with immune effectors such as cytotoxic T lymphocytes. Support for this approach is largely based on success in latency models, which do not fully reflect the makeup of latent reservoirs in individuals on long-term antiretroviral therapy (ART). Recent studies have shown that CD8+ T cells have the potential to recognize defective proviruses, which comprise the vast majority of all infected cells, and that the proviral landscape can be shaped over time due to in vivo clonal expansion of infected CD4+ T cells. Here, we have shown that treating CD4+ T cells from ART-treated individuals with combinations of potent latency-reversing agents and autologous CD8+ T cells consistently reduced cell-associated HIV DNA, but failed to deplete replication-competent virus. These CD8+ T cells recognized and potently eliminated CD4+ T cells that were newly infected with autologous reservoir virus, ruling out a role for both immune escape and CD8+ T cell dysfunction. Thus, our results suggest that cells harboring replication-competent HIV possess an inherent resistance to CD8+ T cells that may need to be addressed to cure infection.

  13. Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells.

    Science.gov (United States)

    Potikanond, Saranyapin; Sookkhee, Siriwoot; Na Takuathung, Mingkwan; Mungkornasawakul, Pitchaya; Wikan, Nitwara; Smith, Duncan R; Nimlamool, Wutigri

    2017-01-01

    Kaempferia parviflora (KP) has been traditionally used as a folk remedy to treat several diseases including cancer, and several studies have reported cytotoxic activities of extracts of KP against a number of different cancer cell lines. However, many aspects of the molecular mechanism of action of KP remain unclear. In particular, the ability of KP to regulate cancer cell growth and survival signaling is still largely unexplored. The current study aimed to investigate the effects of KP on cell viability, cell migration, cell invasion, cell apoptosis, and on signaling pathways related to growth and survival of cervical cancer cells, HeLa. We discovered that KP reduced HeLa cell viability in a concentration-dependent manner. The potent cytotoxicity of KP against HeLa cells was associated with a dose-dependent induction of apoptotic cell death as determined by flow cytometry and observation of nuclear fragmentation. Moreover, KP-induced cell apoptosis was likely to be mediated through the intrinsic apoptosis pathway since caspase 9 and caspase 7, but not BID, were shown to be activated after KP exposure. Based on the observation that KP induced apoptosis in HeLa cell, we further investigated the effects of KP at non-cytotoxic concentrations on suppressing signal transduction pathways relevant to cell growth and survival. We found that KP suppressed the MAPK and PI3K/AKT signaling pathways in cells activated with EGF, as observed by a significant decrease in phosphorylation of ERK1/2, Elk1, PI3K, and AKT. The data suggest that KP interferes with the growth and survival of HeLa cells. Consistent with the inhibitory effect on EGF-stimulated signaling, KP potently suppressed the migration of HeLa cells. Concomitantly, KP was demonstrated to markedly inhibit HeLa cell invasion. The ability of KP in suppressing the migration and invasion of HeLa cells was associated with the suppression of matrix metalloproteinase-2 production. These data strongly suggest that KP may slow

  14. Prostate cancer cell lines under hypoxia exhibit greater stem-like properties.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Ma

    Full Text Available Hypoxia is an important environmental change in many cancers. Hypoxic niches can be occupied by cancer stem/progenitor-like cells that are associated with tumor progression and resistance to radiotherapy and chemotherapy. However, it has not yet been fully elucidated how hypoxia influences the stem-like properties of prostate cancer cells. In this report, we investigated the effects of hypoxia on human prostate cancer cell lines, PC-3 and DU145. In comparison to normoxia (20% O(2, 7% O(2 induced higher expressions of HIF-1α and HIF-2α, which were associated with upregulation of Oct3/4 and Nanog; 1% O(2 induced even greater levels of these factors. The upregulated NANOG mRNA expression in hypoxia was confirmed to be predominantly retrogene NANOGP8. Similar growth rates were observed for cells cultivated under hypoxic and normoxic conditions for 48 hours; however, the colony formation assay revealed that 48 hours of hypoxic pretreatment resulted in the formation of more colonies. Treatment with 1% O(2 also extended the G(0/G(1 stage, resulting in more side population cells, and induced CD44 and ABCG2 expressions. Hypoxia also increased the number of cells positive for ABCG2 expression, which were predominantly found to be CD44(bright cells. Correspondingly, the sorted CD44(bright cells expressed higher levels of ABCG2, Oct3/4, and Nanog than CD44(dim cells, and hypoxic pretreatment significantly increased the expressions of these factors. CD44(bright cells under normoxia formed significantly more colonies and spheres compared with the CD44(dim cells, and hypoxic pretreatment even increased this effect. Our data indicate that prostate cancer cells under hypoxia possess greater stem-like properties.

  15. Cleistopholine isolated from Enicosanthellum pulchrum exhibits apoptogenic properties in human ovarian cancer cells.

    Science.gov (United States)

    Nordin, Noraziah; Majid, Nazia Abdul; Mohan, Syam; Dehghan, Firouzeh; Karimian, Hamed; Rahman, Mashitoh Abdul; Ali, Hapipah Mohd; Hashim, Najihah Mohd

    2016-04-15

    Cleistopholine is a natural alkaloid present in plants with numerous biological activities. However, cleistopholine has yet to be isolated using modern techniques and the mechanism by which this alkaloid induces apoptosis in cancer cells remains to be elucidated. This study aims to isolate cleistopholine from the roots of Enicosanthellum pulchrum by using preparative-HPLC technique and explore the mechanism by which this alkaloid induces apoptosis in human ovarian cancer (CAOV-3) cells in vitro from 24 to 72 h. This compound may be developed as an anticancer agent that induces apoptosis in ovarian cancer cells. Cytotoxicity was assessed via the cell viability assay and changes in cell morphology were observed via the acridine orange/propidium iodide (AO/PI) assay. The involvement of apoptotic pathways was evaluated through caspase analysis and multiple cytotoxicity assays. Meanwhile, early and late apoptotic events via the Annexin V-FITC and DNA laddering assays, respectively. The mechanism of apoptosis was explored at the molecular level by evaluating the expression of specific genes and proteins. In addition, the proliferation of CAOV-3-cells treated with cleistopholine was analysed using the cell cycle arrest assay. The IC50 of cleistopholine (61.4 µM) was comparable with that of the positive control cisplatin (62.8 µM) at 24 h of treatment. Apoptos is was evidenced by cell membrane blebbing, chromatin compression and formation of apoptotic bodies. The initial phase of apoptosis was detected at 24 h by the increase in Annexin V-FITC binding to cell membranes. A DNA ladder was formed at 48 h, indicating DNA fragmentation in the final phase of apoptosis. The mitochondria participated in the process by stimulating the intrinsic pathway via caspase 9 with a reduction in mitochondrial membrane potential (MMP) and an increase in cytochrome c release. Cell death was further validated through the mRNA and protein overexpression of Bax, caspase 3 and caspase 9 in the

  16. T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

    Science.gov (United States)

    Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

    2016-10-27

    It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment

  17. Transgenic Chinese hamster V79 cell lines which exhibit variable levels of gpt mutagenesis

    International Nuclear Information System (INIS)

    Klein, C.B.; Rossman, T.G.

    1990-01-01

    The Escherichia coli gpt gene coding for xanthine-guanine phosphoribosyl transferase has been stably transfected into HPRT - Chinese hamster V79 cells. Several gpt - cell lines have been established, which retain the sequence(s) even after long-term culture without selection for gpt. While spontaneous mutagenesis to gpt - occurs rather frequently for most cell lines, it cannot be correlated with either the number of plasmid integration sites or deletion of the plasmid sequence(s). One transgenic cell line (g12), which continuously maintains a low spontaneous mutation frequency was used in comparative mutagenesis studies with wild-type V79 cells (gpt vs. hprt). Alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and β-propiolactone (BPL) are shown to be equally toxic and mutagenic in both g12 and V79 cells. UV and X-rays are also equally toxic to both cell lines. The data presented here suggests that g12 cells may be useful to study mammalian mutagenesis by agents which yield limited response at the hprt locus

  18. Geranylated 4-Phenylcoumarins Exhibit Anticancer Effects against Human Prostate Cancer Cells through Caspase-Independent Mechanism.

    Directory of Open Access Journals (Sweden)

    Noor Shahirah Suparji

    Full Text Available Geranylated 4-phenylcoumarins, DMDP-1 & -2 isolated from Mesua elegans were investigated for anticancer potential against human prostate cancer cells. Treatment with DMDP-1 & -2 resulted in cell death in a time and dose dependent manner in an MTT assay on all cancer cell lines tested with the exception of lung adenocarcinoma cells. DMDP-1 showed highest cytotoxic efficacy in PC-3 cells while DMDP-2 was most potent in DU 145 cells. Flow cytometry indicated that both coumarins were successful to induce programmed cell death after 24 h treatment. Elucidation on the mode-of-action via protein arrays and western blotting demonstrated death induced without any significant expressions of caspases, Bcl-2 family proteins and cleaved PARP, thus suggesting the involvement of caspase-independent pathways. In identifying autophagy, analysis of GFP-LC3 showed increased punctate in PC-3 cells pre-treated with CQ and treated with DMDP-1. In these cells decreased expression of autophagosome protein, p62 and cathepsin B further confirmed autophagy. In contrary, the DU 145 cells pre-treated with CQ and treated with DMDP-2 has reduced GFP-LC3 punctate although the number of cells with obvious GFP-LC3 puncta was significantly increased in the inhibitor-treated cells. The increase level of p62 suggested leakage of cathepsin B into the cytosol to trigger potential downstream death mediators. This correlated with increased expression of cathepsin B and reduced expression after treatment with its inhibitor, CA074. Also auto-degradation of calpain-2 upon treatment with DMDP-1 &-2 and its inhibitor alone, calpeptin compared with the combination treatment, further confirmed involvement of calpain-2 in PC-3 and DU 145 cells. Treatment with DMDP-1 & -2 also showed up-regulation of total and phosphorylated p53 levels in a time dependent manner. Hence, DMDP-1 & -2 showed ability to activate multiple death pathways involving autophagy, lysosomal and endoplasmic reticulum death

  19. Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

    DEFF Research Database (Denmark)

    Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia

    2013-01-01

    Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and human skin......, MSC populations obtained from different tissues exhibit significant differences in their proliferation, differentiation and molecular phenotype, which should be taken into consideration when planning their use in clinical protocols....

  20. CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Zhang, Heyu; Nan, Xu; Li, Xuefen; Chen, Yan; Zhang, Jianyun; Sun, Lisha; Han, Wenlin; Li, Tiejun

    2014-01-01

    Highlights: • Down-regulation of CMTM5 expression in OSCC tissues was found. • The promoter methylation status of CMTM5 was measured. • CMTM5-v1 inhibited cell proliferation and migration and induced apoptosis. • CMTM5 might act as a putative tumor suppressor gene in OSCC. - Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma

  1. CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Heyu [Central Laboratory, Peking University School of Stomatology, Beijing (China); Nan, Xu [Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing (China); Li, Xuefen [Central Laboratory, Peking University School of Stomatology, Beijing (China); Chen, Yan; Zhang, Jianyun [Department of Oral Pathology, Peking University School of Stomatology, Beijing (China); Sun, Lisha [Central Laboratory, Peking University School of Stomatology, Beijing (China); Han, Wenlin [Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing (China); Li, Tiejun, E-mail: litiejun22@vip.sina.com [Department of Oral Pathology, Peking University School of Stomatology, Beijing (China)

    2014-05-02

    Highlights: • Down-regulation of CMTM5 expression in OSCC tissues was found. • The promoter methylation status of CMTM5 was measured. • CMTM5-v1 inhibited cell proliferation and migration and induced apoptosis. • CMTM5 might act as a putative tumor suppressor gene in OSCC. - Abstract: Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma.

  2. Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation

    International Nuclear Information System (INIS)

    Ding, Ke; Liu, Wen-ying; Zeng, Qiang; Hou, Fang; Xu, Jian-zhong; Yang, Zhong

    2017-01-01

    Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering.

  3. Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation.

    Science.gov (United States)

    Ding, Ke; Liu, Wen-Ying; Zeng, Qiang; Hou, Fang; Xu, Jian-Zhong; Yang, Zhong

    2017-03-01

    Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ke, E-mail: dingke@med.uestc.edu.cn [Department of Pediatric Surgery, School of medicine, University of Electronic Science and Technology of China, Chengdu 610072 (China); Sichuan Academy of Medical Sciences & Sichuan Provincial People' s Hospital, Chengdu 610072 (China); Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Liu, Wen-ying; Zeng, Qiang; Hou, Fang [Department of Pediatric Surgery, School of medicine, University of Electronic Science and Technology of China, Chengdu 610072 (China); Sichuan Academy of Medical Sciences & Sichuan Provincial People' s Hospital, Chengdu 610072 (China); Xu, Jian-zhong, E-mail: xjzspine@163.com [Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Yang, Zhong, E-mail: zyang1999@163.com [Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2017-03-01

    Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering.

  5. Mouse Embryonic Fibroblasts (MEF) Exhibit a Similar but not Identical Phenotype to Bone Marrow Stromal Stem Cells (BMSC)

    DEFF Research Database (Denmark)

    Saeed, Hamid; Taipaleenmäki, Hanna; Aldahmash, Abdullah M

    2012-01-01

    Mouse embryonic fibroblasts have been utilized as a surrogate stem cell model for the postnatal bone marrow-derived stromal stem cells (BMSC) to study mesoderm-type cell differentiation e.g. osteoblasts, adipocytes and chondrocytes. However, no formal characterization of MEF phenotype has been...... by real-time PCR analysis. Compared to BMSC, MEF exhibited a more enhanced differentiation into adipocyte and chondrocyte lineages. Interestingly, both MEF and BMSC formed the same amount of heterotopic bone and bone marrow elements upon in vivo subcutaneous implantation with hydroxyapatite...... and differentiation to osteoblasts, adipocytes and chondrocytes....

  6. Fisetin and polymeric micelles encapsulating fisetin exhibit potent cytotoxic effects towards ovarian cancer cells.

    Science.gov (United States)

    Xiao, Xue; Zou, Juan; Fang, Yin; Meng, Yibo; Xiao, Chao; Fu, Jiaxin; Liu, Shiyu; Bai, Peng; Yao, Yuan

    2018-03-15

    The anti-tumor activities of Natural compounds and their derivatives are of great interest to pharmaceutical industries. Fisetin is one of prospective natural compounds in this regard but unfortunately with poor hydrophilicity. The effects of unmodified and modified fisetin in cultured ovarian cancer cells were compared by transmission electronmicroscopy to determine apoptotic bodies, MTT assay to quantitate cell numbers, and fluorescence activated cell sorting analyse of various markers to determine the apoptotic state. In addition, the efficacy of fisetin and fisetin-micelles in vivo was determined by using immunocompromised mice. Apoptosis was measured by established markers using both western blot analysis and immunochemistry. Angiogenesis in a xenograft mouse model carring SKOV3 cells was evaluated by color Doppler ultrasound and immunohistochemistry. Multiple lines of evidence indicated that fisetin and fisetin micelles induce apoptosis in ovarian cancer cells in a dose-dependent manner. Histological analysis, terminal deoxynucleotidyltransferase-mediated nick-end labeling assay, western blot, immunohistochemical detection and microvessel density detection demonstrated that fisetin and fisetin micelles induced increased tumor apoptosis, proliferation suppression and antiangiogenesis activities. As far as we know, the present study is the first time to demonstrate the potency of both fisetin and fisetin micelles inducing apoptosis in ovarian cancer cells. Further studies will be needed to validate the therapeutic potential of fisetin and fisetin micelles in ovarian cancer treatment.

  7. Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

    Science.gov (United States)

    Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

    2013-10-15

    Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

  8. Technology Exhibition

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1979-09-15

    Linked to the 25th Anniversary celebrations, an exhibition of some of CERN's technological achievements was opened on 22 June. Set up in a new 600 m{sup 2} Exhibition Hall on the CERN site, the exhibition is divided into eight technology areas — magnets, vacuum, computers and data handling, survey and alignment, radiation protection, beam monitoring and handling, detectors, and workshop techniques.

  9. Live cell plasma membranes do not exhibit a miscibility phase transition over a wide range of temperatures.

    Science.gov (United States)

    Lee, Il-Hyung; Saha, Suvrajit; Polley, Anirban; Huang, Hector; Mayor, Satyajit; Rao, Madan; Groves, Jay T

    2015-03-26

    Lipid/cholesterol mixtures derived from cell membranes as well as their synthetic reconstitutions exhibit well-defined miscibility phase transitions and critical phenomena near physiological temperatures. This suggests that lipid/cholesterol-mediated phase separation plays a role in the organization of live cell membranes. However, macroscopic lipid-phase separation is not generally observed in cell membranes, and the degree to which properties of isolated lipid mixtures are preserved in the cell membrane remain unknown. A fundamental property of phase transitions is that the variation of tagged particle diffusion with temperature exhibits an abrupt change as the system passes through the transition, even when the two phases are distributed in a nanometer-scale emulsion. We support this using a variety of Monte Carlo and atomistic simulations on model lipid membrane systems. However, temperature-dependent fluorescence correlation spectroscopy of labeled lipids and membrane-anchored proteins in live cell membranes shows a consistently smooth increase in the diffusion coefficient as a function of temperature. We find no evidence of a discrete miscibility phase transition throughout a wide range of temperatures: 14-37 °C. This contrasts the behavior of giant plasma membrane vesicles (GPMVs) blebbed from the same cells, which do exhibit phase transitions and macroscopic phase separation. Fluorescence lifetime analysis of a DiI probe in both cases reveals a significant environmental difference between the live cell and the GPMV. Taken together, these data suggest the live cell membrane may avoid the miscibility phase transition inherent to its lipid constituents by actively regulating physical parameters, such as tension, in the membrane.

  10. Immersive Exhibitions

    DEFF Research Database (Denmark)

    Achiam, Marianne

    2015-01-01

    The immersive exhibition is a specialized exhibition genre in museums, which creates the illusion of time and place by representing key characteristics of a reference world and by integrating the visitor in this three-dimensionally reconstructed world (Mortensen 2010). A successful representation...... of the reference world depends on three criteria: whether the exhibition is staged as a coherent whole with all the displayed objects supporting the representation, whether the visitor is integrated as a component of the exhibition, and whether the content and message of the exhibition become dramatized...

  11. CD44+CD24+ subset of PANC-1 cells exhibits radiation resistance via decreased levels of reactive oxygen species.

    Science.gov (United States)

    Wang, Lei; Li, Pengping; Hu, Wei; Xia, Youyou; Hu, Chenxi; Liu, Liang; Jiang, Xiaodong

    2017-08-01

    Emerging evidence has suggested that pancreatic adenocarcinoma is sustained by pancreatic cancer stem cells. The present study aimed to investigate the expression patterns of the pancreatic cancer stem cell surface markers cluster of differentiation CD44 and CD24 in a pancreatic adenocarcinoma cell line, and to investigate the possible mechanisms for their radiation resistance. Flow cytometry was used to analyze the expression patterns of CD44 and CD24 in the pancreatic adenocarcinoma PANC-1 cell line. In addition, a multi-target click model was used to fit cell survival curves and determine the sensitizer enhancement ratio. The apoptosis and cycle distribution of the four cell subsets was determined using flow cytometry, and the level of reactive oxygen species (ROS) was determined using the 2',7'-dichlorofluorescin diacetate probe. The present results identified that the ratios of CD44 + and CD24 + in the sorted PANC-1 cell line were 92.0 and 4.7%, respectively. Prior to radiation, no statistically significant differences were observed among the four groups. Following treatment with 6 MV of X-rays, the rate of apoptosis was decreased in the CD44 + CD24 + group compared with other subsets. The percentage of G0/G1 cells was highest in the CD44 + CD24 + group compared with the three other groups, which exhibited increased radiosensitivity. In addition, the level of ROS in the CD44 + CD24 + group was reduced compared with the other groups. In summary, the results of the present study indicated that CD44 + CD24 + exhibited stem cell properties. The lower level of ROS and apoptosis in CD44 + CD24 + cells may contribute to their resistance to radiation in pancreatic adenocarcinoma.

  12. Mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.

    Science.gov (United States)

    Mvubu, Nontobeko Eunice; Pillay, Balakrishna; Gamieldien, Junaid; Bishai, William; Pillay, Manormoney

    2016-12-01

    Although pulmonary epithelial cells are integral to innate and adaptive immune responses during Mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. Changes in gene expression induced in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11, F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq). The Illumina HiSeq 2000 platform generated 50 bp reads that were mapped to the human genome (Hg19) using Tophat (2.0.10). Differential gene expression induced by the different strains in infected relative to the uninfected cells was quantified and compared using Cufflinks (2.1.0) and MeV (4.0.9), respectively. Gene expression varied among the strains with the total number of genes as follows: F15/LAM4/KZN (1187), Beijing (1252), F11 (1639), F28 (870), Unique (886) and H37Rv (1179). A subset of 292 genes was commonly induced by all strains, where 52 genes were down-regulated while 240 genes were up-regulated. Differentially expressed genes were compared among the strains and the number of induced strain-specific gene signatures were as follows: F15/LAM4/KZN (138), Beijing (52), F11 (255), F28 (55), Unique (186) and H37Rv (125). Strain-specific molecular gene signatures associated with functional pathways were observed only for the Unique and H37Rv strains while certain biological functions may be associated with other strain signatures. This study demonstrated that strains of M. tuberculosis induce differential gene expression and strain-specific molecular signatures in pulmonary epithelial cells. Specific signatures induced by clinical strains of M. tuberculosis can be further explored for novel host-associated biomarkers and adjunctive immunotherapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Coptis chinensis Franch. exhibits neuroprotective properties against oxidative stress in human neuroblastoma cells.

    Science.gov (United States)

    Friedemann, Thomas; Otto, Benjamin; Klätschke, Kristin; Schumacher, Udo; Tao, Yi; Leung, Alexander Kai-Man; Efferth, Thomas; Schröder, Sven

    2014-08-08

    The dried rhizome of Coptis chinensis Franch. (family Ranunculaceae) is traditionally used in Chinese medicine for the treatment of inflammatory diseases and diabetes. Recent studies showed a variety of activities of Coptis chinensis Franch. alkaloids, including neuroprotective, neuroregenerative, anti-diabetic, anti-oxidative and anti-inflammatory effects. However, there is no report on the neuroprotective effect of Coptis chinensis Franch. watery extract against tert-butylhydroperoxide (t-BOOH) induced oxidative damage. The aim of the study is to investigate neuroprotective properties of Coptis chinensis Franch. rhizome watery extract (CRE) and to evaluate its potential mechanism of action. Neuroprotective properties on t-BOOH induced oxidative stress were investigated in SH-SY5Y human neuroblastoma cells. Cells were pretreated with CRE for 2 h or 24 h followed by 2 h of treatment with t-BOOH. To evaluate the neuroprotective effect of CRE, cell viability, cellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and the apoptotic rate were determined and microarray analyses, as well as qRT-PCR analyses were conducted. Two hours of exposure to 100 µM t-BOOH resulted in a significant reduction of cell viability, increased apoptotic rate, declined mitochondrial membrane potential (MMP) and increased ROS production. Reduction of cell viability, increased apoptotic rate and declined mitochondrial membrane potential (MMP) could be significantly reduced in cells pretreated with CRE (100 µg/ml) for 2h or 24h ahead of t-BOOH exposure with the greatest effect after 24h of pretreatment; however ROS production was not changed significantly. Furthermore, microarray analyses revealed that the expressions of 2 genes; thioredoxin-interacting protein (TXNIP) and mitochondrially encoded NADH dehydrogenase 1, were significantly regulated. Down regulation of TXNIP was confirmed by qRT-PCR. Due to its neuroprotective properties CRE might be a potential

  14. Cells exposed to nanosecond electrical pulses exhibit biomarkers of mechanical stress

    Science.gov (United States)

    Roth, Caleb C.; Barnes, Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Moen, Erick K.; Glickman, Randolph D.

    2015-03-01

    Exposure of cells to very short (stressors on a cell, including electrical, electro-chemical, and mechanical stress. Thus, nsEP exposure is not a "clean" insult, making determination of the mechanism of nanoporation quite difficult. We hypothesize that nsEP exposure creates acoustic shock waves capable of causing nanoporation. Microarray analysis of primary adult human dermal fibroblasts (HDFa) exposed to nsEP, indicated several genes associated with mechanical stress were selectively upregulated 4 h post exposure. The idea that nanoporation is caused by external mechanical force from acoustic shock waves has, to our knowledge, not been investigated. This work will critically challenge the existing paradigm that nanoporation is caused solely by an electric-field driven event and could provide the basis for a plausible explanation for electroporation.

  15. Viola tricolor Induces Apoptosis in Cancer Cells and Exhibits Antiangiogenic Activity on Chicken Chorioallantoic Membrane

    Directory of Open Access Journals (Sweden)

    Hamid Reza Sadeghnia

    2014-01-01

    Full Text Available In the present study, the cytotoxic and apoptogenic properties of hydroalcoholic extract and ethyl acetate (EtOAc, n-butanol, and water fractions (0–800 μg/mL of Viola tricolor were investigated in Neuro2a mouse neuroblastoma and MCF-7 human breast cancer cells. In addition, antiangiogenic effect of EtOAc fraction was evaluated on chicken chorioallantoic membrane (CAM. The quality of EtOAc fraction was also characterized using high performance liquid chromatography (HPLC fingerprint. Cytotoxicity assay revealed that EtOAc fraction was the most potent among all fractions with maximal effect on MCF-7 and minimal toxicity against normal murine fibroblast L929 cells. Apoptosis induction by EtOAc fraction was confirmed by increased sub-G1 peak of propidium iodide (PI stained cells. This fraction triggered the apoptotic pathway by increased Bax/Bcl-2 ratio and cleaved caspase-3 level. Moreover, treatment with EtOAc fraction significantly decreased the diameter of vessels on CAM, while the number of newly formed blood vessels was not suppressed significantly. Analysis of quality of EtOAc fraction using HPLC fingerprint showed six major peaks with different retention times. The results of the present study suggest that V. tricolor has potential anticancer property by inducing apoptosis and inhibiting angiogenesis.

  16. Fetal colon cell line FHC exhibits tumorigenic phenotype, complex karyotype, and TP53 gene mutation

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Jirsová, Pavla; Brázdová, Marie; Hýžďalová, Martina; Kočí, Lenka; Vydra, D.; Trojanec, R.; Pernicová, Zuzana; Lentvorská, L.; Hajdúch, M.; Hofmanová, Jiřina; Kozubík, Alois

    2010-01-01

    Roč. 197, č. 2 (2010), s. 107-116 ISSN 0165-4608 R&D Projects: GA MŠk ME 919; GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA204/08/1560; GA AV ČR(CZ) 1QS500040507; GA MZd NS9600 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : colon epithelial cells * TP53 * MYC Subject RIV: BO - Biophysics Impact factor: 1.551, year: 2010

  17. Novel cytotoxic exhibition mode of antimicrobial peptide anoplin in MEL cells, the cell line of murine Friend leukemia virus-induced leukemic cells.

    Science.gov (United States)

    Zhu, Li-Na; Fu, Cai-Yun; Zhang, Shi-Fu; Chen, Wei; Jin, Yuan-Ting; Zhao, Fu-Kun

    2013-09-01

    Anoplin is a recently discovered antimicrobial peptide (AMP) isolated from the venom sac of the spider wasp Anoplius samariensis, and it is one of the shortest α-helical AMP found naturally to date consisting of only ten amino acids. Previous results showed that anoplin exhibits potent antimicrobial activity but little hemolytic activity. In this study, we synthesized anoplin, studied its cytotoxicity in Friend virus-induced leukemia cells [murine erythroleukemia (MEL) cells], and proposed its possible mechanism. Our results showed that anoplin could inhibit the proliferation of MEL cells in a dose-dependent and time-dependent manner via disrupting the integrity of cell membrane, which indicated that anoplin exerts its cytotoxicity efficacy. In addition, the cell cycle distribution of MEL cells was arrested in the G₀/G₁ phase significantly. However, anoplin could not induce obvious apoptosis in MEL cells, as well as anoplin could not induce visible changes on morphology and quantity in the bone marrow cells isolated from normal mice. All of these results indicate that anoplin, as generally believed, is a selective AMP, a value characteristic in the design of safe therapeutic agents. The cytotoxicity of anoplin on MEL cells was mainly attributable to the plasma membrane perturbation and also to the intracellular events such as the arrest of cell cycle. Although this is an initial study that explored the activity of anoplin in vitro rather than in vivo, with the increasing resistance of conventional chemotherapy, there is no doubt that anoplin has desirable feature to be developed as a novel and selective anticancer agent. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

  18. SIRT1 exhibits antioxidative effects in HT22 cells induced by tert-butyl alcohol.

    Science.gov (United States)

    Ma, Junxiang; Song, Dongmei; Zhang, Yuanyuan; Chen, Li; Zhang, Shixuan; Jia, Jiaxin; Chen, Tian; Guo, Caixia; Tian, Lin; Gao, Ai; Niu, Piye

    2018-02-01

    Tertiary butyl alcohol (TBA) is a principal metabolite of methyl tertiary-butyl ether (MTBE), a common pollutant worldwide in the ground or underground water, which is found to produce nervous system damage. Nevertheless, few data regarding the effects of TBA has been reported. Studies indicated that oxidative stress plays a pivotal role in MTBE neurotoxic mechanism. Sirtuin 1 (SIRT1) has been reported to exert a neuroprotective effect on various neurologic diseases via resistance to oxidative stress by deacetylating its substrates. In this study, we examined levels of oxidative stress after exposure to TBA for 6 h in HT22 cells and HT22 cells with SIRT1 silencing (transfected with SIRT1 siRNA) or high expression (preconditioned with agonists SRT1720). We found that TBA activated oxidative stress by increasing generation of intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and Oxidized glutathione (GSSG), and decreasing contents of superoxide dismutase (SOD) and glutathione reductase (GSH). In additional, levels of TBA-induced oxidative stress were aggravated when SIRT1 silenced but alleviated when SIRT1 enhanced. Our study indicated that SIRT1 mitigated oxidative stress induced by TBA. © 2017 Wiley Periodicals, Inc.

  19. A spiking network model of cerebellar Purkinje cells and molecular layer interneurons exhibiting irregular firing

    Directory of Open Access Journals (Sweden)

    William eLennon

    2014-12-01

    Full Text Available While the anatomy of the cerebellar microcircuit is well studied, how it implements cerebellar function is not understood. A number of models have been proposed to describe this mechanism but few emphasize the role of the vast network Purkinje cells (PKJs form with the molecular layer interneurons (MLIs – the stellate and basket cells. We propose a model of the MLI-PKJ network composed of simple spiking neurons incorporating the major anatomical and physiological features. In computer simulations, the model reproduces the irregular firing patterns observed in PKJs and MLIs in vitro and a shift toward faster, more regular firing patterns when inhibitory synaptic currents are blocked. In the model, the time between PKJ spikes is shown to be proportional to the amount of feedforward inhibition from an MLI on average. The two key elements of the model are: (1 spontaneously active PKJs and MLIs due to an endogenous depolarizing current, and (2 adherence to known anatomical connectivity along a parasagittal strip of cerebellar cortex. We propose this model to extend previous spiking network models of the cerebellum and for further computational investigation into the role of irregular firing and MLIs in cerebellar learning and function.

  20. Exhibit Engineering

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    Science museums define the objectives of their exhibitions in terms of visitor learning outcomes. Yet, exhibit designers lack theoretical and empirical research findings on which to base the creation of such educational environments. Here, this shortcoming is addressed through the development...... of tools and processes to guide the design of educational science exhibits. The guiding paradigm for this development is design-based research, which is characterised by an iterative cycle of design, enactment, and analysis. In the design phase, an educational intervention is planned and carried out based...... on the generation of theoretical ideas for exhibit design is offered in a fourth and parallel research undertaking, namely the application of the notion of cultural border-crossing to a hypothetical case of exhibit design....

  1. Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions

    NARCIS (Netherlands)

    Nagao, Keisuke; Ginhoux, Florent; Leitner, Wolfgang W.; Motegi, Sei-Ichiro; Bennett, Clare L.; Clausen, Björn E.; Merad, Miriam; Udey, Mark C.

    2009-01-01

    A new langerin(+) DC subset has recently been identified in murine dermis (langerin(+) dDC), but the lineage and functional relationships between these cells and langerin(+) epidermal Langerhans cells (LC) are incompletely characterized. Selective expression of the cell adhesion molecule EpCAM by LC

  2. Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells

    DEFF Research Database (Denmark)

    Sjövall, Fredrik; Morota, Saori; Persson, Johan Mikael

    2013-01-01

    to 7). Mitochondrial DNA (mtDNA), cytochrome c (Cyt c), and citrate synthase (CS) were measured as indicators of cellular mitochondrial content. RESULTS: In intact PBICs with endogenous substrates, a gradual increase in cellular respiration reached 173% of controls after 1 week (P = 0......INTRODUCTION: In sepsis, mitochondria have been associated with both initial dysfunction and subsequent upregulation (biogenesis). However, the evolvement of mitochondrial function in sepsis over time is largely unknown, and we therefore investigated mitochondrial respiration in peripheral blood.......001). In permeabilized cells, respiration using substrates of complex I, II, and IV were significantly increased days 1 to 2, reaching 137%, 130%, and 173% of controls, respectively. In parallel, higher levels of CS activity, mtDNA, and Cyt c content in PBICs (211%, 243%, and 331% of controls for the respective...

  3. Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines

    Science.gov (United States)

    Rabquer, Bradley J.; Ohara, Ray A.; Stinson, William A.; Campbell, Phillip L.; Amin, M. Asif; Balogh, Beatrix; Zakhem, George; Renauer, Paul A.; Lozier, Ann; Arasu, Eshwar; Haines, G. Kenneth; Kahaleh, Bashar; Schiopu, Elena; Khanna, Dinesh; Koch, Alisa E.

    2016-01-01

    Objectives. Angiogenesis plays a critical role in SSc (scleroderma). The aim of this study was to examine the expression of growth-regulated protein-γ (Gro-γ/CXCL3), granulocyte chemotactic protein 2 (GCP-2/CXCL6) and their receptor CXCR2 in endothelial cells (ECs) isolated from SSc skin and determine whether these cells mount an angiogenic response towards pro-angiogenic chemokines. The downstream signalling pathways as well as the pro-angiogenic transcription factor inhibitor of DNA-binding protein 1 (Id-1) were also examined. Methods. Skin biopsies were obtained from patients with dcSSc. ECs were isolated via magnetic positive selection. Angiogenesis was measured by EC chemotaxis assay. Results. Gro-γ/CXCL3 and GCP-2/CXCL6 were minimally expressed in both skin types but elevated in SSc serum. Pro-angiogenic chemokine mRNA was greater in SSc ECs than in normal ECs. SSc ECs did not migrate to vascular endothelial growth factor (VEGF), Gro-γ/CXCL3, GCP-2/CXCL6 or CXCL16. The signalling pathways stimulated by these chemokines were also dysregulated. Id-1 mRNA in SSc ECs was lower compared with normal ECs, and overexpression of Id-1 in SSc ECs increased their ability to migrate towards VEGF and CXCL16. Conclusion. Our results show that SSc ECs are unable to respond to pro-angiogenic chemokines despite their increased expression in serum and ECs. This might be due to the differences in the signalling pathways activated by these chemokines in normal vs SSc ECs. In addition, the lower expression of Id-1 also decreases the angiogenic response. The inability of pro-angiogenic chemokines to promote EC migration provides an additional mechanism for the impaired angiogenesis that characterizes SSc. PMID:26705326

  4. Niclosamide, an oral antihelmintic drug, exhibits antimetastatic activity in hepatocellular carcinoma cells through downregulating twist-mediated CD10 expression.

    Science.gov (United States)

    Chien, Ming-Hsien; Ho, Yung-Chuan; Yang, Shun-Fa; Yang, Yi-Chieh; Lai, Szu-Yu; Chen, Wan-Shen; Chen, Ming-Jenn; Yeh, Chao-Bin

    2018-02-26

    Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, especially, in eastern Asia, and its prognosis is poor once metastasis occurs. Niclosamide, a US Food and Drug Administration-approved antihelmintic drug, was shown to inhibit the growth of various cancers including HCC, but the effect of niclosamide on cell motility and the underlying mechanism have not yet been completely defined. The present study demonstrated that niclosamide, at 0-40 nM, concentration-dependently inhibited wound closure and the migratory/invasive capacities of human Huh7 and SK-Hep-1 HCC cells without exhibiting cytotoxicity. A protease array analysis showed that CD10 was dramatically downregulated in Huh7 cells after niclosamide treatment. Western blot and flow cytometric assays further demonstrated that CD10 expression was concentration-dependently downregulated in Huh7 and SK-Hep-1 cells after niclosamide treatment. Mechanistic investigations found that niclosamide suppressed Twist-mediated CD10 transactivation. Moreover, knockdown of CD10 expression by CD10 small interfering RNA in HCC cells suppressed cell migratory/invasive abilities and overexpression of CD10 relieved the migration inhibition induced by niclosamide. Taken together, our results indicated that niclosamide could be a potential agent for inhibiting metastasis of HCC, and CD10 is an important target of niclosamide for suppressing the motility of HCC cells. © 2018 Wiley Periodicals, Inc.

  5. A Developed NK-92MI Cell Line with Siglec-7neg Phenotype Exhibits High and Sustainable Cytotoxicity against Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Chin-Han Huang

    2018-04-01

    Full Text Available Altered sialic acid processing that leads to upregulation of cell surface sialylation is recognized as a key change in malignant tissue glycosylation. This cancer-associated hypersialylation directly impacts the signaling interactions between tumor cells and their surrounding microenvironment, especially the interactions mediated by immune cell surface sialic acid-binding immunoglobulin-like lectins (Siglecs to relay inhibitory signals for cytotoxicity. First, we obtained a Siglec-7neg NK-92MI cell line, NK-92MI-S7N, by separating a group of Siglec-7neg cell population from an eight-month-long-term NK-92MI in vitro culture by fluorescence-activated cell sorting (FACS. The effect of Siglec-7 loss on NK-92MI-S7N cells was characterized by the cell morphology, proliferation, and cytotoxic activity via FACS, MTS assay, cytotoxic assay, and natural killer (NK degranulation assay. We found the expression levels of Siglec-7 in NK-92MI were negatively correlated with NK cytotoxicity against leukemia cells. This NK-92MI-S7N cell not only shared very similar phenotypes with its parental cells but also possessed a high and sustainable killing activity. Furthermore, this Siglec-7neg NK line was unexpectedly capable of eliminating a NK-92MI-resistant leukemia cell, THP-1, through enhancing the effector-target interaction. In this study, a NK cell line with high and sustainable cytotoxicity was established and this cell may provide a potential application in NK-based treatment for leukemia patients.

  6. Arterial grafts exhibiting unprecedented cellular infiltration and remodeling in vivo: the role of cells in the vascular wall.

    Science.gov (United States)

    Row, Sindhu; Peng, Haofan; Schlaich, Evan M; Koenigsknecht, Carmon; Andreadis, Stelios T; Swartz, Daniel D

    2015-05-01

    To engineer and implant vascular grafts in the arterial circulation of a pre-clinical animal model and assess the role of donor medial cells in graft remodeling and function. Vascular grafts were engineered using Small Intestinal Submucosa (SIS)-fibrin hybrid scaffold and implanted interpositionally into the arterial circulation of an ovine model. We sought to demonstrate implantability of SIS-Fibrin based grafts; examine the remodeling; and determine whether the presence of vascular cells in the medial wall was necessary for cellular infiltration from the host and successful remodeling of the implants. We observed no occlusions or anastomotic complications in 18 animals that received these grafts. Notably, the grafts exhibited unprecedented levels of host cell infiltration that was not limited to the anastomotic sites but occurred through the lumen as well as the extramural side, leading to uniform cell distribution. Incoming cells remodeled the extracellular matrix and matured into functional smooth muscle cells as evidenced by expression of myogenic markers and development of vascular reactivity. Interestingly, tracking the donor cells revealed that their presence was beneficial but not necessary for successful grafting. Indeed, the proliferation rate and number of donor cells decreased over time as the vascular wall was dominated by host cells leading to significant remodeling and development of contractile function. These results demonstrate that SIS-Fibrin grafts can be successfully implanted into the arterial circulation of a clinically relevant animal model, improve our understanding of vascular graft remodeling and raise the possibility of engineering mural cell-free arterial grafts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Withanolide D Exhibits Similar Cytostatic Effect in Drug-Resistant and Drug-Sensitive Multiple Myeloma Cells

    Directory of Open Access Journals (Sweden)

    Mark E. Issa

    2017-09-01

    Full Text Available In spite of recent therapeutic advances, multiple myeloma (MM remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs. MM-CSCs are equipped with the necessary tools that render them highly resistant to virtually all conventional therapies. In this study, the growth inhibitory effects of withanolide D (WND, a steroidal lactone isolated from Withania somnifera, on drug-sensitive tumoral plasma cells and drug-resistant MM cells have been investigated. In MTT/XTT assays, WND exhibited similar cytostatic effects between drug-resistant and drug-sensitive cell lines in the nM range. WND also induced cell death and apoptosis in MM-CSCs and RPMI 8226 cells, as examined by the calcein/ethidium homodimer and annexin V/propidium iodide stainings, respectively. To determine whether P-glycoprotein (P-gp efflux affected the cytostatic activity of WND, P-gp was inhibited with verapamil and results indicated that the WND cytostatic effect in MM-CSCs was independent of P-gp efflux. Furthermore, WND did not increase the accumulation of the fluorescent P-gp substrate rhodamine 123 in MM-CSCs, suggesting that WND may not inhibit P-gp at the tested relevant doses. Therefore, the WND-induced cytostatic effect may be independent of P-gp efflux. These findings warrant further investigation of WND in MM-CSC animal models.

  8. An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity

    Science.gov (United States)

    Somasekharan, Syam Prakash; El-Naggar, Amal; Sorensen, Poul H.

    2016-01-01

    Research on marine natural products as potential anticancer agents is still limited. In the present study, an aqueous extract of a Canadian marine microalgal preparation was assessed for anticancer activities using various assays and cell lines of human cancers, including lung, prostate, stomach, breast, and pancreatic cancers, as well as an osteosarcoma. In vitro, the microalgal extract exhibited marked anticolony forming activity. In addition, it was more toxic, as indicated by increased apoptosis, to nonadherent cells (grown in suspension) than to adherent cells. In vivo, an antimetastatic effect of the extract was observed in NOD-SCID mice carrying subrenal capsule xenografts of PC3 prostate cancer cells. The results of the present study suggest that the antimetastatic effect of the aqueous microalgal extract is based on inhibition of colony forming ability of cancer cells and the preferential killing of suspended cancer cells. Further research aimed at identification of the molecular basis of the anticancer activities of the microalgal extract appears to be warranted. PMID:27656243

  9. An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity

    Directory of Open Access Journals (Sweden)

    Syam Prakash Somasekharan

    2016-01-01

    Full Text Available Research on marine natural products as potential anticancer agents is still limited. In the present study, an aqueous extract of a Canadian marine microalgal preparation was assessed for anticancer activities using various assays and cell lines of human cancers, including lung, prostate, stomach, breast, and pancreatic cancers, as well as an osteosarcoma. In vitro, the microalgal extract exhibited marked anticolony forming activity. In addition, it was more toxic, as indicated by increased apoptosis, to nonadherent cells (grown in suspension than to adherent cells. In vivo, an antimetastatic effect of the extract was observed in NOD-SCID mice carrying subrenal capsule xenografts of PC3 prostate cancer cells. The results of the present study suggest that the antimetastatic effect of the aqueous microalgal extract is based on inhibition of colony forming ability of cancer cells and the preferential killing of suspended cancer cells. Further research aimed at identification of the molecular basis of the anticancer activities of the microalgal extract appears to be warranted.

  10. Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE.

    Science.gov (United States)

    Hatfield, Julianne K; Brown, Melissa A

    2015-10-01

    Innate lymphoid cells are immune cells that reside in tissues that interface with the external environment and contribute to the first line defense against pathogens. However, they also have roles in promoting chronic inflammation. Here we demonstrate that group 3 ILCs, (ILC3s - CD45+Lin-IL-7Rα+RORγt+), are normal residents of the meninges and exhibit disease-induced accumulation and activation in EAE. In addition to production of the pro-inflammatory cytokines IL-17 and GM-CSF, ILC3s constitutively express CD30L and OX40L, molecules required for memory T cell survival. We show that disease-induced trafficking of transferred wild type T cells to the meninges is impaired in ILC3-deficient Rorc-/- mice. Furthermore, lymphoid tissue inducer cells, a c-kit+ ILC3 subset that promotes ectopic lymphoid follicle development, a hallmark of many autoimmune diseases, are reduced in the meninges of EAE-resistant c-kit mutant Kit(W/Wv) mice. We propose that ILC3s sustain neuroinflammation by supporting T cell survival and reactivation in the meninges. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Vesicles mimicking normal and cancer cell membranes exhibit differential responses to the cell-penetrating peptide Pep-1.

    Science.gov (United States)

    Almarwani, Bashiyar; Phambu, Esther Nzuzi; Alexander, Christopher; Nguyen, Ha Aimee T; Phambu, Nsoki; Sunda-Meya, Anderson

    2018-06-01

    The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the blue shift of its maximal emission wavelength. DSC data show that Pep-1 induces segregation of lipids. At high peptide concentration, IR data indicate that the interaction of Pep-1 is relatively stronger with normal cell membrane than with cancer cell membrane through the phosphate groups, while the interaction is weaker with normal cell membrane than with cancer cell membrane through the carbonyl groups. TGA and DSC data reveal that vesicles of normal cell membrane are thermally more stable than vesicles of cancer cell membrane. This suggests that the additional lipid PS included in cancer cell membrane has a destabilizing effect on the membrane structure. SEM images reveal that Pep-1 form superstructures including spherical particles and fibrils in the presence of both model membranes. PS seems to enhance peptide transport across cellular membranes. The biophysical techniques in this study provide valuable insights into the properties of CPPs in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies

    International Nuclear Information System (INIS)

    Ye Ling; Lin Jianguo; Sun Yuliang; Bennouna, Soumaya; Lo, Michael; Wu Qingyang; Bu Zhigao; Pulendran, Bali; Compans, Richard W.; Yang Chinglai

    2006-01-01

    Recombinant baculoviruses (rBV) expressing Ebola virus VP40 (rBV-VP40) or GP (rBV-GP) proteins were generated. Infection of Sf9 insect cells by rBV-VP40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. Ebola virus-like particles (VLPs) were produced by coinfection of Sf9 cells with rBV-VP40 and rBV-GP, and incorporation of Ebola GP into VLPs was demonstrated by SDS-PAGE and Western blot analysis. Recombinant baculovirus infection of insect cells yielded high levels of VLPs, which were shown to stimulate cytokine secretion from human dendritic cells similar to VLPs produced in mammalian cells. The immunogenicity of Ebola VLPs produced in insect cells was evaluated by immunization of mice. Analysis of antibody responses showed that most of the GP-specific antibodies were of the IgG2a subtype, while no significant level of IgG1 subtype antibodies specific for GP was induced, indicating the induction of a Th1-biased immune response. Furthermore, sera from Ebola VLP immunized mice were able to block infection by Ebola GP pseudotyped HIV virus in a single round infection assay, indicating that a neutralizing antibody against the Ebola GP protein was induced. These results show that production of Ebola VLPs in insect cells using recombinant baculoviruses represents a promising approach for vaccine development against Ebola virus infection

  13. DNA excision repair in cell extracts from human cell lines exhibiting hypersensitivity to DNA-damaging agents

    International Nuclear Information System (INIS)

    Hansson, J.; Keyse, S.M.; Lindahl, T.; Wood, R.D.

    1991-01-01

    Whole cell extracts from human lymphoid cell lines can perform in vitro DNA repair synthesis in plasmids damaged by agents including UV or cis-diamminedichloroplatinum(II) (cis-DDP). Extracts from xeroderma pigmentosum (XP) cells are defective in repair synthesis. We have now studied in vitro DNA repair synthesis using extracts from lymphoblastoid cell lines representing four human hereditary syndromes with increased sensitivity to DNA-damaging agents. Extracts of cell lines from individuals with the sunlight-sensitive disorders dysplastic nevus syndrome or Cockayne's syndrome (complementation groups A and B) showed normal DNA repair synthesis in plasmids with UV photoproducts. This is consistent with in vivo measurements of the overall DNA repair capacity in such cell lines. A number of extracts were prepared from two cell lines representing the variant form of XP (XP-V). Half of the extracts prepared showed normal levels of in vitro DNA repair synthesis in plasmids containing UV lesions, but the remainder of the extracts from the same cell lines showed deficient repair synthesis, suggesting the possibility of an unusually labile excision repair protein in XP-V. Fanconi's anemia (FA) cells show cellular hypersensitivity to cross-linking agents including cis-DDP. Extracts from cell lines belonging to two different complementation groups of FA showed normal DNA repair synthesis in plasmids containing cis-DDP or UV adducts. Thus, there does not appear to be an overall excision repair defect in FA, but the data do not exclude a defect in the repair of interstrand DNA cross-links

  14. Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells.

    Science.gov (United States)

    Li, Jing; Yue, Lanzhu; Wang, Huaquan; Liu, Chunyan; Liu, Hui; Tao, Jinglian; Qi, Weiwei; Wang, Yihao; Zhang, Wei; Fu, Rong; Shao, Zonghong

    2016-01-01

    Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration. Furthermore, expression rates of perforin and granzyme B in BM CD3+CD8+ cells (cytotoxic T lymphocyte, CTL) positively correlated with levels of IL-17 but negatively correlated with BM blast percentage and could be significantly increased after stimulation with human recombinant IL-17 (rhIL-17). Our results suggested that Th17 cells might play an antitumor effect in the pathogenesis of MDS through IL-17/CTL pathway.

  15. Embryonic stem cells deficient for Brca2 or Blm exhibit divergent genotoxic profiles that support opposing activities during homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Marple, Teresa [Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive San Antonio, TX 78245-3207 (United States); Kim, Tae Moon [Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive San Antonio, TX 78245-3207 (United States); Hasty, Paul [Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive San Antonio, TX 78245-3207 (United States)]. E-mail: hastye@uthscsa.edu

    2006-12-01

    The breast cancer susceptibility protein, Brca2 and the RecQ helicase, Blm (Bloom syndrome mutated) are tumor suppressors that maintain genome integrity, at least in part, through homologous recombination (HR). Brca2 facilitates HR by interacting with Rad51 in multiple regions, the BRC motifs encoded by exon 11 and a single domain encoded by exon 27; however, the exact importance of these regions is not fully understood. Blm also interacts with Rad51 and appears to suppress HR in most circumstances; however, its yeast homologue Sgs1 facilitates HR in response to some genotoxins. To better understand the biological importance of these two proteins, we performed a genotoxic screen on mouse embryonic stem (ES) cells impaired for either Brca2 or Blm to establish their genotoxic profiles (a cellular dose-response to a wide range of agents). This is the first side-by-side comparison of these two proteins in an identical genetic background. We compared cells deleted for Brca2 exon 27 to cells reduced for Blm expression and find that the Brca2- and Blm-impaired cells exhibit genotoxic profiles that reflect opposing activities during HR. Cells deleted for Brca2 exon 27 are hypersensitive to {gamma}-radiation, streptonigrin, mitomycin C and camptothecin and mildly resistant to ICRF-193 which is similar to HR defective cells null for Rad54. By contrast, Blm-impaired cells are hypersensitive to ICRF-193, mildly resistant to camptothecin and mitomycin C and more strongly resistant to hydroxyurea. These divergent profiles support the notion that Brca2 and Blm perform opposing functions during HR in mouse ES cells.

  16. Fe-MIL-101 exhibits selective cytotoxicity and inhibition of angiogenesis in ovarian cancer cells via downregulation of MMP.

    Science.gov (United States)

    Wang, Jiaqiang; Chen, Daomei; Li, Bin; He, Jiao; Duan, Deliang; Shao, Dandan; Nie, Minfang

    2016-05-18

    Though metal-organic frameworks (MOFs) have inspired potential applications in biomedicine, cytotoxicity studies of MOFs have been relatively rare. Here we demonstrate for the first time that an easily available MOF, Fe-MIL-101, possesses intrinsic activity against human SKOV3 ovarian cancer cells and suppress the proliferation of SKOV3 cells (IC50 = 23.6 μg mL(-1)) and normal mouse embryonic fibroblasts (BABL-3T3, IC50 = 78.3 μg mL(-1)) cells. It was more effective against SKOV3 cells than typical anticancer drugs such as artesunate (ART, IC50 = 96.9 μg mL(-1)) and oxaliplatin (OXA, IC50 = 64.4 μg mL(-1)), but had less effect on normal BABL-3T3 cells compared with ART (IC50 = 36.6 μg mL(-1)) and OXA (IC50 = 13.8 μg mL(-1)). Fe-MIL-101 induced apoptosis of human umbilical vein endothelial cells (HUVECs) via G0/G1 cell cycle arrest and decreased the mitochondrial membrane potential in HUVECs and induced apoptosis. Furthermore, Fe-MIL-101 exhibited stronger antiangiogenic effects in HUVEC cells than antiangiogenic inhibitor (SU5416) via downregulation the expression of MMP-2/9. Our results reveal a new role of Fe-MIL-101 as a novel, non-toxic anti-angiogenic agent that restricted ovarian tumour growth. These findings could open a new avenue of using MOFs as potential therapeutics in angiogenesis-dependent diseases, including ovarian cancer.

  17. Resveratrol, Acetyl-Resveratrol, and Polydatin Exhibit Antigrowth Activity against 3D Cell Aggregates of the SKOV-3 and OVCAR-8 Ovarian Cancer Cell Lines

    OpenAIRE

    Hogg, Simon J.; Chitcholtan, Kenny; Hassan, Wafaa; Sykes, Peter H.; Garrill, Ashley

    2015-01-01

    Resveratrol has aroused significant scientific interest as it has been claimed that it exhibits a spectrum of health benefits. These include effects as an anti-inflammatory and an antitumour compound. The purpose of this study was to investigate and compare any potential antigrowth effects of resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, on 3D cell aggregates of the EGFR/Her-2 positive and negative ovarian cancer cell lines SKOV-3 and OVCAR-8, respectively. Results...

  18. Men with Sickle Cell Anemia and Priapism Exhibit Increased Hemolytic Rate, Decreased Red Blood Cell Deformability and Increased Red Blood Cell Aggregate Strength.

    Directory of Open Access Journals (Sweden)

    Kizzy-Clara Cita

    Full Text Available To investigate the association between priapism in men with sickle cell anemia (SCA and hemorheological and hemolytical parameters.Fifty-eight men with SCA (median age: 38 years were included; 28 who had experienced priapism at least once during their life (priapism group and 30 who never experienced this complication (control group. Twenty-two patients were treated with hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC deformability at 30 Pa (ektacytometry and RBC aggregation properties (laser backscatter versus time. Blood viscosity was measured at a shear rate of 225 s-1 using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH, aspartate aminotransferase (ASAT, total bilirubin (BIL levels and reticulocyte (RET percentage to calculate a hemolytic index.Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01, LDH (p = 0.03, RET (p = 0.03 levels and hemolytic indices (p = 0.02. Higher RBC aggregates strength (p = 0.01 and lower RBC deformability (p = 0.005 were observed in patients with priapism compared to controls. After removing the hydroxycarbamide-treated patients, RBC deformability (p = 0.01 and RBC aggregate strength (p = 0.03 were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01 than controls.Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.

  19. Autoreactive effector/memory CD4+ and CD8+ T cells infiltrating grafted and endogenous islets in diabetic NOD mice exhibit similar T cell receptor usage.

    Directory of Open Access Journals (Sweden)

    Ramiro Diz

    Full Text Available Islet transplantation provides a "cure" for type 1 diabetes but is limited in part by recurrent autoimmunity mediated by β cell-specific CD4(+ and CD8(+ T cells. Insight into the T cell receptor (TCR repertoire of effector T cells driving recurrent autoimmunity would aid the development of immunotherapies to prevent islet graft rejection. Accordingly, we used a multi-parameter flow cytometry strategy to assess the TCR variable β (Vβ chain repertoires of T cell subsets involved in autoimmune-mediated rejection of islet grafts in diabetic NOD mouse recipients. Naïve CD4(+ and CD8(+ T cells exhibited a diverse TCR repertoire, which was similar in all tissues examined in NOD recipients including the pancreas and islet grafts. On the other hand, the effector/memory CD8(+ T cell repertoire in the islet graft was dominated by one to four TCR Vβ chains, and specific TCR Vβ chain usage varied from recipient to recipient. Similarly, islet graft- infiltrating effector/memory CD4(+ T cells expressed a limited number of prevalent TCR Vβ chains, although generally TCR repertoire diversity was increased compared to effector/memory CD8(+ T cells. Strikingly, the majority of NOD recipients showed an increase in TCR Vβ12-bearing effector/memory CD4(+ T cells in the islet graft, most of which were proliferating, indicating clonal expansion. Importantly, TCR Vβ usage by effector/memory CD4(+ and CD8(+ T cells infiltrating the islet graft exhibited greater similarity to the repertoire found in the pancreas as opposed to the draining renal lymph node, pancreatic lymph node, or spleen. Together these results demonstrate that effector/memory CD4(+ and CD8(+ T cells mediating autoimmune rejection of islet grafts are characterized by restricted TCR Vβ chain usage, and are similar to T cells that drive destruction of the endogenous islets.

  20. Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sultana Mehbuba Hossain

    2018-03-01

    Full Text Available Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells. Citrate- or succinate-modified CA particles were synthesized with different concentrations of sodium citrate or sodium succinate, respectively, in the absence or presence of doxorubicin. The drug loading efficiency of the particles and their cellular uptake were observed by quantifying fluorescence intensity. The average diameter and surface charge of the particles were determined using Zetasizer. Cell viability was assessed by MTT assay. Citrate-modified carbonate apatite (CMCA exhibited the highest (31.38% binding affinity for doxorubicin and promoted rapid cellular uptake of the drug, leading to the half-maximal inhibitory concentration 1000 times less than that of the free drug in MCF-7 cells. Hence, CMCA nanoparticles with greater surface area enhance cytotoxicity in different breast cancer cells by enabling higher loading and more efficient cellular uptake of the drug.

  1. 6-Hydroxyflavone and derivatives exhibit potent anti-inflammatory activity among mono-, di- and polyhydroxylated flavones in kidney mesangial cells.

    Directory of Open Access Journals (Sweden)

    Xing Wang

    Full Text Available Inflammatory responses by kidney mesangial cells play a critical role in the glomerulonephritis. The anti-inflammatory potential of nineteen mono-, di- and polyhydroxylated flavones including fisetin, quercetin, morin, tricetin, gossypetin, apigenin and myricetin were investigated on rat mesangial cells with lipopolysaccharide (LPS as the inflammatory stimuli. 6-Hydroxyflavone and 4',6-dihydroxyflavone exhibited high activity with IC50 in the range of 2.0 μM, a much better inhibition potential in comparison to the well-studied polyhydroxylated flavones. Interestingly, the anti-inflammatory activity was not due to direct quenching of NO radicals. Investigation on derivatives with methylation, acetylation or sulfation of 6-hydroxyl group revealed that 6-methoxyflavone was the most potent with an IC50 of 192 nM. Mechanistic study indicated that the anti-inflammatory activity of 6-methoxyflavone arose via the inhibition of LPS-induced downstream inducible NO synthase in mesangial cells. The identification of 6-hydroxyflavone and 6-methoxyflavone with potent anti-inflammatory activity in kidney mesangial cells provides a new flavone scaffold and direction to develop naturally derived products for potential nephritis prevention and treatment.

  2. Meliae cortex extract exhibits anti-allergic activity through the inhibition of Syk kinase in mast cells

    International Nuclear Information System (INIS)

    Lee, Jun Ho; Ko, Na Young; Kim, Nam Wook; Mun, Se Hwan; Kim, Jie Wan; Her, Erk; Kim, Bo Kyung; Seo, Dong Wan; Chang, Hyun Wook; Moon, Tae Chul; Han, Jeung Whan; Kim, Young Mi; Choi, Wahn Soo

    2007-01-01

    The anti-allergic action of various Oriental medicinal herbs was investigated using in vitro and in vivo experimental models. Of these extracts, the ethanol extract of Meliae cortex (MC) exhibited the most potent activity in mast cells; its IC 50 values were 29 ± 1.5 μg/ml for antigen stimulation and 57 ± 3.4 μg/ml for thapsigargin stimulation. It inhibited compound-48/80-induced systemic anaphylaxis by 52.9% at a dose of 300 mg/kg in mice; it also inhibited the expression of the proinflammatory mediator TNF-α. With regard to its mechanism of action, MC suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell signaling processes and that of Akt in a dose-dependent manner. It also inhibited the MAP kinase ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. Taken together, these results suggest that the anti-allergic activity of MC may be due to the inhibition of histamine secretion and cytokine expression through the Syk inhibition in mast cells

  3. Skin cell isolation and expansion for cell transplantation is limited in patients using tobacco, alcohol, or are exhibiting diabetes mellitus.

    Science.gov (United States)

    Johnen, Christa; Hartmann, Bernd; Steffen, Ingo; Bräutigam, Kirsten; Witascheck, Tom; Toman, Nidal; Küntscher, Markus V; Gerlach, Jörg C

    2006-03-01

    The aim of this exploratory study was to investigate the isolation and expansion of keratinocytes and fibroblasts from donors with certain medical histories. Biopsies were taken from donors (N=32) falling into one or more of the following categories: a history of heavy smoking and/or alcohol abuse, drug abuse, diabetes mellitus or steroid treatment. Cells from donors who did not fall into any of the above-mentioned categories were used as controls. Proliferation and growth behaviour of cells were analyzed by measurement of passage duration, absorbance (MTT-assay) and light microscopy. Donors with a specific medical history required larger biopsy areas than the control group for isolating a sufficient number of fibroblasts and keratinocytes. Times to confluence were significantly prolonged and absorbances (MTT) were significantly reduced in several donor groups when compared to control cultures. Biopsies from donors with steroid treatment, drug abuse and combined nicotine and alcohol abuse could not be established beyond passage 0 degrees or 1 degree, respectively. We conclude that isolation and expansion of skin cells from donors with certain medical histories may require larger biopsies, prolonged expansion times or may even result in failure. These findings may therefore be of clinical importance in the field of autologous skin cell transplantation.

  4. Human Exhibitions

    DEFF Research Database (Denmark)

    Andreassen, Rikke

    light on the staging of exhibitions, the daily life of the exhibitees, the wider connections between shows across Europe and the thinking of the time on matters of race, science, gender and sexuality. A window onto contemporary racial understandings, the book presents interviews with the descendants...... of displayed people, connecting the attitudes and science of the past with both our (continued) modern fascination with ‘the exotic’, and contemporary language and popular culture. As such, it will be of interest to scholars of sociology, anthropology and history working in the areas of gender and sexuality...

  5. Zika Virus Exhibits Lineage-Specific Phenotypes in Cell Culture, in Aedes aegypti Mosquitoes, and in an Embryo Model

    Directory of Open Access Journals (Sweden)

    Katherine A. Willard

    2017-12-01

    Full Text Available Zika virus (ZIKV has quietly circulated in Africa and Southeast Asia for the past 65 years. However, the recent ZIKV epidemic in the Americas propelled this mosquito-borne virus to the forefront of flavivirus research. Based on historical evidence, ZIKV infections in Africa were sporadic and caused mild symptoms such as fever, skin rash, and general malaise. In contrast, recent Asian-lineage ZIKV infections in the Pacific Islands and the Americas are linked to birth defects and neurological disorders. The aim of this study is to compare replication, pathogenicity, and transmission efficiency of two historic and two contemporary ZIKV isolates in cell culture, the mosquito host, and an embryo model to determine if genetic variation between the African and Asian lineages results in phenotypic differences. While all tested isolates replicated at similar rates in Vero cells, the African isolates displayed more rapid viral replication in the mosquito C6/36 cell line, yet they exhibited poor infection rates in Aedes aegypti mosquitoes compared to the contemporary Asian-lineage isolates. All isolates could infect chicken embryos; however, infection with African isolates resulted in higher embryo mortality than infection with Asian-lineage isolates. These results suggest that genetic variation between ZIKV isolates can significantly alter experimental outcomes.

  6. Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling

    International Nuclear Information System (INIS)

    Tateishi, Kento; Ashihara, Eishi; Honsho, Shoken; Takehara, Naofumi; Nomura, Tetsuya; Takahashi, Tomosaburo; Ueyama, Tomomi; Yamagishi, Masaaki; Yaku, Hitoshi; Matsubara, Hiroaki; Oh, Hidemasa

    2007-01-01

    Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardiomyocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3β may be crucial modulators for hCSC maintenance in human heart

  7. Induced Foxp3+ T cells colonising tolerated allografts exhibit the hypomethylation pattern typical of mature regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Robert eHilbrands

    2016-04-01

    Full Text Available Regulatory T cells expressing the transcription factor Foxp3 require acquisition of a specific hypomethylation pattern to ensure optimal functional commitment, limited lineage plasticity and long-term maintenance of tolerance. A better understanding of the molecular mechanisms involved in the generation of these epigenetic changes in vivo will contribute to the clinical exploitation of Foxp3+Treg. Here we show that both in vitro and in vivo generated antigen specific Foxp3+Treg can acquire Treg-specific epigenetic characteristics and prevent skin graft rejection in an animal model.

  8. Macrolide Antibiotics Exhibit Cytotoxic Effect under Amino Acid-Depleted Culture Condition by Blocking Autophagy Flux in Head and Neck Squamous Cell Carcinoma Cell Lines

    Science.gov (United States)

    Hirasawa, Kazuhiro; Moriya, Shota; Miyahara, Kana; Kazama, Hiromi; Hirota, Ayako; Takemura, Jun; Abe, Akihisa; Inazu, Masato; Hiramoto, Masaki; Tsukahara, Kiyoaki

    2016-01-01

    Autophagy, a self-digestive system for cytoplasmic components, is required to maintain the amino acid pool for cellular homeostasis. We previously reported that the macrolide antibiotics azithromycin (AZM) and clarithromycin (CAM) have an inhibitory effect on autophagy flux, and they potently enhance the cytocidal effect of various anticancer reagents in vitro. This suggests that macrolide antibiotics can be used as an adjuvant for cancer chemotherapy. Since cancer cells require a larger metabolic demand than normal cells because of their exuberant growth, upregulated autophagy in tumor cells has now become the target for cancer therapy. In the present study, we examined whether macrolides exhibit cytotoxic effect under an amino acid-starving condition in head and neck squamous cancer cell lines such as CAL 27 and Detroit 562 as models of solid tumors with an upregulated autophagy in the central region owing to hypovascularity. AZM and CAM induced cell death under the amino acid-depleted (AAD) culture condition in these cell lines along with CHOP upregulation, although they showed no cytotoxicity under the complete culture medium. CHOP knockdown by siRNA in the CAL 27 cells significantly suppressed macrolide-induced cell death under the AAD culture condition. CHOP-/- murine embryonic fibroblast (MEF) cell lines also attenuated AZM-induced cell death compared with CHOP+/+ MEF cell lines. Using a tet-off atg5 MEF cell line, knockout of atg5, an essential gene for autophagy, also induced cell death and CHOP in the AAD culture medium but not in the complete culture medium. This suggest that macrolide-induced cell death via CHOP induction is dependent on autophagy inhibition. The cytotoxicity of macrolide with CHOP induction was completely cancelled by the addition of amino acids in the culture medium, indicating that the cytotoxicity is due to the insufficient amino acid pool. These data suggest the possibility of using macrolides for “tumor-starving therapy”. PMID

  9. Kefir exhibits anti‑proliferative and pro‑apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion.

    Science.gov (United States)

    Khoury, Nathalie; El-Hayek, Stephany; Tarras, Omayr; El-Sabban, Marwan; El-Sibai, Mirvat; Rizk, Sandra

    2014-11-01

    Kefir, a fermented milk product, exhibits anti‑tumoral activity in vivo; yet its mechanism of action remains elusive. Recent studies have focused on the mechanism of action of kefir on cancer cells in vitro. The current study aims at examining the effect of kefir on cell survival, proliferation, and motility of colorectal cancer (CRC) cells. Kefir's anti‑cancer potential was tested on CRC cell lines, Caco‑2 and HT‑29, through cytotoxicity, proliferation, and apoptotic assays. The expression of certain genes involved in proliferation and apoptosis was measured using reverse transcriptase‑polymerase chain reaction (RT‑PCR) and western blotting. To assess the effect of kefir on cancer metastasis, wound‑healing and time‑lapse movies, in addition to collagen‑based invasion assay, were used. The results show that cell‑free fractions of kefir exhibit an anti‑proliferative effect on Caco‑2 and HT‑29 cells. Analysis of DNA content by flow cytometry revealed the ability of kefir to induce cell cycle arrest at the G1 phase. Kefir was also found to induce apoptosis, as seen by cell death ELISA. Results from RT‑PCR showed that kefir decreases the expression of transforming growth factor α (TGF‑α); and transforming growth factor‑β1 (TGF‑β1) in HT‑29 cells. Western blotting results revealed an upregulation in Bax:Bcl‑2 ratio, confirming the pro‑apoptotic effect of kefir, and an increase in p53 independent‑p21 expression upon kefir treatment. MMP expression was not altered by kefir treatment. Furthermore, results from time‑lapse motility movies, wound‑healing, and invasion assays showed no effect on the motility of colorectal as well as breast (MCF‑7 and MB‑MDA‑231) cancer cells upon kefir treatment. Our data suggest that kefir is able to inhibit the proliferation and induce apoptosis in HT‑29 and Caco‑2 CRC cells, yet it does not exhibit a significant effect on the motility and invasion of these cells in vitro.

  10. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

    Directory of Open Access Journals (Sweden)

    Galati Gaspare

    2009-07-01

    Full Text Available Abstract Background Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA. Methods The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols. Results Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6 as well as a tumor-line (HL60. Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA. Conclusion Resveratrol is

  11. CD4+ FOXP3+ Regulatory T Cells Exhibit Impaired Ability to Suppress Effector T Cell Proliferation in Patients with Turner Syndrome.

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    Young Ah Lee

    Full Text Available We investigated whether the frequency, phenotype, and suppressive function of CD4+ FOXP3+ regulatory T cells (Tregs are altered in young TS patients with the 45,X karyotype compared to age-matched controls.Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4-35.9 years and healthy controls (n = 16 were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (- (n = 7 and TS (+ (n = 17. Tregs sorted for CD4+ CD25bright were co-cultured with autologous CD4+ CD25- target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function.Despite a lower frequency of CD4+ T cells in the TS (- and TS (+ patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively, both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively. There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+ CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+ CD25- T cells was significantly impaired in the TS (- and TS (+ patients compared to controls (P = 0.003 and P = 0.041. Meanwhile, both the TS (- and TS (+ groups had lower frequencies of naïve cells (P = 0.001 for both but higher frequencies of effector memory cells (P = 0.004 and P = 0.002 than did the healthy control group.The Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells.

  12. Canine Mammary Cancer Stem Cells are Radio- and Chemo-Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    International Nuclear Information System (INIS)

    Pang, Lisa Y.; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J.

    2011-01-01

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology

  13. Canine Mammary Cancer Stem Cells are Radio- and Chemo-Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Lisa Y., E-mail: lisa.pang@ed.ac.uk; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J. [Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG (United Kingdom)

    2011-03-30

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

  14. Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

    Science.gov (United States)

    Rao, Sambasiva P.; Sancho, Jose; Campos-Rivera, Juanita; Boutin, Paula M.; Severy, Peter B.; Weeden, Timothy; Shankara, Srinivas; Roberts, Bruce L.; Kaplan, Johanne M.

    2012-01-01

    Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact. PMID:22761788

  15. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis.

    Directory of Open Access Journals (Sweden)

    Sambasiva P Rao

    Full Text Available Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs display the highest number while natural killer (NK cells, plasmacytoid dendritic cells (pDCs and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact.

  16. Arabidopsis brassinosteroid biosynthetic mutant dwarf7-1 exhibits slower rates of cell division and shoot induction

    Directory of Open Access Journals (Sweden)

    Schulz Burkhard

    2010-12-01

    Full Text Available Abstract Background Plant growth depends on both cell division and cell expansion. Plant hormones, including brassinosteroids (BRs, are central to the control of these two cellular processes. Despite clear evidence that BRs regulate cell elongation, their roles in cell division have remained elusive. Results Here, we report results emphasizing the importance of BRs in cell division. An Arabidopsis BR biosynthetic mutant, dwarf7-1, displayed various characteristics attributable to slower cell division rates. We found that the DWARF4 gene which encodes for an enzyme catalyzing a rate-determining step in the BR biosynthetic pathways, is highly expressed in the actively dividing callus, suggesting that BR biosynthesis is necessary for dividing cells. Furthermore, dwf7-1 showed noticeably slower rates of callus growth and shoot induction relative to wild-type control. Flow cytometric analyses of the nuclei derived from either calli or intact roots revealed that the cell division index, which was represented as the ratio of cells at the G2/M vs. G1 phases, was smaller in dwf7-1 plants. Finally, we found that the expression levels of the genes involved in cell division and shoot induction, such as PROLIFERATING CELL NUCLEAR ANTIGEN2 (PCNA2 and ENHANCER OF SHOOT REGENERATION2 (ESR2, were also lower in dwf7-1 as compared with wild type. Conclusions Taken together, results of callus induction, shoot regeneration, flow cytometry, and semi-quantitative RT-PCR analysis suggest that BRs play important roles in both cell division and cell differentiation in Arabidopsis.

  17. Multi-nucleate retinal pigment epithelium cells of the human macula exhibit a characteristic and highly specific distribution.

    Science.gov (United States)

    Starnes, Austin C; Huisingh, Carrie; McGwin, Gerald; Sloan, Kenneth R; Ablonczy, Zsolt; Smith, R Theodore; Curcio, Christine A; Ach, Thomas

    2016-01-01

    The human retinal pigment epithelium (RPE) is reportedly 3% bi-nucleated. The importance to human vision of multi-nucleated (MN)-RPE cells could be clarified with more data about their distribution in central retina. Nineteen human RPE-flatmounts (9 ≤ 51 years, 10 > 80 years) were imaged at 12 locations: 3 eccentricities (fovea, perifovea, near periphery) in 4 quadrants (superior, inferior, temporal, nasal). Image stacks of lipofuscin-attributable autofluorescence and phalloidin labeled F-actin cytoskeleton were obtained using a confocal fluorescence microscope. Nuclei were devoid of autofluorescence and were marked using morphometric software. Cell areas were approximated by Voronoi regions. Mean number of nuclei per cell among eccentricity/quadrant groups and by age were compared using Poisson and binominal regression models. A total of 11,403 RPE cells at 200 locations were analyzed: 94.66% mono-, 5.31% bi-, 0.02% tri-nucleate, and 0.01% with 5 nuclei. Age had no effect on number of nuclei. There were significant regional differences: highest frequencies of MN-cells were found at the perifovea (9.9%) and near periphery (6.8%). The fovea lacked MN-cells almost entirely. The nasal quadrant had significantly more MN-cells compared to other quadrants, at all eccentricities. This study demonstrates MN-RPE cells in human macula. MN-cells may arise due to endoreplication, cell fusion, or incomplete cell division. The topography of MN-RPE cells follows the topography of photoreceptors; with near-absence at the fovea (cones only) and high frequency at perifovea (highest rod density). This distribution might reflect specific requirements of retinal metabolism or other mechanisms addressable in further studies.

  18. Combination of Vorinostat and caspase‐8 inhibition exhibits high anti‐tumoral activity on endometrial cancer cells

    OpenAIRE

    Bergadà, Laura; Sorolla, Annabel; Yeramian, Andree; Eritja, Nuria; Mirantes, Cristina; Matias-Guiu, Xavier; Dolcet, Xavier

    2013-01-01

    Histone deacetylase inhibitors such as Vorinostat display anti‐neoplastic activity against a variety of solid tumors. Here, we have investigated the anti‐tumoral activity of Vorinostat on endometrial cancer cells. We have found that Vorinostat caused cell growth arrest, loss of clonogenic growth and apoptosis of endometrial cancer cells. Vorinostat‐induced the activation of caspase‐8 and ‐9, the initiators caspases of the extrinsic and the intrinsic apoptotic pathways, respectively. Next, we ...

  19. HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice.

    Science.gov (United States)

    Kruse, Robert L; Shum, Thomas; Tashiro, Haruko; Barzi, Mercedes; Yi, Zhongzhen; Whitten-Bauer, Christina; Legras, Xavier; Bissig-Choisat, Beatrice; Garaigorta, Urtzi; Gottschalk, Stephen; Bissig, Karl-Dimiter

    2018-04-06

    Chronic hepatitis B virus (HBV) infection remains incurable. Although HBsAg-specific chimeric antigen receptor (HBsAg-CAR) T cells have been generated, they have not been tested in animal models with authentic HBV infection. We generated a novel CAR targeting HBsAg and evaluated its ability to recognize HBV+ cell lines and HBsAg particles in vitro. In vivo, we tested whether human HBsAg-CAR T cells would have efficacy against HBV-infected hepatocytes in human liver chimeric mice. HBsAg-CAR T cells recognized HBV-positive cell lines and HBsAg particles in vitro as judged by cytokine production. However, HBsAg-CAR T cells did not kill HBV-positive cell lines in cytotoxicity assays. Adoptive transfer of HBsAg-CAR T cells into HBV-infected humanized mice resulted in accumulation within the liver and a significant decrease in plasma HBsAg and HBV-DNA levels compared with control mice. Notably, the fraction of HBV core-positive hepatocytes among total human hepatocytes was greatly reduced after HBsAg-CAR T cell treatment, pointing to noncytopathic viral clearance. In agreement, changes in surrogate human plasma albumin levels were not significantly different between treatment and control groups. HBsAg-CAR T cells have anti-HBV activity in an authentic preclinical HBV infection model. Our results warrant further preclinical exploration of HBsAg-CAR T cells as immunotherapy for HBV. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  20. Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and impaired spleen structure.

    Science.gov (United States)

    Kim, Soochan; Han, Sinsuk; Lee, Ye Eun; Jung, Woong-Jae; Lee, Hyung Soo; Kim, Yong-Sun; Choi, Eun-Kyoung; Kim, Mi-Yeon

    2016-01-01

    The cellular prion protein is expressed in almost all tissues, including the central nervous system and lymphoid tissues. To investigate the effects of the prion protein in lymphoid cells and spleen structure formation, we used prion protein-deficient (Prnp(0/0)) Zürich I mice generated by inactivation of the Prnp gene. Prnp(0/0) mice had decreased lymphocytes, in particular, CD4 T cells and lymphoid tissue inducer (LTi) cells. Decreased CD4 T cells resulted from impaired expression of CCL19 and CCL21 in the spleen rather than altered chemokine receptor CCR7 expression. Importantly, some of the white pulp regions in spleens from Prnp(0/0) mice displayed impaired T zone structure as a result of decreased LTi cell numbers and altered expression of the lymphoid tissue-organizing genes lymphotoxin-α and CXCR5, although expression of the lymphatic marker podoplanin and CXCL13 by stromal cells was not affected. In addition, CD3(-)CD4(+)IL-7Rα(+) LTi cells were rarely detected in impaired white pulp in spleens of these mice. These data suggest that the prion protein is required to form the splenic white pulp structure and for development of normal levels of CD4 T and LTi cells. Copyright © 2015. Published by Elsevier GmbH.

  1. Novel histone deacetylase inhibitor AR-42 exhibits antitumor activity in pancreatic cancer cells by affecting multiple biochemical pathways.

    Directory of Open Access Journals (Sweden)

    Yi-Jin Chen

    Full Text Available Pancreatic cancer is one of the most lethal types of cancer with a 5-year survival rate of ~5%. Histone deacetylases (HDACs participate in many cellular processes, including carcinogenesis, and pharmacological inhibition of HDACs has emerged as a potential therapeutic strategy. In this study, we explored antitumor activity of the novel HDAC inhibitor AR-42 in pancreatic cancer.Human pancreatic cancer cell lines BxPC-3 and PANC-1 were used in this study. Real-time PCR, RT-PCR, and western blotting were employed to investigate expression of specific genes and proteins, respectively. Translocation of apoptosis-inducing factor was investigated by immunofluorescence and subcellular fractionation. The number of apoptotic cells, cell cycle stages, and reactive oxygen species (ROS generation levels were determined by flow cytometry. Cell invasiveness was examined by the Matrigel invasion assay. Efficacy of AR-42 in vivo was evaluated by utilizing BxPC-3 xenograft mouse model.AR-42 inhibited pancreatic cancer cell proliferation by causing G2/M cell cycle arrest via regulating expression levels of genes and proteins involved in cell cycle. AR-42 also induced ROS generation and DNA damage, triggering apoptosis of pancreatic cancer cells via both caspase-3-dependent and caspase-3-independent pathways. In addition, AR-42 increased expression levels of negative regulators of p53 (miR-125b, miR-30d, and miR33, which could contribute to lower expression level of mutant p53 in pancreatic cancer cells. Cell invasion assay showed that AR-42 reduced cancer cell aggressiveness and significantly diminished BxPC-3 xenograft tumor growth in vivo.AR-42, a novel HDAC inhibitor, inhibited pancreatic cancer cells by regulating p53 expression, inducing cell cycle arrest, particularly at the G2/M stage, and activating multiple apoptosis pathways. Additionally, AR-42 inhibited cell invasiveness and potently suppressed pancreatic cancer tumors in vivo. We conclude that by

  2. Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease.

    Science.gov (United States)

    Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Hsu, Ching-Ju; Lin, Shinn-Zong; Tu, Chi-Tang; Chang, Li-Hsun; Wu, Ping-An; Liu, Shih-Ping

    2018-03-01

    Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

  3. Ethacrynic acid exhibits selective toxicity to chronic lymphocytic leukemia cells by inhibition of the Wnt/beta-catenin pathway.

    Directory of Open Access Journals (Sweden)

    Desheng Lu

    Full Text Available BACKGROUND: Aberrant activation of Wnt/beta-catenin signaling promotes the development of several cancers. It has been demonstrated that the Wnt signaling pathway is activated in chronic lymphocytic leukemia (CLL cells, and that uncontrolled Wnt/beta-catenin signaling may contribute to the defect in apoptosis that characterizes this malignancy. Thus, the Wnt signaling pathway is an attractive candidate for developing targeted therapies for CLL. METHODOLOGY/PRINCIPAL FINDINGS: The diuretic agent ethacrynic acid (EA was identified as a Wnt inhibitor using a cell-based Wnt reporter assay. In vitro assays further confirmed the inhibitory effect of EA on Wnt/beta-catenin signaling. Cell viability assays showed that EA selectively induced cell death in primary CLL cells. Exposure of CLL cells to EA decreased the expression of Wnt/beta-catenin target genes, including LEF-1, cyclin D1 and fibronectin. Immune co-precipitation experiments demonstrated that EA could directly bind to LEF-1 protein and destabilize the LEF-1/beta-catenin complex. N-acetyl-L-cysteine (NAC, which can react with the alpha, beta-unsaturated ketone in EA, but not other anti-oxidants, prevented the drug's inhibition of Wnt/beta-catenin activation and its ability to induce apoptosis in CLL cells. CONCLUSIONS/SIGNIFICANCE: Our studies indicate that EA selectively suppresses CLL survival due to inhibition of Wnt/beta-catenin signaling. Antagonizing Wnt signaling in CLL with EA or related drugs may represent an effective treatment of this disease.

  4. MCF-7 human mammary adenocarcinoma cells exhibit augmented responses to human insulin on a collagen IV surface

    DEFF Research Database (Denmark)

    Listov-Saabye, Nicolai; Jensen, Marianne Blirup; Kiehr, Benedicte

    2009-01-01

    Human mammary cell lines are extensively used for preclinical safety assessment of insulin analogs. However, it is essentially unknown how mitogenic responses can be optimized in mammary cell-based systems. We developed an insulin mitogenicity assay in MCF-7 human mammary adenocarcinoma cells......, under low serum (0.1% FCS) and phenol red-free conditions, with 3H thymidine incorporation as endpoint. Based on EC50 values determined from 10-fold dilution series, beta-estradiol was the most potent mitogen, followed by human IGF-1, human AspB10 insulin and native human insulin. AspB10 insulin...... was significantly more mitogenic than native insulin, validating the ability of the assay to identify hypermitogenic human insulin analogs. With MCF-7 cells on a collagen IV surface, the ranking of mitogens was maintained, but fold mitogenic responses and dynamic range and steepness of dose-response curves were...

  5. An integrated analysis of genes and pathways exhibiting metabolic differences between estrogen receptor positive breast cancer cells

    International Nuclear Information System (INIS)

    Mandal, Soma; Davie, James R

    2007-01-01

    The sex hormone estrogen (E2) is pivotal to normal mammary gland growth and differentiation and in breast carcinogenesis. In this in silico study, we examined metabolic differences between ER(+)ve breast cancer cells during E2 deprivation. Public repositories of SAGE and MA gene expression data generated from E2 deprived ER(+)ve breast cancer cell lines, MCF-7 and ZR75-1 were compared with normal breast tissue. We analyzed gene ontology (GO), enrichment, clustering, chromosome localization, and pathway profiles and performed multiple comparisons with cell lines and tumors with different ER status. In all GO terms, biological process (BP), molecular function (MF), and cellular component (CC), MCF-7 had higher gene utilization than ZR75-1. Various analyses showed a down-regulated immune function, an up-regulated protein (ZR75-1) and glucose metabolism (MCF-7). A greater percentage of 77 common genes localized to the q arm of all chromosomes, but in ZR75-1 chromosomes 11, 16, and 19 harbored more overexpressed genes. Despite differences in gene utilization (electron transport, proteasome, glycolysis/gluconeogenesis) and expression (ribosome) in both cells, there was an overall similarity of ZR75-1 with ER(-)ve cell lines and ER(+)ve/ER(-)ve breast tumors. This study demonstrates integral metabolic differences may exist within the same cell subtype (luminal A) in representative ER(+)ve cell line models. Selectivity of gene and pathway usage for strategies such as energy requirement minimization, sugar utilization by ZR75-1 contrasted with MCF-7 cells, expressing genes whose protein products require ATP utilization. Such characteristics may impart aggressiveness to ZR75-1 and may be prognostic determinants of ER(+)ve breast tumors

  6. Tivantinib (ARQ-197) exhibits anti-tumor activity with down-regulation of FAK in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Xi, Wei-Hong; Yang, Li-Yun; Cao, Zhong-Yi; Qian, Yong

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide and the 5 years survival rate of the patients is about 60% in the USA, due to acquired chemotherapeutic resistance and metastasis of the disease. In this study, we found that tivantinib, a selective MET inhibitor, suppresses OCSS cell proliferation and colony formation, however, anti-tumor activities induced by tivantinib are independent of the inhibition of MET signaling pathway. In addition, tivantinib cause G2/M cell cycle arrest and caspases-dependent apoptosis in OSCC cell lines. We also found that tivantinib dose-dependently suppressed the activation and expression of FAK. In all, these data suggested that tivantinib may be developed as a chemotherapeutic agent to effectively treat certain cancers including OSCC. - Highlights: • Tivantinib suppresses OSCC cell growth independent of the inhibition of HGF/MET signaling pathway. • Tivantinib blocks cell cycle and induces caspases-mediated apoptosis. • Tivantinib elicits its anti-tumor activity with the inhibition of FAK signaling pathway

  7. Tivantinib (ARQ-197) exhibits anti-tumor activity with down-regulation of FAK in oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Wei-Hong [Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Nanchang University, Nanchang 330006 (China); Yang, Li-Yun [Department of Blood Transfusion, First Affiliated Hospital, Nanchang University, Nanchang 330006 (China); Cao, Zhong-Yi, E-mail: m18070383032@163.com [Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Nanchang University, Nanchang 330006 (China); Qian, Yong, E-mail: yfykqkqy@163.com [Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Nanchang University, Nanchang 330006 (China)

    2015-02-20

    Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide and the 5 years survival rate of the patients is about 60% in the USA, due to acquired chemotherapeutic resistance and metastasis of the disease. In this study, we found that tivantinib, a selective MET inhibitor, suppresses OCSS cell proliferation and colony formation, however, anti-tumor activities induced by tivantinib are independent of the inhibition of MET signaling pathway. In addition, tivantinib cause G2/M cell cycle arrest and caspases-dependent apoptosis in OSCC cell lines. We also found that tivantinib dose-dependently suppressed the activation and expression of FAK. In all, these data suggested that tivantinib may be developed as a chemotherapeutic agent to effectively treat certain cancers including OSCC. - Highlights: • Tivantinib suppresses OSCC cell growth independent of the inhibition of HGF/MET signaling pathway. • Tivantinib blocks cell cycle and induces caspases-mediated apoptosis. • Tivantinib elicits its anti-tumor activity with the inhibition of FAK signaling pathway.

  8. Citrobacter amalonaticus phytase on the cell surface of Pichia pastoris exhibits high pH stability as a promising potential feed supplement.

    Science.gov (United States)

    Li, Cheng; Lin, Ying; Huang, Yuanyuan; Liu, Xiaoxiao; Liang, Shuli

    2014-01-01

    Phytase expressed and anchored on the cell surface of Pichia pastoris avoids the expensive and time-consuming steps of protein purification and separation. Furthermore, yeast cells with anchored phytase can be used as a whole-cell biocatalyst. In this study, the phytase gene of Citrobacter amalonaticus was fused with the Pichia pastoris glycosylphosphatidylinositol (GPI)-anchored glycoprotein homologue GCW61. Phytase exposed on the cell surface exhibits a high activity of 6413.5 U/g, with an optimal temperature of 60°C. In contrast to secreted phytase, which has an optimal pH of 5.0, phytase presented on the cell surface is characterized by an optimal pH of 3.0. Moreover, our data demonstrate that phytase anchored on the cell surface exhibits higher pH stability than its secreted counterpart. Interestingly, our in vitro digestion experiments demonstrate that phytase attached to the cell surface is a more efficient enzyme than secreted phytase.

  9. Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential.

    Science.gov (United States)

    Yu, Yuan; Li, Jialu; Zhu, Xuejun; Tang, Xiaowen; Bao, Yangyi; Sun, Xiang; Huang, Yuhui; Tian, Fang; Liu, Xiaomei; Yang, Lin

    2017-01-01

    Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies]), are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells. To pursue the possibility of translating those immunotoxins into clinics, we humanized the nanobody sequences (designated as dhuVHH6) as well as further truncated the Pseudomonas exotoxin A (PE)-derived PE38 toxin to produce a more protease-resistant form, which is named as PE-LR, by deleting majority of PE domain II. Three new types of immunotoxins, dhuVHH6-PE38, dVHH6-PE-LR, and dhuVHH6-PE-LR, were successfully constructed. These recombinant immunotoxins were expressed in Escherichia coli and showed that nanobody immunotoxins have the benefits of easy soluble expression in a prokaryotic expression system. Flow cytometry results revealed that all immunotoxins still maintained the ability to bind specifically to CD7-positive T lymphocyte strains without binding to CD7-negative control cells. Laser scanning confocal microscopy revealed that these proteins can be endocytosed into the cytoplasm after binding with CD7-positive cells and that this phenomenon was not observed in CD7-negative cells. WST-8 experiments showed that all immunotoxins retained the highly effective and specific growth inhibition activity in CD7-positive cell lines and primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Further in vivo animal model experiments showed that humanized dhuVHH6-PE38 immunotoxin can tolerate higher doses and extend the survival of NOD-Prkdc em26 Il2rg em26 Nju (NCG) mice

  10. MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells

    International Nuclear Information System (INIS)

    Wang, Zhigang; Zhang, Xiaoping; Yang, Zhili; Du, Hangxiang; Wu, Zhenqian; Gong, Jianfeng; Yan, Jun; Zheng, Qi

    2012-01-01

    Highlights: ► MiR-145 targets a putative binding site in the 3′UTR of PAK4. ► MiR-145 played an important role in inhibiting cell growth by directly targeting PAK4. ► MiR-145 may function as tumor suppressors. -- Abstract: MicroRNAs (miRNAs) are regulators of numerous cellular events; accumulating evidence indicates that miRNAs play a key role in a wide range of biological functions, such as cellular proliferation, differentiation, and apoptosis in cancer. Down-regulated expression of miR-145 has been reported in colon cancer tissues and cell lines. The molecular mechanisms underlying miR-145 and the regulation of colon carcinogenesis remain unclear. In this study, we investigated the levels of miR-145 in human colon cancer cells using qRT-PCR and found markedly decreased levels compared to normal epithelial cells. We identified PAK4 as a novel target of miR-145 using informatics screening. Additionally, we demonstrated that miR-145 targets a putative binding site in the 3′UTR of PAK4 and that its abundance is inversely associated with miR-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. Furthermore, restoration of miR-145 by mimics in SW620 cells significantly attenuated cell growth in vitro, in accordance with the inhibitory effects induced by siRNA mediated knockdown of PAK4. Taken together, these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.

  11. MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhigang [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China); Zhang, Xiaoping [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine (China); Yang, Zhili; Du, Hangxiang; Wu, Zhenqian; Gong, Jianfeng; Yan, Jun [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China); Zheng, Qi, E-mail: zhengqi1957@yahoo.com.cn [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer MiR-145 targets a putative binding site in the 3 Prime UTR of PAK4. Black-Right-Pointing-Pointer MiR-145 played an important role in inhibiting cell growth by directly targeting PAK4. Black-Right-Pointing-Pointer MiR-145 may function as tumor suppressors. -- Abstract: MicroRNAs (miRNAs) are regulators of numerous cellular events; accumulating evidence indicates that miRNAs play a key role in a wide range of biological functions, such as cellular proliferation, differentiation, and apoptosis in cancer. Down-regulated expression of miR-145 has been reported in colon cancer tissues and cell lines. The molecular mechanisms underlying miR-145 and the regulation of colon carcinogenesis remain unclear. In this study, we investigated the levels of miR-145 in human colon cancer cells using qRT-PCR and found markedly decreased levels compared to normal epithelial cells. We identified PAK4 as a novel target of miR-145 using informatics screening. Additionally, we demonstrated that miR-145 targets a putative binding site in the 3 Prime UTR of PAK4 and that its abundance is inversely associated with miR-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. Furthermore, restoration of miR-145 by mimics in SW620 cells significantly attenuated cell growth in vitro, in accordance with the inhibitory effects induced by siRNA mediated knockdown of PAK4. Taken together, these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.

  12. A bursal pentapeptide (BPP-I), a novel bursal-derived peptide, exhibits antiproliferation of tumor cell and immunomodulator activity.

    Science.gov (United States)

    Feng, Xiu L; Liu, Qing T; Cao, Rui B; Zhou, Bin; Wang, Fang Q; Deng, Wen L; Qiu, Ya F; Zhang, Yu; Ishag, Hassan; Ma, Zhi Y; Zheng, Qi S; Chen, Pu Y

    2012-06-01

    The bursa of Fabricius (BF) is the central humoral immune organ unique to birds. Here, we isolated a novel bursal pentapeptide I (BPP-I), LGPGP, from BF. BPP-I could play inhibition effect on MCF-7 but not on CEF or Vero cell proliferation in vitro, and enhance antitumor factor p53 protein expression. Also, BPP-I stimulated antibody production in a dose-dependent manner in hybridoma cell. Furthermore, BPP-I could induce various immune responses in mice immunization experiments, including increase antibody production and cytokines IL-4 and IFN-γ level, and induce T-cell immunophenotyping. These results suggest that BPP-I is a potential immunomodulator of antitumor and immunity. The study could provide some novel insights on the probable candidate reagent for the antitumor and immune improvement.

  13. Combination of Vorinostat and caspase-8 inhibition exhibits high anti-tumoral activity on endometrial cancer cells.

    Science.gov (United States)

    Bergadà, Laura; Sorolla, Annabel; Yeramian, Andree; Eritja, Nuria; Mirantes, Cristina; Matias-Guiu, Xavier; Dolcet, Xavier

    2013-08-01

    Histone deacetylase inhibitors such as Vorinostat display anti-neoplastic activity against a variety of solid tumors. Here, we have investigated the anti-tumoral activity of Vorinostat on endometrial cancer cells. We have found that Vorinostat caused cell growth arrest, loss of clonogenic growth and apoptosis of endometrial cancer cells. Vorinostat-induced the activation of caspase-8 and -9, the initiators caspases of the extrinsic and the intrinsic apoptotic pathways, respectively. Next, we investigated the role of the extrinsic pathway in apoptosis triggered by Vorinostat. We found that Vorinostat caused a dramatic decrease of FLIP mRNA and protein levels. However, overexpression of the long from of FLIP did not block Vorinostat-induced apoptosis. To further investigate the role of extrinsic apoptotic pathway in Vorinostat-induced apoptosis, we performed an shRNA-mediated knock-down of caspase-8. Surprisingly, downregulation of caspase-8 alone caused a marked decrease in clonogenic ability and reduced the growth of endometrial cancer xenografts in vivo, revealing that targeting caspase-8 may be an attractive target for anticancer therapy on endometrial tumors. Furthermore, combination of caspase-8 inhibition and Vorinostat treatment caused an enhancement of apoptotic cell death and a further decrease of clonogenic growth of endometrial cancer cells. More importantly, combination of Vorinostat and caspase-8 inhibition caused a nearly complete inhibition of tumor xenograft growth. Finally, we demonstrate that cell death triggered by Vorinostat alone or in combination with caspase-8 shRNAs was inhibited by the anti-apoptotic protein Bcl-XL. Our results suggest that combinatory therapies using Vorinostat treatment and caspase-8 inhibition can be an effective treatment for endometrial carcinomas. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential

    Directory of Open Access Journals (Sweden)

    Yu Y

    2017-03-01

    Full Text Available Yuan Yu,1–3 Jialu Li,1–3 Xuejun Zhu,4 Xiaowen Tang,2,5 Yangyi Bao,6 Xiang Sun,6 Yuhui Huang,1,2 Fang Tian,4 Xiaomei Liu,1,2 Lin Yang1–3 1The Cyrus Tang Hematology Center, 2Collaborative Innovation Center of Hematology, Soochow University, 3Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 4Central Laboratory, Department of Hematology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, 5Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 6Department of Hematology-Oncology, The First People’s Hospital of Hefei, Hefei, People’s Republic of China Background: Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies], are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells. To pursue the possibility of translating those immunotoxins into clinics, we humanized the nanobody sequences (designated as dhuVHH6 as well as further truncated the Pseudomonas exotoxin A (PE-derived PE38 toxin to produce a more protease-resistant form, which is named as PE-LR, by deleting majority of PE domain II. Methods and results: Three new types of immunotoxins, dhuVHH6-PE38, dVHH6-PE-LR, and dhuVHH6-PE-LR, were successfully constructed. These recombinant immunotoxins were expressed in Escherichia coli and showed that nanobody immunotoxins have the benefits of easy soluble expression in a prokaryotic expression system. Flow cytometry results revealed that

  15. A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells

    Directory of Open Access Journals (Sweden)

    Lin Li

    2010-08-01

    Full Text Available Abstract Background Targeting Signal Transducer and Activator of Transcription 3 (STAT3 signaling is an attractive therapeutic approach for most types of human cancers with constitutively activated STAT3. A novel small molecular STAT3 inhibitor, FLLL32 was specifically designed from dietary agent, curcumin to inhibit constitutive STAT3 signaling in multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cells. Results FLLL32 was found to be a potent inhibitor of STAT3 phosphorylation, STAT3 DNA binding activity, and the expression of STAT3 downstream target genes in vitro, leading to the inhibition of cell proliferation as well as the induction of Caspase-3 and PARP cleavages in human multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cell lines. However, FLLL32 exhibited little inhibition on some tyrosine kinases containing SH2 or both SH2 and SH3 domains, and other protein and lipid kinases using a kinase profile assay. FLLL32 was also more potent than four previously reported JAK2 and STAT3 inhibitors as well as curcumin to inhibit cell viability in these cancer cells. Furthermore, FLLL32 selectively inhibited the induction of STAT3 phosphorylation by Interleukin-6 but not STAT1 phosphorylation by IFN-γ. Conclusion Our findings indicate that FLLL32 exhibits potent inhibitory activity to STAT3 and has potential for targeting multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cells expressing constitutive STAT3 signaling.

  16. Mouse NK cell-mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing.

    Science.gov (United States)

    Sun, Kai; Alvarez, Maite; Ames, Erik; Barao, Isabel; Chen, Mingyi; Longo, Dan L; Redelman, Doug; Murphy, William J

    2012-02-09

    Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49(+) subsets in BMC rejection by using β2-microglobulin deficient (β2m(-/-)) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind "self-MHC" were found to be the dominant subset responsible for β2m(-/-) BMC rejection. This provides in vivo evidence for host MHC class I-dependent functional education. Interestingly, all H2(d) strain mice regardless of background were able to resist significantly greater amounts of β2m(-/-), but not wild-type BMC than H2(b) mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability.

  17. Using Drawings of the Brain Cell to Exhibit Expertise in Neuroscience: Exploring the Boundaries of Experimental Culture

    Science.gov (United States)

    Hay, David B.; Williams, Darren; Stahl, Daniel; Wingate, Richard J.

    2013-01-01

    This paper explores the research perspective of neuroscience by documenting the brain cell (neuron) drawings of undergraduates, trainee scientists, and leading neuroscience researchers in a single research-intensive university. Qualitative analysis, drawing-sorting exercises, and hierarchical cluster analysis are used to answer two related…

  18. CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold

    Directory of Open Access Journals (Sweden)

    Mi K

    2015-04-01

    Full Text Available Kun Mi,1 Zhihua Xing2 1Department of Biochemistry and Molecular Biology, Sichuan Cancer Hospital and Institute, 2Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Background: Self-assembling peptide nanofiber scaffolds have been shown to be a ­permissive biological material for tissue repair, cell proliferation, differentiation, etc. Recently, a subpopulation (CD44+/CD24- of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells have different phenotypes in self-assembling COCH3-RADARADARADARADA-CONH2 (RADA16 peptide nanofiber scaffold compared with Matrigel® (BD Biosciences, Two Oak Park, Bedford, MA, USA and collagen I.Methods: CD44 and CD24 expression was determined by flow cytometry. Cell proliferation was measured by 5-bromo-2'-deoxyuridine assay and DNA content measurement. Immunostaining was used to indicate the morphologies of cells in three-dimensional (3D cultures of different scaffolds and the localization of β-catenin in the colonies. Western blot was used to determine the expression of signaling proteins. In vitro migration assay and inoculation into nude mice were used to evaluate invasion and tumorigenesis in vivo.Results: The breast cancer cell line MDA-MB-435S contained a high percentage (>99% of CD44+/CD24- cells, which exhibited phenotypic reversion in 3D RADA16 nanofiber scaffold compared with collagen I and Matrigel. The newly formed reverted acini-like colonies reassembled a basement membrane and reorganized their cytoskeletons. At the same time, cells cultured and embedded in RADA16 peptide scaffold exhibited growth arrest. Also, they exhibited different migration potential, which links their migration ability with their cellular morphology. Consistent with studies in vitro, the in vivo tumor

  19. Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Chan-on W

    2015-04-01

    Full Text Available Waraporn Chan-on,1 Nguyen Thi Bich Huyen,2 Napat Songtawee,3 Wilasinee Suwanjang,1 Supaluk Prachayasittikul,3 Virapong Prachayasittikul2 1Center for Research and Innovation, 2Department of Clinical Microbiology and Applied Technology, 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand Purpose: Fork head box M1 (FoxM1 is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA. A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ and nitroxoline (NQ, represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells.Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl-5-(3-carboxymethoxyphenyl-(4-sulfophenyl-2H-tetrazolium (MTS assay. Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction.Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment

  20. Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4 exhibits growth inhibitory effects in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Shayan eSarkar

    2015-10-01

    Full Text Available The gene Par-4 (Prostate Apoptosis Response 4 was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4 selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV and apoplast signal peptide (aTP in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SAC-Par-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes O-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MTT, apoptosis induction assays, and NF-κB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era.

  1. The Florida manatee (Trichechus manatus latirostris) T cell receptor loci exhibit V subgroup synteny and chain-specific evolution

    Science.gov (United States)

    Breaux, Breanna; Hunter, Margaret; Cruz-Schneider, Maria Paula; Sena, Leonardo; Bonde, Robert K.; Criscitiello, Michael F.

    2018-01-01

    The Florida manatee (Trichechus manatus latirostris) has limited diversity in the immunoglobulin heavy chain. We therefore investigated the antigen receptor loci of the other arm of the adaptive immune system: the T cell receptor. Manatees are the first species from Afrotheria, a basal eutherian superorder, to have an in-depth characterization of all T cell receptor loci. By annotating the genome and expressed transcripts, we found that each chain has distinct features that correlates to their individual functions. The genomic organization also plays a role in modulating sequence conservation between species. There were extensive V subgroup synteny blocks in the TRA and TRB loci between T. m. latirostrisand human. Increased genomic locus complexity correlated to increased locus synteny. We also identified evidence for a VHD pseudogene for the first time in a eutherian mammal. These findings emphasize the value of including species within this basal eutherian radiation in comparative studies.

  2. Multivalent Soluble Antigen Arrays Exhibit High Avidity Binding and Modulation of B Cell Receptor-Mediated Signaling to Drive Efficacy against Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Hartwell, Brittany L; Pickens, Chad J; Leon, Martin; Berkland, Cory

    2017-06-12

    A pressing need exists for antigen-specific immunotherapies (ASIT) that induce selective tolerance in autoimmune disease while avoiding deleterious global immunosuppression. Multivalent soluble antigen arrays (SAgA PLP:LABL ), consisting of a hyaluronic acid (HA) linear polymer backbone cografted with multiple copies of autoantigen (PLP) and cell adhesion inhibitor (LABL) peptides, are designed to induce tolerance to a specific multiple sclerosis (MS) autoantigen. Previous studies established that hydrolyzable SAgA PLP:LABL , employing a degradable linker to codeliver PLP and LABL, was therapeutic in experimental autoimmune encephalomyelitis (EAE) in vivo and exhibited antigen-specific binding with B cells, targeted the B cell receptor (BCR), and dampened BCR-mediated signaling in vitro. Our results pointed to sustained BCR engagement as the SAgA PLP:LABL therapeutic mechanism, so we developed a new version of the SAgA molecule using nonhydrolyzable conjugation chemistry, hypothesizing it would enhance and maintain the molecule's action at the cell surface to improve efficacy. "Click SAgA" (cSAgA PLP:LABL ) uses hydrolytically stable covalent conjugation chemistry (Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC)) rather than a hydrolyzable oxime bond to attach PLP and LABL to HA. We explored cSAgA PLP:LABL B cell engagement and modulation of BCR-mediated signaling in vitro through flow cytometry binding and calcium flux signaling assays. Indeed, cSAgA PLP:LABL exhibited higher avidity B cell binding and greater dampening of BCR-mediated signaling than hydrolyzable SAgA PLP:LABL . Furthermore, cSAgA PLP:LABL exhibited significantly enhanced in vivo efficacy compared to hydrolyzable SAgA PLP:LABL , achieving equivalent efficacy at one-quarter of the dose. These results indicate that nonhydrolyzable conjugation increased the avidity of cSAgA PLP:LABL to drive in vivo efficacy through modulated BCR-mediated signaling.

  3. Neuropilin-1highCD4+CD25+ Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis

    Directory of Open Access Journals (Sweden)

    Yu-Lei Gao

    2016-01-01

    Full Text Available Regulatory T cells (Tregs appear to be involved in sepsis-induced immune dysfunction; neuropilin-1 (Nrp-1 was identified as a surface marker for CD4+CD25+Tregs. In the current study, we investigated the negative immunoregulation of Nrp-1highCD4+CD25+Tregs and the potential therapeutic value of Nrp-1 in sepsis. Splenic CD4+CD25+Tregs from cecal ligation and puncture (CLP mouse models were further segregated into Nrp-1highTregs and Nrp-1lowTregs; they were cocultured with CD4+CD25−  T cells. The expression of forkhead/winged helix transcription factor-3 (Foxp-3, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4, membrane associated transforming growth factor-β (TGF-βm+, apoptotic rate, and secretive ability [including TGF-β and interleukin-10 (IL-10] for various types of Tregs, as well as the immunosuppressive ability of Tregs on CD4+CD25−  T cells, were determined. Meanwhile, the impact of recombinant Nrp-1 polyclonal antibody on the demethylation of Foxp-3-TSDR (Treg-specific demethylated region was measured in in vitro study. Sepsis per se markedly promoted the expression of Nrp-1 of CD4+CD25+Tregs. Foxp-3/CTLA-4/TGF-βm+ of Nrp-1highTregs were upregulated by septic challenge. Nrp-1highTregs showed strong resilience to apoptosis and secretive ability and the strongest immunosuppressive ability on CD4+CD25−  T cells. In the presence of lipopolysaccharide (LPS, the recombinant Nrp-1 polyclonal antibody reduced the demethylation of Foxp-3-TSDR. Nrp-1highTregs might reveal primary negative immunoregulation in sepsis; Nrp-1 could represent a new potential therapeutic target for the study of immune regulation in sepsis.

  4. How the Venom from the Ectoparasitoid Wasp Nasonia vitripennis Exhibits Anti-Inflammatory Properties on Mammalian Cell Lines

    Science.gov (United States)

    Danneels, Ellen L.; Gerlo, Sarah; Heyninck, Karen; Van Craenenbroeck, Kathleen; De Bosscher, Karolien; Haegeman, Guy; de Graaf, Dirk C.

    2014-01-01

    With more than 150,000 species, parasitoids are a large group of hymenopteran insects that inject venom into and then lay their eggs in or on other insects, eventually killing the hosts. Their venoms have evolved into different mechanisms for manipulating host immunity, physiology and behavior in such a way that enhance development of the parasitoid young. The venom from the ectoparasitoid Nasonia vitripennis inhibits the immune system in its host organism in order to protect their offspring from elimination. Since the major innate immune pathways in insects, the Toll and Imd pathways, are homologous to the NF-κB pathway in mammals, we were interested in whether a similar immune suppression seen in insects could be elicited in a mammalian cell system. A well characterized NF-κB reporter gene assay in fibrosarcoma cells showed a dose-dependent inhibition of NF-κB signaling caused by the venom. In line with this NF-κB inhibitory action, N. vitripennis venom dampened the expression of IL-6, a prototypical proinflammatory cytokine, from LPS-treated macrophages. The venom also inhibited the expression of two NF-κB target genes, IκBα and A20, that act in a negative feedback loop to prevent excessive NF-κB activity. Surprisingly, we did not detect any effect of the venom on the early events in the canonical NF-κB activation pathway, leading to NF-κB nuclear translocation, which was unaltered in venom-treated cells. The MAP kinases ERK, p38 and JNK are other crucial regulators of immune responses. We observed that venom treatment did not affect p38 and ERK activation, but induced a prolonged JNK activation. In summary, our data indicate that venom from N. vitripennis inhibits NF-κB signaling in mammalian cells. We identify venom-induced up regulation of the glucocorticoid receptor-regulated GILZ as a most likely molecular mediator for this inhibition. PMID:24821138

  5. A Fungus-Inducible Pepper Carboxylesterase Exhibits Antifungal Activity by Decomposing the Outer Layer of Fungal Cell Walls.

    Science.gov (United States)

    Seo, Hyo-Hyoun; Park, Ae Ran; Lee, Hyun-Hwa; Park, Sangkyu; Han, Yun-Jeong; Hoang, Quyen T N; Choi, Gyung Ja; Kim, Jin-Cheol; Kim, Young Soon; Kim, Jeong-Il

    2018-05-01

    Colletotrichum species are major fungal pathogens that cause devastating anthracnose diseases in many economically important crops. In this study, we observed the hydrolyzing activity of a fungus-inducible pepper carboxylesterase (PepEST) on cell walls of C. gloeosporioides, causing growth retardation of the fungus by blocking appressorium formation. To determine the cellular basis for the growth inhibition, we observed the localization of PepEST on the fungus and found the attachment of the protein on surfaces of conidia and germination tubes. Moreover, we examined the decomposition of cell-wall materials from the fungal surface after reaction with PepEST, which led to the identification of 1,2-dithiane-4,5-diol (DTD) by gas chromatography mass spectrometry analysis. Exogenous DTD treatment did not elicit expression of defense-related genes in the host plant but did trigger the necrosis of C. gloeosporioides. Furthermore, the DTD compound displayed protective effects on pepper fruits and plants against C. gloeosporioides and C. coccodes, respectively. In addition, DTD was also effective in preventing other diseases, such as rice blast, tomato late blight, and wheat leaf rust. Therefore, our results provide evidence that PepEST is involved in hydrolysis of the outmost layer of the fungal cell walls and that DTD has antifungal activity, suggesting an alternative strategy to control agronomically important phytopathogens.

  6. Date syrup-derived polyphenols attenuate angiogenic responses and exhibits anti-inflammatory activity mediated by vascular endothelial growth factor and cyclooxygenase-2 expression in endothelial cells.

    Science.gov (United States)

    Taleb, Hajer; Morris, R Keith; Withycombe, Cathryn E; Maddocks, Sarah E; Kanekanian, Ara D

    2016-07-01

    Bioactive components such as polyphenols, present in many plants, are purported to have anti-inflammatory and antiangiogenic properties. Date syrup, produced from date fruit of the date palm tree, has traditionally been used to treat a wide range of diseases with etiologies involving angiogenesis and inflammation. It was hypothesized that polyphenols in date syrup reduce angiogenic responses such as cell migration, tube formation, and matrix metalloproteinase activity in an inflammatory model by exhibiting anti-inflammatory activity mediated by vascular endothelial growth factor (VEGF) and the prostaglandin enzyme cyclooxygenase-2 (COX-2) in endothelial cells. Date syrup polyphenols at 60 and 600μg/mL reduced inflammation and suppressed several stages of angiogenesis, including endothelial cell migration, invasion, matrix metalloproteinase activity, and tube formation, without evidence of cytotoxicity. VEGF and COX-2 expression induced by tumor necrosis factor-alpha at both gene expression and protein level was significantly reduced by date syrup polyphenols in comparison to untreated cells. In conclusion, polyphenols in date syrup attenuated angiogenic responses and exhibited anti-inflammatory activity mediated by VEGF and COX-2 expression in endothelial cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. EBV Positive Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia Patients Exhibit Increased Anti-dUTPase Antibodies

    Directory of Open Access Journals (Sweden)

    Marshall Williams

    2018-05-01

    Full Text Available The Epstein-Barr virus (EBV, which is a ubiquitous γ-herpesvirus, establishes a latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over the last 20 years, and account for approximately 1.5% of all cancers worldwide and 1.8% of all cancer deaths. However, the potential involvement/contribution of lytic proteins to the pathophysiology of EBV-associated cancers is not well understood. We have previously demonstrated that the EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase modulates innate and adaptive immune responses by engaging the Toll-Like Receptor 2 (TLR2, which leads to the modulation of downstream genes involved in oncogenesis, chronic inflammation, and in effector T-cell function. Furthermore, examination of serum samples from diffuse large B-cell lymphoma (DLBCL and chronic lymphocytic leukemia patients revealed the presence of increased levels of anti-dUTPase antibodies in both cohorts compared to controls with the highest levels (3.67-fold increase observed in DLBCL female cases and the lowest (2.12-fold increase in DLBCL males. Using computer-generated algorithms, dUTPase amino acid sequence alignments, and functional studies of BLLF3 mutants, we identified a putative amino acid motif involved with TLR2 interaction. These findings suggest that the EBV-dUTPase: TLR2 interaction is a potential molecular target that could be used for developing novel therapeutics (small molecules/vaccines.

  8. Patients With High Bone Mass Phenotype Exhibit Enhanced Osteoblast Differentiation and Inhibition of Adipogenesis of Human Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Qiu, Weimin; Andersen, Tom; Bollerslev, Jens

    2007-01-01

    in iliac crest bone biopsies from patients with the HBM phenotype and controls. We also used retrovirus-mediated gene transduction to establish three different human mesenchymal stem cell (hMSC) strains stably expressing wildtype LRP5 (hMSC-LRP5WT), LRP5T244 (hMSC-LRP5T244, inactivation mutation leading...... to osteoporosis), or LRP5T253 (hMSC-LRP5T253, activation mutation leading to high bone mass). We characterized Wnt signaling activation using a dual luciferase assay, cell proliferation, lineage biomarkers using real-time PCR, and in vivo bone formation. Results: In bone biopsies, we found increased trabecular...... mineralized bone when implanted subcutaneously with hydroxyapatite/tricalcium phosphate in SCID/NOD mice. Conclusions: LRP5 mutations and the level of Wnt signaling determine differentiation fate of hMSCs into osteoblasts or adipocytes. Activation of Wnt signaling can thus provide a novel approach to increase...

  9. Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

    Science.gov (United States)

    Dyment, Nathaniel A.; Lu, Yinhui; Rao, Marepalli; Shearn, Jason T.; Rowe, David W.; Kadler, Karl E.; Butler, David L.

    2015-01-01

    The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair. PMID:25266738

  10. CAR T Cells Releasing IL-18 Convert to T-Bethigh FoxO1low Effectors that Exhibit Augmented Activity against Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Markus Chmielewski

    2017-12-01

    Full Text Available Adoptive therapy with chimeric antigen receptor (CAR-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bethigh FoxO1low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines. IL-18 CAR T cell treatment was accompanied by an overall change in the immune cell landscape associated with the tumor. More specifically, CD206− M1 macrophages and NKG2D+ NK cells increased in number, whereas Tregs, suppressive CD103+ DCs, and M2 macrophages decreased, suggesting that “iIL18 TRUCKs” can be used to sensitize large solid tumor lesions for successful immune destruction.

  11. Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4

    Directory of Open Access Journals (Sweden)

    Patricia Fernandez

    2014-10-01

    Full Text Available Summary: Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis. : The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique tool for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Using a genome-wide RNAi screen, Fernandez et al. now identify the bromodomain protein BRD4 as a mediator of the oncogenic resistance of HGPS cells. This tumor-protective function of BRD4 involves inhibition of oncogenic dedifferentiation and is also active in non-HGPS cells in a tissue-specific manner.

  12. The hop constituent xanthohumol exhibits hepatoprotective effects and inhibits the activation of hepatic stellate cells at different levels

    Directory of Open Access Journals (Sweden)

    Ralf eWeiskirchen

    2015-05-01

    Full Text Available Xanthohumol is the principal prenylated flavonoid of the female inflorescences of the hop plant. In recent years, various beneficial xanthohumol effects including anti-inflammatory, antioxidant, hypoglycemic activities, and anticancer effects have been revealed. This review summarizes present studies indicating that xanthohumol also inhibits several critical pathophysiological steps during the development and course of chronic liver disease, including the activation and pro-fibrogenic genotype of hepatic stellate cells. Also the various mechanism of action and molecular targets of the beneficial xanthohumol effects will be described. Furthermore, the potential use of xanthohumol or a xanthohumol-enriched hop extract as therapeutic agent to combat the progression of chronic liver disease will be discussed. It is notable that in addition to its hepatoprotective effects, xanthohumol also holds promise as a therapeutic agent for treating obesity, dysregulation of glucose metabolism and other components of the metabolic syndrome including hepatic steatosis. Thus, therapeutic xanthohumol application appears as a promising strategy, particularly in obese patients, to inhibit the development as well as the progression of non-alcoholic fatty liver disease.

  13. γ-ray hypersensitivity and faulty DNA repair in cultured cells from humans exhibiting familial cancer proneness

    International Nuclear Information System (INIS)

    Paterson, M.C.; Smith, P.J.; Bech-Hansen, N.T.; Smith, B.P.; Sell, B.M.

    1979-01-01

    The most significant danger to irradiated individuals is the induction of cancer. Ataxia telangiectasia (AT) is known as a disorder linking radiosensitivity with cancer proneness, and AT is a rare inherited disorder. This is the degenerative multisystem affliction that is transmitted as a simple autosomal recessive trait. Cell culture studies disclosed the relationship between the cellular hypersensitivity to γ-ray inactivation in vitro and the propensity to develop cancer in vivo. The molecular evidence for the defects in the repair of radiogenic DNA damage has as yet been obtained only for AT, and it seems likely that anomalous DNA repair may not be the key causal factor in the development of some of the clinical abnormalities associated with the disease, including the tendency to develop lymphoproliferative cancer. Nevertheless, AT, Rothmund-Thomson syndrome (RTS), and acute myelogenous leukemia (AML) family show promise as the models for elucidating the importance of cellular radiosensitivity and imperfect DNA repair in the induction of cancer by radiation and radiomimetic carcinogens in the biosphere. Expanded efforts are required to identify heterozygosity for the AT genes in general population and to assess the role of the interaction between this genetic make-up and environmental carcinogens in the occurrence of common cancers. (Yamashita, S.)

  14. Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice

    Directory of Open Access Journals (Sweden)

    Takuto Oyama

    2016-06-01

    Full Text Available Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA. MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high-biofilm formers (H-BF and low-biofilm formers (L-BF. These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections.

  15. Dairy Cows Naturally Infected with Bovine Leukemia Virus Exhibit Abnormal B- and T-Cell Phenotypes after Primary and Secondary Exposures to Keyhole Limpet Hemocyanin

    Science.gov (United States)

    Frie, Meredith C.; Sporer, Kelly R. B.; Benitez, Oscar J.; Wallace, Joseph C.; Droscha, Casey J.; Bartlett, Paul C.; Coussens, Paul M.

    2017-01-01

    Bovine leukemia virus (BLV) is a retrovirus that is highly prevalent in US dairy herds: over 83% are BLV infected and the within-herd infection rate can be almost 50% on average. While BLV is known to cause lymphosarcomas, only 5% or fewer infected cattle will develop lymphoma; this low prevalence of cancer has historically not been a concern to dairy producers. However, more recent research has found that BLV+ cows without lymphoma produce less milk and have shorter lifespans than uninfected herdmates. It has been hypothesized that BLV infection interferes with normal immune function in infected cattle, and this could lead to reduced dairy production. To assess how naturally infected BLV+ cows responded to a primary and secondary immune challenge, 10 BLV+ and 10 BLV− cows were injected subcutaneously with keyhole limpet hemocyanin (KLH) and dimethyldioctadecylammonium bromide. B- and T-cell responses were characterized over the following 28 days. A total of 56 days after primary KLH exposure, cows were re-injected with KLH and B- and T-cell responses were characterized again over the following 28 days. BLV+ cows produced less KLH-specific IgM after primary immune stimulation; demonstrated fewer CD45R0+ B cells, altered proportions of CD5+ B cells, altered expression of CD5 on CD5+ B cells, and reduced MHCII surface expression on B cells ex vivo; exhibited reduced B-cell activation in vitro; and displayed an increase in BLV proviral load after KLH exposure. In addition, BLV+ cows had a reduced CD45R0+γδ+ T-cell population in the periphery and demonstrated a greater prevalence of IL4-producing T cells in vitro. All together, our results demonstrate that both B- and T-cell immunities are disrupted in BLV+ cows and that antigen-specific deficiencies can be detected in BLV+ cows even after a primary immune exposure. PMID:28770217

  16. Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

    Science.gov (United States)

    Munisvaradass, Rusheni; Kumar, Suresh; Govindasamy, Chandramohan; Alnumair, Khalid S.; Mok, Pooi Ling

    2017-01-01

    Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non–transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours. PMID:28885562

  17. An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential.

    Directory of Open Access Journals (Sweden)

    Ayaka Yanagida

    Full Text Available Hepatoblasts, hepatic stem/progenitor cells in liver development, have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In regenerative medicine and drug screening for the treatment of severe liver diseases, human induced pluripotent stem (iPS cell-derived mature functional hepatocytes are considered to be a potentially good cell source. However, induction of proliferation of these cells is difficult ex vivo. To circumvent this problem, we generated hepatic progenitor-like cells from human iPS cells using serial cytokine treatments in vitro. Highly proliferative hepatic progenitor-like cells were purified by fluorescence-activated cell sorting using antibodies against CD13 and CD133 that are known cell surface markers of hepatic stem/progenitor cells in fetal and adult mouse livers. When the purified CD13(highCD133(+ cells were cultured at a low density with feeder cells in the presence of suitable growth factors and signaling inhibitors (ALK inhibitor A-83-01 and ROCK inhibitor Y-27632, individual cells gave rise to relatively large colonies. These colonies consisted of two types of cells expressing hepatocytic marker genes (hepatocyte nuclear factor 4α and α-fetoprotein and a cholangiocytic marker gene (cytokeratin 7, and continued to proliferate over long periods of time. In a spheroid formation assay, these cells were found to express genes required for mature liver function, such as cytochrome P450 enzymes, and secrete albumin. When these cells were cultured in a suitable extracellular matrix gel, they eventually formed a cholangiocytic cyst-like structure with epithelial polarity, suggesting that human iPS cell-derived hepatic progenitor-like cells have a bipotent differentiation ability. Collectively these data indicate that this novel procedure using an in vitro expansion system is useful for not only liver regeneration but also for the determination of molecular mechanisms that

  18. CD11c-positive cells from brain, spleen, lung, and liver exhibit site-specific immune phenotypes and plastically adapt to new environments.

    Science.gov (United States)

    Immig, Kerstin; Gericke, Martin; Menzel, Franziska; Merz, Felicitas; Krueger, Martin; Schiefenhövel, Fridtjof; Lösche, Andreas; Jäger, Kathrin; Hanisch, Uwe-Karsten; Biber, Knut; Bechmann, Ingo

    2015-04-01

    The brain's immune privilege has been also attributed to the lack of dendritic cells (DC) within its parenchyma and the adjacent meninges, an assumption, which implies maintenance of antigens rather than their presentation in lymphoid organs. Using mice transcribing the green fluorescent protein under the promoter of the DC marker CD11c (itgax), we identified a juxtavascular population of cells expressing this DC marker and demonstrated their origin from bone marrow and local microglia. We now phenotypically compared this population with CD11c/CD45 double-positive cells from lung, liver, and spleen in healthy mice using seven-color flow cytometry. We identified unique, site-specific expression patterns of F4/80, CD80, CD86, CX3CR1, CCR2, FLT3, CD103, and MHC-II. Furthermore, we observed the two known CD45-positive populations (CD45(high) and CD45(int) ) in the brain, whereas liver, lung, and spleen exhibited a homogeneous CD45(high) population. CD11c-positive microglia lacked MHC-II expression and CD45(high) /CD11c-positive cells from the brain have a lower percentage of MHC-II-positive cells. To test whether phenotypical differences are fixed by origin or specifically develop due to environmental factors, we transplanted brain and spleen mononuclear cells on organotypic slice cultures from brain (OHSC) and spleen (OSSC). We demonstrate that adaption and ramification of MHC-II-positive splenocytes is paralleled by down-regulation of MHC-II, whereas brain-derived mononuclear cells neither ramified nor up-regulated MHC-II in OSSCs. Thus, brain-derived mononuclear cells maintain their MHC-II-negative phenotype within the environment of an immune organ. Intraparenchymal CD11c-positive cells share immunophenotypical characteristics of DCs from other organs but remain unique for their low MHC-II expression. © 2014 Wiley Periodicals, Inc.

  19. Lichen Secondary Metabolites in Flavocetraria cucullata Exhibit Anti-Cancer Effects on Human Cancer Cells through the Induction of Apoptosis and Suppression of Tumorigenic Potentials

    Science.gov (United States)

    Nguyen, Thanh Thi; Yoon, Somy; Yang, Yi; Lee, Ho-Bin; Oh, Soonok; Jeong, Min-Hye; Kim, Jong-Jin; Yee, Sung-Tae; Crişan, Florin; Moon, Cheol; Lee, Kwang Youl; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

    2014-01-01

    Lichens are symbiotic organisms which produce distinct secondary metabolic products. In the present study, we tested the cytotoxic activity of 17 lichen species against several human cancer cells and further investigated the molecular mechanisms underlying their anti-cancer activity. We found that among 17 lichens species, F. cucullata exhibited the most potent cytotoxicity in several human cancer cells. High performance liquid chromatography analysis revealed that the acetone extract of F. cucullata contains usnic acid, salazinic acid, Squamatic acid, Baeomycesic acid, d-protolichesterinic acid, and lichesterinic acid as subcomponents. MTT assay showed that cancer cell lines were more vulnerable to the cytotoxic effects of the extract than non-cancer cell lines. Furthermore, among the identified subcomponents, usnic acid treatment had a similar cytotoxic effect on cancer cell lines but with lower potency than the extract. At a lethal dose, treatment with the extract or with usnic acid greatly increased the apoptotic cell population and specifically activated the apoptotic signaling pathway; however, using sub-lethal doses, extract and usnic acid treatment decreased cancer cell motility and inhibited in vitro and in vivo tumorigenic potentials. In these cells, we observed significantly reduced levels of epithelial-mesenchymal transition (EMT) markers and phosphor-Akt, while phosphor-c-Jun and phosphor-ERK1/2 levels were only marginally affected. Overall, the anti-cancer activity of the extract is more potent than that of usnic acid alone. Taken together, F. cucullata and its subcomponent, usnic acid together with additional component, exert anti-cancer effects on human cancer cells through the induction of apoptosis and the inhibition of EMT. PMID:25360754

  20. Attachment, invasion, chemotaxis, and proteinase expression of B16-BL6 melanoma cells exhibiting a low metastatic phenotype after exposure to dietary restriction of tyrosine and phenylalanine.

    Science.gov (United States)

    Uhlenkott, C E; Huijzer, J C; Cardeiro, D J; Elstad, C A; Meadows, G G

    1996-03-01

    We previously reported that low levels of tyrosine (Tyr) and phenylalanine (Phe) alter the metastatic phenotype of B16-BL6 (BL6) murine melanoma and select for tumor cell populations with decreased lung colonizing ability. To more specifically characterize the effects of Tyr and Phe restriction on the malignant phenotype of BL6, we investigated in vitro attachment, invasion, proteinase expression, and chemotaxis of high and low metastatic BL6 variants. High metastatic variant cells were isolated from subcutaneous tumors of mice fed a nutritionally complete diet (ND cells) and low metastatic variant cells were isolated from mice fed a diet restricted in Tyr and Phe (LTP cells). Results indicate that attachment to reconstituted basement membrane (Matrigel) was significantly reduced in LTP cells as compared to ND cells. Attachment to collagen IV, laminin, and fibronectin were similar between the two variants. Invasion through Matrigel and growth factor-reduced Matrigel were significantly decreased in LTP cells as compared to ND cells. Zymography revealed the presence of M(r) 92,000 and M(r) 72,000 progelatinases, tissue plasminogen activator, and urokinase plasminogen activator in the conditioned medium of both variants; however, there were no differences in activity of these secreted proteinases between the two variants. Growth of the variants on growth factor-reduced Matrigel similarly induced expression of the M(r) 92,000 progelatinase. The variants exhibited similar chemotactic responses toward laminin. However, the chemotactic response toward fibronectin by LTP cells was significantly increased. MFR5, a monoclonal antibody which selectively blocks function of the alpha 5 chain of the alpha 5 beta 1 integrin, VLA-5, decreased the chemotactic response toward fibronectin of ND cells by 37%; the chemotactic response by LTP cells was reduced by 49%. This effect was specific for fibronectin-mediated chemotaxis since the chemotaxis toward laminin and invasion through

  1. Strategies to prepare TiO2 thin films, doped with transition metal ions, that exhibit specific physicochemical properties to support osteoblast cell adhesion and proliferation

    International Nuclear Information System (INIS)

    Dhayal, Marshal; Kapoor, Renu; Sistla, Pavana Goury; Pandey, Ravi Ranjan; Kar, Satabisha; Saini, Krishan Kumar; Pande, Gopal

    2014-01-01

    Metal ion doped titanium oxide (TiO 2 ) thin films, as bioactive coatings on metal or other implantable materials, can be used as surfaces for studying the cell biological properties of osteogenic and other cell types. Bulk crystallite phase distribution and surface carbon–oxygen constitution of thin films, play an important role in determining the biological responses of cells that come in their contact. Here we present a strategy to control the polarity of atomic interactions between the dopant metal and TiO 2 molecules and obtain surfaces with smaller crystallite phases and optimal surface carbon–oxygen composition to support the maximum proliferation and adhesion of osteoblast cells. Our results suggest that surfaces, in which atomic interactions between the dopant metals and TiO 2 were less polar, could support better adhesion, spreading and proliferation of cells. - Highlights: • Electrochemical properties of dopants control the nature of TiO 2 thin films. • A model explains the correlation of dopant properties and behaviour of TiO 2 films. • Dopants with less polar interaction with TiO 2 exhibit better biological activity

  2. Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity on bacteria, protozoan parasites, insects, and human cancer cells.

    Science.gov (United States)

    Kuhn-Nentwig, Lucia; Willems, Jean; Seebeck, Thomas; Shalaby, Tarek; Kaiser, Marcel; Nentwig, Wolfgang

    2011-01-01

    Cupiennin 1a, a cytolytic peptide isolated from the venom of the spider Cupiennius salei, exhibits broad membranolytic activity towards bacteria, trypanosomes, and plasmodia, as well as human blood and cancer cells. In analysing the cytolytic activity of synthesised all-D: - and all-L: -cupiennin 1a towards pro- and eukaryotic cells, a stereospecific mode of membrane destruction could be excluded. The importance of negatively charged sialic acids on the outer leaflet of erythrocytes for the binding and haemolytic activity of L: -cupiennin 1a was demonstrated. Reducing the overall negative charges of erythrocytes by partially removing their sialic acids or by protecting them with tri- or pentalysine results in reduced haemolytic activity of the peptide.

  3. ]thiophene-Based Nonfullerene Acceptor with High Crystallinity Exhibiting Single Junction Solar Cell Efficiencies Greater than 13% with Low Voltage Losses

    KAUST Repository

    Fei, Zhuping

    2018-01-10

    A new synthetic route, to prepare an alkylated indacenodithieno[3,2-b]thiophene-based nonfullerene acceptor (C8-ITIC), is reported. Compared to the reported ITIC with phenylalkyl side chains, the new acceptor C8-ITIC exhibits a reduction in the optical band gap, higher absorptivity, and an increased propensity to crystallize. Accordingly, blends with the donor polymer PBDB-T exhibit a power conversion efficiency (PCE) up to 12.4%. Further improvements in efficiency are found upon backbone fluorination of the donor polymer to afford the novel material PFBDB-T. The resulting blend with C8-ITIC shows an impressive PCE up to 13.2% as a result of the higher open-circuit voltage. Electroluminescence studies demonstrate that backbone fluorination reduces the energy loss of the blends, with PFBDB-T/C8-ITIC-based cells exhibiting a small energy loss of 0.6 eV combined with a high JSC of 19.6 mA cm-2 .

  4. ]thiophene-Based Nonfullerene Acceptor with High Crystallinity Exhibiting Single Junction Solar Cell Efficiencies Greater than 13% with Low Voltage Losses

    KAUST Repository

    Fei, Zhuping; Eisner, Flurin D.; Jiao, Xuechen; Azzouzi, Mohammed; Rö hr, Jason A.; Han, Yang; Shahid, Munazza; Chesman, Anthony S. R.; Easton, Christopher D.; McNeill, Christopher R.; Anthopoulos, Thomas D.; Nelson, Jenny; Heeney, Martin

    2018-01-01

    A new synthetic route, to prepare an alkylated indacenodithieno[3,2-b]thiophene-based nonfullerene acceptor (C8-ITIC), is reported. Compared to the reported ITIC with phenylalkyl side chains, the new acceptor C8-ITIC exhibits a reduction in the optical band gap, higher absorptivity, and an increased propensity to crystallize. Accordingly, blends with the donor polymer PBDB-T exhibit a power conversion efficiency (PCE) up to 12.4%. Further improvements in efficiency are found upon backbone fluorination of the donor polymer to afford the novel material PFBDB-T. The resulting blend with C8-ITIC shows an impressive PCE up to 13.2% as a result of the higher open-circuit voltage. Electroluminescence studies demonstrate that backbone fluorination reduces the energy loss of the blends, with PFBDB-T/C8-ITIC-based cells exhibiting a small energy loss of 0.6 eV combined with a high JSC of 19.6 mA cm-2 .

  5. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Hao Hong

    Full Text Available New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM were then genetically modified to express an anti-L1-CAM CAR (CE7R, which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p. administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.

  6. Britain exhibition at CERN

    CERN Multimedia

    Bertin; CERN PhotoLab

    1969-01-01

    The United Kingdom inaugurated the Industrial Exhibitions in 1968, and it wasn't till 1971 that other countries staged exhibitions at CERN. This photo was taken in 1969, at the second British exhibition, where 16 companies were present.

  7. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Yerly Vargas Casanova

    2017-09-01

    Full Text Available Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922 and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

  8. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines.

    Science.gov (United States)

    Vargas Casanova, Yerly; Rodríguez Guerra, Jorge Antonio; Umaña Pérez, Yadi Adriana; Leal Castro, Aura Lucía; Almanzar Reina, Giovanni; García Castañeda, Javier Eduardo; Rivera Monroy, Zuly Jenny

    2017-09-29

    Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)₂K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

  9. Streptomyces colonosanans sp. nov., A Novel Actinobacterium Isolated from Malaysia Mangrove Soil Exhibiting Antioxidative Activity and Cytotoxic Potential against Human Colon Cancer Cell Lines

    Science.gov (United States)

    Law, Jodi Woan-Fei; Ser, Hooi-Leng; Duangjai, Acharaporn; Saokaew, Surasak; Bukhari, Sarah I.; Khan, Tahir M.; Ab Mutalib, Nurul-Syakima; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

    2017-01-01

    Streptomyces colonosanans MUSC 93JT, a novel strain isolated from mangrove forest soil located at Sarawak, Malaysia. The bacterium was noted to be Gram-positive and to form light yellow aerial and vivid yellow substrate mycelium on ISP 2 agar. The polyphasic approach was used to determine the taxonomy of strain MUSC 93JT and the strain showed a range of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. Phylogenetic and 16S rRNA gene sequence analysis indicated that closely related strains include Streptomyces malachitofuscus NBRC 13059T (99.2% sequence similarity), Streptomyces misionensis NBRC 13063T (99.1%), and Streptomyces phaeoluteichromatogenes NRRL 5799T (99.1%). The DNA–DNA relatedness values between MUSC 93JT and closely related type strains ranged from 14.4 ± 0.1 to 46.2 ± 0.4%. The comparison of BOX-PCR fingerprints indicated MUSC 93JT exhibits a unique DNA profile. The genome of MUSC 93JT consists of 7,015,076 bp. The DNA G + C content was determined to be 69.90 mol%. The extract of strain MUSC 93JT was demonstrated to exhibit potent antioxidant activity via ABTS, metal chelating, and SOD assays. This extract also exhibited anticancer activity against human colon cancer cell lines without significant cytotoxic effect against human normal colon cells. Furthermore, the chemical analysis of the extract further emphasizes the strain is producing chemo-preventive related metabolites. Based on this polyphasic study of MUSC 93JT, it is concluded that this strain represents a novel species, for which the name Streptomyces colonosanans sp. nov. is proposed. The type strain is MUSC 93JT (= DSM 102042T = MCCC 1K02298T). PMID:28559892

  10. Streptomyces colonosanans sp. nov., A Novel Actinobacterium Isolated from Malaysia Mangrove Soil Exhibiting Antioxidative Activity and Cytotoxic Potential against Human Colon Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Jodi Woan-Fei Law

    2017-05-01

    Full Text Available Streptomyces colonosanans MUSC 93JT, a novel strain isolated from mangrove forest soil located at Sarawak, Malaysia. The bacterium was noted to be Gram-positive and to form light yellow aerial and vivid yellow substrate mycelium on ISP 2 agar. The polyphasic approach was used to determine the taxonomy of strain MUSC 93JT and the strain showed a range of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. Phylogenetic and 16S rRNA gene sequence analysis indicated that closely related strains include Streptomyces malachitofuscus NBRC 13059T (99.2% sequence similarity, Streptomyces misionensis NBRC 13063T (99.1%, and Streptomyces phaeoluteichromatogenes NRRL 5799T (99.1%. The DNA–DNA relatedness values between MUSC 93JT and closely related type strains ranged from 14.4 ± 0.1 to 46.2 ± 0.4%. The comparison of BOX-PCR fingerprints indicated MUSC 93JT exhibits a unique DNA profile. The genome of MUSC 93JT consists of 7,015,076 bp. The DNA G + C content was determined to be 69.90 mol%. The extract of strain MUSC 93JT was demonstrated to exhibit potent antioxidant activity via ABTS, metal chelating, and SOD assays. This extract also exhibited anticancer activity against human colon cancer cell lines without significant cytotoxic effect against human normal colon cells. Furthermore, the chemical analysis of the extract further emphasizes the strain is producing chemo-preventive related metabolites. Based on this polyphasic study of MUSC 93JT, it is concluded that this strain represents a novel species, for which the name Streptomyces colonosanans sp. nov. is proposed. The type strain is MUSC 93JT (= DSM 102042T = MCCC 1K02298T.

  11. Caryophyllene oxide exhibits anti-cancer effects in MG-63 human osteosarcoma cells via the inhibition of cell migration, generation of reactive oxygen species and induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Zheng Pan

    2016-12-01

    Full Text Available The main objective of the present study was to evaluate the antitumor and apoptotic effects of caryophyllene oxide in MG-63 human osteosarcoma cells. Cell viability of these cells was evaluated by MTT assay while as in vitro wound healing assay was used to study the effect of caryophyllene oxide on cell migration. Fluorescence microscopy and transmission electron microscopy were used to study the changes in cell morphology once the cells undergo apoptosis. Caryophyllene oxide significantly led to cytotoxicity in MG-63 cells showing dose-dependent as well as time-dependent effects. Caryophyllene oxide led to an inhibition of wound closure significantly. At caryophyllene oxide doses of 20, 80 and 120 µM, the percentage of cell migration was shown to be 94.2, 67.1 and 14.8% respectively. With an increase in the caryophyllene oxide dose, the extent of apoptosis also increased characterized by cellular shrinkage, membrane blebbing, chromatin condensation and apoptotic body formation.

  12. Intracellular haemolytic agents of Heterocapsa circularisquama exhibit toxic effects on H. circularisquama cells themselves and suppress both cell-mediated haemolytic activity and toxicity to rotifers (Brachionus plicatilis).

    Science.gov (United States)

    Nishiguchi, Tomoki; Cho, Kichul; Yasutomi, Masumi; Ueno, Mikinori; Yamaguchi, Kenichi; Basti, Leila; Yamasaki, Yasuhiro; Takeshita, Satoshi; Kim, Daekyung; Oda, Tatsuya

    2016-10-01

    A harmful dinoflagellate, Heterocapsa circularisquama, is highly toxic to shellfish and the zooplankton rotifer Brachionus plicatilis. A previous study found that H. circularisquama has both light-dependent and -independent haemolytic agents, which might be responsible for its toxicity. Detailed analysis of the haemolytic activity of H. circularisquama suggested that light-independent haemolytic activity was mediated mainly through intact cells, whereas light-dependent haemolytic activity was mediated by intracellular agents which can be discharged from ruptured cells. Because H. circularisquama showed similar toxicity to rotifers regardless of the light conditions, and because ultrasonic ruptured H. circularisquama cells showed no significant toxicity to rotifers, it was suggested that live cell-mediated light-independent haemolytic activity is a major factor responsible for the observed toxicity to rotifers. Interestingly, the ultrasonic-ruptured cells of H. circularisquama suppressed their own lethal effect on the rotifers. Analysis of samples of the cell contents (supernatant) and cell fragments (precipitate) prepared from the ruptured H. circularisquama cells indicated that the cell contents contain inhibitors for the light-independent cell-mediated haemolytic activity, toxins affecting H. circularisquama cells themselves, as well as light-dependent haemolytic agents. Ethanol extract prepared from H. circularisquama, which is supposed to contain a porphyrin derivative that displays photosensitising haemolytic activity, showed potent toxicity to Chattonella marina, Chattonella antiqua, and Karenia mikimotoi, as well as to H. circularisquama at the concentration range at which no significant toxicity to rotifers was observed. Analysis on a column of Sephadex LH-20 revealed that light-dependent haemolytic activity and inhibitory activity on cell-mediated light-independent haemolytic activity existed in two separate fractions (f-2 and f-3), suggesting that both

  13. Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine

    Directory of Open Access Journals (Sweden)

    Arkadiusz Dziedzic

    2016-03-01

    Full Text Available The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628, cultivated with the mixture of Dulbecco's modified Eagle’s medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 μg/mL and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl-2,5-diphenyl-2H-tetrazolium bromide (MTT assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 μg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50 after 48 h was estimated at 5.19 μg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting

  14. Human umbilical cord mesenchymal stromal cells exhibit immature nucleus pulposus cell phenotype in a laminin-rich pseudo-three-dimensional culture system.

    Science.gov (United States)

    Chon, Brian H; Lee, Esther J; Jing, Liufang; Setton, Lori A; Chen, Jun

    2013-10-02

    Cell supplementation to the herniated or degenerated intervertebral disc (IVD) is a potential strategy to promote tissue regeneration and slow disc pathology. Human umbilical cord mesenchymal stromal cells (HUCMSCs) - originating from the Wharton's jelly - remain an attractive candidate for such endeavors with their ability to differentiate into multiple lineages. Previously, mesenchymal stem cells (MSCs) have been studied as a potential source for disc tissue regeneration. However, no studies have demonstrated that MSCs can regenerate matrix with unique characteristics matching that of immature nucleus pulposus (NP) tissues of the IVD. In our prior work, immature NP cells were found to express specific laminin isoforms and laminin-binding receptors that may serve as phenotypic markers for evaluating MSC differentiation to NP-like cells. The goal of this study is to evaluate these markers and matrix synthesis for HUCMSCs cultured in a laminin-rich pseudo-three-dimensional culture system. HUCMSCs were seeded on top of Transwell inserts pre-coated with Matrigel™, which contained mainly laminin-111. Cells were cultured under hypoxia environment with three differentiation conditions: NP differentiation media (containing 2.5% Matrigel™ solution to provide for a pseudo-three-dimensional laminin culture system) with no serum, or the same media supplemented with either insulin-like growth factor-1 (IGF-1) or transforming growth factor-β1 (TGF-β1). Cell clustering behavior, matrix production and the expression of NP-specific laminin and laminin-receptors were evaluated at days 1, 7, 13 and 21 of culture. Data show that a pseudo-three-dimensional culture condition (laminin-1 rich) promoted HUCMSC differentiation under no serum conditions. Starting at day 1, HUCMSCs demonstrated a cell clustering morphology similar to that of immature NP cells in situ and that observed for primary immature NP cells within the similar laminin-rich culture system (prior study

  15. OTX2 exhibits cell-context-dependent effects on cellular and molecular properties of human embryonic neural precursors and medulloblastoma cells

    Directory of Open Access Journals (Sweden)

    Ravinder Kaur

    2015-10-01

    Full Text Available Medulloblastoma (MB is the most common malignant primary pediatric brain tumor and is currently divided into four subtypes based on different genomic alterations, gene expression profiles and response to treatment: WNT, Sonic Hedgehog (SHH, Group 3 and Group 4. This extensive heterogeneity has made it difficult to assess the functional relevance of genes to malignant progression. For example, expression of the transcription factor Orthodenticle homeobox2 (OTX2 is frequently dysregulated in multiple MB variants; however, its role may be subtype specific. We recently demonstrated that neural precursors derived from transformed human embryonic stem cells (trans-hENs, but not their normal counterparts (hENs, resemble Groups 3 and 4 MB in vitro and in vivo. Here, we tested the utility of this model system as a means of dissecting the role of OTX2 in MB using gain- and loss-of-function studies in hENs and trans-hENs, respectively. Parallel experiments with MB cells revealed that OTX2 exerts inhibitory effects on hEN and SHH MB cells by regulating growth, self-renewal and migration in vitro and tumor growth in vivo. This was accompanied by decreased expression of pluripotent genes, such as SOX2, and was supported by overexpression of SOX2 in OTX2+ SHH MB and hENs that resulted in significant rescue of self-renewal and cell migration. By contrast, OTX2 is oncogenic and promotes self-renewal of trans-hENs and Groups 3 and 4 MB independent of pluripotent gene expression. Our results demonstrate a novel role for OTX2 in self-renewal and migration of hENs and MB cells and reveal a cell-context-dependent link between OTX2 and pluripotent genes. Our study underscores the value of human embryonic stem cell derivatives as alternatives to cell lines and heterogeneous patient samples for investigating the contribution of key developmental regulators to MB progression.

  16. Avicequinone C Isolated from Avicennia marina Exhibits 5α-Reductase-Type 1 Inhibitory Activity Using an Androgenic Alopecia Relevant Cell-Based Assay System

    Directory of Open Access Journals (Sweden)

    Ruchy Jain

    2014-05-01

    Full Text Available Avicennia marina (AM exhibits various biological activities and has been traditionally used in Egypt to cure skin diseases. In this study, the methanolic heartwood extract of AM was evaluated for inhibitory activity against 5α-reductase (5α-R [E.C.1.3.99.5], the enzyme responsible for the over-production of 5α-dihydrotestosterone (5α-DHT causing androgenic alopecia (AGA. An AGA-relevant cell-based assay was developed using human hair dermal papilla cells (HHDPCs, the main regulator of hair growth and the only cells within the hair follicle that are the direct site of 5α-DHT action, combined with a non-radioactive thin layer chromatography (TLC detection technique. The results revealed that AM is a potent 5α-R type 1 (5α-R1 inhibitor, reducing the 5α-DHT production by 52% at the final concentration of 10 µg/mL. Activity-guided fractionation has led to the identification of avicequinone C, a furanonaphthaquinone, as a 5α-R1 inhibitor with an IC50 of 9.94 ± 0.33 µg/mL or 38.8 ± 1.29 µM. This paper is the first to report anti-androgenic activity through 5α-R1 inhibition of AM and avicequinone C.

  17. Human Dental Pulp-Derived Cells Produce Bone-Like Tissue and Exhibit Bone Cell-Like Responsiveness to Mechanical Loading

    DEFF Research Database (Denmark)

    Kraft, David Christian Evar; Melsen, Birte; Bindslev, Dorthe Arenholt

    2010-01-01

    and characterize cell lines from human 3rd molar dental pulp tissue to determine whether human dental pulp-derived cells (DPCs) are osteogenic and responsive to mechanical loading by pulsating fluid flow (PFF) in vitro. Methods: Human DPCs used for this study were characterized by measuring proliferation....... We also assessed bone formation by DPCs on hydroxyapatite-tricalcium phosphate granules after subcutaneous implantation in mice. Results: We found that DPCs are intrinsically mechanosensitive and, like osteogenic cells, respond to PFF-induced fluid shear stress. Implantation of DPCs resulted...... remodeling in vivo, and therefore provide a promising new tool for regenerative dentistry, for example mineralized tissue engineering to restore bone defects in relation to periodontitis, periimplantatis and orofacial surgery. Experiments in progress have proven that DPCSs are also useful for assessing...

  18. Human Breast Adipose-Derived Stem Cells Transfected with the Stromal Cell-Derived Factor-1 Receptor CXCR4 Exhibit Enhanced Viability in Human Autologous Free Fat Grafts

    Directory of Open Access Journals (Sweden)

    Fang-tian Xu

    2014-11-01

    Full Text Available Background: The main complication of autologous free fat tissue transplantation is fat resorption and calcification due to the ischemic necrosis of fat. The promotion of transplant neovascularization soon after autologous free fat grafts may reduce these outcomes. In adulthood, stromal cell-derived factor-1 (SDF-1 and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4 are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. We hypothesized that CXCR4 may improve the long-term survival of free fat tissue transplants by recruiting endothelial progenitor cells (EPCs and may therefore improve graft revascularization. In this study, we aimed to determine the effect of human breast adipose-derived stem cells (HBASCs transfected with the CXCR4 gene on the survival rate of human autologous free fat transplants in nude mice. Methods: Human breast adipose-derived stem cells (HBASCs were expanded ex vivo for 3 passages, labeled with green fluorescent protein (GFP and transfected with CXCR4 or left untransfected. Autologous fat tissues were mixed with the GFP-labeled, CXCR4-transfected HBASCs (group A, GFP-labeled HBASCs (group B, the known vascularization-promoting agent VEGF (group C, or medium (group D and then injected subcutaneously into 32 nude mice at 4 spots in a random fashion. Six months later, the transplanted tissue volume and histology were evaluated, and neo-vascularization was quantified by counting the capillaries. CXCR4 and SDF-1α mRNA expression in the transplants was determined using real-time quantitative PCR analysis (qPCR. Results: The data revealed that the control (group D transplant volume survival was 28.3 ± 4.5%. Mixing CXCR4-transfected (group A and untransfected (group B HBASCs significantly increased transplant volume survival (79.5 ± 8.3% and 67.2 ± 5.9%, respectively, whereas VEGF-transfected HBASCs (group C were less effective (41.2 ± 5.1%. Histological

  19. Effector/memory T cells of the weanling mouse exhibit Type 2 cytokine polarization in vitro and in vivo in the advanced stages of acute energy deficit.

    Science.gov (United States)

    Steevels, Tessa A M; Hillyer, Lyn M; Monk, Jennifer M; Fisher, Megan E; Woodward, Bill D

    2010-06-01

    Our objective was to determine whether the polarizing cytokine profile of the effector/memory T-cell compartment reflects the profound decline of cell-mediated inflammatory competence that characterizes acute prepubescent malnutrition. Weanling C57BL/6J mice were permitted free access to a complete purified diet, free access to an isocaloric low-protein diet or restricted intake of the complete diet for 14 days. First, interleukin (IL)-4 and interferon (IFN)-gamma concentrations generated in vitro by splenic and nodal effector/memory T cells were assessed following exposure to plate-bound anti-CD3. Second, net systemic production of IFN-gamma and IL-4 by the effector/memory T-cell compartment was assessed by the in vivo cytokine capture assay following anti-CD3 stimulation. In vitro stimulation generated less IFN-gamma (P=.002) but more IL-4 (P=.05) by T cells from the restricted-intake group relative to the age-matched control group. Similarly, in vivo stimulation generated low serum levels of antibody-captured IFN-gamma in the restricted-intake group vis-à-vis the age-matched control group (P=.01), while the IL-4 response was sustained (P=.39). By contrast, the 14-day low-protein model exhibited no change in T-cell cytokine signature either in vitro or in vivo. However, following extended consumption of the low-protein diet (26 days), carcass energy losses exceeded those of the 14-day protocol and serum levels of in vivo antibody-captured IFN-gamma were low after anti-CD3 challenge relative to the age-matched control group (P=.02), while levels of captured IL-4 remained unaffected (P=.07). Acute weanling malnutrition elicits a Type 2 polarizing cytokine character on the part of the effector/memory T-cell compartment, but only in the most advanced stages of energy decrement. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  20. Adipose-derived mesenchymal stromal cells from aged patients with coronary artery disease keep mesenchymal stromal cell properties but exhibit characteristics of aging and have impaired angiogenic potential.

    Science.gov (United States)

    Efimenko, Anastasia; Dzhoyashvili, Nina; Kalinina, Natalia; Kochegura, Tatiana; Akchurin, Renat; Tkachuk, Vsevolod; Parfyonova, Yelena

    2014-01-01

    Tissue regeneration is impaired in aged individuals. Adipose-derived mesenchymal stromal cells (ADSCs), a promising source for cell therapy, were shown to secrete various angiogenic factors and improve vascularization of ischemic tissues. We analyzed how patient age affected the angiogenic properties of ADSCs. ADSCs were isolated from subcutaneous fat tissue of patients with coronary artery disease (CAD; n = 64, 43-77 years old) and without CAD (n = 31, 2-82 years old). ADSC phenotype characterized by flow cytometry was CD90(+)/CD73(+)/CD105(+)/CD45(-)/CD31(-) for all samples, and these cells were capable of adipogenic and osteogenic differentiation. ADSCs from aged patients had shorter telomeres (quantitative reverse transcription polymerase chain reaction) and a tendency to attenuated telomerase activity. ADSC-conditioned media (ADSC-CM) stimulated capillary-like tube formation by endothelial cells (EA.hy926), and this effect significantly decreased with the age of patients both with and without CAD. Angiogenic factors (vascular endothelial growth factor, placental growth factor, hepatocyte growth factor, angiopoetin-1, and angiogenin) in ADSC-CM measured by enzyme-linked immunosorbent assay significantly decreased with patient age, whereas levels of antiangiogenic factors thrombospondin-1 and endostatin did not. Expression of angiogenic factors in ADSCs did not change with patient age (real-time polymerase chain reaction); however, gene expression of factors related to extracellular proteolysis (urokinase and its receptor, plasminogen activator inhibitor-1) and urokinase-type plasminogen activator receptor surface expression increased in ADSCs from aged patients with CAD. ADSCs from aged patients both with and without CAD acquire aging characteristics, and their angiogenic potential declines because of decreasing proangiogenic factor secretion. This could restrict the effectiveness of autologous cell therapy with ADSCs in aged patients.

  1. Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

    Science.gov (United States)

    Peters, Erica B; Liu, Betty; Christoforou, Nicolas; West, Jennifer L; Truskey, George A

    2015-10-01

    Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p < 0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.

  2. Digital collections and exhibits

    CERN Document Server

    Denzer, Juan

    2015-01-01

    Today's libraries are taking advantage of cutting-edge technologies such as flat panel displays using touch, sound, and hands-free motions to design amazing exhibits using everything from simple computer hardware to advanced technologies such as the Microsoft Kinect. Libraries of all types are striving to add new interactive experiences for their patrons through exciting digital exhibits, both online and off. Digital Collections and Exhibits takes away the mystery of designing stunning digital exhibits to spotlight library trea

  3. Y and Ni Co-Doped BaZrO3 as a Proton-Conducting Solid Oxide Fuel Cell Electrolyte Exhibiting Superior Power Performance

    KAUST Repository

    Shafi, Shahid P.

    2015-10-16

    The fabrication of anode supported single cells based on BaZr0.8Y0.2O3-δ (BZY20) electrolyte is challenging due to its poor sinteractive nature. The acceleration of shrinkage behavior, improved sinterability and larger grain size were achieved by the partial substitution of Zr with Ni in the BZY perovskite. Phase pure Ni-doped BZY powders of nominal compositions BaZr0.8-xY0.2NixO3-δ were synthesized up to x = 0.04 using a wet chemical combustion synthesis route. BaZr0.76Y0.2Ni0.04O3-δ (BZYNi04) exhibited adequate total conductivity and the open circuit voltage (OCV) values measured on the BZYNi04 pellet suggested lack of significant electronic contribution. The improved sinterability of BZYNi04 assisted the ease in film fabrication and this coupled with the application of an anode functional layer and a suitable cathode, PrBaCo2O5+δ (PBCO), resulted in a superior fuel cell power performance. With humidified hydrogen and static air as the fuel and oxidant, respectively, a peak power density value of 428 and 240 mW cm−2 was obtained at 700 and 600°C, respectively.

  4. Exhibiting Epistemic Objects

    DEFF Research Database (Denmark)

    Tybjerg, Karin

    2017-01-01

    of exhibiting epistemic objects that utilize their knowledge-generating potential and allow them to continue to stimulate curiosity and generate knowledge in the exhibition. The epistemic potential of the objects can then be made to work together with the function of the exhibition as a knowledge-generating set...

  5. Discrimination? - Exhibition of posters

    OpenAIRE

    Jakimovska, Jana

    2017-01-01

    Participation in the exhibition with the students form the Art Academy. The exhibition consisted of 15 posters tackling the subjects of hate speech and discrimination. The exhibition happened thanks to the invitation of the Faculty of Law at UGD, and it was a part of a larger event of launching books on the aforementioned subjects.

  6. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    International Nuclear Information System (INIS)

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.

    2013-01-01

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level

  7. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

    2013-08-15

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

  8. Pharmacology of a selective cyclooxygenase-2 inhibitor, HN-56249: a novel compound exhibiting a marked preference for the human enzyme in intact cells.

    Science.gov (United States)

    Berg, J; Fellier, H; Christoph, T; Kremminger, P; Hartmann, M; Blaschke, H; Rovensky, F; Towart, R; Stimmeder, D

    2000-04-01

    HN-56249 (3-(2,4-dichlorothiophenoxy)-4-methylsulfonylamino-benzenesu lfonamide), a highly selective cyclooxygenase (COX)-2 inhibitor, is the prototype of a novel series of COX inhibitors comprising bicyclic arylethersulfonamides; of this series HN-56249 is the most potent and selective human COX-2 inhibitor. HN-56249 inhibited platelet aggregation as a measure of COX-1 activity only moderately (IC50 26.5+/-1.7 microM). In LPS-stimulated monocytic cells the release of prostaglandin (PG) F1alpha as a measure of COX-2 was markedly inhibited (IC50 0.027+/-0.001 microM). Thus, HN-56249 showed an approximately 1000-fold selectivity for COX-2 in intact cells. In whole blood assays HN-56249 showed a potent inhibitory activity for COX-2 (IC50 0.78+/-0.37 microM) only. COX-1 was only weakly inhibited (IC50 867+/-181 microM). Hence, HN-56249 exhibited a greater than 1000-fold selectivity for whole blood COX-2. HN-56249 surpassed the COX-2 selectivities of the COX-2 selective inhibitors 3-cyclohexyloxy-4-methylsulfonylamino-nitrobenzene (NS-398) and 6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanone (flosulide) in the intact cell assays by eight- and threefold, respectively, and in the whole blood assays by approximately 40-fold. Following i.v. administration HN-56249 inhibited carrageenan-induced rat paw oedema only moderately (ID50 26.2+/-5.7 mg/kg, mean +/- SEM), approximately tenfold less potent than indomethacin (ID50 2.1+/-0.2 mg/kg, mean +/- SEM). After oral administration HN-56249 reversed thermal hyperalgesia in the carrageenan-induced rat paw oedema test, however, some 30-fold less potently than diclofenac. Comparing the inhibitory potency of HN-56249 against human COX-2 with that against murine COX-2 in intact cells revealed a 300-fold selectivity for the human enzyme. Similar effects were observed with other COX-2-selective arylethersulfonamides. In contrast, non-COX-2-selective arylethersulfonamides, including a highly selective COX-1 inhibitor, inhibited

  9. Exhibition; Image display agency

    International Nuclear Information System (INIS)

    Normazlin Ismail

    2008-01-01

    This article touches on the role of Malaysian Nuclear Agency as nuclear research institutions to promote, develop and encourage the peaceful uses of nuclear technology in its agricultural, medical, manufacturing, industrial, health and environment for the development of the country running successfully. Maturity of Malaysian Nuclear Agency in dealing with nuclear technology that are very competitive and globalization cannot be denied. On this basis Malaysian Nuclear Agency was given the responsibility to strengthen the nuclear technology in Malaysia. One way is through an exhibition featuring the research, discoveries and new technology products of the nuclear technology. Through this exhibition is to promote the nuclear technology and introduce the image of the agency in the public eye. This article also states a number of exhibits entered by the Malaysian Nuclear Agency and achievements during the last exhibition. Authors hope that the exhibition can be intensified further in the future.

  10. Primate Cerebellar Granule Cells Exhibit a Tonic GABAAR Conductance that is not Affected by Alcohol: A Possible Cellular Substrate of the Low Level of Response Phenotype.

    Directory of Open Access Journals (Sweden)

    Claudia eMohr

    2013-11-01

    Full Text Available In many rodent brain regions, alcohol increases vesicular release of GABA, resulting in an increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs and the magnitude of tonic GABAA receptor (GABAAR currents. A neglected issue in translating the rodent literature to humans is the possibility that phylogenetic differences alter the actions of alcohol. To address this issue we made voltage-clamp recordings from granule cells (GCs in cerebellar slices from the non-human primate, Macaca fascicularis. We found that similar to Sprague Dawley rats (SDRs, non-human primate (NHP GCs exhibit a tonic conductance generated by 6 subunit containing GABAARs, as evidenced by its blockade by the broad spectrum GABAAR antagonist, GABAzine (10M, inhibition by 6 selective antagonist, furosemide (100M, and enhancement by THDOC (10-20nM and THIP (500nM. In contrast to SDR GCs, in most NHP GCs (~60%, application of EtOH (25-105mM did not increase sIPSC frequency or the tonic GABAAR current. In a minority of cells (~40%, EtOH did increase sIPSC frequency and the tonic current. The relative lack of response to EtOH was associated with reduced expression of neuronal nitric oxide synthase (nNOS, which we recently reported mediates EtOH-induced enhancement of vesicular GABA release in rats. The EtOH-induced increase in tonic GABAAR current was significantly smaller in NHPs than in SDRs, presumably due to less GABA release, because there were no obvious differences in the density of GABAARs or GABA transporters between SDR and NHP GCs. Thus, EtOH does not directly modulate 6 subunit GABAARs in NHPs. Instead, EtOH enhanced GABAergic transmission is mediated by enhanced GABA release. Further, SDR GC responses to alcohol are only representative of a subpopulation of NHP GCs. This suggests that the impact of EtOH on NHP cerebellar physiology will be reduced compared to SDRs, and will likely have different computational and behavioral

  11. Council Chamber exhibition

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    To complete the revamp of CERN’s Council Chamber, a new exhibition is being installed just in time for the June Council meetings.   Panels will showcase highlights of CERN’s history, using some of the content prepared for the exhibitions marking 50 years of the PS, which were displayed in the main building last November. The previous photo exhibition in the Council Chamber stopped at the 1970s. To avoid the new panels becoming quickly out of date, photos are grouped together around specific infrastructures, rather than following a classic time-line. “We have put the focus on the accelerators – the world-class facilities that CERN has been offering researchers over the years, from the well-known large colliders to the lesser-known smaller facilities,” says Emma Sanders, who worked on the content. The new exhibition will be featured in a future issue of the Bulletin with photos and an interview with Fabienne Marcastel, designer of the exhibit...

  12. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's 50th anniversary celebrations. Fifty candles for CERN, an international laboratory renowned for fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting exhibitions of plastic arts and performances entitled: Accelerated Particles. Several works will be exhibited and performed in two 'salons'. Salon des matières: An exhibition of plastic arts From Tues 12 October to Wed 3 November 2004 Tuesdays to Fridays: 16:00 to 19:00 Saturdays: 14:00 to 18:00 Exhibition open late on performance nights, entrance free Salon des particules: Musical and visual performances Tues 12 and Mon 25 October from 20:00 to 23:00 Preview evening for both events: Tues 12 October from 18:...

  13. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's fiftieth anniversary celebrations. The fiftieth anniversary of a world famous organization like CERN, an international laboratory specializing in fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting two "salons" consisting of an exhibition of plastic arts and evenings of music and visual arts performances with the collective title of "Accelerated Particles". Several works will be exhibited and performed. Salon des matières: An exhibition of plastic arts Until Wednesday 3 November 2004. Tuesdays to Fridays: 4.00 p.m. to 7.00 p.m. Saturdays: 2.00 p.m. to 6.00 p.m. Doors open late on the evening of the performances. Salon des ...

  14. Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers.

    Directory of Open Access Journals (Sweden)

    Leila M Lopes-Bezerra

    2018-03-01

    Full Text Available Sporotrichosis is a subcutaneous mycosis caused by pathogenic species of the Sporothrix genus. A new emerging species, Sporothrix brasiliensis, is related to cat-transmitted sporotrichosis and has severe clinical manifestations. The cell wall of pathogenic fungi is a unique structure and impacts directly on the host immune response. We reveal and compare the cell wall structures of Sporothrix schenckii and S. brasiliensis using high-pressure freezing electron microscopy to study the cell wall organization of both species. To analyze the components of the cell wall, we also used infrared and 13C and 1H NMR spectroscopy and the sugar composition was determined by quantitative high-performance anion-exchange chromatography. Our ultrastructural data revealed a bi-layered cell wall structure for both species, including an external microfibrillar layer and an inner electron-dense layer. The inner and outer layers of the S. brasiliensis cell wall were thicker than those of S. schenckii, correlating with an increase in the chitin and rhamnose contents. Moreover, the outer microfibrillar layer of the S. brasiliensis cell wall had longer microfibrils interconnecting yeast cells. Distinct from those of other dimorphic fungi, the cell wall of Sporothrix spp. lacked α-glucan component. Interestingly, glycogen α-particles were identified in the cytoplasm close to the cell wall and the plasma membrane. The cell wall structure as well as the presence of glycogen α-particles varied over time during cell culture. The structural differences observed in the cell wall of these Sporothrix species seemed to impact its uptake by monocyte-derived human macrophages. The data presented here show a unique cell wall structure of S. brasiliensis and S. schenckii during the yeast parasitic phase. A new cell wall model for Sporothrix spp. is therefore proposed that suggests that these fungi molt sheets of intact cell wall layers. This observation may have significant

  15. Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

    Science.gov (United States)

    Walker, Louise A.; Niño-Vega, Gustavo; Mora-Montes, Héctor M.; Neves, Gabriela W. P.; Villalobos-Duno, Hector; Barreto, Laura; Garcia, Karina; Franco, Bernardo; Martínez-Álvarez, José A.; Munro, Carol A.; Gow, Neil A. R.

    2018-01-01

    Sporotrichosis is a subcutaneous mycosis caused by pathogenic species of the Sporothrix genus. A new emerging species, Sporothrix brasiliensis, is related to cat-transmitted sporotrichosis and has severe clinical manifestations. The cell wall of pathogenic fungi is a unique structure and impacts directly on the host immune response. We reveal and compare the cell wall structures of Sporothrix schenckii and S. brasiliensis using high-pressure freezing electron microscopy to study the cell wall organization of both species. To analyze the components of the cell wall, we also used infrared and 13C and 1H NMR spectroscopy and the sugar composition was determined by quantitative high-performance anion-exchange chromatography. Our ultrastructural data revealed a bi-layered cell wall structure for both species, including an external microfibrillar layer and an inner electron-dense layer. The inner and outer layers of the S. brasiliensis cell wall were thicker than those of S. schenckii, correlating with an increase in the chitin and rhamnose contents. Moreover, the outer microfibrillar layer of the S. brasiliensis cell wall had longer microfibrils interconnecting yeast cells. Distinct from those of other dimorphic fungi, the cell wall of Sporothrix spp. lacked α-glucan component. Interestingly, glycogen α-particles were identified in the cytoplasm close to the cell wall and the plasma membrane. The cell wall structure as well as the presence of glycogen α-particles varied over time during cell culture. The structural differences observed in the cell wall of these Sporothrix species seemed to impact its uptake by monocyte-derived human macrophages. The data presented here show a unique cell wall structure of S. brasiliensis and S. schenckii during the yeast parasitic phase. A new cell wall model for Sporothrix spp. is therefore proposed that suggests that these fungi molt sheets of intact cell wall layers. This observation may have significant effects on localized and

  16. An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum

    NARCIS (Netherlands)

    Higuera, Gustavo A; Iaffaldano, Grazia; Bedar, Meiwand; Shpak, Guy; Broersen, Robin; Munshi, Shashini T; Dupont, Catherine; Gribnau, Joost; de Vrij, Femke M S; Kushner, Steven A; De Zeeuw, Chris I

    2017-01-01

    The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it has not

  17. An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum

    NARCIS (Netherlands)

    G.A. Higuera (Gustavo A.); Iaffaldano, G. (Grazia); Bedar, M. (Meiwand); G. Shpak (Guy); R. Broersen (Robin); S.T. Munshi (Shashini T.); Dupont, C. (Catherine); J.H. Gribnau (Joost); F.M.S. Vrij (Femke); S.A. Kushner (Steven); C.I. de Zeeuw (Chris)

    2017-01-01

    textabstractThe directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it

  18. Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2 mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells.

    Science.gov (United States)

    Sirohi, Vijay Kumar; Popli, Pooja; Sankhwar, Pushplata; Kaushal, Jyoti Bala; Gupta, Kanchan; Manohar, Murli; Dwivedi, Anila

    2017-06-01

    Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. International Space Station exhibit

    Science.gov (United States)

    2000-01-01

    The International Space Station (ISS) exhibit in StenniSphere at John C. Stennis Space Center in Hancock County, Miss., gives visitors an up-close look at the largest international peacetime project in history. Step inside a module of the ISS and glimpse how astronauts will live and work in space. Currently, 16 countries contribute resources and hardware to the ISS. When complete, the orbiting research facility will be larger than a football field.

  20. Upcycling CERN Exhibitions

    CERN Multimedia

    Katarina Anthony

    2015-01-01

    Summer is coming - and with it, a new Microcosm exhibition showcasing CERN (see here). But while the new exhibit is preparing to enchant visitors, many have been asking about the site's former content. Will it simply be out with the old and in with the new? Not as such!   The plasma ball from Microcosm is now on display at the LHCb site. As Microcosm's new content is moving in, its old content is moving up. From LHCb to IdeaSquare, former Microcosm displays and objects are being installed across the CERN site. "Microcosm featured many elements that were well suited to life outside of the exhibition," says Emma Sanders, Microcosm project leader in the EDU group. "We didn't want this popular content to go to waste, and so set out to find them new homes across CERN." The LHCb experiment has received a number of Microcosm favourites, including the Rutherford experiment, the cosmic ray display and the Thomson experiment. "We&...

  1. Online Exhibits & Concept Maps

    Science.gov (United States)

    Douma, M.

    2009-12-01

    Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors

  2. Acrolein-Induced Oxidative Stress and Cell Death Exhibiting Features of Apoptosis in the Yeast Saccharomyces cerevisiae Deficient in SOD1.

    Science.gov (United States)

    Kwolek-Mirek, Magdalena; Zadrąg-Tęcza, Renata; Bednarska, Sabina; Bartosz, Grzegorz

    2015-04-01

    The yeast Saccharomyces cerevisiae is a useful eukaryotic model to study the toxicity of acrolein, an important environmental toxin and endogenous product of lipid peroxidation. The study was aimed at elucidation of the cytotoxic effect of acrolein on the yeast deficient in SOD1, Cu, Zn-superoxide dismutase which is hypersensitive to aldehydes. Acrolein generated within the cell from its precursor allyl alcohol caused growth arrest and cell death of the yeast cells. The growth inhibition involved an increase in production of reactive oxygen species and high level of protein carbonylation. DNA condensation and fragmentation, exposition of phosphatidylserine at the cell surface as well as decreased dynamic of actin microfilaments and mitochondria disintegration point to the induction of apoptotic-type cell death besides necrotic cell death.

  3. A case of atomic bomb survivor exhibiting a high frequency of peripheral blood TCRαβ+CD4-8-T cells

    International Nuclear Information System (INIS)

    Kusunoki, Yoichiro; Hirai, Yuko; Yamaoka, Mika; Morishita, Yukari; Tanabe, Kazumi; Takahashi, Keiko; Koyama, Kazuaki; Akiyama, Mitoshi

    1990-01-01

    In a healthy A-bomb female survivor aged 47, a high incidence of TCRαβ + CD4 - 8 - T cells (8.7%) was detected in the peripheral blood lymphocytes. Thirteen TCRαβ + CD4 - 8 - T cell clones were established and were analyzed by using a T-cell receptor (TCR) β chain cDNA as a probe. These clones were different from each other in TCR gene reconstitution pattern, surface phenotype, and cytotoxic activity. These findings indicated multi-clonal proliferation of TCRαβ + CD4 - 8 - T cell. (N.K.)

  4. A Caulobacter MreB mutant with irregular cell shape exhibits compensatory widening to maintain a preferred surface area to volume ratio

    Science.gov (United States)

    Harris, Leigh K.; Dye, Natalie A.; Theriot, Julie A.

    2014-01-01

    Summary Rod-shaped bacteria typically elongate at a uniform width. To investigate the genetic and physiological determinants involved in this process, we studied a mutation in the morphogenetic protein MreB in Caulobacter crescentus that gives rise to cells with a variable-width phenotype, where cells have regions that are both thinner and wider than wild-type. During growth, individual cells develop a balance of wide and thin regions, and mutant MreB dynamically localizes to poles and thin regions. Surprisingly, the surface area to volume ratio of these irregularly-shaped cells is, on average, very similar to wild-type. We propose that, while mutant MreB localizes to thin regions and promotes rod-like growth there, wide regions develop as a compensatory mechanism, allowing cells to maintain a wild-type-like surface area to volume ratio. To support this model, we have shown that cell widening is abrogated in growth conditions that promote higher surface area to volume ratios, and we have observed individual cells with high ratios return to wild-type levels over several hours by developing wide regions, suggesting that compensation can take place at the level of individual cells. PMID:25266768

  5. RNAi silenced Dd-grp94 (Dictyostelium discoideum glucose-regulated protein 94 kDa) cell lines in Dictyostelium exhibit marked reduction in growth rate and delay in development.

    Science.gov (United States)

    Baviskar, Sandhya N; Shields, Malcolm S

    2010-01-01

    Glucose-regulated 94 kDa protein (Grp94) is a resident of the endoplasmic reticulum (ER) of multicellular eukaryotes. It is a constitutively expressed protein that is overexpressed in certain abnormal conditions of the cell such as depletion of glucose and calcium, and low oxygen and pH. The protein is also implicated in diseased conditions like cancer and Alzheimer's disease. In this study, the consequences of downregulation of Grp94 were investigated at both unicellular and multicellular stages of Dictyostelium discoideum. Previous studies have shown the expression of Dd-Grp94 (Dictyostelium discoideum glucose-regulated 94 kDa protein) in wild-type cells varies during development, and overexpression of Dd-Grp94 leads to abnormal cell shape and inhibition of development (i.e., formation of fruiting bodies). Grp94 is a known calcium binding protein and an efficient calcium buffer. Therefore, in the present study we hypothesized that downregulation of Dd-Grp94 protein would affect Dictyostelium cell structure, growth, and development. We found that Dd-grp94 RNAi recombinants exhibited reduced growth rate, cell size, and a subtle change in cell motility compared to the parental cells. The recombinants also exhibited a delay in development and small fruiting bodies. These results establish that Dd-grp94 plays a crucial role in determining normal cell structure, growth and differentiation.

  6. Grass-specific CD4+ T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy

    Science.gov (United States)

    Archila, LD; DeLong, JH; Wambre, E; James, EA; Robinson, DM; Kwok, WW

    2014-01-01

    Background Conceptually, allergic responses may involve cross-reactivity by antibodies or T-cells. While IgE cross-reactivity amongst grass pollen allergens has been observed, cross-reactivity at the allergen-specific T-cell level has been less documented. Identification of the patterns of cross-reactivity may improve our understanding, allowing optimization of better immunotherapy strategies. Objectives We use Phleum pratense as model for the studying of cross-reactivity at the allergen-specific CD4+ T cell level amongst DR04:01 restricted Pooideae grass pollen T-cell epitopes. Methods After In vitro culture of blood mononucleated cells from Grass-pollen allergic subjects with specific Pooideae antigenic epitopes, dual tetramer staining with APC-labeled DR04:01/Phleum pratense tetramers and PE-labeled DR04:01/Pooideae grass homolog tetramers was assessed to identify cross-reactivity amongst allergen-specific DR04:01-restricted T-cells in 6 subjects. Direct ex vivo staining enabled the comparison of frequency and phenotype of different Pooideae grass pollen reactive T-cells. Intracellular cytokine staining (ICS) assays were also used to examine phenotypes of these T-cells. Results T-cells with various degree of cross reactive profiles could be detected. Poa p 1 97-116, Lol p 1 221-240, Lol p 5a 199-218, and Poa p 5a 199-218 were identified as minimally-cross-reactive T-cell epitopes that do not show cross reactivity to Phl p 1 and Phl p 5a epitopes. Ex vivo tetramer staining assays demonstrated T-cells that recognized these minimally-cross reactive T-cell epitopes are present in Grass-pollen allergic subjects. Conclusions Our results suggest that not all Pooideae grass epitopes with sequence homology are cross-reactive. Non-cross reactive T-cells with comparable frequency, phenotype and functionality to Phl p-specific T-cells, suggest that a multiple allergen system should be considered for immunotherapy instead of a mono allergen system. PMID:24708411

  7. Grass-specific CD4(+) T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy.

    Science.gov (United States)

    Archila, L D; DeLong, J H; Wambre, E; James, E A; Robinson, D M; Kwok, W W

    2014-07-01

    Conceptually, allergic responses may involve cross-reactivity by antibodies or T-cells. While IgE cross-reactivity among grass-pollen allergens has been observed, cross-reactivity at the allergen-specific T-cell level has been less documented. Identification of the patterns of cross-reactivity may improve our understanding, allowing optimization of better immunotherapy strategies. We use Phleum pratense as model for the studying of cross-reactivity at the allergen-specific CD4(+) T cell level among DR04:01 restricted Pooideae grass-pollen T-cell epitopes. After in vitro culture of blood mono-nucleated cells from grass-pollen-allergic subjects with specific Pooideae antigenic epitopes, dual tetramer staining with APC-labelled DR04:01/Phleum pratense tetramers and PE-labelled DR04:01/Pooideae grass homolog tetramers was assessed to identify cross-reactivity among allergen-specific DR04:01-restricted T-cells in six subjects. Direct ex vivo staining enabled the comparison of frequency and phenotype of different Pooideae grass-pollen reactive T-cells. Intracellular cytokine staining (ICS) assays were also used to examine phenotypes of these T-cells. T-cells with various degrees of cross-reactive profiles could be detected. Poa p 1 97-116 , Lol p 1 221-240 , Lol p 5a 199-218 , and Poa p 5a 199-218 were identified as minimally cross-reactive T-cell epitopes that do not show cross-reactivity to Phl p 1 and Phl p 5a epitopes. Ex vivo tetramer staining assays demonstrated T-cells that recognized these minimally cross-reactive T-cell epitopes are present in Grass-pollen-allergic subjects. Our results suggest that not all Pooideae grass epitopes with sequence homology are cross-reactive. Non-cross-reactive T-cells with comparable frequency, phenotype and functionality to Phl p-specific T-cells suggest that a multiple allergen system should be considered for immunotherapy instead of a mono-allergen system. © 2014 John Wiley & Sons Ltd.

  8. Mobile exhibition in Mexico

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1960-04-15

    Since January this year, a mobile atomic energy exhibition has been touring the principal cities of Mexico. In organizing this exhibition, the National Nuclear Energy Commission of Mexico was assisted by the International Atomic Energy Agency which has placed its second mobile radioisotope laboratory at the disposal of the Mexican authorities. In many States of the Republic, the visit of the mobile laboratory has given a powerful impetus to atomic training and research. Universities have made use of the laboratory for the training of young scientists in the basic isotope techniques. As a sequel to the work initiated with its aid, some universities are planning to start regular training courses in this field. The laboratory, which is a gift to the Agency from the United States, has been put to its first assignment in Mexico. It will shortly be sent to Argentina for a period of six months for use in training courses. IAEA's first mobile radioisotope unit, also donated by the United States, has been used for training purposes in Austria, the Federal Republic of Germany, Greece and Yugoslavia, and has now been sent to the Far East

  9. Mobile exhibition in Mexico

    International Nuclear Information System (INIS)

    1960-01-01

    Since January this year, a mobile atomic energy exhibition has been touring the principal cities of Mexico. In organizing this exhibition, the National Nuclear Energy Commission of Mexico was assisted by the International Atomic Energy Agency which has placed its second mobile radioisotope laboratory at the disposal of the Mexican authorities. In many States of the Republic, the visit of the mobile laboratory has given a powerful impetus to atomic training and research. Universities have made use of the laboratory for the training of young scientists in the basic isotope techniques. As a sequel to the work initiated with its aid, some universities are planning to start regular training courses in this field. The laboratory, which is a gift to the Agency from the United States, has been put to its first assignment in Mexico. It will shortly be sent to Argentina for a period of six months for use in training courses. IAEA's first mobile radioisotope unit, also donated by the United States, has been used for training purposes in Austria, the Federal Republic of Germany, Greece and Yugoslavia, and has now been sent to the Far East

  10. Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy".

    Science.gov (United States)

    Beyer, Marc; Karbach, Julia; Mallmann, Michael R; Zander, Thomas; Eggle, Daniela; Classen, Sabine; Debey-Pascher, Svenja; Famulok, Michael; Jäger, Elke; Schultze, Joachim L

    2009-05-15

    Immune-mediated tumor rejection relies on fully functional T-cell responses and neutralization of an adverse tumor microenvironment. In clinical trials, we detected peptide-specific but non-tumor-reactive and therefore not fully functional CD8(+) T cells post-vaccination against tumor antigens. Understanding the molecular mechanisms behind nontumor reactivity will be a prerequisite to overcome this CD8(+) T-cell deviation. We report that these non-tumor-reactive CD8(+) T cells are characterized by a molecular program associated with hallmarks of "division arrest anergy." Non-tumor-reactive CD8(+) T cells are characterized by coexpression of CD7, CD25, and CD69 as well as elevated levels of lck(p505) and p27(kip1). In vivo quantification revealed high prevalence of non-tumor-reactive CD8(+) T cells with increased levels during cancer vaccination. Furthermore, their presence was associated with a trend toward shorter survival. Dynamics and frequencies of non-target-reactive CD8(+) T cells need to be further addressed in context of therapeutic vaccine development in cancer, chronic infections, and autoimmune diseases.

  11. Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

    Energy Technology Data Exchange (ETDEWEB)

    Langland, Gregory T.; Yannone, Steven M.; Langland, Rachel A.; Nakao, Aki; Guan, Yinghui; Long, Sydney B.T.; Vonguyen, Lien; Chen, David J.; Gray, Joe W; Chen, Fanqing

    2009-09-07

    The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.

  12. Enhanced production of alkaline thermostable keratinolytic protease from calcium alginate immobilized cells of thermoalkalophilic Bacillus halodurans JB 99 exhibiting dehairing activity.

    Science.gov (United States)

    Shrinivas, Dengeti; Kumar, Raghwendra; Naik, G R

    2012-01-01

    The thermoalkalophilic Bacillus halodurans JB 99 cells known for production of novel thermostable alkaline keratinolytic protease were immobilized in calcium alginate matrix. Batch and repeated batch cultivation using calcium alginate immobilized cells were studied for alkaline protease production in submerged fermentation. Immobilized cells with 2.5% alginate and 350 beads/flask of initial cell loading showed enhanced production of alkaline protease by 23.2% (5,275 ± 39.4 U/ml) as compared to free cells (4,280 ± 35.4 U/ml) after 24 h. In the semicontinuous mode of cultivation, immobilized cells under optimized conditions produced an appreciable level of alkaline protease in up to nine cycles and reached a maximal value of 5,975 U/ml after the seventh cycle. The enzyme produced from immobilized cells efficiently degraded chicken feathers in the presence of a reducing agent which can help the poultry industry in the management of keratin-rich waste and obtaining value-added products.

  13. The ethyl acetate fraction of corn silk exhibits dual antioxidant and anti-glycation activities and protects insulin-secreting cells from glucotoxicity.

    Science.gov (United States)

    Chang, Chia-Chuan; Yuan, Wei; Roan, Hsiao-Yuh; Chang, Jia-Ling; Huang, Hsiu-Chen; Lee, Yu-Ching; Tsay, Huey Jen; Liu, Hui-Kang

    2016-11-03

    In this study, we aimed to develop a Stigmata Maydis (corn silk) fraction with dual bio-activities against oxidative stress and protein glycation to protect β-cells from diabetes-induced failure. Corn silk fractions were prepared by partition and chemically characterised by thin-layer chromatography. Free radical scavenging assay, glycation assay, and cell-based viability test (neutral red) were employed to decide the best fraction. Cell death analysis was executed by annexin V/ Propidium iodide staining. Cell proliferation was measured by WST-1. Finally, β-cell function was evaluated by β-cell marker gene expression (RT-PCR) and acute insulin secretion test. Four corn silk fractions were prepared from an ethanolic crude extract of corn silk. In vitro assays indicate ethyl acetate fraction (YMS-EA) was the most potent fraction. YMS-EA also attenuated the hydrogen peroxide- or methylglyoxal-induced induction of reactive oxygen species, reduction of cell viability, and inhibition of cell proliferation. However, YMS-EA was unable to prevent hydrogen peroxide-induced apoptosis or advanced glycation end-products-induced toxicity. Under hyperglycemic conditions, YMS-EA effectively reduced ROS levels, improved mRNA expression of insulin, glucokinase, and PDX-1, and enhanced glucose-stimulated insulin secretion. The similarity of bioactivities among apigenin, luteolin, and YMS-EA indicated that dual activities of YMS-EA might be derived from those compounds. We concluded that YMS-EA fraction could be developed as a preventive food agent against the glucotoxicity to β-cells in Type 2 diabetes.

  14. Anniversary Exhibition. Nechvolodov.

    Directory of Open Access Journals (Sweden)

    - -

    2006-03-01

    Full Text Available On the 10th of August, 2005 in Tartu (the second biggest educational and cultural city in Estonia Stanislav Nechvolodov's exhibition was opened to show the 5-year cycle of his work, traditional for the author and his admirers. At the opening ceremony Nechvolodov said that the exhibition was the last one and appointed on his 70th anniversary.The architectural and building society in Irkutsk remembers Stanislav Nechvolodov as an architect working on dwelling and civil buildings in 1960-70s. Below are some extracts from the Estonian press.«Postimees» newspaper, December 1993. The interview «Expressionistic naturalist, conservative Nechvolodov» by journalist Eric Linnumyagi. He asks about all the details and describes the troubles experienced by Nechvolodov during the perestroika period in Estonia, for example: the Tartu University refused to install the sculpture of Socrat, the art school refused to engage him as an instructor, the sculpture of Socrat moved to Vrotzlav, Poland, and Nechvolodov moved to Poland to read lectures there.«Tartu» newspaper, November 2000. Mats Oun, artist, says in the article «Nechvolodov: a man of Renaissance»: «Nechvolodov works in Estonia, his works are placed in many local and foreign museums. Regardless some insignificant faults, he deserves a high estimation, and his manysided open exhibition can be an example for other artists. He is a man of Renaissance».

  15. Artemisinic acid exhibits antitumor activity in MCF-7 breast cancer cells through the inhibition of angiogenesis, VEGF, m-TOR and AKT signalling pathways

    Directory of Open Access Journals (Sweden)

    Yan Cui

    2016-09-01

    Full Text Available The aim of the present study was to evaluate the antitumor and anti-angiogenic effects of artemisinic acid in MCF-7 human breast cancer cells. Various cell signalling pathways (VEGF, m-TOR and AKT signalling pathways and MTT assay were used. The in vivo antitumor activity of artemisinic acid was evaluated by means of tumor xenograft mouse model. Transwell cell migration assay was used to examine the chemotactic motility of the human umbilical vascular endothelial cells (HUVECs, while as endothelial cell capillary-like tube formation assay was used to evaluate the effect of artemisinic acid on the tube formation in HUVECs. We found that artemisinic acid considerably reduced both the volume and weight of concrete tumors and reduced angiogenesis in a xenograft mouse tumor model in vivo. Further, artemisinic acid suppressed the VEGF-induced cell migration and capillary-like tube formation of HUVECs in a dose-dependent manner. Artemisinic acid was found to suppress the VEGF-induced phosphorylation of VEGFR2 and also the activity of AKT and m-TOR.

  16. HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

    Science.gov (United States)

    Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D; Ndung'u, Thumbi; Ndhlovu, Zaza M

    2017-04-01

    Immune control of viral infections is heavily dependent on helper CD4 + T cell function. However, the understanding of the contribution of HIV-specific CD4 + T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4 + T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4 + T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4 + T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4 + T cells in HIV controllers than progressors ( P = 0.0001), and these expanded Gag-specific CD4 + T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control ( r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4 + T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4 + T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4 + T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4 + T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV

  17. 6-Shogaol induces apoptosis in human hepatocellular carcinoma cells and exhibits anti-tumor activity in vivo through endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Rong Hu

    Full Text Available 6-Shogaol is an active compound isolated from Ginger (Zingiber officinale Rosc. In this work, we demonstrated that 6-shogaol induces apoptosis in human hepatocellular carcinoma cells in relation to caspase activation and endoplasmic reticulum (ER stress signaling. Proteomic analysis revealed that ER stress was accompanied by 6-shogaol-induced apoptosis in hepatocellular carcinoma cells. 6-shogaol affected the ER stress signaling by regulating unfolded protein response (UPR sensor PERK and its downstream target eIF2α. However, the effect on the other two UPR sensors IRE1 and ATF6 was not obvious. In prolonged ER stress, 6-shogaol inhibited the phosphorylation of eIF2α and triggered apoptosis in SMMC-7721 cells. Salubrinal, an activator of the PERK/eIF2α pathway, strikingly enhanced the phosphorylation of eIF2α in SMMC-7721 cells with no toxicity. However, combined treatment with 6-shogaol and salubrinal resulted in significantly increase of apoptosis and dephosphorylation of eIF2α. Overexpression of eIF2α prevented 6-shogaol-mediated apoptosis in SMMC-7721 cells, whereas inhibition of eIF2α by small interfering RNA markedly enhanced 6-shogaol-mediated cell death. Furthermore, 6-shogaol-mediated inhibition of tumor growth of mouse SMMC-7721 xenograft was associated with induction of apoptosis, activation of caspase-3, and inactivation of eIF2α. Altogether our results indicate that the PERK/eIF2α pathway plays an important role in 6-shogaol-mediated ER stress and apoptosis in SMMC-7721 cells in vitro and in vivo.

  18. Malignant progressive tumor cell clone exhibits significant up-regulation of cofilin-2 and 27-kDa modified form of cofilin-1 compared to regressive clone.

    Science.gov (United States)

    Kuramitsu, Yasuhiro; Wang, Yufeng; Okada, Futoshi; Baron, Byron; Tokuda, Kazuhiro; Kitagawa, Takao; Akada, Junko; Nakamura, Kazuyuki

    2013-09-01

    QR-32 is a regressive murine fibrosarcoma cell clone which cannot grow when they are transplanted in mice; QRsP-11 is a progressive malignant tumor cell clone derived from QR-32 which shows strong tumorigenicity. A recent study showed there to be differentially expressed up-regulated and down-regulated proteins in these cells, which were identified by proteomic differential display analyses by using two-dimensional gel electrophoresis and mass spectrometry. Cofilins are small proteins of less than 20 kDa. Their function is the regulation of actin assembly. Cofilin-1 is a small ubiquitous protein, and regulates actin dynamics by means of binding to actin filaments. Cofilin-1 plays roles in cell migration, proliferation and phagocytosis. Cofilin-2 is also a small protein, but it is mainly expressed in skeletal and cardiac muscles. There are many reports showing the positive correlation between the level of cofilin-1 and cancer progression. We have also reported an increased expression of cofilin-1 in pancreatic cancer tissues compared to adjacent paired normal tissues. On the other hand, cofilin-2 was significantly less expressed in pancreatic cancer tissues. Therefore, the present study investigated the comparison of the levels of cofilin-1 and cofilin-2 in regressive QR-32 and progressive QRsP-11cells by western blotting. Cofilin-2 was significantly up-regulated in QRsP-11 compared to QR-32 cells (p<0.001). On the other hand, the difference of the intensities of the bands of cofilin-1 (18 kDa) in QR-32 and QRsP-11 was not significant. However, bands of 27 kDa showed a quite different intensity between QR-32 and QRsP-11, with much higher intensities in QRsP-11 compared to QR-32 (p<0.001). These results suggested that the 27-kDa protein recognized by the antibody against cofilin-1 is a possible biomarker for progressive tumor cells.

  19. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    International Nuclear Information System (INIS)

    Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.; Longo, D.L.

    1984-01-01

    The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells

  20. CD11b⁺, Ly6G⁺ cells produce type I interferon and exhibit tissue protective properties following peripheral virus infection.

    Directory of Open Access Journals (Sweden)

    Matthew A Fischer

    2011-11-01

    Full Text Available The goal of the innate immune system is containment of a pathogen at the site of infection prior to the initiation of an effective adaptive immune response. However, effector mechanisms must be kept in check to combat the pathogen while simultaneously limiting undesirable destruction of tissue resulting from these actions. Here we demonstrate that innate immune effector cells contain a peripheral poxvirus infection, preventing systemic spread of the virus. These innate immune effector cells are comprised primarily of CD11b⁺Ly6C⁺Ly6G⁻ monocytes that accumulate initially at the site of infection, and are then supplemented and eventually replaced by CD11b⁺Ly6C⁺Ly6G⁺ cells. The phenotype of the CD11b⁺Ly6C⁺Ly6G⁺ cells resembles neutrophils, but the infiltration of neutrophils typically occurs prior to, rather than following, accumulation of monocytes. Indeed, it appears that the CD11b⁺Ly6C⁺Ly6G⁺ cells that infiltrated the site of VACV infection in the ear are phenotypically distinct from the classical description of both neutrophils and monocyte/macrophages. We found that CD11b⁺Ly6C⁺Ly6G⁺ cells produce Type I interferons and large quantities of reactive oxygen species. We also observed that depletion of Ly6G⁺ cells results in a dramatic increase in tissue damage at the site of infection. Tissue damage is also increased in the absence of reactive oxygen species, although reactive oxygen species are typically thought to be damaging to tissue rather than protective. These data indicate the existence of a specialized population of CD11b⁺Ly6C⁺Ly6G⁺ cells that infiltrates a site of virus infection late and protects the infected tissue from immune-mediated damage via production of reactive oxygen species. Regulation of the action of this population of cells may provide an intervention to prevent innate immune-mediated tissue destruction.

  1. Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Su, Yinghan; Sun, Bin; Lin, Xuejing; Zhao, Xinying; Ji, Weidan; He, Miaoxia; Qian, Haihua; Song, Xianmin; Yang, Jianmin; Wang, Jianmin; Chen, Jie

    2016-08-02

    In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.

  2. Dental pulp-derived stromal cells exhibit a higher osteogenic potency than bone marrow-derived stromal cells in vitro and in a porcine critical-size bone defect model

    Directory of Open Access Journals (Sweden)

    Jensen Jonas

    2016-01-01

    Full Text Available Introduction: The osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSCs was compared with that of dental pulp-derived stromal cells (DPSCs in vitro and in a pig calvaria critical-size bone defect model. Methods: BMSCs and DPSCs were extracted from the tibia bone marrow and the molar teeth of each pig, respectively. BMSCs and DPSCs were cultured in monolayer and on a three-dimensional (3D polycaprolactone (PCL – hyaluronic acid – tricalcium phosphate (HT-PCL scaffold. Population doubling (PD, alkaline phosphatase (ALP activity, and calcium deposition were measured in monolayer. In the 3D culture ALP activity, DNA content, and calcium deposition were evaluated. Six non-penetrating critical-size defects were made in each calvarium of 14 pigs. Three paired sub-studies were conducted: (1 empty defects vs. HT-PCL scaffolds; (2 PCL scaffolds vs. HT-PCL scaffolds; and (3 autologous BMSCs on HT-PCL scaffolds vs. autologous DPSCs on HT-PCL scaffolds. The observation time was five weeks. Bone volume fractions (BV/TV were assessed with micro-computed tomography (μCT and histomorphometry. Results and discussion: The results from the in vitro study revealed a higher ALP activity and calcium deposition of the DPSC cultures compared with BMSC cultures. Significantly more bone was present in the HT-PCL group than in both the pure PCL scaffold group and the empty defect group in vivo. DPSCs generated more bone than BMSCs when seeded on HT-PCL. In conclusion, DPSCs exhibited a higher osteogenic potential compared with BMSCs both in vitro and in vivo, making it a potential cell source for future bone tissue engineering.

  3. Y and Ni Co-Doped BaZrO3 as a Proton-Conducting Solid Oxide Fuel Cell Electrolyte Exhibiting Superior Power Performance

    KAUST Repository

    Shafi, Shahid P.; Bi, Lei; Boulfrad, Samir; Traversa, Enrico

    2015-01-01

    The fabrication of anode supported single cells based on BaZr0.8Y0.2O3-δ (BZY20) electrolyte is challenging due to its poor sinteractive nature. The acceleration of shrinkage behavior, improved sinterability and larger grain size were achieved

  4. FLAG-induced remission in a patient with acute mast cell leukemia (MCL exhibiting t(7;10(q22;q26 and KIT D816H

    Directory of Open Access Journals (Sweden)

    Peter Valent

    2014-01-01

    Full Text Available Mast cell leukemia (MCL is a life-threatening disease associated with high mortality and drug-resistance. Only few patients survive more than 12 months. We report on a 55-year-old female patient with acute MCL diagnosed in May 2012. The disease was characterized by a rapid increase in white blood cells and mast cells (MC in the peripheral blood, and a rapid increase of serum tryptase levels. The KIT D816H mutation was detected in the blood and bone marrow (BM. Induction chemotherapy with high-dose ARA-C and fludarabine (FLAG was administered. Unexpectedly, the patient entered a hematologic remission with almost complete disappearance of neoplastic MC and a decrease of serum tryptase levels to normal range after 2 cycles of FLAG. Consecutively, the patient was prepared for allogeneic stem cell transplantation. However, shortly after the third cycle of FLAG, tryptase levels increased again, immature MC appeared in the blood, and the patient died from cerebral bleeding. Together, this case shows that intensive chemotherapy regimens, like FLAG, may induce remission in acute MCL. However, treatment responses are short-lived and the overall outcome remains dismal in these patients. We propose to separate this acute type of MCL from more subacute or chronic variants of MCL.

  5. FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures

    DEFF Research Database (Denmark)

    Wong, Kah Keng; Gascoyne, Duncan M; Soilleux, Elizabeth J

    2016-01-01

    frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which...

  6. Synsepalum dulcificum extracts exhibit cytotoxic activity on human colorectal cancer cells and upregulate c-fos and c-jun early apoptotic gene expression

    Directory of Open Access Journals (Sweden)

    Jichang Seong

    2018-01-01

    Full Text Available Objective: To explore cytotoxicity of Synsepalum dulcificum (S. dulcificum Daniell (Sapotaceae on human colon cancer (HCT-116 and HT-29, human monocytic leukemia (THP-1 and normal (HDFn cell lines, and its effect on the expression of early apoptotic genes, c-fos and c-jun. Methods: Leaf, stem and berry of S. dulcificum were separately extracted by using 2 solvents, 10% ethanol (EtOH and 80% methanol (MeOH. PrestoBlue® cell viability assay and qRT-PCR assay were conducted to examine the above objectives respectively. Results: Stem MeOH, stem EtOH, and berry EtOH extracts of S. dulcificum were cytotoxic to HCT-116 and HT-29 human colon cancer cells. For HCT-116, IC50 values of these 3 extracts were not significantly different (P>0.05 from that of the positive control bleomycin (IC50 of 33.57 μg/mL, while for HT-29, IC50 values of these 3 extracts were significantly lower (P<0.05 than that of bleomycin (IC50 of 25.24 μg/mL. None of the extracts were cytotoxic to the THP-1 monocytic leukemia cells and HDFn normal human dermal fibroblasts. For both HCT-116 and HT-29, these extracts significantly up-regulated (P<0.05 the expression of c-fos and c-jun compared to the untreated negative control. Conclusions: The results of this study suggest that cytotoxicity of stem MeOH, stem EtOH, and berry EtOH extracts of S. dulcificum on HCT-116 and HT-29 colon cancer cells is due to the induced apoptosis which is caused by the up-regulation of the expression of early apoptotic genes, c-fos and c-jun.

  7. Pitanga (Eugenia uniflora L.) fruit juice and two major constituents thereof exhibit anti-inflammatory properties in human gingival and oral gum epithelial cells.

    Science.gov (United States)

    Josino Soares, Denise; Walker, Jessica; Pignitter, Marc; Walker, Joel Michael; Imboeck, Julia Maria; Ehrnhoefer-Ressler, Miriam Margit; Montenegro Brasil, Isabella; Somoza, Veronika

    2014-11-01

    Pitanga, Eugenia uniflora L., is a tropical fruit, which may be consumed as juice. While beneficial health effects of Eugenia uniflora L. leaf extracts have extensively been studied, limited data are available on an anti-inflammatory potential of pitanga juice. The aim of the presented study was to investigate anti-inflammatory properties of pitanga juice with regards to a prevention of inflammation-related periodontal diseases. For this purpose, six healthy volunteers swirled pitanga juice, containing 35% pitanga pulp, for 10 min. Thereafter, oral gum epithelial cells were harvested using a sterile brush and stimulated with lipopolysaccharides from Porphyromonas gingivalis (PG-LPS) for 6 h. Furthermore, human gingival fibroblasts (HGF-1) were used to elucidate the anti-inflammatory potential of pitanga juice constituents, cyanidin-3-glucoside and oxidoselina-1,3,7(11)-trien-8-one, in juice representative concentrations of 119 μg ml(-1) and 30 μg ml(-1), respectively. For the first time, an anti-inflammatory impact of pitanga juice on gingival epithelial cells was shown by means of an attenuation of IL-8 release by 55 ± 8.2% and 52 ± 11% in non-stimulated and PG-LPS-stimulated cells, respectively. In addition, both cyanidin-3-glucoside and oxidoselina-1,3,7(11)-trien-8-one reduced the LPS-stimulated CXCL8 mRNA expression by 50 ± 15% and 37 ± 18% and IL-8 release by 52 ± 9.9% and 45 ± 3.7% in HGF-1 cells, when concomitantly incubated with 10 μg ml(-1)PG-LPS for 6 h, revealing an anti-inflammatory potential of the volatile compound oxidoselina-1,3,7(11)-trien-8-one for the first time.

  8. Estrogen receptor β exhibited anti-tumor effects on osteosarcoma cells by regulating integrin, IAP, NF-kB/BCL-2 and PI3K/Akt signal pathway

    Directory of Open Access Journals (Sweden)

    Minfei Yang

    2017-11-01

    Full Text Available This study aimed to investigate the effects of Estrogen receptor β (ERβ on osteosarcoma cells, and explore the regulatory mechanisms involved in this process. Osteosarcoma U2-OS cells consisted four groups, and treated by E2, E2 + LY294002 (ERβ agonists, E2 + ERβ siRNA, E2 + ERβ siRNA + LY294002, respectively. Cell counting kit 8 (CCK-8 assay was performed to detect the cell viability of U2-OS cells in each group. The effects of ERβ on the migration and invasion ability of U2-OS cells were examined by wound healing assay and transwell cell culture chamber, respectively. The expression of Inhibitor of apoptosis protein (IAP and integrin α5 in U2-OS cells of each group was detected by quantitative RT-PCR, and the expression of phosphorylated p65 (p-p65, p-AKT and Bcl-2 was detected by western blotting. The cell viability, migration and invasion ability of U2-OS cells were significantly increased by ERβ siRNA, but inhibited by ERβ agonists LY294002 (p < 0.05. ERβ siRNA significantly downregulated Integrin α5 and unregulated IAP in U2-OS cells (p < 0.05. The expression of p-p65, p-AKT and Bcl-2 was significantly reduced by LY294002, but increased by ERβ siRNA (p < 0.05. In conclusion, ERβ exhibited obvious anti-tumor effects on osteosarcoma cells by regulating integrin, IAP, NF-kBBCL-2 and PI3K/Akt signal pathway. Keywords: Estrogen receptor β, Osteosarcoma, Anti-tumor, Regulatory mechanism

  9. CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells

    DEFF Research Database (Denmark)

    Fjelbye, Jonas; Antvorskov, Julie C; Buschard, Karsten

    2015-01-01

    .05) and peritoneal cavity (80.8% decrease; P challenge, which suggests an important regulatory and protective role of CD1d-dependent NKT cells in CHS in our model, at least in part via regulation of IL-10 producing B(regs) ....... knockout (CD1d KO) and wild-type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0...

  10. Topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages.

    Science.gov (United States)

    Pati, Rashmirekha; Mehta, Ranjit Kumar; Mohanty, Soumitra; Padhi, Avinash; Sengupta, Mitali; Vaseeharan, Baskarlingam; Goswami, Chandan; Sonawane, Avinash

    2014-08-01

    Here we studied immunological and antibacterial mechanisms of zinc oxide nanoparticles (ZnO-NPs) against human pathogens. ZnO-NPs showed more activity against Staphylococcus aureus and least against Mycobacterium bovis-BCG. However, BCG killing was significantly increased in synergy with antituberculous-drug rifampicin. Antibacterial mechanistic studies showed that ZnO-NPs disrupt bacterial cell membrane integrity, reduce cell surface hydrophobicity and down-regulate the transcription of oxidative stress-resistance genes in bacteria. ZnO-NP treatment also augmented the intracellular bacterial killing by inducing reactive oxygen species production and co-localization with Mycobacterium smegmatis-GFP in macrophages. Moreover, ZnO-NPs disrupted biofilm formation and inhibited hemolysis by hemolysin toxin producing S. aureus. Intradermal administration of ZnO-NPs significantly reduced the skin infection, bacterial load and inflammation in mice, and also improved infected skin architecture. We envision that this study offers novel insights into antimicrobial actions of ZnO-NPs and also demonstrates ZnO-NPs as a novel class of topical anti-infective agent for the treatment of skin infections. This in-depth study demonstrates properties of ZnO nanoparticles in infection prevention and treatment in several skin infection models, dissecting the potential mechanisms of action of these nanoparticles and paving the way to human applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. XH-14, a novel danshen methoxybenzo[b]furan derivative, exhibits anti-inflammatory properties in lipopolysaccharide-treated RAW 264.7 cells

    Directory of Open Access Journals (Sweden)

    Park Geun-Mook

    2013-01-01

    Full Text Available Abstract Background XH-14 isolated from Salvia miltiorrhiza is a bioactive component and adenosine antagonist. In the present study, we evaluated anti-inflammatory properties of XH-14 in murine macrophages. Methods RAW 264.7 murine macrophage cell line was cultured with various concentrations of XH-14 in the absence or presence of lipopolysaccharide (LPS. LPS-induced release and mRNA expression of inflammatory mediators were examined by ELISA and real-time PCR. The modification of signal pathways involved in inflammatory reactions was determined by Western blotting analysis. Results XH-14 suppressed the generation of nitric oxide (NO and prostaglandin E2, and the expression of inducible NO synthase and cyclooxygenase-2 induced by LPS. Similarly, XH-14 inhibited the release of pro-inflammatory cytokines induced by LPS in RAW 264.7 cells. The underlying mechanism of XH-14 on anti-inflammatory action was correlated with down-regulation of mitogen-activated protein kinase and activator protein-1 activation. Conclusions XH-14 inhibits the production of several inflammatory mediators and so might be useful for the treatment of various inflammatory diseases.

  12. Obese First-Degree Relatives of Patients with Type 2 Diabetes with Elevated Triglyceride Levels Exhibit Increased β-Cell Function

    Science.gov (United States)

    Torres-Rasgado, Enrique; Porchia, Leonardo M.; Ruiz-Vivanco, Guadalupe; Gonzalez-Mejia, M. Elba; Báez-Duarte, Blanca G.; Pulido-Pérez, Patricia; Rivera, Alicia; Romero, Jose R.

    2015-01-01

    Abstract Background: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and β-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). Methods: We studied 372 FDR-T2DM subjects (ages,18–65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob−) or obese (Ob+)] and TGs levels (TG−, Mexico with NGT and revealed a class of obese subjects with elevated TGs and β-cell function, which may precede PT2DM. PMID:25423015

  13. Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6

    DEFF Research Database (Denmark)

    Scheele, Camilla; Nielsen, Søren; Broholm, Christa

    2012-01-01

    isolated satellite cells from skeletal muscle of people that were healthy (He), obese (Ob) or were obese and had type 2 diabetes (DM), and differentiated them in vitro into myocytes. Down-regulation of IL-6Rα was conserved in Ob myocytes. In addition, acute IL-6 administration for 30, 60 and 120 minutes......Obesity and type 2 diabetes are associated with chronically elevated systemic levels of IL-6, a pro-inflammatory cytokine with a role in skeletal muscle metabolism that signals through the IL-6 receptor (IL-6Rα). We hypothesized that skeletal muscle in obesity-associated type 2 diabetes develops...... a resistance to IL-6. By utilizing western blot analysis, we demonstrate that IL-6Rα protein was down regulated in skeletal muscle biopsies from obese persons with and without type 2 diabetes. To further investigate the status of IL-6 signaling in skeletal muscle in obesity-associated type 2 diabetes, we...

  14. Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro.

    Science.gov (United States)

    Tezcan, Gulcin; Taskapilioglu, Mevlut Ozgur; Tunca, Berrin; Bekar, Ahmet; Demirci, Hilal; Kocaeli, Hasan; Aksoy, Secil Ak; Egeli, Unal; Cecener, Gulsah; Tolunay, Sahsine

    2017-06-01

    Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive (GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive therapy. In the present study, the potential anti-angiogenic and anti-invasive effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+) tumours. OLE (2mg/mL) caused a significant reduction in tumour weight, vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004; respectively) that was associated with reducing the expression of VEGFA, MMP-2 and MMP-9. This effect was synergistically increased in combination with bevacizumab. Therefore, our current findings may contribute to research on drugs that inhibit the invasiveness of GBM. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Ternary Organic Solar Cells with Coumarin7 as the Donor Exhibiting Greater Than 10% Power Conversion Efficiency and a High Fill Factor of 75.

    Science.gov (United States)

    Chen, Xin-Wei; Tao, Si-Lu; Fan, Cong; Chen, Dong-Cheng; Zhou, Ling; Lin, Hui; Zheng, Cai-Jun; Su, Shi-Jian

    2017-09-06

    Ternary bulk heterojunction (BHJ) is a brilliant photovoltaic technology for improving the performance of organic solar cells (OSCs), because the light absorption range can be significantly extended by using multiple donors or acceptor materials. In this paper, coumarin7 (C7), a small organic molecule typical led used in organic light-emitting diodes, was initially exploited as second electron-donor component in ternary bulk heterojunction OSCs along with conventional blend system spolythieno[3,4-b]-thiophene/benzodithiophene(PTB7) and [6,6]-phenyl-C71 -butyric acid methyl(PC 71 BM). A champion PCE value of 10.28% was realized in the ternary OSCs when incorporated with 10 wt % C7 doping ratio in the donors, corresponding to about 35% enhancement compared with the PTB7:PC 71 BM-based OSCs, a high fill factor (FF) of 75.03%, a short-circuit currentdensity (J sc ) of 18.72 mA cm -2 and an open-circuit voltage (V oc ) of 0.73 V. The enhanced performance of the ternary OSCs can be attributed to the simultaneous improvement of the FF and the J sc . In addition to extended light absorption, a perfect nanofiber filament active layer morphology is obtained due to the good compatibility between C7 and PTB7, which facilitates the balance of charge transportation and the suppression of charge recombination. This investigation suggests that coumarin derivatives, which have completely different structure with polymer donors, can also be used to fabricate ternary solar cells and have the potential applications to obtain amazing performance after further device engineering and optimization.

  16. Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

    Science.gov (United States)

    Lamont, Matthew G; Weber, John T

    2015-06-01

    The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Evolved osmotolerant Escherichia coli mutants frequently exhibit defective N-acetylglucosamine catabolism and point mutations in cell shape-regulating protein MreB.

    Science.gov (United States)

    Winkler, James D; Garcia, Carlos; Olson, Michelle; Callaway, Emily; Kao, Katy C

    2014-06-01

    Biocatalyst robustness toward stresses imposed during fermentation is important for efficient bio-based production. Osmotic stress, imposed by high osmolyte concentrations or dense populations, can significantly impact growth and productivity. In order to better understand the osmotic stress tolerance phenotype, we evolved sexual (capable of in situ DNA exchange) and asexual Escherichia coli strains under sodium chloride (NaCl) stress. All isolates had significantly improved growth under selection and could grow in up to 0.80 M (47 g/liter) NaCl, a concentration that completely inhibits the growth of the unevolved parental strains. Whole genome resequencing revealed frequent mutations in genes controlling N-acetylglucosamine catabolism (nagC, nagA), cell shape (mrdA, mreB), osmoprotectant uptake (proV), and motility (fimA). Possible epistatic interactions between nagC, nagA, fimA, and proV deletions were also detected when reconstructed as defined mutations. Biofilm formation under osmotic stress was found to be decreased in most mutant isolates, coupled with perturbations in indole secretion. Transcriptional analysis also revealed significant changes in ompACGL porin expression and increased transcription of sulfonate uptake systems in the evolved mutants. These findings expand our current knowledge of the osmotic stress phenotype and will be useful for the rational engineering of osmotic tolerance into industrial strains in the future. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  18. Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.

    Science.gov (United States)

    Pasquier, Jennifer; Thomas, Binitha; Hoarau-Véchot, Jessica; Odeh, Tala; Robay, Amal; Chidiac, Omar; Dargham, Soha R; Turjoman, Rebal; Halama, Anna; Fakhro, Khalid; Menzies, Robert; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Rafii, Arash; Malik, Rayaz A; Talal, Talal; Abi Khalil, Charbel

    2017-11-27

    Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

  19. Endothelin-A-receptor antagonism with atrasentan exhibits limited activity on the KU-19-19 bladder cancer cell line in a mouse model.

    Science.gov (United States)

    Herrmann, Edwin; Tiemann, Arne; Eltze, Elke; Bolenz, Christian; Bremer, Christoph; Persigehl, Thorsten; Hertle, Lothar; Wülfing, Christian

    2009-10-01

    The endothelin axis consists of endothelin-1 (ET-1) and its two receptors, ET(A)- and ET(B)-receptor (ET(A)-R and ET(B)-R). In several tumor entities, the ET(A)-R plays a significant role as a drug target. In our study, we investigated whether inhibition of ET(A)-R with atrasentan leads to an antitumor effect in urinary bladder carcinoma as well. Twenty nude mice with thymic aplasia were subcutaneously administered 2 x 10(6) KU-19-19 bladder cancer cells in the right flank. Starting on the 22nd day after the injection, ten animals were treated with atrasentan (2.5 mg/kg BW intraperitoneally), and another ten animals were treated with placebo. During treatment, absolute tumor growth and relative growth rate over time were determined. After the end of treatment, the mitosis and necrosis rates, microvessel density, and receptor density in the tumor tissue were analyzed by immunohistochemistry. In addition, the expression intensities of ET-1, ET(A)-R, and ET(B)-R were evaluated semiquantitatively and compared between the groups. No significant differences between the active-treatment and placebo groups were detected, either with respect to absolute tumor growth (P = 0.333) or mitosis rate (P = 0.217). In the analysis of the necrosis rate and receptor density for ET(A)-R, a trend toward higher values in the active-treatment group (mean necrosis rate = 63.67%, receptor density: 1.417) than in the placebo group (mean necrosis rate = 46.25%, receptor density: 1.270) was found; however, neither difference was statistically significant (P = 0.08 and 0.219, respectively). ET(A)-R blockade with atrasentan in a bladder cancer xenograft model shows no significant antitumor effect.

  20. Construction of a novel selection system for endoglucanases exhibiting carbohydrate-binding modules optimized for biomass using yeast cell-surface engineering.

    Science.gov (United States)

    Nakanishi, Akihito; Bae, Jungu; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2012-10-23

    To permit direct cellulose degradation and ethanol fermentation, Saccharomyces cerevisiae BY4741 (Δsed1) codisplaying 3 cellulases (Trichoderma reesei endoglucanase II [EG], T. reesei cellobiohydrolase II [CBH], and Aspergillus aculeatus β-glucosidase I [BG]) was constructed by yeast cell-surface engineering. The EG used in this study consists of a family 1 carbohydrate-binding module (CBM) and a catalytic module. A comparison with family 1 CBMs revealed conserved amino acid residues and flexible amino acid residues. The flexible amino acid residues were at positions 18, 23, 26, and 27, through which the degrading activity for various cellulose structures in each biomass may have been optimized. To select the optimal combination of CBMs of EGs, a yeast mixture with comprehensively mutated CBM was constructed. The mixture consisted of yeasts codisplaying EG with mutated CBMs, in which 4 flexible residues were comprehensively mutated, CBH, and BG. The yeast mixture was inoculated in selection medium with newspaper as the sole carbon source. The surviving yeast consisted of RTSH yeast (the mutant sequence of CBM: N18R, S23T, S26S, and T27H) and wild-type yeast (CBM was the original) in a ratio of 1:46. The mixture (1 RTSH yeast and 46 wild-type yeasts) had a fermentation activity that was 1.5-fold higher than that of wild-type yeast alone in the early phase of saccharification and fermentation, which indicates that the yeast mixture with comprehensively mutated CBM could be used to select the optimal combination of CBMs suitable for the cellulose of each biomass.

  1. X-ray irradiation and Rho-kinase inhibitor additively induce invasiveness of the cells of the pancreatic cancer line, MIAPaCa-2, which exhibits mesenchymal and amoeboid motility

    International Nuclear Information System (INIS)

    Fujita, Mayumi; Otsuka, Yoshimi; Yamada, Shigeru; Iwakawa, Mayumi; Imai, Takashi

    2011-01-01

    Tumor cells can migrate and invade tissue by two modes of motility: mesenchymal and amoeboid. X-ray or γ-ray irradiation increases the invasiveness of tumor cells with mesenchymal motility through the induction of matrix metalloproteinases (MMP), and this increase is suppressed by MMP inhibitors (MMPI). However, the effects of X-ray or γ-ray irradiation on the invasiveness of tumor cells with amoeboid motility remain unclear. We investigated the effect of irradiation on amoeboid motility by using cells of the human pancreatic cancer line, MIAPaCa-2, which exhibits both modes of motility. The X-ray-induced invasiveness of MIAPaCa-2 cells was associated with the upregulation of MMP2 at both the RNA and protein levels and was inhibited by MMPI treatment. Amoeboid-mesenchymal transition was slightly induced after irradiation. The MMPI treatment caused mesenchymal-amoeboid transition without significant increase in invasiveness, while the ROCK inhibitor (ROCKI) stimulated amoeboid-mesenchymal transition and enhanced invasiveness under both non-irradiated and irradiated conditions. This ROCKI-induced transition was accompanied by the upregulation of MMP2 mRNA and protein. Exposure to both irradiation and ROCKI further enhanced MMP2 expression and had an additive effect on the invasiveness of MIAPaCa-2 cells. Additionally, exposure to MMPI led to significant suppression of both radiation-induced and the basal invasiveness of MIAPaCa-2 cells. This suggests that ROCKI treatment, especially with concomitant X-ray irradiation, can induce invasion of cancer cells and should be used only for certain types of cancer cells. Simultaneous use of inhibitors, ROCKI and MMPI may be effective in suppressing invasiveness under both X-ray-irradiated and non-irradiated conditions. (author)

  2. Exhibition

    CERN Multimedia

    Staff Association

    2014-01-01

    Energie sombre, matière noire J.-J. Dalmais - J. Maréchal Du 11 au 27 novembre 2014, CERN Meyrin, Bâtiment principal A l’image des particules atomiques qui ont tissé des liens pour créer la matière, deux artistes haut bugistes croisent leurs regards et conjuguent leurs expressions singulières pour faire naître une vision commune de l’univers, produit des forces primordiales. Les sculptures de Jean-Jacques Dalmais et les peintures de Jacki Maréchal se rencontrent pour la première fois et se racontent par un enrichissement mutuel la belle histoire de la Vie. Dialogue magique des œuvres en mouvement qui questionnent en écho l’énergie sombre et la matière noire. Cette harmonieuse confluence de jeux de miroir et de résonnance illumine de poésie et de sobriété l’espace expos&...

  3. Exhibition

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    2017-01-01

    Gaïa Manuella Cany Du 10 au 28 avril 2017 CERN Meyrin, Bâtiment principal Oiseau - Manuella Cany. Tableaux abstraits inspirés de vues satellites ou photos prises du ciel. Certains sont à la frontière du figuratif alors que d'autres permettent de laisser libre cours à son imagination. Aux détails infinis, ces tableaux sont faits pour être vus de loin et de près grâce à une attention toute particulière apportée aux effets de matières et aux couleurs le long de volutes tantôt nuancées tantôt contrastées.   Pour plus d’informations : staff.association@cern.ch | Tél: 022 766 37 38

  4. Exhibition

    CERN Document Server

    Staff Association

    2018-01-01

    En dehors des frontières Maxence Piquet Du 2 au 11 mai 2018 | CERN Meyrin, Bâtiment principal Exposition de peinture d'un artiste autodidacte Maxence Piquet (signature artiste M-P), avec différentes techniques (acrylique, huile, fusain, collage...) et sur différents supports. Un art souvent brut et parfois provoquant, avec des touches expressionnistes et cubistes principale origine de son art. Des œuvres souvent vivent et colorées... Cette exposition est la première en dehors d ses frontières Lorraine et a pour but de faire voyager son art au regard du plus grand nombre . Pour plus d’informations et demandes d’accès : staff.association@cern.ch | Tél: 022 766 37 38

  5. Exhibition

    CERN Multimedia

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    2016-01-01

    The Elementary Particles of Painting Alfonso Fratteggiani Bianchi and Ermanno Imbergamo From September 26 to October 7, 2016 CERN Meyrin, Main Building With intentions similar to those of CERN physicists, the artist Alfonso Fratteggiani Bianchi investigates the color pigment, studying its interaction with light and with the support on which it is deposited. He creates monochrome paintings by spreading the color pigment in the pure state on stones, without using glue or any other type of adhesive. With intentions similar to artists, the physicist Ermanno Imbergamo investigates the use of luminescent wavelength shifters, materials commonly used in Particle Physics, for art. He creates other monochrome artworks, which disclose further aspects of interaction among light, color pigments and support. For more information: staff.association@cern.ch | Tel: 022 767 28 19

  6. Exhibition

    CERN Multimedia

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    2016-01-01

    COLORATION Sandra Duchêne From September 5 to 16, 2016 CERN Meyrin, Main Building La recherche de l’Universel. Après tout ! C’est de l’Amour ! What else to say ? …La couleur, l’ENERGIE de la vie…

  7. Exhibition

    CERN Multimedia

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    2014-01-01

      Parallels vision Astronomical subjects which evoke extrasensory kinetic visions Alberto Di Fabio From 8 to 10 October, CERN Meyrin, Main Building In the framework of Italy@cern, the Staff Association presents Alberto Di Fabio. Di Fabio’s work is inspired by the fundamental laws of the physical world, as well as organic elements and their interrelation. His paintings and works on paper merge the worlds of art and science, depicting natural forms and biological structures in vivid colour and imaginative detail. For all additional information: staff.association@cern.ch | Tel: 022 767 28 19

  8. Exhibition

    CERN Multimedia

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    2017-01-01

    Le Point Isabelle Gailland Du 20 février au 3 mars 2017 CERN Meyrin, Bâtiment principal La Diagonale - Isabelle Gailland. Au départ, un toujours même point minuscule posé au centre de ce que la toile est un espace. Une réplique d'autres points, condensés, alignés, isolés, disséminés construiront dans leur extension, la ligne. Ces lignes, croisées, courbées, déviées, prolongées, seront la structure contenant et séparant la matière des couleurs. La rotation de chaque toile en cours d'exécution va offrir un accès illimité à la non-forme et à la forme. Le point final sera l'ouverture sur différents points de vue de ce que le point et la ligne sont devenus une représentation pour l'œil et l'im...

  9. Exhibition

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    2018-01-01

    La danse mécanique Daria Grigoryeva Du 22 mai au 1er juin 2018 | CERN Meyrin, Bâtiment principal La danse mécanique est une métaphore large. La mécanique établit les règles et les limites, les frontières dans lesquelles la vie et la créativité peuvent se développer. La musique est « mathématique », une poupée mécanique se tourne toujours dans la même direction, selon les règles prescrites par la nature les fleurs fleurissent au printemps. Même s'ils ne le voulaient pas. La participation à la "danse mécanique" est prédéterminée et inévitable. Il ne reste plus qu'à comprendre comment le faire "magnifiquement". En tout, il y a une signification cachée et un...

  10. Exhibition

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    2017-01-01

    Still Life Jérémy Bajulaz Du 25 septembre au 6 octobre 2017 CERN Meyrin, Main Building (Aubergine - Jérémy Bajulaz) Né en 1991 en Haute-Savoie, France. Diplômé de l'Ecole Emile Cohl à Lyon, Jérémy Bajulaz intègre en 2014 le programme d'artiste en résidence au Centre Genevois de Gravure Contemporaine. C'est là que son travail prendra corps, autour de la lumière et de ses vibrations aux travers de sujets comme le portrait et la nature morte, dans le souci de l'observation; le regard prenant une place importante dans le processus créatif. Lauréat 2017 du VII Premio AAAC, son travail a été présenté dans de nombreuses expositions collectives, en 2015 au Bâtiment d’Art Contemporain de Genève, en 2016 au 89e Salon de Lyon et du ...

  11. Exhibition

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    2017-01-01

    Œuvres recentes Fabienne Wyler Du 6 au 17 février 2017 CERN Meyrin, Bâtiment principal L'escalier du diable B - aquarelle, encre de Chine XLV - Fabienne Wyler. En relation avec certains procédés d’écriture contemporaine (par ex. Webern ou certaines musiques conçues par ordinateur), les compositions picturales de Fabienne Wyler s’élaborent à partir de « modules » (groupes de quadrangles) qu’elle reproduit en leur faisant subir toutes sortes de transformations et de déplacements : étirements, renversements, rotations, effet miroir, transpositions, déphasages, superpositions, etc., et ceci à toutes les échelles. Au fil des œuvres sont apparues des séries intitulées, Bifurcations, Intermittences, Attracteurs étranges, Polyrythmies. Ces titres ont un lien &e...

  12. Exhibition

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    2017-01-01

    Les vibrantes Patrick Robbe-Grillet Du 30 octobre au 10 novembre 2017 CERN Meyrin, Main Building Patrick Robbe-Grillet - Feux d'artifices Qui est Patrick Robbe-Grillet ? Artiste Franco-Suisse, né en 1968 à Genève. En recherche du sentiment de paix, autodidacte, après un séjour en Chine en 2000, puis au Japon en 2002, suivi d’un long questionnement, il trouve sa voie dans la peinture, élément libérateur de sa créativité et expression de sa sensibilité à fleur de peau. « La Chine m’a enseigné les courbes, les nuances. Le Japon, la ligne droite, la rigueur. » Vous avez su rendre visible l'invisible ! - commentaire de Monsieur Fawaz Gruosi Pour plus d’informations et demandes d’accès : staff.association@cern.ch | Tél : 022 766 37 38

  13. Exhibition

    CERN Multimedia

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    2017-01-01

    La couleur des jours oriSio Du 2 au 12 mai 2017 CERN Meyrin, Bâtiment principal oriSio - Motus Suite à un fort intérêt pour la Chine et une curiosité pour un médium très ancien, la laque ! Je réinterprète cet art à travers un style abstrait. Je présente ici des laques sur aluminium, travaillés au plasma et ensuite colorés à l’aide de pigments pour l’essentiel. Mes œuvres je les veux brutes, déchirées, évanescentes, gondolées, voire trouées mais avec une belle approche de profondeur de la couleur.   Pour plus d’informations : staff.association@cern.ch | Tél: 022 766 37 38

  14. Exhibition

    CERN Multimedia

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    2011-01-01

    Jan Hladky, physicien de l'Institut de Physique de l'Académie des Sciences de la République tchèque, et membre de la collaboration Alice, expose ses œuvres au Bâtiment principal du 20 avril au 6 mai. Son exposition est dédiée aux victimes du séisme de Sendai. Des copies de ses œuvres seront mises en vente et les sommes récoltées seront versées au profit des victimes.

  15. Exhibition

    CERN Multimedia

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    2016-01-01

    La mosaïque ou quand détruire permet de construire Lauren Decamps Du 28 novembre au 9 décembre 2016 CERN Meyrin, Bâtiment principal Paysage d'Amsterdam - Lauren Decamps On ne doit jamais rien détruire qu'on ne soit sûr de pouvoir remplacer aussi avantageusement " écrivait Plutarque dans ses Œuvres morales du 1er siècle après JC. L'artiste mosaïste Lauren Decamps adhère à cette idée et tente à sa manière de donner une nouvelle vie à ses matériaux en les taillant puis les réassemblant, créant ainsi des œuvres abstraites et figuratives.

  16. Exhibition

    CERN Multimedia

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    2017-01-01

    Firmament des toiles Joëlle Lalagüe Du 6 au 16 juin 2017 CERN Meyrin, Bâtiment principal Phylaë Voyage - Joëlle Lalagüe. Each picture is an invitation for a cosmic trip. This is a whispering of soul, which comes from origins. A symphony of the world, some notes of love, a harmony for us to fly to infinity. Pour plus d’informations et demandes d'accès : staff.association@cern.ch | Tél: 022 766 37 38

  17. Exhibition

    CERN Multimedia

    Staff Association

    2018-01-01

    Univers Du 9 au 20 avril 2018 | CERN Meyrin, Bâtiment principal Stéphanie Cousin Obsédée par les rêves, les mondes surréalistes et insolites, je m’empare de formes provenant des mes propres travaux photographiques ou d’images que je modifie et mixe. Je fais évoluer mes univers oniriques de femmes-animaux ainsi que mes espaces et natures imaginaires. Avec ma démarche artistique, je cherche à mettre en images nos rêves et nos cauchemars, l’irréel et le surréel, le mystique et les affres de notre inconscient. Je cherche à représenter tout ce qui sommeille au plus profond de nous-même à l’aide de symboles, parfois en utilisant des images de cultures ancestrales. Photographie-collage, je cherche à ajouter quelques notes à la définition de la photographie du 21iè...

  18. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Harmonie Nathalie Lenoir Du 4 au 15 septembre 2017 CERN Meyrin, Bâtiment principal Peindre est un langage. Le tracé du pinceau sur le lin en est l'expression. A qui appartient un tableau en définitive ? A celui qui l'a peint ? A celui qui le regarde ? A celui qui l'emporte ? La peinture est une émotion partagée... Laissez-vous projeter de l'autre côté de la toile, prenez un moment pour rêver, en harmonie avec les éléments, parce-que la peinture parle à votre âme… Pour plus d’informations et demandes d’accès : staff.association@cern.ch | Tél : 022 766 37 38

  19. Exhibition

    CERN Multimedia

    Staff Association

    2018-01-01

    Cosmos KOLI Du 15 au 26 janvier 2018 CERN Meyrin, Main Building (Nébuleuse d'Orion- KOLI) KOLI, Artiste confirmé, diplômé de l’Académie de Beaux Arts de Tirana, depuis 26 ans en Suisse, où il a participé à maintes expositions collectives et organisé 10 expositions privées avec  beaucoup de succès, s’exprime actuellement dans un bonheur de couleur et de matières qui côtoient des hautes sphères… le cosmos ! Gagnant d’un premier prix lors d’une exposition collective organisée par le consulat Italien, il s’est installé au bord du lac dans le canton de Vaud où il vit depuis maintenant déjà 13 ans. www.kolicreation.com Pour plus d’informations et demandes d’accès : staff.association@cern.ch | T&eacut...

  20. Exhibition at the AAA library

    DEFF Research Database (Denmark)

    2013-01-01

    Sonnesgade 11 The exhibition at the AAA library presents selected work produced by students prior to the exhibition of installations in project and praxis constructing an archive at Sonnesgade 11. The exhibition at Sonnesgade 11 was the culmination of collaboration with SLETH architects and studio...

  1. The World of Virtual Exhibitions

    Directory of Open Access Journals (Sweden)

    Irena Eiselt

    2013-09-01

    Full Text Available EXTENDED ABSTRACTSpecial collections of the National and University Library (NUK hide a lot of items of precious value. The Slovenian cultural heritage is stored on paper or on other media as a part of the library’s Manuscripts, Incunabula and Rare Books Collection, Old Prints Collection, Maps and Pictorial Collection, Music Collection, Ephemera Collection, Serials Collection, and Slovenian Diaspora Publications Collection. Only a small part of the treasures is temporary revealed to the public on special exhibitions. The idea of virtual exhibitions of library treasures was born in 2005. The library aimed to exhibit precious items of special collections of high historical or artistic value. In 2008 the first two virtual exhibitions were created in-house offering access to the rich collections of old postcards of Ljubljana at the beginning of 20th century kept in the Maps and Pictorial Collection of NUK. They were soon followed by other virtual exhibitions. At the beginning they were organised in the same way as physical exhibitions, afterwards different programs were used for creation of special effects (for ex. 3D wall. About two years ago it was decided that the creation of virtual exhibitions will be simplified. Files of digitised and borndigital library materials in jpg format are imported to MS PowerPoint 2010. Each jpg file is now formatted by adding a frame, a description … to the slides which are saved as jpg files. The last step is the import of jpg files into Cooliris application used for NUK web exhibitions. In the paper the virtual exhibition design and creation, the technical point of view and criteria for the selection of exhibition content are explained following the example of the virtual exhibitions the Old Postcards of Ljubljana, Photo Ateliers in Slovenia, a collection of photographs Four Seasons by Fran Krašovec and photos of Post-Earthquake Ljubljana in 1895.

  2. Photowalk Exhibition opens at Microcosm

    CERN Document Server

    Katarina Anthony

    2011-01-01

    The winning photographs from the 2010 Global Particle Physics Photowalk competition will go on display at Microcosm from 11 February to 2 April. The exhibition is part of a global photography event taking place over three continents, with Photowalk exhibitions opening simultaneously at Fermilab in the US, KEK in Japan and here at CERN.   DESY wire chamber - First place people's choice; second place global jury competition. Photographer: Hans-Peter Hildebrandt  If you were one of the 1,300 photography lovers who voted in last year’s Photowalk competition, this exhibition is your chance to see the winning entries in print. The exhibition will take place in the downstairs gallery of Microcosm, overlooking the garden. 15 photographs will be on display, with each of the laboratories that participated in Photowalk represented by their 3 winning entries. Among them will be the “people’s choice” sunburst photo of a particle detector at DESY (Photo 1), and...

  3. Globe exhibit wins international acclaim

    CERN Multimedia

    Katarina Anthony

    2011-01-01

    The Globe’s “Universe of Particles” exhibition has recently received four prestigious awards for its avant-garde design. This external praise is great encouragement for the CERN exhibitions currently on the drawing board.   The Universe of Particles exhibition has won 4 awards for its avant-garde design. Back in 2008, the design company Atelier Brückner was presented with a challenge: to design the layout of a new permanent exhibition for CERN, one that would epitomize both the Organization and its research. The brief was concise but complex: the exhibit had to be symbolic of the Organization, use modern technology, engage and immerse visitors, and, preferably, use touch-screen technology. With the help of IArt, an interactive technology firm, and based on the content provided by CERN’s Education Group, Atelier Brückner developed the “Universe of Particles” exhibit as it is today. Its principal concept centred on the s...

  4. Greenhouse Earth: A Traveling Exhibition

    International Nuclear Information System (INIS)

    Booth, W.H.; Caesar, S.

    1992-09-01

    The Franklin Institute Science Museum provided an exhibit entitled the Greenhouse Earth: A Traveling Exhibition. This 3500 square-foot exhibit on global climate change was developed in collaboration with the Association of Science-Technology Centers. The exhibit opened at The Franklin Institute on February 14, 1992, welcoming 291,000 visitors over its three-month stay. During its three-year tour, Greenhouse Earth will travel to ten US cities, reaching two million visitors. Greenhouse Earth aims to deepen public understanding of the scientific issues of global warming and the conservation measures that can be taken to slow its effects. The exhibit features hands-on exhibitry, interactive computer programs and videos, a theater production, a ''demonstration cart,'' guided tours, and lectures. supplemental educational programs at the Institute included a teachers preview, a symposium on climate change, and a ''satellite field trip.'' The development of Greenhouse Earth included front-end and formative evaluation procedures. Evaluation includes interviews with visitors, prototypes, and summative surveys for participating museums. During its stay in Philadelphia, Greenhouse Earth was covered by the local and national press, with reviews in print and broadcast media. Greenhouse Earth is the first large-scale museum exhibit to address global climate change

  5. Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction.

    Science.gov (United States)

    Zhu, Yongxia; Wei, Wei; Ye, Tinghong; Liu, Zhihao; Liu, Li; Luo, Yong; Zhang, Lidan; Gao, Chao; Wang, Ningyu; Yu, Luoting

    2016-01-01

    Cancer is still a major public health issue worldwide, and new therapeutics with anti-tumor activity are still urgently needed. The anti-tumor activity of TH-39, which shows potent anti-proliferative activity against K562 cells with an IC50 of 0.78 µM, was investigated using immunoblot, co-immunoprecipitation, the MTT assay, and flow cytometry. Mechanistically, TH-39 may disrupt the interaction between Hec1 and Nek2 in K562 cells. Moreover, TH-39 inhibited cell proliferation in a concentration- and time-dependent manner by influencing the morphology of K562 cells and inducing G0/G1 phase arrest. G0/G1 phase arrest was associated with down-regulation of CDK2-cyclin E complex and CDK4/6-cyclin D complex activities. Furthermore, TH-39 also induced cell apoptosis, which was associated with activation of caspase-3, down-regulation of Bcl-2 expression and up-regulation of Bax. TH-39 could also decrease mitochondrial membrane potential (Δψm) and increase reactive oxygen species (ROS) accumulation in K562 cells. The results indicated that TH-39 might induce apoptosis via the ROS-mitochondrial apoptotic pathway. This study highlights the potential therapeutic efficacy of the anti-cancer compound TH-39 in treatment-resistant chronic myeloid leukemia. © 2016 The Author(s) Published by S. Karger AG, Basel.

  6. Exhibition - Mathematics, A Beautiful Elsewhere

    CERN Multimedia

    2011-01-01

    From 21 October 2011 to 18 March 2012, the Fondation Cartier pour l’art contemporain will present the exhibition Mathematics: A Beautiful Elsewhere, an exhibition developed in association with the Institut des Hautes Études Scientifiques (IHÉS) and under the patronage of UNESCO. For this unprecedented event, the foundation invited mathematicians to work with artists with whom it has previously worked to create an exhibition that allows visitors to see, hear, do, interpret and think about mathematics. By bringing mathematics into its premises, the Fondation Cartier is itself undergoing the “sudden change of scenery” described by mathematician Alexandre Grothendieck. More information is available here. Fondation Cartier pour l’art contemporain 261, boulevard Raspail 75014 Paris http://fondation.cartier.com Private Visit For professors, researchers and all the staff of Mathematics departments...

  7. The pyrethroid metabolites 3-phenoxybenzoic acid and 3-phenoxybenzyl alcohol do not exhibit estrogenic activity in the MCF-7 human breast carcinoma cell line or Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Laffin, Brian; Chavez, Marco; Pine, Michelle

    2010-01-01

    Synthetic pyrethroids are one of the most frequently and widely used class of insecticides, primarily because they have a higher insect to mammalian toxicity ratio than organochlorines or organophosphates. The basic structure of pyrethroids can be characterized as an acid joined to an alcohol by an ester bond. Pyrethroid degradation occurs through either oxidation at one or more sites located in the alcohol or acid moieties or hydrolysis at the central ester bond, the latter reaction being important for mammalian metabolism of most pyrethroids. The primary alcohol liberated from the ester cleavage is hydroxylated to 3-phenoxybenzyl alcohol, which for most pyrethroids is then oxidized to 3-phenoxybenzoic acid. These products may then be conjugated with amino acids, sulfates, sugars, or sugar acids. In vitro studies have suggested that some of the pyrethroids may have estrogenic activity. Interestingly, the chemical structure of specific pyrethroid metabolites indicates that they may be more likely to interact with the estrogen receptor than the parent compounds. Two of the pyrethroid metabolites, 3-phenoxybenzoic acid (3PBA) and 3-phenoxybenzyl alcohol (3PBalc) have been reported to have endocrine activity using a yeast based assay. 3PBAlc exhibited estrogenic activity with reported EC 50 s of 6.67 x 10 -6 and 2 x 10 -5 while 3PBAcid exhibited anti-estrogenic activity with a calculated IC 50 of 6.5 x 10 -5 . To determine if the metabolites were able to cause the same effects in a mammalian system, the estrogen-dependent cell line, MCF-7, was utilized. Cells were treated with 1.0, 10.0 or 100.0 μM concentrations of each metabolite and cytotoxicity was assessed. The two lowest concentrations of both metabolites did not induce cell death and even appeared to increase proliferation over that of the control cells. However, when cellular proliferation was measured using a Coulter counter neither metabolite stimulated proliferation (1.0 nM, 10.0 nM, or 10.0 μM) or

  8. Learning from Exhibitions: Chuck Close.

    Science.gov (United States)

    Johnson, Mark M.

    1998-01-01

    Discusses the artwork of Chuck Close, who is well known for his over-sized portraits of fellow artists and anonymous sitters, and the exhibition of his work that premiered at New York's Museum of Modern Art before traveling to other cities in the United States. (CMK)

  9. Directed Differentiation of Human-Induced Pluripotent Stem Cells to Mesenchymal Stem Cells.

    Science.gov (United States)

    Lian, Qizhou; Zhang, Yuelin; Liang, Xiaoting; Gao, Fei; Tse, Hung-Fat

    2016-01-01

    Multipotent stromal cells, also known as mesenchymal stem cells (MSCs), possess great potential to generate a wide range of cell types including endothelial cells, smooth muscle cells, bone, cartilage, and lipid cells. This protocol describes in detail how to perform highly efficient, lineage-specific differentiation of human-induced pluripotent stem cells (iPSCs) with an MSCs fate. The approach uses a clinically compliant protocol with chemically defined media, feeder-free conditions, and a CD105 positive and CD24 negative selection to achieve a single cell-based MSCs derivation from differentiating human pluripotent cells in approximately 20 days. Cells generated with this protocol express typical MSCs surface markers and undergo adipogenesis, osteogenesis, and chondrogenesis similar to adult bone marrow-derived MSCs (BM-MSCs). Nonetheless, compared with adult BM-MSCs, iPSC-MSCs display a higher proliferative capacity, up to 120 passages, without obvious loss of self-renewal potential and constitutively express MSCs surface antigens. MSCs generated with this protocol have numerous applications, including expansion to large scale cell numbers for tissue engineering and the development of cellular therapeutics. This approach has been used to rescue limb ischemia, allergic disorders, and cigarette smoke-induced lung damage and to model mesenchymal and vascular disorders of Hutchinson-Gilford progeria syndrome (HGPS).

  10. Shikonin, a constituent of Lithospermum erythrorhizon exhibits anti-allergic effects by suppressing orphan nuclear receptor Nr4a family gene expression as a new prototype of calcineurin inhibitors in mast cells.

    Science.gov (United States)

    Wang, Xiaoyu; Hayashi, Shusaku; Umezaki, Masahito; Yamamoto, Takeshi; Kageyama-Yahara, Natsuko; Kondo, Takashi; Kadowaki, Makoto

    2014-12-05

    Over the last few decades, food allergy (FA) has become a common disease in infants in advanced countries. However, anti-allergic medicines available in the market have no effect on FA, and consequently effective drug therapies for FA are not yet available. We have already demonstrated that mucosal mast cells play an essential role in the development of FA in a murine model. Thus, we screened many constituents from medicinal herbs for the ability to inhibit rat basophilic leukemia-2H3 mast-like cell degranulation, and found that shikonin, a naphthoquinone dye from Lithospermum erythrorhizon, exhibited the most potent inhibitory effect among them. Furthermore, shikonin extremely inhibited the IgE/antigen-induced and calcium ionophore-induced upregulation of tumor necrosis factor (TNF)-α mRNA expression in mucosal-type bone marrow-derived mast cells (mBMMCs). Global gene expression analysis confirmed by real-time PCR revealed that shikonin drastically inhibited the IgE/antigen-induced and calcium ionophore-induced upregulation of mRNA expression of the nuclear orphan receptor 4a family (Nr4a1, Nr4a2 and Nr4a3) in mBMMCs, and knockdown of Nr4a1 or Nr4a2 suppressed the IgE/antigen-induced upregulation of TNF-α mRNA expression. Computational docking simulation of a small molecule for a target protein is a useful technique to elucidate the molecular mechanisms underlying the effects of drugs. Therefore, the simulation revealed that the predicted binding sites of shikonin to immunophilins (cyclophilin A and FK506 binding protein (FKBP) 12) were almost the same as the binding sites of immunosuppressants (cyclosporin A and FK506) to immunophilins. Indeed, shikonin inhibited the calcineurin activity to a similar extent as cyclosporin A that markedly suppressed the IgE/antigen-enhanced mRNA expression of TNF-α and the Nr4a family in mBMMCs. These findings suggest that shikonin suppresses mucosal mast cell activation by reducing Nr4a family gene expression through the

  11. Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity

    Science.gov (United States)

    2012-01-01

    Background As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time. Methods Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann Whitney U test with a significance level of p curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK. Conclusions Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory properties in vitro lead to analgesia in vivo will need to be confirmed in an appropriate animal model. PMID:22909087

  12. Mobile Technologies in Museum Exhibitions

    OpenAIRE

    Sandra Medić; Nataša Pavlović

    2014-01-01

    In order to be up–to–date and give visitors a memorable and unique experience, museums are including usage of digital technologies in their exhibitions. Even though museums in Serbia are very important part of tourism offer, they still have traditional settings that are poorly interpreted. The majority of them have a scientific and historical review which is unattractive for various target groups of visitors and for museums it’s important to continually try out new ways in interpretation of t...

  13. A New Exhibition in Microcosm

    CERN Document Server

    2000-01-01

    Sebastien Pelletier explains states of matter to an enthusiastic group of youngsters during the opening of a new exhibition in Microcosm last week. The Fun with Physics workshop will be offered to all 13-14 year olds in school groups visiting CERN this year. The new Microcosm contents have been developed in collaboration with the local teaching community, and cover particles and the forces that act between them.

  14. "Big Science" exhibition at Balexert

    CERN Multimedia

    2008-01-01

    CERN is going out to meet those members of the general public who were unable to attend the recent Open Day. The Laboratory will be taking its "Big Science" exhibition from the Globe of Science and Innovation to the Balexert shopping centre from 19 to 31 May 2008. The exhibition, which shows the LHC and its experiments through the eyes of a photographer, features around thirty spectacular photographs measuring 4.5 metres high and 2.5 metres wide. Welcomed and guided around the exhibition by CERN volunteers, shoppers at Balexert will also have the opportunity to discover LHC components on display and watch films. "Fun with Physics" workshops will be held at certain times of the day. Main hall of the Balexert shopping centre, ground floor, from 9.00 a.m. to 7.00 p.m. Monday to Friday and from 10 a.m. to 6 p.m. on the two Saturdays. Call for volunteers All members of the CERN personnel are invited to enrol as volunteers to help welcom...

  15. Mobile Technologies in Museum Exhibitions

    Directory of Open Access Journals (Sweden)

    Sandra Medić

    2014-10-01

    Full Text Available In order to be up–to–date and give visitors a memorable and unique experience, museums are including usage of digital technologies in their exhibitions. Even though museums in Serbia are very important part of tourism offer, they still have traditional settings that are poorly interpreted. The majority of them have a scientific and historical review which is unattractive for various target groups of visitors and for museums it’s important to continually try out new ways in interpretation of their settings. Because technology continues to rapidly change the way we communicate, cultural institutions should adapt to new ways of communication with their visitors. This paper examines mobile technologies that can be used in museums to give visitors a different experience and transfer the knowledge innovatively. In that way it will be presented the modern concept of presentation of museum exhibitions, focusing on usage of mobile devices through mobile applications and QR codes. The paper provides the broad understanding of usage mobile technologies in museum exhibitions with its advantages and limitations. The research results can help the museums management to improve interpretation and communication with visitors and enrich the visitor experience.

  16. Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress

    Directory of Open Access Journals (Sweden)

    Worman Howard J

    2005-06-01

    Full Text Available Abstract Background Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670 is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists of short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT, within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein. Results We studied a new case of a 5 year-old girl with HGPS and found a heterozygous point mutation, G608G, in LMNA. Complementary DNA sequencing of RNA showed that this mutation resulted in the deletion of 50 amino acids in the carboxyl-terminal tail domain of prelamin A. We characterized a primary dermal fibroblast cell line derived from the subject's skin. These cells expressed the mutant protein and exhibited a normal growth rate at early passage in primary culture but showed alterations in nuclear morphology. Expression levels and overall distributions of nuclear lamins and emerin, an integral protein of the inner nuclear membrane, were not dramatically altered. Ultrastructural analysis of the nuclear envelope using electron microscopy showed that chromatin is in close association to the nuclear lamina, even in areas with abnormal nuclear envelope morphology. The fibroblasts were hypersensitive to heat shock, and demonstrated a delayed response to heat stress. Conclusion Dermal fibroblasts from a subject with HGPS expressing a mutant truncated lamin A have dysmorphic nuclei, hypersensitivity to heat shock, and delayed response to heat stress. This suggests that the mutant protein, even when expressed at low levels, causes defective cell stability, which may be responsible for phenotypic

  17. Contemporary Developments in Cinema Exhibition

    OpenAIRE

    Hanson, Stuart

    2014-01-01

    he work offered for this PhD by Published Works charts the history of cinema exhibition in Britain from the late 1950s to the present. At the start of this period, cinemagoing as a form of public entertainment entered a long period of decline that was only arrested with the development and growth of multiplex cinemas in the 1980s and 1990s. Despite these changes, the feature film itself remained a culturally and commercially valuable artefact, though increasingly this meant the Hollywood fil...

  18. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    DEFF Research Database (Denmark)

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza

    2015-01-01

    , the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have...

  19. Collaborative virtual environments art exhibition

    Science.gov (United States)

    Dolinsky, Margaret; Anstey, Josephine; Pape, Dave E.; Aguilera, Julieta C.; Kostis, Helen-Nicole; Tsoupikova, Daria

    2005-03-01

    This panel presentation will exhibit artwork developed in CAVEs and discuss how art methodologies enhance the science of VR through collaboration, interaction and aesthetics. Artists and scientists work alongside one another to expand scientific research and artistic expression and are motivated by exhibiting collaborative virtual environments. Looking towards the arts, such as painting and sculpture, computer graphics captures a visual tradition. Virtual reality expands this tradition to not only what we face, but to what surrounds us and even what responds to our body and its gestures. Art making that once was isolated to the static frame and an optimal point of view is now out and about, in fully immersive mode within CAVEs. Art knowledge is a guide to how the aesthetics of 2D and 3D worlds affect, transform, and influence the social, intellectual and physical condition of the human body through attention to psychology, spiritual thinking, education, and cognition. The psychological interacts with the physical in the virtual in such a way that each facilitates, enhances and extends the other, culminating in a "go together" world. Attention to sharing art experience across high-speed networks introduces a dimension of liveliness and aliveness when we "become virtual" in real time with others.

  20. Enrico Fermi exhibition at CERN

    CERN Multimedia

    2002-01-01

    A touring exhibition celebrating the centenary of Enrico Fermi's birth in 1901 will be on display at CERN (Main Building, Mezzanine) from 12-27 September. You are cordially invited to the opening celebration on Thursday 12 September at 16:00 (Main Building, Council Chamber), which will include speechs from: Luciano Maiani Welcome and Introduction Arnaldo Stefanini Celebrating Fermi's Centenary in Documents and Pictures Antonino Zichichi The New 'Centro Enrico Fermi' at Via Panisperna Ugo Amaldi Fermi at Via Panisperna and the birth of Nuclear Medicine Jack Steinberger Fermi in Chicago Valentin Telegdi A Close-up of Fermi and the screening of a documentary video about Fermi: Scienziati a Pisa: Enrico Fermi (Scientists at Pisa: Enrico Fermi) created by Francesco Andreotti for La Limonaia from early film, photographs and sound recordings (In Italian, with English subtitles - c. 30 mins). This will be followed by an aperitif on the Mezz...

  1. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. EU Climate Change Exhibition Held

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>On April 25, the CPAFFC, the China-EU Association (CEUA) and the Delegation of the European Commission to China jointly held the opening ceremony for the EU Exhibition on Climate Change in the CPAFFC. He Luli, former vice chairperson of the NPC Standing Committee and honorary president of the CEUA, Jose Manuel Barroso, president of the European Commission, and Li Jianping, vice president of the CPAFFC, attended the opening ceremony and made speeches. Honorary President He Luli highly praised the achievements made by China and the EU in their longtime cooperation of mutual benefits in various fields including environmental protection. She said, for many years China and EU have both committed to the development of all-round strategic partnership and establishment of a multi-level mechanism of political dialogue. She expressed, with increasing enthusiasm the CEUA would continue to actively carry out nongovernmental exchanges between China and the EU, and promote cooperation between the two sides in the fields of economy, society, environmental protection, science and technology, culture, etc.

  3. 13-methyltetradecanoic acid exhibits anti-tumor activity on T-cell lymphomas in vitro and in vivo by down-regulating p-AKT and activating caspase-3.

    Directory of Open Access Journals (Sweden)

    Qingqing Cai

    Full Text Available 13-Methyltetradecanoic acid (13-MTD, a saturated branched-chain fatty acid purified from soy fermentation products, induces apoptosis in human cancer cells. We investigated the inhibitory effects and mechanism of action of 13-MTD on T-cell non-Hodgkin's lymphoma (T-NHL cell lines both in vitro and in vivo. Growth inhibition in response to 13-MTD was evaluated by the cell counting kit-8 (CCK-8 assay in three T-NHL cell lines (Jurkat, Hut78, EL4 cells. Flow cytometry analyses were used to monitor the cell cycle and apoptosis. Proteins involved in 13-MTD-induced apoptosis were examined in Jurkat cells by western blotting. We found that 13-MTD inhibited proliferation and induced the apoptosis of T-NHL cell lines. 13-MTD treatment also induced a concentration-dependent arrest of Jurkat cells in the G1-phase. During 13-MTD-induced apoptosis in Jurkat cells, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP, a caspase enzymolysis product were detected after incubation for 2 h, and increased after extending the incubation time. However, there was no change in the expression of Bcl-2 or c-myc proteins. The appearance of apoptotic Jurkat cells was accompanied by the inhibition of AKT and nuclear factor-kappa B (NF-κB phosphorylation. In addition, 13-MTD could also effectively inhibit the growth of T-NHL tumors in vivo in a xenograft model. The tumor inhibition rate in the experimental group was 40%. These data indicate that 13-MTD inhibits proliferation and induces apoptosis through the down-regulation of AKT phosphorylation followed by caspase activation, which may provide a new approach for treating T-cell lymphomas.

  4. HIV controllers exhibit enhanced frequencies of major histocompatibility complex class II tetramer+ Gag-specific CD4+ T cells in chronic clade C HIV-1 infection

    DEFF Research Database (Denmark)

    Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos

    2017-01-01

    Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibilit...

  5. 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol negatively regulates activation of STAT3 and ERK pathways and exhibits anti-cancer effects in HepG2 cells.

    Science.gov (United States)

    Ai, Hui-Han; Zhou, Zi-Long; Sun, Lu-Guo; Yang, Mei-Ting; Li, Wei; Yu, Chun-Lei; Song, Zhen-Bo; Huang, Yan-Xin; Wu, Yin; Liu, Lei; Yang, Xiao-Guang; Zhao, Yu-Qing; Bao, Yong-Li; Li, Yu-Xin

    2017-11-01

    The pro-inflammatory cytokine interleukin 6 (IL-6), via activating its downstream JAK/STAT3 and Ras/ERK signaling pathways, is involved in cell growth, proliferation and anti-apoptotic activities in various malignancies. To screen inhibitors of IL-6 signaling, we constructed a STAT3 and ERK dual-pathway responsive luciferase reporter vector (Co.RE). Among several candidates, the natural compound 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH 3 -PPD, GS25) was identified to clearly inhibit the luciferase activity of Co.RE. GS25 was confirmed to indeed inhibit activation of both STAT3 and ERK pathways and expression of downstream target genes of IL-6, and to predominantly decrease the viability of HepG2 cells via induction of cell cycle arrest and apoptosis. Interestingly, GS25 showed preferential inhibition of HepG2 cell viability relative to normal liver L02 cells. Further investigation showed that GS25 could not induce apoptosis and block activation of STAT3 and ERK pathways in L02 cells as efficiently as in HepG2 cells, which may result in differential effects of GS25 on malignant and normal liver cells. In addition, GS25 was found to potently suppress the expression of endogenous STAT3 at a higher concentration and dramatically induce p38 phosphorylation in HepG2 cells, which could mediate its anti-cancer effects. Finally, we demonstrated that GS25 also inhibited tumor growth in HepG2 xenograft mice. Taken together, these findings indicate that GS25 elicits its anti-cancer effects on HepG2 cells through multiple mechanisms and has the potential to be used as an inhibitor of IL-6 signaling. Thus, GS25 may be developed as a treatment for hepatocarcinoma with low toxicity on normal liver tissues as well as other inflammation-associated diseases.

  6. Artefacts and the performance of an exhibition

    DEFF Research Database (Denmark)

    Svabo, Connie

    2008-01-01

    The article explores the role of mediating artefacts in children's encounters with a museum of natural history. Using actor network theory it explores how a specific artefact shapes the way users relate to exhibited objects and how the artefact guides users' movements in the exhibition....... The mediated performance of an exhibition is explored through an empirical case....

  7. Affordances and distributed cognition in museum exhibitions

    DEFF Research Database (Denmark)

    Achiam, Marianne; May, Michael; Marandino, Martha

    2014-01-01

    consistent framework. Here, we invoke the notions of affordance and distributed cognition to explain in a coherent way how visitors interact with exhibits and exhibit spaces and make meaning from those interactions, and we exemplify our points using observations of twelve visitors to exhibits at a natural...... history museum. We show how differences in exhibit characteristics give rise to differences in the interpretive strategies used by visitors in their meaning-making process, and conclude by discussing how the notions of affordance and distributed cognition can be used in an exhibit design perspective....

  8. Investigating Design Research Landscapes through Exhibition

    DEFF Research Database (Denmark)

    Jönsson, Li; Hansen, Flemming Tvede; Mäkelä, Maarit

    2013-01-01

    What characterizes a design research exhibition compared to a traditional design and art exhibition? How do you show the very materialities of the design experiments as a means for communicating knowledge of research and of practice? How do you present, review and utilize such an exhibition......? With those questions in mind, the intention and challenge for the Nordes 2013 Design Research Exhibition was to expand on current notions of staging research enquires in design research conference contexts. Artefacts, installations, performances, and other materialities that relate to the theme...... of the conference - Experiments in Design Research – were displayed as tools to express and communicate different design research enquires. Through this paper we will describe the Nordes exhibition as a specific case that renders questions visible in relation to how to utilize a design research exhibition...

  9. Superconductive microstrip exhibiting negative differential resistivity

    International Nuclear Information System (INIS)

    Huebener, R.P.; Gallus, D.E.

    1975-01-01

    A device capable of exhibiting negative differential electrical resistivity over a range of values of current and voltage is formed by vapor-depositing a thin layer of a material capable of exhibiting superconductivity on an insulating substrate, establishing electrical connections at opposite ends of the deposited strip, and cooling the alloy into its superconducting range. The device will exhibit negative differential resistivity when biased in the current-induced resistive state

  10. Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Zou, Xuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Cao, Ke; Xu, Jie; Yue, Tingting [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Dai, Fang; Zhou, Bo [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou (China); Lu, Wuyuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Feng, Zhihui, E-mail: zhfeng@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Liu, Jiankang, E-mail: j.liu@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China)

    2013-11-01

    Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the

  11. Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

    International Nuclear Information System (INIS)

    Li, Yuan; Zou, Xuan; Cao, Ke; Xu, Jie; Yue, Tingting; Dai, Fang; Zhou, Bo; Lu, Wuyuan; Feng, Zhihui; Liu, Jiankang

    2013-01-01

    Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the major

  12. A Heuristic for Improving Transmedia Exhibition Experience

    DEFF Research Database (Denmark)

    Selvadurai, Vashanth; Rosenstand, Claus Andreas Foss

    2017-01-01

    in the scientific field of designing transmedia experience in an exhibition context that links the pre- and post-activities to the actual visit (during-activities). The result of this study is a preliminary heuristic for establishing a relation between the platform and content complexity in transmedia exhibitions....

  13. Memory and Mourning: An Exhibit History

    Science.gov (United States)

    Eberle, Scott G.

    2005-01-01

    Mounted by the Strong Museum in Rochester, New York, in 1993, and traveling nationally thereafter, the exhibit Memory and Mourning provided historical and contemporary perspectives to help museum guests explore their own reactions to loss and grief. In the process the exhibit's development team encountered a range of philosophical, historical,…

  14. Let's play game exhibitions : A curator's perspective

    NARCIS (Netherlands)

    de Vos, Jesse; Glas, M.A.J.|info:eu-repo/dai/nl/330981447; van Vught, J.F.|info:eu-repo/dai/nl/413532682

    2017-01-01

    The Netherlands Institute for Sound and Vision is home to The Experience, a museum exhibiting the history of media in the Netherlands. For ten months in 2016 and 2017, The Experience hosted a temporary exhibition entitled Let’s YouTube . During the Let’s YouTube game month, we programmed a ten-day

  15. Science Fiction Exhibits as STEM Gateways

    Science.gov (United States)

    Robie, Samantha

    Women continue to hold less than a quarter of all STEM jobs in the United States, prompting many museums to develop programs and exhibits with the express goal of interesting young girls in scientific fields. At the same time, a number of recent museum exhibits have harnessed the popularity of pop culture and science fiction in order to interest general audiences in STEM subject matter, as well as using the exhibits as springboards to expand or shift mission goals and focus. Because science fiction appears to be successful at raising interest in STEM fields, it may be an effective way to garner the interest of young girls in STEM in particular. This research seeks to describe the ways in which museums are currently using science fiction exhibits to interest young girls in STEM fields and careers. Research focused on four institutions across the country hosting three separate exhibits, and included staff interviews and content analysis of exhibit descriptions, promotional materials, a summative evaluation and supplementary exhibit productions. In some ways, science fiction exhibits do serve young girls, primarily through the inclusion of female role models, staff awareness, and prototype testing to ensure interactives are attractive to girls as well as to boys. However, STEM appears to be underutilized, which may be partly due to a concern within the field that the outcome of targeting a specific gender could be construed as "stereotyping".

  16. The Culture of Exhibitions and Conservation

    Directory of Open Access Journals (Sweden)

    Dimitrios Doumas

    2013-11-01

    Full Text Available The article reflects on temporary exhibitions from a theoretical as well as practical perspective. Regarded as a particularly effective mass-communication medium, exhibitions have a dual nature: they are scholarly undertakings, bringing off a curator’s vision and, simultaneously, they are projects with economic implications that need to be well managed and administered. The role of conservation in the making of temporary exhibitions, either in-house or touring, is here discussed in relation to how work is planned and prioritized as well as how time is managed and staff is allocated. Reference to weaknesses that lessen the crucial input of conservation in the decision-making process is also made. Much of the debate, which focuses on art exhibitions, concerns practicalities encountered in a private museum that extend from the very early stages of selecting objects for display to the mounting of an exhibition.

  17. Holland at CERN – Industrial exhibition

    CERN Multimedia

    GS Department

    2010-01-01

    Sponsored by EVD, an agency of the Dutch Ministry of the Economy From 8 to 11 November 2010 Industrial Exhibition Administration Building Bldg. 61 9-00 - 17-30 Twenty seven companies will present their latest technology at the industrial exhibition "Holland at CERN". Dutch industry will exhibit products and technologies which are related to the field of particle physics. Individual interviews will take place directly at the stands in the Main Building. The firms will contact relevant users/technicians but any user wishing to make contact with a particular firm is welcome to use the contact details which are available from each departmental secretariat or at the following URL: http://gs-dep.web.cern.ch/gs-dep/groups/sem/ls/Industrial_Exhibitions.htm#Industrial_exhibitions You will find the list of exhibitors below. LIST OF EXHIBITORS: Schelde Exotech Vernooy BV Triumph Group INCAA Computers DeMaCo Holland bv TNO Science & Industry Janssen Precision Engi...

  18. The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear

    Directory of Open Access Journals (Sweden)

    Paudyal Anju

    2010-08-01

    Full Text Available Abstract Background The planar cell polarity (PCP signalling pathway is fundamental to a number of key developmental events, including initiation of neural tube closure. Disruption of the PCP pathway causes the severe neural tube defect of craniorachischisis, in which almost the entire brain and spinal cord fails to close. Identification of mouse mutants with craniorachischisis has proven a powerful way of identifying molecules that are components or regulators of the PCP pathway. In addition, identification of an allelic series of mutants, including hypomorphs and neomorphs in addition to complete nulls, can provide novel genetic tools to help elucidate the function of the PCP proteins. Results We report the identification of a new N-ethyl-N-nitrosourea (ENU-induced mutant with craniorachischisis, which we have named chuzhoi (chz. We demonstrate that chuzhoi mutant embryos fail to undergo initiation of neural tube closure, and have characteristics consistent with defective convergent extension. These characteristics include a broadened midline and reduced rate of increase of their length-to-width ratio. In addition, we demonstrate disruption in the orientation of outer hair cells in the inner ear, and defects in heart and lung development in chuzhoi mutants. We demonstrate a genetic interaction between chuzhoi mutants and both Vangl2Lp and Celsr1Crsh mutants, strengthening the hypothesis that chuzhoi is involved in regulating the PCP pathway. We demonstrate that chuzhoi maps to Chromosome 17 and carries a splice site mutation in Ptk7. This mutation results in the insertion of three amino acids into the Ptk7 protein and causes disruption of Ptk7 protein expression in chuzhoi mutants. Conclusions The chuzhoi mutant provides an additional genetic resource to help investigate the developmental basis of several congenital abnormalities including neural tube, heart and lung defects and their relationship to disruption of PCP. The chuzhoi mutation

  19. Quinoline compound KM11073 enhances BMP-2-dependent osteogenic differentiation of C2C12 cells via activation of p38 signaling and exhibits in vivo bone forming activity.

    Directory of Open Access Journals (Sweden)

    Seung-hwa Baek

    Full Text Available Recombinant human bone morphogenetic protein (rhBMP-2 has been approved by the FDA for clinical application, but its use is limited due to high cost and a supra-physiological dose for therapeutic efficacy. Therefore, recent studies have focused on the generation of new therapeutic small molecules to induce bone formation or potentiate the osteogenic activity of BMP-2. Here, we show that [4-(7-chloroquinolin-4-yl piperazino][1-phenyl-5-(trifluoromethyl-1H-pyrazol-4-yl]methanone (KM11073 strongly enhances the BMP-2-stimulated induction of alkaline phosphatase (ALP, an early phase biomarker of osteoblast differentiation, in bi-potential mesenchymal progenitor C2C12 cells. The KM11073-mediated ALP induction was inhibited by the BMP antagonist noggin, suggesting that its osteogenic activity occurs via BMP signaling. In addition, a pharmacological inhibition study suggested the involvement of p38 activation in the osteogenic action of KM11073 accompanied by enhanced expression of BMP-2, -6, and -7 mRNA. Furthermore, the in vivo osteogenic activity of KM11073 was confirmed in zebrafish and mouse calvarial bone formation models, suggesting the possibility of its single use for bone formation. In conclusion, the combination of rhBMP-2 with osteogenic small molecules could reduce the use of expensive rhBMP-2, mitigating the undesirable side effects of its supra-physiological dose for therapeutic efficacy. Moreover, due to their inherent physical properties, small molecules could represent the next generation of regenerative medicine.

  20. A mini-exhibition with maximum content

    CERN Multimedia

    Laëtitia Pedroso

    2011-01-01

    The University of Budapest has been hosting a CERN mini-exhibition since 8 May. While smaller than the main travelling exhibition it has a number of major advantages: its compact design alleviates transport difficulties and makes it easier to find suitable venues in the Member States. Its content can be updated almost instantaneously and it will become even more interactive and high-tech as time goes by.   The exhibition on display in Budapest. The purpose of CERN's new mini-exhibition is to be more interactive and easier to install. Due to its size, the main travelling exhibition cannot be moved around quickly, which is why it stays in the same country for 4 to 6 months. But this means a long waiting list for the other Member States. To solve this problem, the Education Group has designed a new exhibition, which is smaller and thus easier to install. Smaller maybe, but no less rich in content, as the new exhibition conveys exactly the same messages as its larger counterpart. However, in the slimm...

  1. France at CERN – Industrial exhibition

    CERN Multimedia

    FP Department

    2012-01-01

    Industrial Exhibition Administration Building Bldg 61 – 1st Floor Tuesday 27 March: 9 a.m. – 5.30 p.m. Wednesday 28 March: 9 a.m. – 2 p.m.   About thirty French companies are presenting their latest technological advances during the industrial exhibition "France at CERN", featuring products and technologies specifically related to CERN activities. Individual B2B meetings can be organized with the sales and technical representatives of participating firms and will take place at either the companies’ exhibition stands or in conference rooms in the Main Building. Individuals wishing to make contact with one or more companies must use the contact details available from each secretariat of department or by using this link. B2B meetings will be coordinated by UBIFRANCE. You will also find the list of exhibiting and participating companies online here. This event is sponsored by the French subsidiary of RS Components, the most important distri...

  2. High Quality Virtual Reality for Architectural Exhibitions

    DEFF Research Database (Denmark)

    Kreutzberg, Anette

    2016-01-01

    This paper will summarise the findings from creating and implementing a visually high quality Virtual Reality (VR) experiment as part of an international architecture exhibition. It was the aim to represent the architectural spatial qualities as well as the atmosphere created from combining natural...... and artificial lighting in a prominent not yet built project. The outcome is twofold: Findings concerning the integration of VR in an exhibition space and findings concerning the experience of the virtual space itself. In the exhibition, an important aspect was the unmanned exhibition space, requiring the VR...... experience to be self-explanatory. Observations of different visitor reactions to the unmanned VR experience compared with visitor reactions at guided tours with personal instructions are evaluated. Data on perception of realism, spatial quality and light in the VR model were collected with qualitative...

  3. Medan Convention & Exhibition Center (Arsitektur Ekspresionisme)

    OpenAIRE

    Iskandar, Nurul Auni

    2015-01-01

    Medan is one of the third largest city in Indonesia, which is currently being developed, and a city with lots of activities. In the city of Medan has a high investment opportunities for a convention, because of its strategic position in Southeast Asia and also supported by the facility and the potential for tourism in North Sumatra, Medan city has the potential for industrial MICE (Meeting, Incentive, Conference, Exhibition). The construction of Medan Convention & Exhibition Cente...

  4. The presentation of energy topics at exhibitions

    International Nuclear Information System (INIS)

    Moergeli, H.P.

    1984-01-01

    The author examines the problems confronting an electricity supply company when trying to communicate its energy policy to the general public at exhibitions and fairs. The company has to convey a message of reliable power supplies, increasing demand, the advantages of nuclear energy, the safe storage of radioactive waste and the need for new generating plants. The author describes some of the displays being used to attract the public to the Bern Power Stations stand at the Bern Exhibition 1984. (R.S.)

  5. An Astrobiology Microbes Exhibit and Education Module

    Science.gov (United States)

    Lindstrom, Marilyn M.; Allen, Jaclyn S.; Stocco, Karen; Tobola, Kay; Olendzenski, Lorraine

    2001-01-01

    Telling the story of NASA-sponsored scientific research to the public in exhibits is best done by partnerships of scientists and museum professionals. Likewise, preparing classroom activities and training teachers to use them should be done by teams of teachers and scientists. Here we describe how we used such partnerships to develop a new astrobiology augmentation to the Microbes! traveling exhibit and a companion education module. "Additional information is contained in the original extended abstract."

  6. Turning energy around: an interactive exhibition experience

    Directory of Open Access Journals (Sweden)

    Sarah Kellberg

    2018-05-01

    Full Text Available A transition from the fossil-fuel driven to a sustainable energy system is an enormous global challenge: climate change and finite resources require countries all over the world to change their way of producing, transporting and using energy. The Energiewende (energy transition will require major changes in the current energy supply system in Germany – but also worldwide. These changes will not only affect the technical sector but will also include ecological questions, social issues and political matters. Whether any transition is going to favour large scale solutions or decentralised technologies depends on local situations and global interconnections, and above all on a democratic process. Hence energy transition succeeds or fails with the acceptance and participation of society. To deal with this overwhelmingly complex topic and its multi-layered dependencies, the Deutsches Museum has designed an exhibition providing visitors with background knowledge about the necessities and challenges of energy transition, unpicking the links between the different technical, economic and social challenges. The exhibition accomplishes the task with an engaging and facilitating approach while taking into account the highly emotive aspects of energy transition as a societal issue. This paper presents the concept of the travelling exhibition energie.wenden, relating it to the Deutsches Museum´s tradition of exhibitions as well as to the challenge of how to deal with socio-scientific topics in scientific exhibitions.

  7. CERN exhibition a big hit in Bulgaria

    CERN Multimedia

    2005-01-01

    The first CERN exhibition in Bulgaria attracted many visitors. In the first ever CERN exhibition to be held in Bulgaria, over 1,400 visitors, many of them students and young physicists, visited the 10-day event in Sofia. The CERN mini-exhibition took place at the National Earth and Mankind Museum between 8 and 17 November. Permanently staffed by young physicists from Sofia University, there were exhibits on display about research activities at CERN, as well as four additional posters describing Bulgaria's participation. The inauguration took place on the morning of 8 November in the presence of the Vice-Minister for Science and Education, Mrs. Vanya Dobreva, and some 200 guests. A series of short speeches were followed by a visit to the exhibition. CERN's representative at the event, Ray Lewis, was then asked by Professor Matey Mateev, President of the Union of Physicists in Bulgaria, to say a few words on behalf of the Organization. Numerous journalists were also present at the inauguration. A painting enti...

  8. Education or business? - exhibition of human corpses

    Directory of Open Access Journals (Sweden)

    Grzegorz Wróbel

    2017-09-01

    Full Text Available Exhibition "BODY WORLDS" which are presented exhibits of human remains are presented all over the world and are a major problem for the modern man, as presented on the preparations of the human not only serve scientific research, are not transferred to the medical schools to educate future doctors, but they were made available to the general public in the form of commercial and ambiguous. The aim of this study was to assess the ethical commercialization of human corpses "BODY WORLDS" exhibitions. Individual approach to the problems presented the dignity and value of human remains after death, of course, strongly related to the professed worldview. In the exhibits can be seen in both the scientific interest anatomical structures, as well as desecrated human remains or beautiful by its functional perfection of the body, understood also in terms of art. The question of ethics determines the right to decide for themselves, on the other hand, allows you to protect bodily integrity even after death. "BODY WORLDS" exhibition goes for the moral and ethical boundaries. In terms of people Gunther von Hagens for plastination of human remains which became a very profitable business, and its current activities defined as "plastination business" should be firmly said about the lack of moral principles.

  9. The exploration of the exhibition informatization

    Science.gov (United States)

    Zhang, Jiankang

    2017-06-01

    The construction and management of exhibition informatization is the main task and choke point during the process of Chinese exhibition industry’s transformation and promotion. There are three key points expected to realize a breakthrough during the construction of Chinese exhibition informatization, and the three aspects respectively are adopting service outsourcing to construct and maintain the database, adopting advanced chest card technology to collect various kinds of information, developing statistics analysis to maintain good cutomer relations. The success of Chinese exhibition informatization mainly calls for mature suppliers who can provide construction and maintenance of database, the proven technology, a sense of data security, advanced chest card technology, the ability of data mining and analysis and the ability to improve the exhibition service basing on the commercial information got from the data analysis. Several data security measures are expected to apply during the process of system developing, including the measures of the terminal data security, the internet data security, the media data security, the storage data security and the application data security. The informatization of this process is based on the chest card designing. At present, there are several types of chest card technology: bar code chest card; two-dimension code card; magnetic stripe chest card; smart-chip chest card. The information got from the exhibition data will help the organizers to make relevant service strategies, quantify the accumulated indexes of the customers, and improve the level of the customer’s satisfaction and loyalty, what’s more, the information can also provide more additional services like the commercial trips, VIP ceremonial reception.

  10. Exhibits in libraries a practical guide

    CERN Document Server

    Brown, Mary E

    2005-01-01

    "Ccomprehensive...detailed"--Booklist; "thoroughly reseached...highly recommended"--Journal of Access Services. Library exhibits are more than entertainment for patrons. They can inspire and educate, stimulate an interest that can be explored in a book, or attract visitors who otherwise wouldn't stop by. Displays are also an opportunity for a library to put its creative foot forward or help patrons navigate the facility itself. This comprehensive "how-to" includes everything a librarian or staff member needs to know to put on an exhibit, from hatching ideas to evaluating the end result. Illustrations and photographs show practical methods of planning, labeling and displaying.

  11. How do exhibition visitors describe aesthetic qualities?

    DEFF Research Database (Denmark)

    Thomsen, Bente Dahl; Ravn, Anders Peter

    2007-01-01

    In this investigation, visitors to an art and design exhibition have used an interactive computer program to express the qualities they consider important for an art or design object (artefact). They have then used the program with their individually selected qualities to assess the artefacts. In...

  12. CERN exhibition wins yet another design prize

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    The “Universe of Particles” exhibition in CERN’s Globe wins the silver design prize from the German direct business communications association FAMAB.   Not only do tens of thousands of people visit the “Universe of Particles” exhibition each year, but juries for design prizes are crossing its threshold more and more frequently too. In 2011 alone it claimed 8 awards, including winning outright the 2011 Annual Multimedia award, the iF Communication Design for Corporate Architecture award and the Modern Decoration Media award (the Bulletin already reported on some of these in July 2011). The FAMAB award is the latest to join the prestigious list. The jury of FAMAB’s “ADAM 2011” award was particularly impressed by the hands-on nature of the exhibition, which encourages visitors to get interested in science. They also appreciated the way that the space in the Globe is not just a container for the exhibits, but itself ...

  13. 49 CFR 250.2 - Required exhibits.

    Science.gov (United States)

    2010-10-01

    ... carried; and identification of the ten most important industries served. (6) As Exhibit 6, statement as to... application for the financing has been made, evidencing that they have declined the financing unless guaranteed by the Secretary or specifying the terms upon which they will undertake the financing without such...

  14. CCPIT Machinery Exhibition Succeeded in Kuala Lumpur

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ From August 18 to 20, 2005, China Council for the Promotion of International Trade(CCPIT) held China Machinery and Electronics Trade Exhibition, CME 2005 in Kuala Lumpur, the capital of Malaysia on behalf of China, a good job has been done.

  15. CCPIT Machinery Exhibition Succeeded in Kuala Lumpur

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

      From August 18 to 20, 2005, China Council for the Promotion of International Trade(CCPIT) held China Machinery and Electronics Trade Exhibition, CME 2005 in Kuala Lumpur, the capital of Malaysia on behalf of China, a good job has been done.……

  16. Comic Strips to Accompany Science Museum Exhibits

    Science.gov (United States)

    Chung, Beom Sun; Park, Eun-mi; Kim, Sang-Hee; Cho, Sook-kyoung; Chung, Min Suk

    2016-01-01

    Science museums make the effort to create exhibits with amusing explanations. However, existing explanation signs with lengthy text are not appealing, and as such, visitors do not pay attention to them. In contrast, conspicuous comic strips composed of simple drawings and humors can attract science museum visitors. This study attempted to reveal…

  17. 18 CFR 50.7 - Applications: exhibits.

    Science.gov (United States)

    2010-04-01

    ... systems, including the special protective systems' automatic switching or load shedding system; and (ii... transfer capability (NITC); system protection; and system stability. (3) A stability analysis including... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Applications: exhibits...

  18. Travelling CERN Exhibition ''When Energy Becomes Matter''

    International Nuclear Information System (INIS)

    2001-01-01

    Full text: The European Laboratory for Nuclear Research (CERN) and the H. Niewodniczanski Institute of Nuclear Physics together with the Institute of Physics of the Jagiellonian University and the University of Mining and Metallurgy, and under the auspices of the Polish National Atomic Energy Agency organized in the Museum of Nature in Cracow from October 16 till December 16, 2000 the exhibition ''When Energy Becomes Matter''. The Office of the ''Festival Cracow 2000'' was the main sponsor of that event. The exhibition was a part of the F estival Cracow 2000'' called ''Festival of Youngsters Cracow 2000''. Invitations, posters and information leaflets were sent to more than 3000 schools in southern Poland. The exhibition was divided into four specially designed quadrants. In the first the visitor was informed what kind of scales are in use to describe the Universe and the atom. The second introduced elementary particles via the cosmic ray demonstrations. Particle acceleration was demonstrated with the help of a TV set. The third segment was devoted to the Large Hadron Collider and its experiments: CMS, ATLAS, ALICE and LHCb. The last segment was an attempt to explain what are quarks, leptons and intermediate bosons. In addition it was also explained what is antimatter and why symmetry is broken in Nature. In one of the rooms we arranged the cinema where five movies was continuously presented. Thanks to the Cracow TV it was possible to prepare Polish translations of the films: B ack to creation , P owers of ten , L HC - time machine , S tars underground , and G eneva event . Another attraction of the exhibition was the Internet room equipped with the help of Polish Telecommunication. The exhibition was open seven days per week from 10 to 17 h. During the working days every 20 minutes a new group of about 25-30 people was visiting the exhibition. Each group was guided by students and PhD students from our Institute, Jagiellonian University and University of Mining

  19. LHC INAUGURATION, LHC Fest highlights: exhibition time!

    CERN Multimedia

    2008-01-01

    David Gross, one of the twenty-one Nobel Laureates who have participated in the project.Tuesday 21 October 2008 Accelerating Nobels Colliding Charm, Atomic Cuisine, The Good Anomaly, A Quark Somewhere on the White Paper, Wire Proliferation, A Tale of Two Liquids … these are just some of the titles given to artworks by Physics Nobel Laureates who agreed to make drawings of their prize-winning discoveries (more or less reluctantly) during a special photo session. Science photographer Volker Steger made portraits of Physics Nobel Laureates and before the photo sessions he asked them to make a drawing of their most important discovery. The result is "Accelerating Nobels", an exhibition that combines unusual portraits of and original drawings by twenty-one Nobel laureates in physics whose work is closely related to CERN and the LHC. This exhibition will be one of the highlights of the LHC celebrations on 21 October in the SM18 hall b...

  20. Exhibition: Women and Sciences by Fiami

    CERN Multimedia

    Globe Info

    2011-01-01

    The 19-panel exhibition is on display at CERN's Microcosm from Monday to Saturday from 10.00 a.m. to 5.00 p.m.   Marie Curie won the Nobel Prize for Chemistry one hundred years ago. She is the only woman ever to win two Nobel Prizes, which is a testament to her remarkable work. But throughout history, women have played a role in science either in their own right or alongside other scientists. In this special exhibition, the comic-strip artist Fiami takes a look back at the relationship between women and science through his portraits of Mileva Einstein, Marie-Anne Lavoisier and, of course, Marie Curie. Fiami has recently published an entire album devoted to Marie Curie. Texts in French All ages - Entrance free Femmes et Sciences is on display at Microcosm: From Wednesday 21 September 2011 to Tuesday 20 December 2011.

  1. Kuala Namu Convention And Exhibition Centre

    OpenAIRE

    Gustriana, Trisna

    2017-01-01

    Aerotropolis area development that is expected to accommodate the development of business and commercial appeal and this is the chance for the designer to be able to take advantage of the situation and condition of land as well as possible. So that the revolutionary changes but is able to embrace all stakeholders is the solution needed to development Aerotropolis. Kuala Namu's Convention and Exhibition Center is expected to be a solution for regional development of Kuala Namu a...

  2. 22nd Annual Logistics Conference and Exhibition

    Science.gov (United States)

    2006-04-20

    Bill” Kenwell, Vice President, Sales and Marketing, Maersk 5:30pm-7:30pm Reception in Exhibit Hall Wednesday, April 19, 2006 7:00am-5:30pm...some commercial sales of our products, services and platforms. We provide surface, air, and undersea applications on more than 460 programs for US...diagnostic system & process • Seamless B2B integration with maintenance systems Enabled By… EOATM Overview Sensor Data Maintenance Logs Repair Data Expert

  3. The Factory of the Future, Group Exhibition

    OpenAIRE

    Dean, Lionel T.

    2016-01-01

    3D Printing, The factory of the future, Lieu du Design (centre for Design), Paris This exhibition dedicated entirely to 3D printing technology was billed as “the first in France wholly devoted to exploring the interdisciplinary and multifaceted topic of 3D printing technology and its undeniable influence on everything from industry, to economics, to creative and social issues, demonstrated to the public through achievements in the fields of 3D design, 3D printed architecture, 3D printed fa...

  4. Brazilian air traffic controllers exhibit excessive sleepiness.

    Science.gov (United States)

    Ribas, Valdenilson Ribeiro; de Almeida, Cláudia Ângela Vilela; Martins, Hugo André de Lima; Alves, Carlos Frederico de Oliveira; Alves, Marcos José Pinheiro Cândido; Carneiro, Severino Marcos de Oliveira; Ribas, Valéria Ribeiro; de Vasconcelos, Carlos Augusto Carvalho; Sougey, Everton Botelho; de Castro, Raul Manhães

    2011-01-01

    Excessive sleepiness (ES) is an increased tendency to initiate involuntary sleep for naps at inappropriate times. The objective of this study was to assess ES in air traffic controllers (ATCo). 45 flight protection professionals were evaluated, comprising 30 ATCo, subdivided into ATCo with ten or more years in the profession (ATCo≥10, n=15) and ATCo with less than ten years in the profession (ATCoair traffic controllers exhibit excessive sleepiness.

  5. Naval Meteorology and Oceanography Command exhibit entrance

    Science.gov (United States)

    2000-01-01

    StenniSphere at NASA's John C. Stennis Space Center in Hancock County, Miss., invites visitors to discover why America comes to Stennis Space Center before going into space. Designed to entertain while educating, StenniSphere includes informative displays and exhibits from NASA and other agencies located at Stennis, such as this one from the Naval Meteorology and Oceanography Command. Visitors can 'travel' three-dimensionally under the sea and check on the weather back home in the Weather Center.

  6. Naval Meteorology and Oceanography Command exhibit

    Science.gov (United States)

    2000-01-01

    Designed to entertain while educating, StenniSphere at the John C. Stennis Space Center in Hancock County, Miss., includes informative displays and exhibits from NASA and other agencies located at Stennis, such as this one from the Naval Meteorology and Oceanography Command. Visitors can 'travel' three-dimensionally under the sea and check on the weather back home in the Weather Center. StenniSphere is open free of charge from 9 a.m. to 5 p.m. daily.

  7. Exhibition: Linus Pauling and the Twentieth Century

    CERN Document Server

    2003-01-01

    On April 28 the exhibit Linus Pauling and the Twentieth Century organised by UNIDIR (United Nations Institute for Disarmament Research) and SGI (Soka Gakkai International) as well as with the contributions of CERN and the University of Geneva, opened at the United Nations Office of Geneva. Linus Pauling is the only person to date to have won two unshared Nobel Prizes: Chemistry in 1954 and Peace in 1962. The first was awarded for his landmark research on the nature of the chemical bond and its application in understanding the structure of complex substances. The second one acknowledged his courageous protest against atmospheric nuclear testing and his championship of international peace. The exhibit, for audience of all ages, traces seven decades of Linus Pauling's life and influence on the 20th century. Before starting its European tour at the UNESCO headquarters in Paris, the exhibit opened in 1998 in San Francisco and then travelled within the United-States and to Japan with an attendance of more than one...

  8. Exhibition: Linus Pauling and the Twentieth Century

    CERN Document Server

    2003-01-01

    On April 28 the exhibit Linus Pauling and the Twentieth Century organised by UNIDIR (United Nations Institute for Disarmament Research) and SGI (Soka Gakkai International) as well as with the contributions of CERN and the University of Geneva, opens at the United Nations Office of Geneva. Linus Pauling is the only person to date to have won two unshared Nobel Prizes: Chemistry in 1954 and Peace in 1962. The first was awarded for his landmark research on the nature of the chemical bond and its application in understanding the structure of complex substances. The second one acknowledged his courageous protest against atmospheric nuclear testing and his championship of international peace. The exhibit, for all ages' audiences, traces seven decades of Linus Pauling's life and influence on the 20th century. Before starting its European tour at the UNESCO headquarters in Paris, the exhibit opened in 1998 in San Francisco and then travelled within the United-States and to Japan with an attendance of more than one m...

  9. Bumblebees exhibit the memory spacing effect

    Science.gov (United States)

    Toda, Nicholas R. T.; Song, Jeremy; Nieh, James C.

    2009-10-01

    Associative learning is key to how bees recognize and return to rewarding floral resources. It thus plays a major role in pollinator floral constancy and plant gene flow. Honeybees are the primary model for pollinator associative learning, but bumblebees play an important ecological role in a wider range of habitats, and their associative learning abilities are less well understood. We assayed learning with the proboscis extension reflex (PER), using a novel method for restraining bees (capsules) designed to improve bumblebee learning. We present the first results demonstrating that bumblebees exhibit the memory spacing effect. They improve their associative learning of odor and nectar reward by exhibiting increased memory acquisition, a component of long-term memory formation, when the time interval between rewarding trials is increased. Bombus impatiens forager memory acquisition (average discrimination index values) improved by 129% and 65% at inter-trial intervals (ITI) of 5 and 3 min, respectively, as compared to an ITI of 1 min. Memory acquisition rate also increased with increasing ITI. Encapsulation significantly increases olfactory memory acquisition. Ten times more foragers exhibited at least one PER response during training in capsules as compared to traditional PER harnesses. Thus, a novel conditioning assay, encapsulation, enabled us to improve bumblebee-learning acquisition and demonstrate that spaced learning results in better memory consolidation. Such spaced learning likely plays a role in forming long-term memories of rewarding floral resources.

  10. Exhibition: Dialogue between Science and religion

    CERN Multimedia

    2001-01-01

    Can the theory of the Big Bang reached by physicists and the concept of creation beloved of religion ever be reconciled? The two approaches have at least one point in common: they do not provide a final answer to the mysteries of the birth of the Universe. And this means that dialogue is alays possible between the two. It is to show the potential of such an exchange that Geneva's Société Evangélique organization is opening an exhibition under the title 'Big Bang and Creation', at the Planète Charmilles shopping centre, to run from 19 to 30 March. View of the 'Big Bang and Creation' exhibition. The exhibition is divided into three sections, showing the views of the scientist and those of the believer without setting them up in opposition to one another. In the first section, under a representation of the vault of heaven, the visitor will discover the different ideas explaining the birth of the Universe: Genesis and the Big Bang, and the different dominant theories ...

  11. Art exhibit focuses on African astronomy

    Science.gov (United States)

    Showstack, Randy

    2012-07-01

    Connections between Africans and astronomy are the focus of a new exhibition in the National Museum of African Art in Washington, D. C. "African Cosmos: Stellar Arts," which includes artwork, cultural items, and scientific displays from ancient to contemporary times, is the first major exhibit "that brings together arts and science focused on Africa's contribution to keen observations of the heavens over time," curator Christine Mullen Kreamer said at a 20 June news briefing. Among the exhibit's nearly 100 objects are an ancient Egyptian mummy board that includes a representation of the sky goddess Nut, sculptures by the Dogon people of Mali depicting figures in relation to the cosmos, a video that uses data from two square degrees of the Hubble Space Telescope Cosmic Evolution Survey, and a nearly floor-to-ceiling "Rainbow Serpent" constructed of plastic containers by Benin artist Hazoume. An untitled acrylic painting (Figure 1) by South African Gavin Jantjes evokes a myth of the Khoi San people of southern Africa, as it portrays a girl throwing evening fire embers into the night sky, where they remained as the Milky Way.

  12. Truncated prelamin A expression in HGPS-like patients: a transcriptional study

    NARCIS (Netherlands)

    Barthelemy, F.; Navarro, C; Fayek, R.; Silva, N.; Roll, P.; Sigaudy, S.; Oshima, J.; Bonne, G.; Papadopoulou-Legbelou, K.; Evangeliou, A.E.; Spilioti, M.; Lemerrer, M.; Wevers, R.A.; Morava, E.; Robaglia-Schlupp, A.; Levy, N.; Bartoli, M.; Sandre-Giovannoli, A. De

    2015-01-01

    Premature aging syndromes are rare genetic disorders mimicking clinical and molecular features of aging. A recently identified group of premature aging syndromes is linked to mutation of the LMNA gene encoding lamins A and C, and is associated with nuclear deformation and dysfunction.

  13. Synchronization in multicell systems exhibiting dynamic plasticity

    Indian Academy of Sciences (India)

    Collective behaviour in multicell systems arises from exchange of chemi- ... single type in a multicell system, but environmental influences can sometimes expose this ... cells to change their phenotype has been shown recently [28,29], how ...

  14. Library exhibits and programs boost science education

    Science.gov (United States)

    Dusenbery, Paul B.; Curtis, Lisa

    2012-05-01

    Science museums let visitors explore and discover, but for many families there are barriers—such as cost or distance—that prevent them from visiting museums and experiencing hands-on science, technology, engineering, and mathematics (STEM) learning. Now educators are reaching underserved audiences by developing STEM exhibits and programs for public libraries. With more than 16,000 outlets in the United States, public libraries serve almost every community in the country. Nationwide, they receive about 1.5 billion visits per year, and they offer their services for free.

  15. Radiation-related information at science exhibitions

    Energy Technology Data Exchange (ETDEWEB)

    Bannai, Tadaaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

    1999-09-01

    The aim of the present report was to promote an efficient utilization of science museums providing with educational information concerning radiations. Investigations were made on radiation-related materials exhibited at 38 museums including PR event sites between April 1996 and July 1998 mainly located on Kanto and Tohoku area in Japan. The investigation concerned as to whether the displays on radiation-related material (cosmic rays, X-rays, etc) existed or not, and as to the background of the display as well. As the result, 14 locations had no relevant displays, 10 of them not having things about atomic energy at all. The locations belonging to electricity company mostly had displays related to radiations and atomic energy power generation. A spark chamber was exhibited at 9 locations and a cloud chamber at 3 locations, but only one location among them displayed both. Displays on the actual use of X-radiation were found at 4 locations. Needs to prepare further improved displays exist at the sites visited. (S. Ohno)

  16. CERN Inspires Art in Major New Exhibition

    CERN Document Server

    2001-01-01

    Signatures of the Invisible, an exhibition inspired by CERN, opened at the Atlantis Gallery in London on Thursday, 1 March before going on a world tour. The fruit of a close collaboration between CERN and the London Institute, the exhibition brings together works from many leading European contemporary artists. White wooden boxes on a grey floor... the lids opened, unveiling brilliant white light from a bunch of optical fibres carefully stuck together in the shape of a square. Another holds a treasure of lead glass surrounded by enigmatic black mirrors. What's it all about? Signatures of the Invisible, that's what, a joint project organised by the London Institute, one of the world's largest college of art, and our Laboratory. Damien Foresy from the EST workshop putting finishing touches to the spinning tops of French artist Jérôme Basserode. Monica Sand's boxes are just one of the many works based around materials used in particle detection at CERN that was admired at the opening o...

  17. Children's drawings exhibited in the Globe

    CERN Multimedia

    Elizabeth Roe

    2010-01-01

    "Draw Me A Physicist" has been a success. Members of the public visiting the exhibition in the Globe of Science and Innovation have praised the scientific and creative balance the children of neighbouring France and the Canton of Geneva have obtained through their visit to CERN.   The Draw Me a Physicist exhibition in the Globe For a six-month period 9 to 11-year olds from the Pays de Gex, Meyrin, Satigny and Vernier have been able to enjoy a balance between science and art, through drawing and defining their interpretations of a physicist. In May, eight pairs of drawings from each participating class were selected by the schools to be displayed on the second floor of the Globe. Since the images have been put up, the viewers have enjoyed the contrast between the "before" pictures of vibrant Albert Einsteins to the "after" pictures of casual people sitting in an office. The large room in the Globe has been transformed from a hollow shell int...

  18. Exhibiting the Human/Exhibiting the Cyborg: “Who Am I?”

    Directory of Open Access Journals (Sweden)

    Sophia C. Vackimes

    2013-08-01

    Full Text Available The role of the museum in shaping our relationship to science and technology, particularly cyborgization, is illuminated by a close examination of the Who Am I permanent exhibition in the Wellcome Wing of the Science Museum of London. This innovative exhibition raises real questions both about the human-technology-science relationship but also about museography. In the context of the history and current practices of museums engaging contemporary technological developments the evidence suggest that even as the Who am I? exhibit did break somewhat from previous approaches, especially the didactic presentation of the socially useful, it has not changed the feld as a whole.

  19. Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

    Science.gov (United States)

    Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

    2015-02-01

    The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (PPiper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

  20. Shape-Memory PVDF Exhibiting Switchable Piezoelectricity.

    Science.gov (United States)

    Hoeher, Robin; Raidt, Thomas; Novak, Nikola; Katzenberg, Frank; Tiller, Joerg C

    2015-12-01

    In this study, a material is designed which combines the properties of shape-memory and electroactive polymers. This is achieved by covalent cross-linking of polyvinylidene fluoride. The resulting polymer network exhibits excellent shape-memory properties with a storable strain of 200%, and fixity as well as recovery values of 100%. Programming upon rolling induces the transformation from the nonelectroactive α-phase to the piezoelectric β-phase. The highest β-phase content is found to be 83% for a programming strain of 200% affording a d33 value of -30 pm V(-1). This is in good accordance with literature known values for piezoelectric properties. Thermal triggering this material does not only result in a shape change but also renders the material nonelectroactive. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Applied Gamification in Self-guided Exhibitions

    DEFF Research Database (Denmark)

    Vistisen, Peter; Selvadurai, Vashanth; Krishnasamy, Rameshnath Kala

    2018-01-01

    This paper contributes to the current understanding of applied digital gamification by providing insights from two design cases from the Danish aqua zoo, the North Sea Oceanarium, concerned with self-facilitated exhibitions. Grounded in a short review of the current state of art, we provide two...... empirical case examples, concerning a mobile augmented reality design and an Instagram service. Analyzing the design process behind these cases, we identify some of the challenges arising from applying gamification in practice, and whether these insights verify, extents or contradicts current examples...... of applied gamification research. Specifically, the cases provide insights to the challenge of on-boarding visitors into participating and using the designed products during their visit. In both cases, providing certain incentives for using the app or participating in the Instagram challenge, seemed...

  2. Exhibiting health and medicine as culture

    DEFF Research Database (Denmark)

    Whiteley, Louise; Tybjerg, Karin; Pedersen, Bente Vinge

    2017-01-01

    -being of their visitors, we instead focus on how museums should communicate about health and medicine. Methods: The paper describes three examples of exhibitions at Medical Museion that attempt to display medicine as culture, and draws out three of the key strategies they employ. Results: The three key strategies are: (1......Introduction: This paper discusses the potential role of medical museums in public engagement with health and medicine, based on the work of Medical Museion at the University of Copenhagen. Rather than asking whether cultural venues such as museums can directly improve the well......: There is increasing emphasis on the need for health communication to recognize people’s multiple, lived cultures. We argue that we should also recognize that medical research and practice is itself a form of culture, and as such is multiple and historically shifting. This paper demonstrates that museums are an ideal...

  3. The coordination office at SIREME 2008 exhibition

    International Nuclear Information System (INIS)

    Grotz, Claudia; Cassin, Fabrice; Evrard, Aurelien; Froeding, Veronique; Galaup, Serge; Kaelble, Laure; Persem, Melanie; Regnier, Yannick; )

    2008-01-01

    The French-German office for Renewable energies (OFAEnR) organised several presentations at the occasion of the SIREME International exhibition of renewable energies and energy management. This document brings together these presentations (slides) dealing with: 1 - The new German Renewable Energy Sources Act (EEG) and its impact on wind energy (Claudia Grotz); 2 - Consequences of the July 10, 2006 wind energy tariff bylaw cancelling (Fabrice Cassin); 3 - Wind energy trajectory in France and Germany: a political perspective (Aurelien Evrard); 4 - The wind energy development areas (Veronique Froeding); 5 - A commitment at the heart of our business: renewable energy sources (Serge Galaup); 6 - The wind energy coordination office (Laure Kaelble); 7 - New challenges of the German wind energy market (Melanie Persem); 8 - An industry - a qualification standard (Yannick Regnier)

  4. The Road Transport world exhibition in Paris

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Following the agreement between French and German professionals of automobile and industrial vehicle, the Road Transport world exhibition will take place alternatively in Paris and Hanover. The 1995 meeting has taken place in Paris (September 15-21) and about 20 countries were represented. Road transport is the principal way of goods transportation in France and represent 88% of the traffic explained in tons gross and 70% in tons km. The petroleum dependence of the transportation sector is becoming a worrying problem as the gasoline and diesel fuels taxes will be discussed in the 1996 financial laws project. According to the last ''Worldwide energetic perspectives'' report published by the IEA, in 2010 the transportation sector could absorb more than 60% of the worldwide petroleum consumption. This increase represents a challenge to the petroleum industry to increase the energetic efficiency of the vehicle fuels and the production of diesel fuels, and conversely to reduce the pollution effluents. (J.S.). 4 tabs

  5. Application of an imaging system to a museum exhibition for developing interactive exhibitions

    Science.gov (United States)

    Miyata, Kimiyoshi; Inoue, Yuka; Takiguchi, Takahiro; Tsumura, Norimichi; Nakaguchi, Toshiya; Miyake, Yoichi

    2009-10-01

    In the National Museum of Japanese History, 215,759 artifacts are stored and used for research and exhibitions. In museums, due to the limitation of space in the galleries, a guidance system is required to satisfy visitors' needs and to enhance their understanding of the artifacts. We introduce one exhibition using imaging technology to improve visitors' understanding of a kimono (traditional Japanese clothing) exhibition. In the imaging technology introduced, one data projector, one display with touch panel interface, and magnifiers were used as exhibition tools together with a real kimono. The validity of this exhibition method was confirmed by results from a visitors' interview survey. Second, to further develop the interactive guidance system, an augmented reality system that consisted of cooperation between the projector and a digital video camera was also examined. A white paper board in the observer's hand was used as a projection screen and also as an interface to control the images projected on the board. The basic performance of the proposed system was confirmed; however continuous development was necessary for applying the system to actual exhibitions.

  6. Exhibition of Stochastic Resonance in Vestibular Perception

    Science.gov (United States)

    Galvan-Garza, R. C.; Clark, T. K.; Merfeld, D. M.; Bloomberg, J. J.; Oman, C. M.; Mulavara, A. P.

    2016-01-01

    Astronauts experience sensorimotor changes during spaceflight, particularly during G-transitions. Post flight sensorimotor changes include spatial disorientation, along with postural and gait instability that may degrade operational capabilities of the astronauts and endanger the crew. A sensorimotor countermeasure that mitigates these effects would improve crewmember safety and decrease risk. The goal of this research is to investigate the potential use of stochastic vestibular stimulation (SVS) as a technology to improve sensorimotor function. We hypothesize that low levels of SVS will improve sensorimotor perception through the phenomenon of stochastic resonance (SR), when the response of a nonlinear system to a weak input signal is enhanced by the application of a particular nonzero level of noise. This study aims to advance the development of SVS as a potential countermeasure by 1) demonstrating the exhibition of stochastic resonance in vestibular perception, a vital component of sensorimotor function, 2) investigating the repeatability of SR exhibition, and 3) determining the relative contribution of the semicircular canals (SCC) and otolith (OTO) organs to vestibular perceptual SR. A constant current stimulator was used to deliver bilateral bipolar SVS via electrodes placed on each of the mastoid processes, as previously done. Vestibular perceptual motion recognition thresholds were measured using a 6-degree of freedom MOOG platform and a 150 trial 3-down/1-up staircase procedure. In the first test session, we measured vestibular perceptual thresholds in upright roll-tilt at 0.2 Hz (SCC+OTO) with SVS ranging from 0-700 µA. In a second test session a week later, we re-measured roll-tilt thresholds with 0, optimal (from test session 1), and 1500 µA SVS levels. A subset of these subjects, plus naive subjects, participated in two additional test sessions in which we measured thresholds in supine roll-rotation at 0.2 Hz (SCC) and upright y-translation at 1 Hz

  7. VIRTUAL EXHIBITION AND FRUITION OF ARCHAEOLOGICAL FINDS

    Directory of Open Access Journals (Sweden)

    A. M. Manferdini

    2012-09-01

    Full Text Available During the last two decades, since digital technologies have become more sophisticated in acquiring real data and building faithful copies of them, their improvements have suggested interesting applications in the field of valorisation of Historical, Cultural and Artistic Heritage, with significant consequences in the share and widespread of knowledge. But although several technologies and methodologies for 3d digitization have recently been developed and improved, the lack of a standard procedure and the costs connected to their use still doesn't encourage the systematic digital acquisition of wide collections and heritage. The aim of this paper is to show the state of the art of a project whose aim is to provide a methodology and a procedure to create digital reproductions of artefacts for Institutions called to preserve, manage and enhance the fruition of archaeological finds inside museums or through digital exhibitions. Our project’s aim is to find the most suitable procedure to digitally acquire archaeo logical artefacts that usually have small dimensions and have very complex and detailed surfaces. Within our methodology, particular attention has been paid to the use of widely shared and open-source visualization systems that enhance the involvement of the user by emphasizing three-dimensional characteristics of artefacts through virtual reality.

  8. 77 FR 31420 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2012-05-25

    ... also determine that the exhibition or display of the exhibit objects at The Museum of Modern Art, New...: Game Plan'' imported from abroad for temporary exhibition within the United States, are of cultural...

  9. Metallic Zinc Exhibits Optimal Biocompatibility for Bioabsorbable Endovascular Stents

    Science.gov (United States)

    Bowen, Patrick K.; Guillory, Roger J.; Shearier, Emily R.; Seitz, Jan-Marten; Drelich, Jaroslaw; Bocks, Martin; Zhao, Feng; Goldman, Jeremy

    2015-01-01

    Although corrosion resistant bare metal stents are considered generally effective, their permanent presence in a diseased artery is an increasingly recognized limitation due to the potential for long-term complications. We previously reported that metallic zinc exhibited an ideal biocorrosion rate within murine aortas, thus raising the possibility of zinc as a candidate base material for endovascular stenting applications. This study was undertaken to further assess the arterial biocompatibility of metallic zinc. Metallic zinc wires were punctured and advanced into the rat abdominal aorta lumen for up to 6.5 months. This study demonstrated that metallic zinc did not provoke responses that often contribute to restenosis. Low cell densities and neointimal tissue thickness, along with tissue regeneration within the corroding implant, point to optimal biocompatibility of corroding zinc. Furthermore, the lack of progression in neointimal tissue thickness over 6.5 months or the presence of smooth muscle cells near the zinc implant suggest that the products of zinc corrosion may suppress the activities of inflammatory and smooth muscle cells. PMID:26249616

  10. Chalepin: A Compound from Ruta angustifolia L. Pers Exhibits Cell Cycle Arrest at S phase, Suppresses Nuclear Factor-Kappa B (NF-κB) Pathway, Signal Transducer and Activation of Transcription 3 (STAT3) Phosphorylation and Extrinsic Apoptotic Pathway in Non-small Cell Lung Cancer Carcinoma (A549).

    Science.gov (United States)

    Richardson, Jaime Stella Moses; Aminudin, Norhaniza; Abd Malek, Sri Nurestri

    2017-10-01

    Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells. Cell cycle analysis and caspase 8 activation were conducted using a flow cytometer, and protein expressions in molecular pathways were determined using Western blot technique. Cell cycle analysis showed that cell cycle was arrested at the S phase. Further studies using Western blotting technique showed that cell cycle-related proteins such as cyclins, cyclin-dependent kinases (CDKs), and inhibitors of CDKs correspond to a cell cycle arrest at the S phase. Chalepin also showed inhibition in the expression of inhibitors of apoptosis proteins. Nuclear factor-kappa B (NF-κB) pathway, signal transducer and activation of transcription 3 (STAT-3), cyclooxygenase-2, and c-myc were also downregulated upon treatment with chalepin. Chalepin was found to induce extrinsic apoptotic pathway. Death receptors 4 and 5 showed a dramatic upregulation at 24 h. Analysis of activation of caspase 8 with the flow cytometer showed an increase in activity in a dose- and time-dependent manner. Activation of caspase 8 induced cleavage of BH3-interacting domain death agonist, which initiated a mitochondrial-dependent or -independent apoptosis. Chalepin causes S phase cell cycle arrest, NF-κB pathway inhibition, and STAT-3 inhibition, induces extrinsic apoptotic pathway, and could be an excellent chemotherapeutic agent. This study reports the capacity of an isolated bioactive compound known as chalepin to suppress the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, signal

  11. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

    Directory of Open Access Journals (Sweden)

    Jain PP

    2014-07-01

    Full Text Available Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, AustriaAbstract: Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl-3-trimethylammonium-propane (DOTAP in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited

  12. 77 FR 31909 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2012-05-30

    ... exhibition ``50th Anniversary Remembrance of the Tragedy at Orly,'' imported from abroad by the High Museum of Art for temporary exhibition within the United States, is of cultural significance. The object is... exhibition or display of the exhibit object at the High Museum of Art in Atlanta, Georgia from on or about...

  13. Temporary and Travelling Exhibitions. Museums and Monuments, X.

    Science.gov (United States)

    Daifuku, Hiroshi; And Others

    The permanent exhibition, the most typical form of museum exhibition, has failed to attract repeated visitation, since visitors quickly become familiar with the objects shown. The temporary exhibition evolved as a result for the need of repeated visitation. The temporary exhibition, set up for a period of one to six months, introduces fresh…

  14. Designing immersion exhibits as border-crossing environments

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    2010-01-01

    be applied to achieve an understanding of the immersion exhibit form. The argument proceeds by demonstrating how the characteristics of immersion exhibits, and visitors to them, classify them as microcultures, and examining the implications of this for exhibit design using a hypothetical immersion exhibit...

  15. Creating Virtual Exhibitions for Educational and Cultural Development

    Directory of Open Access Journals (Sweden)

    Gabriela DUMITRESCU

    2014-01-01

    Full Text Available The paper presents different tools and mechanisms to implement a virtual exhibition in different cultural areas, such as museums and libraries. Quality characteristics of virtual exhibitions are identified and described. The possibility to create native mobile applications for virtual exhibitions presentation is analyzed. The functional flow of creating a virtual exhibition is presented and discussed. The Seals - History Treasure exhibition is presented and significant historical documents are revealed.

  16. Porphyromonas gingivalis and Treponema denticola exhibit metabolic symbioses.

    Directory of Open Access Journals (Sweden)

    Kheng H Tan

    2014-03-01

    Full Text Available Porphyromonas gingivalis and Treponema denticola are strongly associated with chronic periodontitis. These bacteria have been co-localized in subgingival plaque and demonstrated to exhibit symbiosis in growth in vitro and synergistic virulence upon co-infection in animal models of disease. Here we show that during continuous co-culture a P. gingivalis:T. denticola cell ratio of 6∶1 was maintained with a respective increase of 54% and 30% in cell numbers when compared with mono-culture. Co-culture caused significant changes in global gene expression in both species with altered expression of 184 T. denticola and 134 P. gingivalis genes. P. gingivalis genes encoding a predicted thiamine biosynthesis pathway were up-regulated whilst genes involved in fatty acid biosynthesis were down-regulated. T. denticola genes encoding virulence factors including dentilisin and glycine catabolic pathways were significantly up-regulated during co-culture. Metabolic labeling using 13C-glycine showed that T. denticola rapidly metabolized this amino acid resulting in the production of acetate and lactate. P. gingivalis may be an important source of free glycine for T. denticola as mono-cultures of P. gingivalis and T. denticola were found to produce and consume free glycine, respectively; free glycine production by P. gingivalis was stimulated by T. denticola conditioned medium and glycine supplementation of T. denticola medium increased final cell density 1.7-fold. Collectively these data show P. gingivalis and T. denticola respond metabolically to the presence of each other with T. denticola displaying responses that help explain enhanced virulence of co-infections.

  17. A content-oriented model for science exhibit engineering

    DEFF Research Database (Denmark)

    Achiam, Marianne

    2013-01-01

    Recently, science museums have begun to review their educational purposes and redesign their pedagogies. At the most basic level, this entails accounting for the performance of individual exhibits, and indeed, in some cases, research indicates shortcomings in exhibit design: While often successful......: as a means to operationalize the link between exhibit features and visitor activities; and as a template to transform scientists’ practices in the research context into visitors’ activities in the exhibit context. The resulting model of science exhibit engineering is presented and exemplified, and its...... implications for science exhibit design are discussed at three levels: the design product, the design process, and the design methodology....

  18. 76 FR 68808 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2011-11-07

    ... also determine that the exhibition or display of the exhibit objects at the Onassis Cultural Center... Century AD,'' imported from abroad for temporary exhibition within the United States, are of cultural... Cultural Affairs, Department of State. [FR Doc. 2011-28805 Filed 11-4-11; 8:45 am] BILLING CODE 4710-05-P ...

  19. 78 FR 7849 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2013-02-04

    ... Century,'' imported from abroad for temporary exhibition within the United States, are of cultural... also determine that the exhibition or display of the exhibit objects at The Yale Center for British Art..., Bureau of Educational and Cultural Affairs, Department of State. [FR Doc. 2013-02401 Filed 2-1-13; 8:45...

  20. A Salamander Tale: Effective Exhibits and Attitude Change

    Science.gov (United States)

    Rollins, Jeffrey; Watson, Sunnie Lee

    2017-01-01

    Little information exists regarding intention behind the design and development of Extension outreach and educational exhibits. An evaluation of response to the exhibit "A Salamander Tale" indicates that the methods used to develop the exhibit resulted in an effective way to present information to an adult audience. Survey questions were…

  1. Characterization of Catalase from Psychrotolerant Psychrobacter piscatorii T-3 Exhibiting High Catalase Activity

    OpenAIRE

    Kimoto, Hideyuki; Yoshimune, Kazuaki; Matsuyma, Hidetoshi; Yumoto, Isao

    2012-01-01

    A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii), that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H2O2 as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein−1) that was higher than that of Micrococcus luteus used for industrial catalase production. Catalase was approximately 10% of the total proteins in the cell extract of the strain. The catalase (PktA) was purif...

  2. Digital Natives: Creating Emergent Exhibitions through Digital Technologies

    DEFF Research Database (Denmark)

    Smith, Rachel Charlotte; Iversen, Ole Sejer; Dindler, Christian

    2011-01-01

    . In this way, digital technology can contribute to the creation of emergent exhibitions in which the exhibition is created in dialogue between audiences and the museum. We present experiences from a current research project, the Digital Natives exhibition, in which digital technology was designed......Digital Technology can support the creation of dialogical spaces in the museum, both playful and reflective, that allow audiences to engage in the ongoing construction and reproduction of cultural heritage creating novel connections between self and others and between past, present and future...... as an integral part of the exhibition to encourage dialogue between audiences and the exhibition materials and thereby investigate how the exhibition emerge as a result of this dialogic co-construction inside the exhibition space. In short, the opportunities offered by digital technologies prompts us to consider...

  3. CERN exhibition attracts over 100,000 visitors in Belgrade

    CERN Multimedia

    Antonella Del Rosso

    2012-01-01

    “This must be an 'all-time record',” says Ray Lewis, CERN travelling exhibition manager. “In all my time with the various permanent and travelling exhibitions that have taken place locally and within our Member States I have never experienced such figures.”   Zarko Obradovic (left), Serbian Minister of Education, Science and Technology, and Rolf Heuer (right), CERN Director-General, at the CERN travelling exhibition in Belgrade. Indeed, in approximately 20 days of exhibition time about 120,000 people, mainly school visiters and the general public, visited the 100 m2 CERN mini-exhibition. It was set up in the centre of Belgrade in October, in association with the meeting of the Restricted European Committee for Future Accelerators (RECFA). After attending the RECFA meeting, CERN's Director-General Rofl Heuer opened the CERN exhibition on the evening of 19 October. Lectures about CERN were held every afternoon, and two public de...

  4. Maintaining students’ Speaking Fluency through Exhibition Examination in Sociolinguistic Studies

    Directory of Open Access Journals (Sweden)

    Khusnul Qhotimah Yuliatuty

    2013-07-01

    Full Text Available Using exhibition for the final project in Sociolinguistic study is really interesting for Universitas Siswa Bangsa Internasional students, especially for 2011 English Department students. Exhibition becomes interesting because this is the new thing to conduct the final project for English Department students’ cohort 2011 at Universitas Siswa Bangsa Internasional. The lecturer divides the students into pairs and each pairs should master one content or topic in Sociolinguistic study.  The students will do the exhibition about the topic that they get in a pairs. The lecturer also gives the students rubric sheet to fill by the visitors. The exhibition will make the students prepare themselves well because they will face many questions about the content which will be delivered by them. Beside, this exhibition also maintains students’ fluency in speaking English because they will explain and answer the questions from visitors with English. This paper tries to focus on how exhibition examination can maintain students’ fluency in speaking English.

  5. The Eugenides Foundation Interactive Exhibition of Science and Technology

    Science.gov (United States)

    Kontogiannis, Ioannis

    2010-01-01

    The Interactive Exhibition of Science and Technology is installed in an area of 1200 m2 at the Eugenides Foundation. 65 interactive exhibits, designed by the "Cites des Science et de l' Industrie" are organised in themes, stimulate the visitors' mind and provoke scientific thinking. Parallel activities take place inside the exhibition, such as live science demonstrations, performed by young scientists. Extra material such as news bulletins (short news, science comics and portraits), educational paths and treasure-hunting based games, all available online as well, are prepared on a monthly basis and provided along with the visit to the exhibition. Through these exhibits and activities, scientific facts are made simple and easy to comprehend using modern presentation tools. We present details on how this exhibition acts complementary to the science education provided by schools, making it a highly sophisticated educational tool.

  6. Students-exhibits interaction at a science center

    Science.gov (United States)

    Botelho, Agostinho; Morais, Ana M.

    2006-12-01

    In this study we investigate students' learning during their interaction with two exhibits at a science center. Specifically, we analyze both students' procedures when interacting with exhibits and their understanding of the scientific concepts presented therein. Bernstein's theory of pedagogic discourse (1990, 2000) provided the sociological foundation to assess the exhibit-student interaction and allowed analysis of the influence of the characteristics of students, exhibits, and interactions on students' learning. Eight students (ages 12ndash;13 years of age) with distinct sociological characteristics participated in the study. Several findings emerged from the results. First, the characteristics of the students, exhibits, and interactions appeared to influence student learning. Second, to most students, what they did interactively (procedures) seems not to have had any direct consequence on what they learned (concept understanding). Third, the data analysis suggest an important role for designers and teachers in overcoming the limitations of exhibit-student interaction.

  7. Creating National Narrative: The Red Guard Art Exhibitions and the National Exhibitions in the Chinese Cultural Revolution 1966 - 1976

    Directory of Open Access Journals (Sweden)

    Winnie Tsang

    2014-06-01

    Full Text Available The artistic development in China experienced drastic changes during the Cultural Revolution from 1966 to 1976. Traditional Chinese art was denounced, whereas propaganda art became predominant in shaping the public’s loyalty towards the Communist Party and the country. Two major groups of art exhibitions emerged during the Revolution—the unofficial Red Guard art exhibitions organized by student activists in collaboration with local communes and art schools between 1966 and 1968, and the state-run national exhibitions from 1972 to 1975. These exhibitions were significant to this period because they were held frequently in the capital city Beijing and occasionally elsewhere, and through art they presented unique revolutionary beliefs to the Chinese people in a public setting. While the Red Guard art exhibitions and the national exhibitions certainly created different national narratives, I argue that the national exhibitions were in fact an attempt to revise the national narrative created by the Red Guard art exhibitions in order to re-establish a more utopian, consistent, and official national narrative. This paper unravels the intricate relationship between the two groups of exhibitions by comparing their exhibition venues, ideological focuses, work selection and quality editing. 

  8. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Liu, Guang-Hui; Barkho, Basam Z; Ruiz, Sergio; Diep, Dinh; Qu, Jing; Yang, Sheng-Lian; Panopoulos, Athanasia D; Suzuki, Keiichiro; Kurian, Leo; Walsh, Christopher; Thompson, James; Boue, Stephanie; Fung, Ho Lim; Sancho-Martinez, Ignacio; Zhang, Kun; Yates, John; Izpisua Belmonte, Juan Carlos

    2011-04-14

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.

  9. Tumor-Protective Mechanism Identified from Premature Aging Disease | Center for Cancer Research

    Science.gov (United States)

    Hutchinson-Gilford Progeria Syndrome (HGPS) is an extraordinarily rare genetic disorder caused by a mutation in the LMNA gene, which encodes architectural proteins of the human cell nucleus. The mutation causes the production of a mutant protein called progerin. Patients with HGPS display signs of premature aging, such as hair loss, slowed growth, weakening of bone and joint integrity, and cardiovascular disease. Most die in their mid-teens of heart disease or stroke. Intriguingly, these patients do not develop another aging-related disease, cancer, despite having dramatically elevated levels of DNA damage. Tom Misteli, Ph.D., of CCR’s Laboratory of Receptor Biology and Gene Expression, and his colleagues hypothesized that, rather than patients not living long enough to develop cancer, a resistance mechanism was operating in HGPS cells to prevent cancer formation. To begin testing this idea, the researchers transformed fibroblasts from HGPS patients or age-matched, healthy controls with telomerase, constitutively-activated HRAS, and SV40 large and small T antigens. Transformed HGPS cells displayed morphological changes and increased proliferation similar to transformed controls but formed fewer colonies in soft agar and fewer tumors when injected into mice. When the investigators examined global gene expression in the two populations of cells, they found that transformed HGPS cells failed to activate many of the genes that are induced in response to transformation in controls, including oncogenic and proliferation pathways. In addition the transformed HGPS cells were unable to undergo oncogenic de-differentiation. Importantly, the tumor resistance in HGPS cells was due to the presence of the progerin protein, which was both necessary and sufficient to protect cells from oncogenic transformation. Together these results suggested that HGPS cells resist cancer-inducing stimuli by not undergoing the genetic reprogramming necessary for tumor initiation. The scientists

  10. Health-promoting properties exhibited by Lactobacillus helveticus strains.

    Science.gov (United States)

    Skrzypczak, Katarzyna; Gustaw, Waldemar; Waśko, Adam

    2015-01-01

    Many strains belonging to lactobacilli exert a variety of beneficial health effects in humans and some of the bacteria are regarded as probiotic microorganisms. Adherence and capabilities of colonization by Lactobacillus strains of the intestinal tract is a prerequisite for probiotic strains to exhibit desired functional properties. The analysis conducted here aimed at screening strains of Lactobacillus helveticus possessing a health-promoting potential. The molecular analysis performed, revealed the presence of a slpA gene encoding the surface S-layer protein SlpA (contributing to the immunostimulatory activity of L. helveticus M 92 probiotic strain) in all B734, DSM, T80, and T105 strains. The product of gene amplification was also identified in a Bifidobacterium animalis ssp. lactis BB12 probiotic strain. SDS-PAGE of a surface protein extract demonstrated the presence of a protein with a mass of about 50 kDa in all strains, which refers to the mass of the S-layer proteins. These results are confirmed by observations carried with transmission electron microscopy, where a clearly visible S-layer was registered in all the strains analyzed. The in vitro study results obtained indicate that the strongest adhesion capacity to epithelial cells (HT-29) was demonstrated by L. helveticus B734, while coaggregation with pathogens was highly diverse among the tested strains. The percentage degree of coaggregation was increasing with the incubation time. After 5 h of incubation, the strongest ability to coaggregate with Escherichia coli was expressed by T104. The T80 strain demonstrated a significant ability to co-aggregate with Staphylococcus aureus, while DSM with Bacillus subtilis. For B734, the highest values of co-aggregation coefficient was noted in samples with Salmonella. The capability of autoaggregation, antibiotic susceptibility, resistance to increasing salt concentrations, and strain survival in simulated small intestinal juice were also analyzed.

  11. Exhibition at CERN's Globe of Science and Innovation

    CERN Multimedia

    Claudia Marcelloni

    2006-01-01

    Here we see pictures of displays at one of the exhibitions held at the Globe of Science and Innovation taken in September 2006. Located opposite the main CERN site, the Globe houses many public exhibitions throughout the year covering many topics from astronomy to particle physics.

  12. Designing Art Exhibitions in an Educational Virtual World

    Science.gov (United States)

    Julian, June; Crooks, Julian

    2011-01-01

    Demonstrating the multiple features of the Cerulean Gallery in Second Life, this research report showcases several exemplar exhibits created by students, artists, and museums. Located in The Educational Media Center, a Second Life teaching and social space, the Cerulean Gallery exhibits functioned as case studies that tested its effectiveness as…

  13. 7 CFR Exhibit A to Subpart Jj of... - Agreement Form

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Agreement Form A Exhibit A to Subpart JJ of Part 2045...) ADMINISTRATIVE REGULATIONS GENERAL Rural Development-Utilization of Gratuitous Services Pt. 2045, Subpt. JJ, Exh. A Exhibit A to Subpart JJ of Part 2045—Agreement Form for utilization of employees of (official...

  14. Perspectives on ... Multiculturalism and Library Exhibits: Sites of Contested Representation

    Science.gov (United States)

    Reece, Gwendolyn J.

    2005-01-01

    This article analyzes a multicultural library exhibit presenting the Palestinian/Israeli conflict as a site of contested representation. Qualitative methodology is used to interrogate the exhibit and its audience reception. Drawing on insights from critical pedagogy, implications for libraries arising from this case study are given and suggestions…

  15. Informing the Development of Science Exhibitions through Educational Research

    Science.gov (United States)

    Laherto, Antti

    2013-01-01

    This paper calls for greater use of educational research in the development of science exhibitions. During the past few decades, museums and science centres throughout the world have placed increasing emphasis on their educational function. Although exhibitions are the primary means of promoting visitors' learning, educational research is not…

  16. 75 FR 6079 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2010-02-05

    ... cultural significance. The objects are imported pursuant to loan agreements with the foreign owners or custodians. I also determine that the exhibition or display of the exhibit objects at the Yale Center for... Professional and Cultural Exchanges, Bureau of Educational and Cultural Affairs, Department of State. [FR Doc...

  17. 7 CFR Exhibit A to Subpart B of... - [Reserved

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false [Reserved] A Exhibit A to Subpart B of Part 1900 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS GENERAL Adverse Decisions and Administrative Appeals Exhibit A to Subpart B of Part 1900 [Reserved] ...

  18. 19 CFR 212.11 - Net worth exhibit.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Net worth exhibit. 212.11 Section 212.11 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE IMPLEMENTATION OF THE EQUAL ACCESS TO JUSTICE ACT Information Required From Applicants § 212.11 Net worth exhibit...

  19. Outreach to Science Faculty and Students through Research Exhibitions

    Science.gov (United States)

    Chan, Tina; Hebblethwaite, Chris

    2014-01-01

    Penfield Library at the State University of New York at Oswego (SUNY Oswego) has a gallery exhibit space near the front entrance that is used to showcase student-faculty research and art class projects. This article features the library's outreach efforts to science faculty and students through research exhibitions. The library held an exhibition…

  20. Modelling the Future: Exhibitions and the Materiality of Education

    Science.gov (United States)

    Lawn, Martin, Ed.

    2009-01-01

    The role of World Exhibitions in the 19th and early 20th centuries was to confirm a relation between the nation state and modernity. As a display about industries, inventions and identities, the Exhibition, in a sense, put entire nations into an elevated, viewable space. It is a significant element in modernity as comparisons can be made, progress…

  1. CERN Industrials Exhibitions - Over 30 Years of Tradition

    CERN Multimedia

    2001-01-01

    Industrial exhibitions have been part of the CERN landscape for 33 years. At least once each year several companies from the same country come to CERN to present their products and services. Now, a new scheme of one-day visits is giving potential exhibitors at CERN a lighter option. The United Kingdom inaugurated the Industrial Exhibitions in 1968, and it wasn't till 1971 that other countries staged exhibitions at CERN. This photo was taken in 1969, at the second British exhibition, where 16 companies were present. Four years after joining CERN, Poland inaugurated its first exhibition at CERN in 1995 in the presence of the former Director-General Chris Llewellyn-Smith. Almost all the Member States have held industrial exhibitions at the Organization. May '68 wasn't only revolutionary in Paris. For the very first time, an industrial exhibition took place at CERN. Great Britain was first to come with eight companies and remains until this day the most devoted country to the programme with 17 exhibitions and ...

  2. Presentation and exhibition activities for promoting theexportof transport services

    Directory of Open Access Journals (Sweden)

    Darya Vladimirovna Nesterova

    2012-03-01

    Full Text Available Development of presentation and exhibition activities is considered as an important factor in providing new competitive advantages at the strategic markets for exporting of transportation services. A specific role for exhibition activities as a factor to overcome market failures arose from imperfect information and incomplete markets is displayed. Exhibitions are considered as a true reflection of most market parameters, as a means to get correct information concerning market capacity and its borders, as an instrument to access to new markets. At the firm level presentation and branding activities should be considered as a modern technology (especially it concerns Russian companies which provide to hold up already existed markets and to conquer new ones. Presentation and branding activities are an effective technology to promote company trade-mark, competitive advantages for market demand increasing. Comparative analysis of the main exhibitions on transport and logistics issues is fulfilled on the data basecollected by authors. Data observes geographical distribution of transport exhibition and exhibition facilities development at several regions for the last years. The analyses allow to revealing a geographical structure of the exhibitions and its distribution by type of transport. The most promising and economically favorable exhibition areas for the promotion of Russian transport services are shown.

  3. The AAAI 2006 Mobile Robot Competition and Exhibition

    OpenAIRE

    Rybski, Paul E.; Forbes, Jeffrey; Burhans, Debra; Dodds, Zach; Oh, Paul; Scheutz, Matthias; Avanzato, Bob

    2007-01-01

    The Fifteenth Annual AAAI Robot Competition and Exhibition was held at the Twenty-First National Conference on Artificial Intelligence in Boston, Massachusetts, in July 2006. This article describes the events that were held at the conference, including the Scavenger Hunt, Human Robot Interaction, and Robot Exhibition.

  4. Sponsorship and exhibitions at Nordic science centres and museums

    DEFF Research Database (Denmark)

    Davidsson, Eva; Sørensen, Helene

    2010-01-01

    Science and technology centres (STC) and science museums tend increasingly to rely on external economic support in order to create new exhibitions. But in what ways may the economic situation affect what is presented in their exhibitions? This article aims to explore how staff members consider...

  5. The Signatures of the Invisible exhibition in Geneva

    CERN Multimedia

    Patrice Loïez

    2002-01-01

    The artist Paola Pivi with her work at the Signatures of the Invisible exhibition in Geneva during February 2002. This piece with needles suspended on nylon thread 'detects' people as they approach. The exhibition was for art inspired by research carried out at CERN.

  6. Displaying lives: the narrative of objects in biographical exhibitions

    Directory of Open Access Journals (Sweden)

    Caterina Albano

    2007-03-01

    Full Text Available Biographical exhibitions are a museum practice that asks for critical consideration. Grounding the argument in critical theory, social studies and museum theory, the article explores the narrative function of objects in biographical exhibitions by addressing the social significance of objects in relation to biography and their relevance when presented into an exhibition display. Central is the concept of objects as ‘biographical relics’ that are culturally fetishized in biographical narratives. This raises questions about biographical reliability and the cultural role that such objects plays in exhibition narratives as bearers of reality and as metonymical icons of the biographical subject. The article considers examples of biographical exhibitions of diverse figures such as Gregor Mendel, Madame de Pompadour and Roland Barthes, and the role that personal items, but also portraits and photographs, play in them.

  7. CERN’s travelling exhibition goes to Austria

    CERN Multimedia

    Mélissa Lanaro

    2011-01-01

    Since April 2009 CERN’s travelling exhibition has been touring through some of the Organization's Member States. After Italy and Denmark it has been on show since February at Austria’s Hartberg Ökopark, a very popular science museum situated some one hundred kilometres from Vienna. To coincide with the CERN exhibition, Austria’s scientific community has organised a series of events for the general public which have had marked success. The exhibition's next destination will be Portugal and preparations are already underway to ensure that it is another resounding success   The travelling exhibition was designed in collaboration with the University of Geneva, as part of the celebrations for its 450th anniversary, and has already notched up a good number of kilometres as it travels from country to country. “In 2010 the exhibition already had around 55,000 visitors,” explains Rolf Landua, who heads the Education Group. Since its inauguration ...

  8. Application of Glass Fiber Reinforced Cement in Exhibition Decoration Project

    Science.gov (United States)

    Wang, Yao

    2018-02-01

    Through the study of GRC material and its application field, the aesthetic characteristics and functional characteristics of GRC materials are demonstrated. The decorative application and technology of GRC material in an art exhibition center are highlighted. The design, application and construction technology of GRC curtain wall and ceiling board in the interior and exterior decoration of art exhibition hall are discussed in detail. The unique advantages of GRC materials in exhibition engineering decoration are fully reflected. In practical design application, the application principle and method are summarized, and an application procedure is formed. The research proves that GRC materials in the art of building decoration engineering has an underrated advantage.

  9. Statistical properties of chaotic dynamical systems which exhibit strange attractors

    International Nuclear Information System (INIS)

    Jensen, R.V.; Oberman, C.R.

    1981-07-01

    A path integral method is developed for the calculation of the statistical properties of turbulent dynamical systems. The method is applicable to conservative systems which exhibit a transition to stochasticity as well as dissipative systems which exhibit strange attractors. A specific dissipative mapping is considered in detail which models the dynamics of a Brownian particle in a wave field with a broad frequency spectrum. Results are presented for the low order statistical moments for three turbulent regimes which exhibit strange attractors corresponding to strong, intermediate, and weak collisional damping

  10. Knowledge Generation in Technology-Enhanced Health Exhibitions

    DEFF Research Database (Denmark)

    Magnussen, Rikke; Kharlamov, Nikita; Zachariasssen, Maria

    2016-01-01

    This paper presents results from eye-tracking studies of audience interaction and knowledge generation in the technology-enhanced health promotion exhibition PULSE at a science centre in Copenhagen, Denmark. The main purpose of the study was to understand what types of knowledge audiences build...... in health promotion exhibitions designed to include direct physical interaction. The current study is part of the larger PULSE project, which aims to develop innovative health promotion activities that include a science museum exhibition as a key setting. The primary target group is families with children...

  11. Postmodern Exhibition Discourse: Anthropological Study of an Art Display Case.

    Directory of Open Access Journals (Sweden)

    Marta Wieczorek

    2015-12-01

    Full Text Available The article studies tendencies in contemporary museum exhibitions and art display trends. While analysing current status quo of art in the museum context, it discusses the limitations of curatorial impact on the audience perception of the displayed objects. The paper presents a case study of a permanent museum exhibition with an added performance element. As argued in the article, such approach allows a stratified narrative and provokes a dialogue between the audience, performers, and curators, fully reflecting postmodern polyphonic tendency. The aim of the article is to comment on postmodern trends in museology, the status of the displayed art (object, and contemporary exhibition identity.

  12. Unimode metamaterials exhibiting negative linear compressibility and negative thermal expansion

    International Nuclear Information System (INIS)

    Dudek, Krzysztof K; Attard, Daphne; Caruana-Gauci, Roberto; Grima, Joseph N; Wojciechowski, Krzysztof W

    2016-01-01

    Unimode metamaterials made from rotating rigid triangles are analysed mathematically for their mechanical and thermal expansion properties. It is shown that these unimode systems exhibit positive Poisson’s ratios irrespective of size, shape and angle of aperture, with the Poisson’s ratio exhibiting giant values for certain conformations. When the Poisson’s ratio in one loading direction is larger than +1, the systems were found to exhibit the anomalous property of negative linear compressibility along this direction, that is, the systems expand in this direction when hydrostatically compressed. Also discussed are the thermal expansion properties of these systems under the assumption that the units exhibit increased rotational agitation once subjected to an increase in temperature. The effect of the geometric parameters on the aforementioned thermo-mechanical properties of the system, are discussed, with the aim of identifying negative behaviour. (paper)

  13. TrayGen: Arranging objects for exhibition and packaging

    KAUST Repository

    Yang, Yongliang; Huang, Qixing

    2013-01-01

    We present a framework, called TrayGen, to generate tray designs for the exhibition and packaging of a collection of objects. Based on principles from shape perception and visual merchandising, we abstract a number of design guidelines on how

  14. "Britain at CERN" exhibition, from 14 to 17 November 2000

    CERN Multimedia

    Patrice Loïez

    2000-01-01

    H.E. Mr. Christopher Hulse, Ambassador of United Kingdom in Switzerland, CERN Director General Luciano Maiani, Sir David Wright, Chief Executive of British Trade International and Roger Cashmore, CERN Director of research visit the Britain at CERN exhibition

  15. Asian Martial Art Exhibitions at the Swiss Castle of Morges

    Directory of Open Access Journals (Sweden)

    Nicolae Gothard Bialokur

    2012-07-01

    Full Text Available This article reports on two unique cultural exhibitions (2005 and 2007 held in Morges, Switzerland. The main theme for these exhibitions was Asian martial arts with a focus on those from Japan, including presentations by notable masters in aikido, karate, judo, kyudo, iaido, kenjutsu, jodo, juttejutsu, kusarigamajutsu, naginatajutsu, tameshigiri, and kendo. On exhibit were artifacts from Morges Castle museum collections as well as numerous ancient objects borrowed specifically for these exhibitions from other Swiss museums and private collections. There was also a lecture on Japanese sword collecting and care, and presentations of Japanese dance, flower arranging (ikebana, the art of tea (châ no yu, châdo, paper folding (origami, traditional kimono dress, and detailed demonstrations on the manufacture of bladed weapons. Text and photography were arranged to record these events for this article, showing how excellent organization and cooperation can introduce high-quality martial traditions to the public.

  16. Editorial Notes: Exhibition Complex: Displaying People, Identity, and Culture

    Directory of Open Access Journals (Sweden)

    Amy Cymbala

    2014-06-01

    Full Text Available Editorial Notes on section relating to submissions from the symposium Exhibition Complex: Displaying People, Identity, and Culture held October 18-20, 2012 at the Carnegie Museum of Art, Pittsburgh, Pennsylvania.

  17. British Museum Exhibition Review: The Jericho Skull, Creating an Ancestor

    Directory of Open Access Journals (Sweden)

    Cara Hirst

    2017-03-01

    Full Text Available The temporary exhibit at the British Museum, open 15th December-19th February, and located to the right of the main entrance in the Raymond and Beverly Sackler Gallery (Room 59; is dedicated to a single Neolithic crania from Jericho, known as the Jericho Skull. This exhibit demonstrates the value of relatively recent technologies in archaeological research, highlighting the previously hidden information made possible through CT scanning and the value of these methods in both archaeological research but also in communicating archaeology in a visually stimulating manner which allows an exhibit to take a single item, and create an in depth exhibit featuring both the original material and two cranial 3D prints along with a facial reconstruction.

  18. Dutch hi-tech companies exhibit at CERN

    CERN Multimedia

    Roberto Cantoni

    2010-01-01

    Twenty-seven Dutch companies will present the state of the art of their technological developments at the industrial exhibition Holland @ CERN from 8 to 11 November. The exhibition is designed to help strengthen the ties between fundamental science and Dutch industry.   The exhibition, supported by the Dutch Ministry of Economic Affairs and organised by the Netherlands National Institute for Subatomic Physics (Nikhef), in cooperation with the Foundation for Fundamental Research on Matter (FOM), the FOM Institute for Plasma Physics Rijnhuizen, and Dutch Scientific, an association of manufacturers of scientific equipment, will be held in the Main Building from 8 to11 November. “The last Holland @ CERN exhibition took place fifteen years ago”, says Robert Klöpping from Nikhef, Dutch Industrial Liaison Officer for CERN and Purchasing Advisor for Grenoble ESRF. “This kind of event is very important for Dutch industry as it allows us to show what Dutch companies c...

  19. Exhibit celebrates five decades of women in engineering

    OpenAIRE

    Gilbert, Karen

    2007-01-01

    "Petticoats and Slide Rules," a historical exhibit on women in engineering from the Society of Women Engineers (SWE), is currently on display in the lobby of Hancock 100 and will remain at Virginia Tech through March of 2007.

  20. The Lynden Pindling Exhibit: the Man, the Dream, the Moment

    Directory of Open Access Journals (Sweden)

    Shananda Miller Hinsey

    2015-06-01

    Full Text Available The Sir Lynden O. Pindling Room at the Harry C. Moore Library and Information Centre of The College of The Bahamas contains an exhibit of over 260 items, including personal effects, gifts, gowns, photographs, speeches and publications. The items included in this special exhibit space are resources that scholars, students and the public may use to research the legacy of the former prime minister and, by extension, the history of The Bahamas.

  1. The 1997 AAAI Mobile Robot Competition and Exhibition

    OpenAIRE

    Arkin, Ronald C.

    1998-01-01

    In July 1997, the Sixth Annual Association for the Advancement of Artificial Intelligence (AAAI) Mobile Robot Competition and Exhibition was held. The competition consisted of four new events: (1) Find Life on Mars; (2) Find the Remote; (3) Home Vacuum; and (4) Hors d'Oeuvres, Anyone? The robot exhibition was the largest in AAAI history. This article presents the history, motivation, and contributions for the event.

  2. Foreign Investors Able to Establish Foreign- exclusively Exhibition Corporations

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Foreign Investors Able to Establish Foreign-exclusively Exhibition Corporations In Feb, Ministry of Commerce issued its 1st decree on temporary regulation for foreign-investing corporations; the regulation allows foreign investors to set up foreign-investing convention & exhibition corporations exclusively or through cooperation with other Chinese corporations, enterprises or organizations. With legal protection on their regulatory management and legal rights, these foreign-investing corporations are in the charge of Department of Foreign Investment Administration, Ministry of Commerce.

  3. Exhibition of Monogamy Relations between Entropic Non-contextuality Inequalities

    International Nuclear Information System (INIS)

    Zhu Feng; Zhang Wei; Huang Yi-Dong

    2017-01-01

    We exhibit the monogamy relation between two entropic non-contextuality inequalities in the scenario where compatible projectors are orthogonal. We show the monogamy relation can be exhibited by decomposing the orthogonality graph into perfect induced subgraphs. Then we find two entropic non-contextuality inequalities are monogamous while the KCBS-type non-contextuality inequalities are not if the orthogonality graphs of the observable sets are two odd cycles with two shared vertices. (paper)

  4. Evaluating Education and Science in the KSC Visitor Complex Exhibits

    Science.gov (United States)

    Erickson, Lance K.

    2000-01-01

    The continuing development of exhibits at the Kennedy Space Center's Visitor Complex is an excellent opportunity for NASA personnel to promote science and provide insight into NASA programs and projects for the approximately 3 million visitors that come to KSC annually. Stated goals for the Visitor Complex, in fact, emphasize science awareness and recommend broadening the appeal of the displays and exhibits for all age groups. To this end, this summer project seeks to evaluate the science content of planned exhibits/displays in relation to these developing opportunities and identify specific areas for enhancement of existing or planned exhibits and displays. To help expand the educational and science content within the developing exhibits at the Visitor Complex, this project was structured to implement the goals of the Visitor Center Director. To accomplish this, the exhibits and displays planned for completion within the year underwent review and evaluation for science content and educational direction. Planning emphasis for the individual displays was directed at combining the elements of effective education with fundamental scientific integrity, within an appealing format.

  5. Exhibits Recognition System for Combining Online Services and Offline Services

    Science.gov (United States)

    Ma, He; Liu, Jianbo; Zhang, Yuan; Wu, Xiaoyu

    2017-10-01

    In order to achieve a more convenient and accurate digital museum navigation, we have developed a real-time and online-to-offline museum exhibits recognition system using image recognition method based on deep learning. In this paper, the client and server of the system are separated and connected through the HTTP. Firstly, by using the client app in the Android mobile phone, the user can take pictures and upload them to the server. Secondly, the features of the picture are extracted using the deep learning network in the server. With the help of the features, the pictures user uploaded are classified with a well-trained SVM. Finally, the classification results are sent to the client and the detailed exhibition’s introduction corresponding to the classification results are shown in the client app. Experimental results demonstrate that the recognition accuracy is close to 100% and the computing time from the image uploading to the exhibit information show is less than 1S. By means of exhibition image recognition algorithm, our implemented exhibits recognition system can combine online detailed exhibition information to the user in the offline exhibition hall so as to achieve better digital navigation.

  6. Designing museum exhibits that facilitate visitor reflection and discussion

    DEFF Research Database (Denmark)

    Skydsgaard, Morten Arnika; Andersen, Hanne Møller; King, Heather

    2016-01-01

    This paper explores how four design principles (curiosity, challenge, narratives and participation) facilitate reflection and discussion among young visitors in the issues-based exhibition Dear, Difficult Body. The investigation is based on a mixed-method approach combining questionnaire and inte......This paper explores how four design principles (curiosity, challenge, narratives and participation) facilitate reflection and discussion among young visitors in the issues-based exhibition Dear, Difficult Body. The investigation is based on a mixed-method approach combining questionnaire...... and interview data. The implementation of design principles resulted in a variety of exhibits which variously prompted reflection and discussion on the part of visitors. Exhibits with narratives, for example, here defined as both personal and expert narratives, were found to be effective in facilitating...... personal reflection but also prompted discussion. Participation, defined as including both physical interaction with exhibits, and dialogic interaction between visitors, facilitated the sharing of ideas and feelings between visitors. Exhibits with elements of curiosity and challenge were found to attract...

  7. A phenomenological investigation of science center exhibition developers' expertise development

    Science.gov (United States)

    Young, Denise L.

    The purpose of this study was to examine the exhibition developer role in the context of United States (U.S.) science centers, and more specifically, to investigate the way science center exhibition developers build their professional expertise. This research investigated how successfully practicing exhibition developers described their current practices, how they learned to be exhibition developers, and what factors were the most important to the developers in building their professional expertise. Qualitative data was gathered from 10 currently practicing exhibition developers from three science centers: the Exploratorium, San Francisco, California; the Field Museum, Chicago, Illinois; and the Science Museum of Minnesota, St. Paul, Minnesota. In-depth, semistructured interviews were used to collect the data. The study embraced aspects of the phenomenological tradition and sought to derive a holistic understanding of the position and how expertise was built for it. The data were methodically coded and organized into themes prior to analysis. The data analysis found that the position consisted of numerous and varied activities, but the developers' primary roles were advocating for the visitor, storytelling, and mediating information and ideas. They conducted these activities in the context of a team and relied on an established exhibition planning process to guide their work. Developers described a process of learning exhibition development that was experiential in nature. Learning through daily practice was key, though they also consulted with mentors and relied on visitor studies to gauge the effectiveness of their work. They were adept at integrating prior knowledge gained from many aspects of their lives into their practice. The developers described several internal factors that contributed to their expertise development including the desire to help others, a natural curiosity about the world, a commitment to learning, and the ability to accept critique. They

  8. 17th European photovoltaic solar energy conference and exhibition, Munich 22.-26.10.2001

    International Nuclear Information System (INIS)

    Nowak, S.

    2002-01-01

    This report for the Swiss Federal Office of Energy (SFOE) summarises the photovoltaics (PV) conference and exhibition held in Munich in October 2001 from the Swiss point of view. The contributions made by representatives of Swiss institutions and companies are presented including papers on the progress being made in third generation crystalline and multi-crystalline silicon technology, amorphous and micro-crystalline silicon solar cells, thin film solar cells based on compound semiconductors and thermo-photovoltaics. Further papers deal with PV modules on the market, building-integrated solar power systems and new developments in PV systems technology. The exhibition that accompanied the conference, including the 12 Swiss exhibitors who were present, is reviewed as are international market developments. Contributions concerning the application of photovoltaics in developing countries are also reviewed

  9. “Accelerating Science” exhibition zooms to Turkey

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    'Accelerating Science', CERN’s travelling science outreach exhibition, has just arrived at the Middle East Technical University (METU) in Ankara, Turkey for a four-month stay there. This is the first time it has moved outside the circle of the Member States. The Turkish venue will inaugurate some new exhibits that have recently been developed by CERN’s software developers.   “It’s been a very busy day,” says Bilge Demirkoz, an associate professor of physics at METU and a member of AMS-02, who had been overseeing the unloading of the lorries when we spoke to her. “As the University doesn’t have a specific exhibition space, the CERN exhibits are going to be housed in the covered tennis courts just behind the cultural and congress centre. It’s a beautiful venue, and there are plenty of parking spaces.” The University has sent invitations to the exhibition to high schools and to about 100 ...

  10. Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity.

    Science.gov (United States)

    Mori, Shogo; Williams, Howard; Cagle, Davey; Karanovich, Kristopher; Horgen, F David; Smith, Roger; Watanabe, Coran M H

    2015-10-09

    A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue.

  11. Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

    OpenAIRE

    Mori, Shogo; Williams, Howard; Cagle, Davey; Karanovich, Kristopher; Horgen, F. David; Smith, Roger; Watanabe, Coran M. H.

    2015-01-01

    A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol re...

  12. Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

    Directory of Open Access Journals (Sweden)

    Shogo Mori

    2015-10-01

    Full Text Available A new bioactive macrolactone, nuiapolide (1 was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue.

  13. The exhibition Lumiere d'Atomes (Atoms light)

    International Nuclear Information System (INIS)

    Foos, Jacques

    1995-01-01

    Full text: This exhibition has been conceived in order to show for everybody, whatever his scientific level, the peaceful uses of transformations (natural or made by Man) and energetic possibilities of the atomic nucleus. The key-ideas of this exhibition were-: - nuclear applications a world of high technology; - nuclear industry men as the others; - nuclear energy an energetic independence. 6 themes were proposed: 1- Atoms and radioactivity; 2- The nuclear power stations; 3- The nuclear fuel cycle; 4- Surety and environment; 5- The other uses of radioactivity; 6- The French choice: The world nuclear data. This exhibition that comprises information posters, paintings, demonstration models, films and video games, was shown for the first time in Paris in april 1991. From this time, it was shown in many regional cities, with the help of SFEN members. 'Lumiere d'Atomes' received in 1991 the SFEN prize for its information on nuclear energy. (author)

  14. Exhibition of Masayuki Miyata's Works of Art

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    To commemorate the 25th anniversary of the signing of the Sino-Japanese Peace and Friendship Treaty, the CPAFFC held the exhibition of Masayuki Miyata's works of art in the Painting Exhibition Hall of the Palace Museum from October 23 to 27, 2003. Miyata's 124 best works were selected for the exhibition, among which works on the subjects about China and those about Japan were half and half. They drew their materials mainly from Chinese classic literary works such as Records of the Historian, Water Margin, Legend of Heroes in the Tang Dynasty, Romance of the Three Kingdoms and Japanese classic The Story of Genji, etc. Also on display were works of the Japa-nese scenery such as Japan's Four Seasons, Snow, Moon and Flowers, etc. and The Red Fujiyama, a work acknowledged by the United Nations.

  15. 75 FR 3862 - Photography in Public Exhibit Space

    Science.gov (United States)

    2010-01-25

    ...NARA has revised its regulations on the use of film, photographic and videotape equipment inside the National Archives Building in Washington, DC. Filming, photographing, and videotaping for personal use will be prohibited in exhibits of the National Archives Experience (NAE) in Washington, DC, including the Declaration of Independence, the Constitution and the Bill of Rights (known as the Charters of Freedom) in the Rotunda of the National Archives Building. In 2003 NARA installed exhibit cases for displaying the Charters and other NAE documents to provide better clarity for viewing the exhibits. NARA seeks to ensure the necessary protection for the documents from the cumulative effects of photographic flash and to enhance the overall visitor experience.

  16. A Managerial Approach To A Controversial Exhibition: The Human Body

    Directory of Open Access Journals (Sweden)

    Viorica Aura Păuş

    2013-12-01

    Full Text Available This paper will analyse the reception of the Human Body exhibition of 2013 in Romania, from a managerial point of view. The research is based on the exhibition visitors’ book, to which a content analysis was applied. The main aim of the paper is to investigate how the ‘Grigore Antipa’ Museum (Romania constructed the cultural context in which the scientific arguments prevailed over the religious ones, turning the exhibition of plastinated human bodies into an accepted public event, with a strong emphasis on education and science (medicine. At the same time, ethical concerns and religious criticism were downplayed by maintaining the focus on the ‘education for health’ frame.

  17. TrayGen: Arranging objects for exhibition and packaging

    KAUST Repository

    Yang, Yongliang

    2013-10-01

    We present a framework, called TrayGen, to generate tray designs for the exhibition and packaging of a collection of objects. Based on principles from shape perception and visual merchandising, we abstract a number of design guidelines on how to organize the objects on the tray for the exhibition of their individual features and mutual relationships. Our framework realizes these guidelines by analyzing geometric shapes of the objects and optimizing their arrangement. We demonstrate that the resultant tray designs not only save space, but also highlight the characteristic of each object and the inter-relations between objects. © 2013 The Eurographics Association and John Wiley & Sons Ltd.

  18. Implementing Mobile Virtual Exhibition to Increase Cultural Heritage Visibility

    Directory of Open Access Journals (Sweden)

    Cristian CIUREA

    2014-01-01

    Full Text Available The paper presents an implementation of iOS mobile application designed as a virtual exhibition, which aims to increase the accessibility and visibility of physical objects that composite cultural heritage elements. Mobile technologies have seen a huge evolution in the last years and people are very attracted by smartphones, tablets and other mobile devices. Taking into consideration the impact of mobile technologies in all the activity fields, an important research objective is to analyze the influence of mobile applications designed as virtual exhibitions on cultural heritage promotion and on people cultural needs.

  19. American Telemedicine Association: First China (Tianjin International Telemedicine Technology Exhibition

    Directory of Open Access Journals (Sweden)

    Jordana Bernard

    2014-09-01

    Full Text Available With the support of Tianjin Municipal People’s Government and the People’s Government of Binhai New Area, the “First China (Tianjin International Telemedicine Technology Exhibition” hosted by the American Telemedicine Association (ATA, will be held October 28- 30, 2014 at the Tianjin Binhai International Convention and Exhibition Center. The three day event will feature keynote sessions, concurrent discussion forums, exhibits (e.g., telemedicine, information technology, mHealth, a venture summit, meet-and-greet sessions for international and domestic companies for potential business collaboration, and policy discussions on China healthcare. For registration information: http://www.atacn.org/en/

  20. Performative exhibition and its different modes of experience

    DEFF Research Database (Denmark)

    Schwarzbart, Judith

    The avant-gardes of the late 60s and 70s challenged many conventions associated with the (classical) modernist art exhibition such as: a static timeless display of autonomous objects, the spectator as a disembodied visual receptor, and the personal experience emphasizing the individual and never...... the social. The avant-gardes have not, however, let to the disappearance of a modernist exhibition format but to a proliferation of formats including some that are more performative in its character, which means: more dynamic, developing over time, with a higher degree of bodily and discursive exchange, and...

  1. One exhibition, many goals. Combining scientific research and risk communication

    Science.gov (United States)

    Charrière, Marie; Bogaard, Thom; Junier, Sandra; Malet, Jean-Philippe; Mostert, Erik

    2015-04-01

    How effective is visual communication to increase awareness of natural hazards and risks? To answer this research question, we developed a research design that was at the same time an experimental setting and an actual communication effort. Throughout the full length of the 2-years project held in the Ubaye valley (southeastern France), we collaborated with local and regional stakeholders (politicians and technicians). During a consultation phase, the communication context was determined, the audience of the project was defined and finally the testing activity-communication effort was determined. We were offered the opportunity to design an exhibition for the local public library. In a consultation phase that corresponded to the design of the exhibition, the stakeholders contributed to its content as well as helping with the funding of the exhibition. Finally, during the experimentation phase, the stakeholders participated in advertising the activity, gathering of participants and designing the scientific survey. In order to assess the effects of the exhibition on risk awareness, several groups of children, teenagers and adults were submitted to a research design, consisting of 1) a pre-test, 2) the visit of the exhibition and 3) a post-test similar to the pre-test. In addition, the children answered a second post-test 3 months after the visit. Close ended questions addressed the awareness indicators mentioned in the literature, i.e. worry level, previous experiences with natural hazards events, exposure to awareness raising, ability to mitigate/respond/prepare, attitude to risk, and demographics. In addition, the post-test included several satisfaction questions concerning the visual tools displayed in the exhibition. A statistical analysis of the changes between the pre- and post- tests (paired t-test, Wilcoxon signed-rank test and bootstrapping) allowed to verify whether the exhibition had an impact on risk awareness or not. In order to deduce which variable

  2. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

    Directory of Open Access Journals (Sweden)

    Francesca Oltolina

    Full Text Available A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM. We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.

  3. The "Gravity-Powered Calculator," a Galilean Exhibit

    Science.gov (United States)

    Cerreta, Pietro

    2014-01-01

    The Gravity-Powered Calculator is an exhibit of the Exploratorium in San Francisco. It is presented by its American creators as an amazing device that extracts the square roots of numbers, using only the force of gravity. But if you analyze his concept construction one can not help but recall the research of Galileo on falling bodies, the inclined…

  4. Exhibition contribution: AN EXPERIMENT WITH THE VOICE TO DESIGN CERAMICS

    DEFF Research Database (Denmark)

    2013-01-01

    The artefacts show how experiential knowledge that the craftsmen gains in a direct physical interaction with a responding material can be transformed and utilized in the use of digital technologies. The exhibition presents an experiment with a 3D interactive and dynamic system to create ceramics ...

  5. Highlights of the inauguration ceremony for the new permanent exhibition

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    The new “Universe of Particles" permanent exhibition in the Globe was unveiled this week to its first visitors. On Monday, 28 June, in the presence of representatives of the local authorities, CERN Director-General Rolf Heuer cut the ribbon; on Tuesday, 29 and Wednesday 30 June the Globe's doors remained open for visits by the CERN personnel.   Cutting the ribbon at the inauguration of the Globe's new permanent exhibition At the conclusion of the inauguration ceremony, the Head of the Education Group, Rolf Landua, expressed his satisfaction: “It's wonderful. We are very happy that it has all turned out so well. Now we look forward to lots of visitors.” The exhibition represents a major addition to the tourist destinations in the region and an important tool for the public awareness of science, which could also be useful for schools. “The purpose of the exhibition is to inspire visitors, to arouse their curiosity about science and to motivate them t...

  6. A simple coordination complex exhibiting colour change on slight ...

    Indian Academy of Sciences (India)

    Administrator

    structure analysis. In 1979, Grenthe and co-worker. reported thermochromism of bis(NN-diethylethane-. 1,2-diamine) copper(II) perchlorate on the basis of ... ture was allowed to cool when white solid KCl sepa- rated out and it was .... A simple coordination complex exhibits colour change on slight structural modification. 733.

  7. Integrating Smart Objects into Self-Guided Exhibitions

    DEFF Research Database (Denmark)

    Krishnasamy, Rameshnath Kala

    2018-01-01

    is to present work-in-progress of implementing two app prototypes: 1) a mixed reality game for smartphones and 2) a digital guide, that uses Bluetooth beacons at a fully automated exhibition in Northern Denmark. Two of key challenges that this research projects revolves around is how to on-board new users...

  8. 7 CFR 28.126 - Loaning of forms and exhibits.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER... Fees and Costs § 28.126 Loaning of forms and exhibits. In the discretion of the Director, limited...

  9. 6th international solid wastes congress and exhibition

    International Nuclear Information System (INIS)

    Ategrus

    1992-01-01

    Proceedings of the sixth International Solid Wastes Congress and exhibition held in Madrid the dates June 14-19, 1992, and organized by ISWA. It sumps up 3 volumes dealing with Environmental Aspects, Administrative Aspects, Waste treatment Technologies, Waste Minimization, Land disposal and Hazardous Wastes

  10. 17 CFR 229.1016 - (Item 1016) Exhibits.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false (Item 1016) Exhibits. 229.1016 Section 229.1016 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION STANDARD INSTRUCTIONS FOR FILING FORMS UNDER SECURITIES ACT OF 1933, SECURITIES EXCHANGE ACT OF 1934 AND ENERGY POLICY AND CONSERVATION ACT OF 1975-REGULATION S-...

  11. Exhibition: Fibre optics, the future is at hand

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    Until 20 June, the Pont de la Machine in Geneva will host an exhibition on fibre optics, sponsored by SIG. CERN, a major user of this technology, was invited to take part with a presentation of some of its scintillating fibre detectors.   The CERN module, designed for the SIG's fibre optics exhibition. Visitors can discover a cosmic ray detector (on the right) and its oscilloscope (on the left), as well as one of the ALFA detector modules (at the back). The Services industriels genevois (SIG), who are in the process of deploying an optical fibre network in Geneva, have decided to showcase this technology with an exhibition entitled “Fibre optique – Le futur à portée de main.” The exhibition, which will be open to the public from 26 April to 20 June, is being held at the Espace ExpoSIG, at the Pont de la Machine in the centre of Geneva. “CERN’s Physics Department was approached by SIG at the start of this year to ...

  12. 27 CFR 4.51 - Exhibiting certificates to Government officials.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exhibiting certificates to Government officials. 4.51 Section 4.51 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Requirements for...

  13. Assessing the User Resistance to Recommender Systems in Exhibition

    Directory of Open Access Journals (Sweden)

    Chulmo Koo

    2017-11-01

    Full Text Available Under the paradigm shift toward smart tourism, the exhibition industry is making efforts to introduce innovative technologies that can provide more diverse and valuable experiences to attendees. However, various new information technologies have failed in a market in practice due to the user’s resistance against it. Since innovative technology, such as booth recommender systems (BRS, is changing, creating uncertainty among consumers, consumer’s resistance to innovative technology can be considered a normal reaction. Therefore, it is important for a company to understand the psychological aspect of the consumer’s resistance and make measures to overcome the resistance. Accordingly, based on the model of Kim and Kankanhalli (2009, by applying the perceived value, the technology acceptance model, and the status quo bias theory, this study focused on the importance of self-efficacy and technical support in the context of using BRS. To do this purpose, a total of 455 survey data that was collected from “Korea franchise exhibition” attendees were used to analyze the proposed model. Structural equation modeling was applied for data analysis. The result shows that perceived value was affected by relative advantage and switching cost, also switching cost reduced the perceived value. However, self-efficacy reduced the switching cost, thereby decreasing the resistance of exhibition attendees. In addition, technical support increased the relative advantage switching cost and the perceived value. Exhibition attendee’s resistance was significantly negatively affected by perceived value, and positively affected by switching cost. The results will provide balanced viewpoints between the relative advantage and switching cost for exhibition marketers, helping to strengthen the competitiveness in terms of sustainable tourism of exhibition.

  14. Poster exhibitions at conferences: are we doing it properly?

    Science.gov (United States)

    Beamish, Andrew J; Ansell, James; Foster, Jessica J; Foster, Kathryn A; Egan, Richard J

    2015-01-01

    Literature exploring the educational value and quality of conference poster presentation is scarce. The aim of this study was to identify and describe the variation in poster exhibitions across a spectrum of conferences attended by trainees. Prospective observational assessment of conference posters was carried out across 7 variables at 4 conferences attended by surgical trainees in 2012. Posters were compared by individual variables and according to overall poster score combining all 7 variables examined. The number of authors listed was also compared. Random samples of consecutively numbered posters were examined at the exhibitions of 4 conferences, which included a UK national medical education conference (Association for the Study of Medical Education), a UK international surgical conference (Association of Surgeons of Great Britain and Ireland), a European oncology conference (European Society of Surgical Oncology), and a North American joint medical and surgical conference (Digestive Diseases Week). Significant variation existed between conferences in posters and their presentation. The proportion of presenters failing to display their posters ranged from 3% to 26% (p posters that were formatted using aims, methods, results, and conclusion sections (81%-93%; p = 0.513) or in the proportion of posters that were identified as difficult to read (24%-28%; p = 0.919). Association for the Study of Medical Education outperformed each of the other exhibitions overall (p Posters with greater than the median of 4 authors performed significantly better across all areas (p Poster exhibitions varied widely, with room for improvement at all 4 conferences. Lessons can be learned by all conferences from each other to improve presenter engagement with and the educational value of poster exhibitions. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  15. Phenotypic Changes Exhibited by E. coli Cultured in Space

    Directory of Open Access Journals (Sweden)

    Luis Zea

    2017-08-01

    Full Text Available Bacteria will accompany humans in our exploration of space, making it of importance to study their adaptation to the microgravity environment. To investigate potential phenotypic changes for bacteria grown in space, Escherichia coli was cultured onboard the International Space Station with matched controls on Earth. Samples were challenged with different concentrations of gentamicin sulfate to study the role of drug concentration on the dependent variables in the space environment. Analyses included assessments of final cell count, cell size, cell envelope thickness, cell ultrastructure, and culture morphology. A 13-fold increase in final cell count was observed in space with respect to the ground controls and the space flight cells were able to grow in the presence of normally inhibitory levels of gentamicin sulfate. Contrast light microscopy and focused ion beam/scanning electron microscopy showed that, on average, cells in space were 37% of the volume of their matched controls, which may alter the rate of molecule–cell interactions in a diffusion-limited mass transport regime as is expected to occur in microgravity. TEM imagery showed an increase in cell envelope thickness of between 25 and 43% in space with respect to the Earth control group. Outer membrane vesicles were observed on the spaceflight samples, but not on the Earth cultures. While E. coli suspension cultures on Earth were homogenously distributed throughout the liquid medium, in space they tended to form a cluster, leaving the surrounding medium visibly clear of cells. This cell aggregation behavior may be associated with enhanced biofilm formation observed in other spaceflight experiments.

  16. Paracoccidioides brasilienses isolates obtained from patients with acute and chronic disease exhibit morphological differences after animal passage

    Directory of Open Access Journals (Sweden)

    SVIDZINSKI Terezinha Inez Estivalet

    1999-01-01

    Full Text Available The basis for virulence in Paracoccidioides brasiliensis is not completely understood. There is a consensus that the sequencial in vitro subcultivation of P. brasiliensis leads to loss of its pathogenicity, which can be reverted by reisolation from animal passage. Attention to morphological and biochemical properties that are regained or demonstrated after animal passage may provide new insights into factors related to the pathogenicity and virulence of P. brasiliensis. We evaluated morphological characters: the percentage of budding cells, number of buds by cell and the diameter of 100 mother cells of yeast-like cells of 30 P. brasiliensis isolates, before and after animal passage. The isolates were obtained from patients with different clinical forms of paracoccidioidomycosis (PCM: acute form (group A, n=15 and chronic form (group C, n=15. The measurement of the yeast cell sizes was carried out with the aid of an Olympus CBB microscope coupled with a micrometer disc. We measured the major transverse and longitudinal axes of 100 viable cells of each preparation. The percentage of budding cells as also the number of buds by cell was not influenced by animal passage, regardless of the source of the strain (acute or chronic groups. The size values of P. brasiliensis isolates from groups A and C, measured before the animal passage exhibited the same behavior. After animal passage, there was a statistically significant difference between the cell sizes of P. brasiliensis isolates recovered from testicles inoculated with strains from groups A and C. The maximum diameter of mother cells from group A isolates exhibited a size of 42.1mm in contrast with 32.9mm exhibited by mother cells from group C (p<0.05. The diameter of 1500 mother cells from group A isolates exhibited a medium size of 16.0mm (SD ± 4.0, a value significantly higher than the 14.1mm (SD = ± 3.3 exhibited by 1500 mother cells from group C isolates (p<0.05. Our results reinforce the

  17. 'Exhibitions and experiments', in celebration of nobel prize in physics

    International Nuclear Information System (INIS)

    Hayashi, Masahito; Nakanishi, Akira; Nakano, Masahiro

    2010-01-01

    The Nobel Prize in Physics for 2008 was awarded to Professors Yoichiro Nambu, Makoto Kobayashi and Toshihide Maskawa. At this opportunity, we held an exhibition to introduce the achievements of the laureates for 10 days at the Omiya campus in May 2009. With the explanations of elementary particle physics, we prepared several experimental instruments with which visitors could play and learn the spontaneous symmetry breaking, cosmic rays, a circle path of an electron in a magnetic field and so on. Our main purpose of the exhibition was, however, not just to explain the contents of the Nobel Prize in Physics, but also to attract students' interests to physics. More than 800 individual students attended during the period, and the survey of questionnaires shows positive contributions to raise the students' awareness of the excitement of physics. (author)

  18. Uranium mining wastes, garden exhibition and health risks

    International Nuclear Information System (INIS)

    Schmidt, Gerhard; Schmidt, Peter; Hinz, Wilko

    2007-01-01

    Available in abstract form only. Full text of publication follows: For more than 40 years the Soviet-German stockholding company SDAG WISMUT mined and milled Uranium in the East of Germany and became up to 1990 the world's third largest Uranium producer. After reunification of Germany, the new found state own company Wismut GmbH was faced with the task of decommissioning and rehabilitation of the mining and milling sites. One of the largest mining areas in the world, that had to be cleaned up, was located close to the municipality of Ronneburg near the City of Gera in Thuringia. After closing the operations of the Ronneburg underground mine and at the 160 m deep open pit mine with a free volume of 84 Mio.m 3 , the open pit and 7 large piles of mine waste, together 112 Mio.m 3 of material, had to be cleaned up. As a result of an optimisation procedure it was chosen to relocate the waste rock piles back into the open pit. After taking this decision and approval of the plan the disposal operation was started. Even though the transport task was done by large trucks, this took 16 years. The work will be finished in 2007, a cover consisting of 40 cm of uncontaminated material will be placed on top of the material, and the re-vegetation of the former open pit area will be established. When in 2002 the City of Gera applied to host the largest garden exhibition in Germany, Bundesgartenschau (BUGA), in 2007, Wismut GmbH supported this plan by offering parts of the territory of the former mining site as an exhibition ground. Finally, it was decided by the BUGA organizers to arrange its 2007 exhibition on grounds in Gera and in the valley adjacent to the former open pit mine, with parts of the remediated area within the fence of the exhibition. (authors)

  19. Environmental enrichment for a mixed-species nocturnal mammal exhibit.

    Science.gov (United States)

    Clark, Fay E; Melfi, Vicky A

    2012-01-01

    Environmental enrichment (EE) is an integral aspect of modern zoo animal management but, empirical evaluation of it is biased toward species housed in single-species groups. Nocturnal houses, where several nocturnal species are housed together, are particularly overlooked. This study investigated whether three species (nine-banded armadillos, Dasypus novemcinctus; Senegal bush babies, Galago senegalensis; two-toed sloths, Choloepus didactylus) in the nocturnal house at Paignton Zoo Environmental Park, UK could be enriched using food-based and sensory EE. Subjects were an adult male and female of each species. EE was deemed effective if it promoted target species-typical behaviors, behavioral diversity, and increased use of enriched exhibit zones. Results from generalized linear mixed models demonstrated that food-based EE elicited the most positive behavioral effects across species. One set of food-based EEs (Kong®, termite mound and hanging food) presented together was associated with a significant increase in species-typical behaviors, increased behavioral diversity, and increased use of enriched exhibit zones in armadillos and bush babies. Although one type of sensory EE (scented pine cones) increased overall exhibit use in all species, the other (rainforest sounds) was linked to a significant decrease in species-typical behavior in bush babies and sloths. There were no intra or interspecies conflicts over EE, and commensalism occurred between armadillos and bush babies. Our data demonstrate that simple food-based and sensory EE can promote positive behavioral changes in a mixed-species nocturnal mammal exhibit. We suggest that both food and sensory EE presented concurrently will maximize opportunities for naturalistic activity in all species. © 2011 Wiley Periodicals, Inc.

  20. Inuit Perspectives on Arctic Environmental Change': A Traveling Exhibition

    Science.gov (United States)

    Sheffield, E. M.; Hakala, J. S.; Gearheard, S.

    2006-12-01

    The Inuit of Nunavut, Canada, have an intimate relationship with their surroundings. As a culture that relies on knowledge of sea ice, snow, and weather conditions for success in hunting, fishing, and healthy wellbeing, Inuit have observed and studied environmental patterns for generations. An ongoing study into their traditional knowledge and their observations of environmental change is being conducted by researcher Dr. Shari Gearheard, who has worked with Inuit communities in Nunavut for over a decade. The results of the research have been published in scientific journals, and to communicate the results to a broader audience, Dr. Gearheard designed an interactive CD-ROM displaying photographs, maps, and interview videos of Inuit Elders' perspectives on the changes they have witnessed. Receiving immediate popularity since its release in 2004, copies of `When the Weather is Uggianaqtuq: Inuit Observations of Environmental Change' have been distributed worldwide, to indigenous peoples, social science and climate change researchers, teachers, students, and the general public. To further disseminate the information contained on the CD-ROM, the National Snow and Ice Data Center and the Museum of Natural History, both of the University of Colorado, are partnering to create an exhibition which will open at the Museum during the International Polar Year in April 2008. The exhibit, tentatively titled `Inuit Perspectives on Arctic Environmental Change,' will feature photographs, graphics, and text in both English and Inuktitut describing environmental change in the North. The goals are to make the information and interpretation contained on the CD-ROM available and more accessible to a broad audience and to raise awareness about Arctic climate change and the important contribution of Inuit knowledge. Following exhibition at the Museum, the exhibit will travel throughout the United States, Alaska, and Nunavut, through a network of museums, schools, libraries, tribal

  1. Assessing the User Resistance to Recommender Systems in Exhibition

    OpenAIRE

    Chulmo Koo; Namho Chung; Juyeon Ham

    2017-01-01

    Under the paradigm shift toward smart tourism, the exhibition industry is making efforts to introduce innovative technologies that can provide more diverse and valuable experiences to attendees. However, various new information technologies have failed in a market in practice due to the user’s resistance against it. Since innovative technology, such as booth recommender systems (BRS), is changing, creating uncertainty among consumers, consumer’s resistance to innovative technology can be cons...

  2. Characterization of Catalase from Psychrotolerant Psychrobacter piscatorii T-3 Exhibiting High Catalase Activity

    Science.gov (United States)

    Kimoto, Hideyuki; Yoshimune, Kazuaki; Matsuyma, Hidetoshi; Yumoto, Isao

    2012-01-01

    A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii), that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H2O2 as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein−1) that was higher than that of Micrococcus luteus used for industrial catalase production. Catalase was approximately 10% of the total proteins in the cell extract of the strain. The catalase (PktA) was purified homogeneously by only two purification steps, anion exchange and hydrophobic chromatographies. The purified catalase exhibited higher catalytic efficiency and higher sensitivity of activity at high temperatures than M. luteus catalase. The deduced amino acid sequence showed the highest homology with catalase of Psycrobacter cryohalolentis, a psychrotolelant bacterium obtained from Siberian permafrost. These findings suggest that the characteristics of the PktA molecule reflected the taxonomic relationship of the isolate as well as the environmental conditions (low temperatures and high concentrations of H2O2) under which the bacterium survives. Strain T-3 efficiently produces a catalase (PktA) at a higher rate than Exiguobacterium oxidotolerans, which produces a very strong activity of catalase (EktA) at a moderate rate, in order to adapt to high concentration of H2O2. PMID:22408420

  3. Creation of Cardiac Tissue Exhibiting Mechanical Integration of Spheroids Using 3D Bioprinting.

    Science.gov (United States)

    Ong, Chin Siang; Fukunishi, Takuma; Nashed, Andrew; Blazeski, Adriana; Zhang, Huaitao; Hardy, Samantha; DiSilvestre, Deborah; Vricella, Luca; Conte, John; Tung, Leslie; Tomaselli, Gordon; Hibino, Narutoshi

    2017-07-02

    This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted and mixed at desired cell ratios. They are co-cultured in individual wells in ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These spheroids are then picked up by a nozzle using vacuum suction and assembled on a needle array using a 3D bioprinter. The spheroids are then allowed to fuse on the needle array. Three days after 3D bioprinting, the spheroids are removed as an intact patch, which is already spontaneously beating. 3D bioprinted cardiac patches exhibit mechanical integration of component spheroids and are highly promising in cardiac tissue regeneration and as 3D models of heart disease.

  4. System for automatic detection of lung nodules exhibiting growth

    Science.gov (United States)

    Novak, Carol L.; Shen, Hong; Odry, Benjamin L.; Ko, Jane P.; Naidich, David P.

    2004-05-01

    Lung nodules that exhibit growth over time are considered highly suspicious for malignancy. We present a completely automated system for detection of growing lung nodules, using initial and follow-up multi-slice CT studies. The system begins with automatic detection of lung nodules in the later CT study, generating a preliminary list of candidate nodules. Next an automatic system for registering locations in two studies matches each candidate in the later study to its corresponding position in the earlier study. Then a method for automatic segmentation of lung nodules is applied to each candidate and its matching location, and the computed volumes are compared. The output of the system is a list of nodule candidates that are new or have exhibited volumetric growth since the previous scan. In a preliminary test of 10 patients examined by two radiologists, the automatic system identified 18 candidates as growing nodules. 7 (39%) of these corresponded to validated nodules or other focal abnormalities that exhibited growth. 4 of the 7 true detections had not been identified by either of the radiologists during their initial examinations of the studies. This technique represents a powerful method of surveillance that may reduce the probability of missing subtle or early malignant disease.

  5. “Draw me a physicist” exhibition opens

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    From 12 to 23 June, the Globe of Science and Innovation will be hosting the “Draw me a physicist” exhibition: over 160 drawings and definitions that illustrate how children see the world of research.   In a child’s imagination, scientists are colourful, slightly eccentric figures with unusual powers. This is what emerges from the exhibition on the second floor of the Globe of Science and Innovation, opening on 12 June. “Draw me a physicist” brings together 160 drawings and definitions by children about the profession of research scientist. The exhibition is the result of a six-month project by CERN and 20 primary school classes from the Pays de Gex and the communes of Meyrin, Satigny and Vernier. Some 400 schoolchildren aged 9 to 11 were asked in class to make drawings and come up with definitions of a physicist. Subsequently they came to CERN, visited one of the Laboratory’s sites, and met and interviewed some physicists. They used t...

  6. Exhibition: Life and Achievements of Maria Sklodowska-Curie

    CERN Multimedia

    CERN Bulletin

    2011-01-01

    The exhibition "Life and Achievements of Maria Sklodowska-Curie” will be held at CERN (Pas Perdus Corridor, 1st floor, building 61) from the 8 to 24 March.   It is organised under the auspices of the Ambassador R. Henczel, Permanent Representative of the Republic of Poland to the UN Office at Geneva to celebrate the 100th anniversary of the Nobel Prize in Chemistry given to Maria Sklodowska-Curie. The exhibition is also one of the events celebrating the 20th anniversary of Poland joining CERN as a Member State. Maria Sklodowska-Curie, Nobel Prize winner both in physics and chemistry, is one of the greatest scientists of Polish origin. The exhibition, consisting of 20 posters, presents her not only as a brilliant scientist, but also an exceptional woman of great heart, character and organizational talents, sensitive to contemporary problems. The authors are Mrs M. Sobieszczak-Marciniak, the director of the Maria Sklodowska-Curie Museum in Warsaw and Mrs H. Krajewska, the direct...

  7. Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis

    International Nuclear Information System (INIS)

    Candelario, Jose; Borrego, Stacey; Reddy, Sita; Comai, Lucio

    2011-01-01

    Lamin A is a component of the nuclear lamina that plays a major role in the structural organization and function of the nucleus. Lamin A is synthesized as a prelamin A precursor which undergoes four sequential post-translational modifications to generate mature lamin A. Significantly, a large number of point mutations in the LMNA gene cause a range of distinct human disorders collectively known as laminopathies. The mechanisms by which mutations in lamin A affect cell function and cause disease are unclear. Interestingly, recent studies have suggested that alterations in the normal lamin A pathway can contribute to cellular dysfunction. Specifically, we and others have shown, at the cellular level, that in the absence of mutations or altered splicing events, increased expression of wild-type prelamin A results in a growth defective phenotype that resembles that of cells expressing the mutant form of lamin A, termed progerin, associated with Hutchinson-Gilford Progeria syndrome (HGPS). Remarkably, the phenotypes of cells expressing elevated levels of wild-type prelamin A can be reversed by either treatment with farnesyltransferase inhibitors or overexpression of ZMPSTE24, a critical prelamin A processing enzyme, suggesting that minor increases in the steady-state levels of one or more prelamin A intermediates is sufficient to induce cellular toxicity. Here, to investigate the molecular basis of the lamin A pathway toxicity, we characterized the phenotypic changes occurring in cells expressing distinct prelamin A variants mimicking specific prelamin A processing intermediates. This analysis demonstrates that distinct prelamin A variants differentially affect cell growth, nuclear membrane morphology, nuclear distribution of lamin A and the fundamental process of transcription. Expression of prelamin A variants that are constitutively farnesylated induced the formation of lamin A aggregates and dramatic changes in nuclear membrane morphology, which led to reduced

  8. NIC (Nuclear Industry in China) exhibition. Press file

    International Nuclear Information System (INIS)

    1998-01-01

    Framatome participated to the NIC exhibition which took place in Beijing (China) on March 1998. This press dossier was distributed to visitors. It presents in a first part the activities of the Framatome group in people's republic of China (new constructions (Daya Bay, Ling Ao project), technological cooperation and contracts in the nuclear domain, technology transfers in the domain of nuclear fuels, activities and daughter companies in the domain of industrial equipments, Framatome Connectors International (FCI) daughter company in the domain of connectors engineering). Then, the general activities of Framatome in the nuclear, industrial equipment, and connectors engineering domains are summarized in the next 3 parts. (J.S.)

  9. Inauguration of the Exhibition of the VolMeur collection

    CERN Multimedia

    Le Meur, Jean-Yves

    2018-01-01

    Several hundred slide photos of CERN, created in the 1980s for the Large Electron-Positron Collider (LEP) have not survived the ravages of time. They have deteriorated so badly that it is often impossible to tell what they are supposed to show. But, in doing so, they have become abstract canvases, true works of art. A dozen of these amazing images have been revealed in CERN Main Building on the 29th of January 2018 and are exhibited up to 9th of February.

  10. Exchange rate policy when the labour market exhibits hysteresis

    OpenAIRE

    Barry, Frank

    1994-01-01

    This paper analyzes the effects of exchange rate shocks in a small open economy whose labor market exhibits hysteresis. The model is used to highlight deficiencies in the response of the Irish authorities to exchange rate crisis of 1992/93. A secondary purpose of the paper, though, is to induce those who accept that the Irish labour market is characterised by hysteresis but who reject the argument made here that a more aggressive devaluation should have been pursued, to spell out the labour-m...

  11. Oxytocin Neurons Exhibit Extensive Functional Plasticity Due To Offspring Age in Mothers and Fathers.

    Science.gov (United States)

    Kelly, Aubrey M; Hiura, Lisa C; Saunders, Alexander G; Ophir, Alexander G

    2017-09-01

    The needs of offspring change as they develop. Thus, parents should concomitantly change their investment based on the age-related needs of the offspring as they mature. Due to the high costs of parental care, it is optimal for parents to exhibit a shift from intense caregiving of young offspring to promoting independence in older offspring. Yet, the neural mechanisms that underlie shifts in parental behavior are poorly understood, and little is known about how the parental brain responds to offspring of different ages. To elucidate mechanisms that relate to shifts in parental behavior as offspring develop, we examined behavioral and neural responses of male and female prairie voles (Microtus ochrogaster), a biparental rodent, to interactions with offspring at different stages of development (ranging from neonatal to weaning age). Importantly, in biparental species, males and females may adjust their behavior differentially as offspring develop. Because the nonapeptides, vasopressin (VP) and oxytocin (OT), are well known for modulating aspects of parental care, we focused on functional activity of distinct VP and OT cell groups within the maternal and paternal brain in response to separation from, reunion (after a brief period of separation) with, or no separation from offspring of different ages. We found several differences in the neural responses of individual VP and OT cell groups that varied based on the age of pups and sex of the parent. Hypothalamic VP neurons exhibit similar functional responses in both mothers and fathers. However, hypothalamic and amygdalar OT neurons exhibit differential functional responses to being separated from pups based on the sex of the parent. Our results also reveal that the developmental stage of offspring significantly impacts neural function within OT, but not VP, cell groups of both mothers and fathers. These findings provide insight into the functional plastic capabilities of the nonapeptide system, specifically in relation

  12. Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres.

    Science.gov (United States)

    Hanft, Laurin M; McDonald, Kerry S

    2010-08-01

    According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length

  13. Chimpanzees and bonobos exhibit emotional responses to decision outcomes.

    Directory of Open Access Journals (Sweden)

    Alexandra G Rosati

    Full Text Available The interface between cognition, emotion, and motivation is thought to be of central importance in understanding complex cognitive functions such as decision-making and executive control in humans. Although nonhuman apes have complex repertoires of emotional expression, little is known about the role of affective processes in ape decision-making. To illuminate the evolutionary origins of human-like patterns of choice, we investigated decision-making in humans' closest phylogenetic relatives, chimpanzees (Pan troglodytes and bonobos (Pan paniscus. In two studies, we examined these species' temporal and risk preferences, and assessed whether apes show emotional and motivational responses in decision-making contexts. We find that (1 chimpanzees are more patient and more risk-prone than are bonobos, (2 both species exhibit affective and motivational responses following the outcomes of their decisions, and (3 some emotional and motivational responses map onto species-level and individual-differences in decision-making. These results indicate that apes do exhibit emotional responses to decision-making, like humans. We explore the hypothesis that affective and motivational biases may underlie the psychological mechanisms supporting value-based preferences in these species.

  14. Exhibition | CERN Micro Club | 1-30 September

    CERN Multimedia

    2014-01-01

    The CERN Micro Club (CMC) is organising an exhibition looking back on the origins of the personal computer, also known as the micro-computer, to mark the 60th anniversary of CERN and the club’s own 30th anniversary.   CERN, Building 567, R-021 and R-029 01.09.2014 - 30.09.2014 from 4.00 to 6.00 p.m. The exhibition will be held in the club’s premises (Building 567, rooms R-0121 and R-029) and will be open Mondays to Thursdays from 1 to 30 September 2014. Come and admire, touch and use makes and models that disappeared from the market many years ago, such as Atari, Commodore, Olivetti, DEC, IBM and Apple II and III, all in good working order and installed with applications and games from the period. Club members will be on hand to tell you about these early computers, which had memories of just of a few kilobytes, whereas those of modern computers can reach several gigabytes or even terabytes.

  15. Industrial Exhibition “11th Germany at CERN“

    CERN Multimedia

    FP Department

    2010-01-01

    Administration Building (Bldg. 60/61) Tuesday 25 January: 11a.m. - 5.30 p.m. Wednesday 26 January: 9 a.m. - 5 p.m. The Federal Ministry of Education and Research (BMBF), together with CERN, will hold the Industrial Exhibition “11th Germany at CERN”. Some 30 German companies will present their latest products/technologies related to the field of particle physics and their services to the scientists and buyers of CERN, establish contacts and find out about future purchasing opportunities. On 25 January, Dr. B. Vierkorn-Rudolph of the Federal Ministry of Education and Research and CERN Director-General, Prof. R. D. Heuer, will open the exhibition, followed by a tour of the stands. The main subjects are: electrical engineering, electronics, informatics, mechanical engineering, vacuum & low temperature technologies, instrumentation and safety. CERN staff wishing to obtain information concerning the programme, the exhibitors and their profiles or to get in contact with exhibitors are r...

  16. Industrial Exhibition “11th Germany at CERN“

    CERN Multimedia

    FP Department

    2011-01-01

    Administration Building (Bldg. 60/61) Tuesday 25 January: 11a.m. - 5.30 p.m. Wednesday 26 January: 9 a.m. - 5 p.m. The Federal Ministry of Education and Research (BMBF), together with CERN, will hold the Industrial Exhibition “11th Germany at CERN”. Some 30 German companies will present their latest products/technologies related to the field of particle physics and their services to the scientists and buyers of CERN, establish contacts and find out about future purchasing opportunities. On 25 January, Dr. B. Vierkorn-Rudolph of the Federal Ministry of Education and Research and CERN Director-General, Prof. R. D. Heuer, will open the exhibition, followed by a tour of the stands. The main subjects are: electrical engineering, electronics, informatics, mechanical engineering, vacuum & low temperature technologies, instrumentation and safety. CERN staff wishing to obtain information concerning the programme, the exhibitors and their profiles or to get in contact with exhibitors are ...

  17. A more modern look for the Council Chamber exhibition

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    When the Council Chamber was renovated, the old photographs displayed on the walls were taken down... they've now been replaced by new panels printed on Plexiglas. The theme of the exhibition is still the history of CERN, but it now features the very latest from graphic design. Fabienne Marcastel, who designed it, tells us more. Two of the new panels recently installed in the Council Chamber. The presentation is simple and elegant. The content is based essentially on the accelerators and the aim of the graphic design is not to attract the public's attention to the panels but rather to provide a pleasant décor for the Chamber's users. "The old photographs stopped at the LEP. The new panels show the history of CERN but also what the Laboratory is like today. Visually, the plan is the starting point, the key to understanding how CERN has changed. It shows how CERN occupies the land it is built on," explains Fabienne Marcastel, the exhibition's graphic designer. The four panels a...

  18. Endophytic Fungi Isolated from Coleus amboinicus Lour Exhibited Antimicrobial Activity.

    Science.gov (United States)

    Astuti, Puji; Sudarsono, Sudarsono; Nisak, Khoirun; Nugroho, Giri Wisnu

    2014-12-01

    Coleus amboinicus is a medicinal plant traditionally used to treat various diseases such as throat infection, cough and fever, diarrhea, nasal congestion and digestive problems. The plant was explored for endophytic fungi producing antimicrobial agents. Screening for endophytic fungi producing antimicrobial agents was conducted using agar plug method and antimicrobial activity of promising ethyl acetate extracts was determined by disc diffusion assay. Thin layer chromatography (TLC) - bioautography was performed to localize the bioactive components within the extract. TLC visualization detection reagents were used to preliminary analyze phytochemical groups of the bioactive compounds. Three endophytic fungi were obtained, two of them showed promising potential. Agar diffusion method showed that endophytic fungi CAL-2 exhibited antimicrobial activity against P. aeruginosa, B. subtilis, S. aureus and S. thypi, whilst CAS-1 inhibited the growth of B. subtilis. TLC bioautography of ethyl acetate extract of CAL-2 revealed at least three bands exhibited antimicrobial activity and at least two bands showed inhibition of B. subtilis growth. Preliminary analysis of the crude extracts suggests that bioactive compounds within CAL-2 extract are terpenoids, phenolics and phenyl propanoid compounds whilst the antimicrobial agents within CAS-1 extract are terpenoids, propylpropanoids, alkaloids or heterocyclic nitrogen compounds. These data suggest the potential of endophytic fungi of C. amboinicus as source for antimicrobial agents.

  19. Endophytic Fungi Isolated from Coleus amboinicus Lour Exhibited Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Puji Astuti

    2014-12-01

    Full Text Available Purpose: Coleus amboinicus is a medicinal plant traditionally used to treat various diseases such as throat infection, cough and fever, diarrhea, nasal congestion and digestive problems. The plant was explored for endophytic fungi producing antimicrobial agents. Methods: Screening for endophytic fungi producing antimicrobial agents was conducted using agar plug method and antimicrobial activity of promising ethyl acetate extracts was determined by disc diffusion assay. Thin layer chromatography (TLC - bioautography was performed to localize the bioactive components within the extract. TLC visualization detection reagents were used to preliminary analyze phytochemical groups of the bioactive compounds. Results: Three endophytic fungi were obtained, two of them showed promising potential. Agar diffusion method showed that endophytic fungi CAL-2 exhibited antimicrobial activity against P. aeruginosa, B. subtilis, S. aureus and S. thypi, whilst CAS-1 inhibited the growth of B. subtilis. TLC bioautography of ethyl acetate extract of CAL-2 revealed at least three bands exhibited antimicrobial activity and at least two bands showed inhibition of B. subtilis growth. Preliminary analysis of the crude extracts suggests that bioactive compounds within CAL-2 extract are terpenoids, phenolics and phenyl propanoid compounds whilst the antimicrobial agents within CAS-1 extract are terpenoids, propylpropanoids, alkaloids or heterocyclic nitrogen compounds. Conclusion: These data suggest the potential of endophytic fungi of C. amboinicus as source for antimicrobial agents.

  20. Peer review and competition in the Art Exhibition Game.

    Science.gov (United States)

    Balietti, Stefano; Goldstone, Robert L; Helbing, Dirk

    2016-07-26

    To investigate the effect of competitive incentives under peer review, we designed a novel experimental setup called the Art Exhibition Game. We present experimental evidence of how competition introduces both positive and negative effects when creative artifacts are evaluated and selected by peer review. Competition proved to be a double-edged sword: on the one hand, it fosters innovation and product diversity, but on the other hand, it also leads to more unfair reviews and to a lower level of agreement between reviewers. Moreover, an external validation of the quality of peer reviews during the laboratory experiment, based on 23,627 online evaluations on Amazon Mechanical Turk, shows that competition does not significantly increase the level of creativity. Furthermore, the higher rejection rate under competitive conditions does not improve the average quality of published contributions, because more high-quality work is also rejected. Overall, our results could explain why many ground-breaking studies in science end up in lower-tier journals. Differences and similarities between the Art Exhibition Game and scholarly peer review are discussed and the implications for the design of new incentive systems for scientists are explained.

  1. Smokers exhibit biased neural processing of smoking and affective images.

    Science.gov (United States)

    Oliver, Jason A; Jentink, Kade G; Drobes, David J; Evans, David E

    2016-08-01

    There has been growing interest in the role that implicit processing of drug cues can play in motivating drug use behavior. However, the extent to which drug cue processing biases relate to the processing biases exhibited to other types of evocative stimuli is largely unknown. The goal of the present study was to determine how the implicit cognitive processing of smoking cues relates to the processing of affective cues using a novel paradigm. Smokers (n = 50) and nonsmokers (n = 38) completed a picture-viewing task, in which participants were presented with a series of smoking, pleasant, unpleasant, and neutral images while engaging in a distractor task designed to direct controlled resources away from conscious processing of image content. Electroencephalogram recordings were obtained throughout the task for extraction of event-related potentials (ERPs). Smokers exhibited differential processing of smoking cues across 3 different ERP indices compared with nonsmokers. Comparable effects were found for pleasant cues on 2 of these indices. Late cognitive processing of smoking and pleasant cues was associated with nicotine dependence and cigarette use. Results suggest that cognitive biases may extend across classes of stimuli among smokers. This raises important questions about the fundamental meaning of cognitive biases, and suggests the need to consider generalized cognitive biases in theories of drug use behavior and interventions based on cognitive bias modification. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  2. Chimpanzees and bonobos exhibit divergent spatial memory development.

    Science.gov (United States)

    Rosati, Alexandra G; Hare, Brian

    2012-11-01

    Spatial cognition and memory are critical cognitive skills underlying foraging behaviors for all primates. While the emergence of these skills has been the focus of much research on human children, little is known about ontogenetic patterns shaping spatial cognition in other species. Comparative developmental studies of nonhuman apes can illuminate which aspects of human spatial development are shared with other primates, versus which aspects are unique to our lineage. Here we present three studies examining spatial memory development in our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (P. paniscus). We first compared memory in a naturalistic foraging task where apes had to recall the location of resources hidden in a large outdoor enclosure with a variety of landmarks (Studies 1 and 2). We then compared older apes using a matched memory choice paradigm (Study 3). We found that chimpanzees exhibited more accurate spatial memory than bonobos across contexts, supporting predictions from these species' different feeding ecologies. Furthermore, chimpanzees - but not bonobos - showed developmental improvements in spatial memory, indicating that bonobos exhibit cognitive paedomorphism (delays in developmental timing) in their spatial abilities relative to chimpanzees. Together, these results indicate that the development of spatial memory may differ even between closely related species. Moreover, changes in the spatial domain can emerge during nonhuman ape ontogeny, much like some changes seen in human children. © 2012 Blackwell Publishing Ltd.

  3. Increased Tolerance to Heavy Metals Exhibited by Swarming Bacteria

    Science.gov (United States)

    Anyan, M.; Shrout, J. D.

    2014-12-01

    Pseudomonas aeruginosa is a ubiquitous, Gram-negative bacterium that utilizes several different modes of motility to colonize surfaces, including swarming, which is the coordinated movement of cells over surfaces in groups. Swarming facilitates surface colonization and biofilm development for P. aeruginosa, and it is known that swarming behavior is influenced by changes in nutrient composition and surface moisture. To understand the fate and cycling of heavy metals in the environment, it is important to understand the interaction and toxicity of these metals upon bacteria. While previous studies have shown surface-attached bacterial biofilms to be highly resistant to heavy metal toxicity, little is known about the influence of heavy metals upon surface motile bacteria and developing biofilms. Using a combination of laboratory assays we examined differences in bacterial behavior in response to two metals, Cd and Ni. We find that surface swarming bacteria are able to grow on 4x and 2.5x more Cd and Ni, respectively, than planktonic cells (i.e., test tube cultures). P. aeruginosa was able to swarm in the presence ≤0.051mM Ni and ≤0.045mM Cd. To investigate the bioavailability of metals to bacteria growing under our examined conditions, we separated cell and supernatant fractions of P. aeruginosa cultures, and used ICP-MS techniques to measure Cd and Ni sorption. A greater percentage of Cd than Ni was sorbed by both cells and supernatant (which contains rhamnolipid, a surfactant known to sorb some metals and improve swarming). While we show that cell products such as rhamnolipid bind heavy metals (as expected) and should limit metal bioavailability, our results suggest at least one additional mechanism (as yet undetermined) that promotes cell survival during swarming in the presence of these heavy metals.

  4. Linalool Exhibits Cytotoxic Effects by Activating Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Mei-Yin Chang

    2014-05-01

    Full Text Available According to recent studies, the Plantaginaceae, which are traditional Chinese herbal remedies, have potential for use in viral infection treatment and cancer therapy. Linalool and p-coumaric acid are two of the biologically active compounds that can be isolated from the Plantaginaceae. This study mainly focused on investigating the bioactivity of linalool as well as the bioactivity of p-coumaric acid in terms of their cytotoxic effects on cancer cells. Whether the mechanisms of such effects are generated through apoptosis and immunoregulatory activity were also investigated. By using WST-1 analysis, it was shown that linalool and p-coumaric acid have good inhibitory effects against breast, colorectal and liver cancer cells. The IC50 values of linalool for those cancer cell types were 224 μM, 222 μM, and 290 μM, respectively, and the IC50 values of p-coumaric acid were 693 μM, 215 μM and 87 μM, respectively. Cell cycle analysis also confirmed that linalool and p-coumaric acid can lead to apoptosis. By using flow cytometry, it was determined that treatment with linalool rather than p-coumaric acid significantly increased the sub-G1 phase and that there were more cells concentrated in the G1 phase. Furthermore, by using cytokine array analysis, we found that linalool can stimulate IFN-γ, IL-13, IL-2, IL-21, IL-21R, IL-4, IL-6sR and TNF-α secretion. This demonstrated that in addition to the bidirectional regulation capabilities found in linalool, it also induces Th1 cellular immune response in T-47D cells. These results showed that linalool holds great potential for use in cancer therapy, and we believe that it could provide an alternative way to take action against tumors.

  5. Engagement In Climate Change Awareness Through Art Exhibitions

    Science.gov (United States)

    Burko, D.

    2016-12-01

    Artists such as myself can influence the public discourse on climate change through compelling imagery transcending data and language. I will speak specifically to how I communicate scientific research to diverse populations by making those issues personal, visceral, and actionable.I began integrating scientific visual data into my aesthetic practice ten years ago by first utilizing archival evidence in the form of repeats, geological charts of recessional lines, graphs, symbols and Landsat maps. I continue to develop visual strategies delivering information on an emotional/non-verbal level. In the past 4 years, I have added the most dramatic layer to my creative process: bearing witness. I've been to the three largest ice fields in the world: Greenland, Antarctica and Argentina's Patagonia, observing the unprecedented pace of glacial melt. The emotional significance of actually being there as an artist is immense. Those expeditions impact my practice, leading to exhibitions that open a dialog with an audience not initially interested in science. In the past 5 years my work has appeared in 6 solo and 19 group exhibits all devoted to the environment. I make myself present in universities, museums and galleries to explain what the images are about. I require universities to include a public component: an all-college lecture or panel where the geography/environmental/sociology/geology departments participate with broad student involvement. I believe that such endeavors are worthwhile and can be models for further efforts to educate an unsuspecting audience. Artists can bridge the gap communicating to a public of art appreciators, nonscientists - how easy it is to understand geology and global warming. This social engagement can even inspire and result in attitudinal changes. A viewer's initial emotional response to my large paintings and photographs evolves into comprehension as a dialog about their content is revealed. By sharing my personal story about my

  6. Case study of virtual reality in CNC machine tool exhibition

    Directory of Open Access Journals (Sweden)

    Kao Yung-Chou

    2017-01-01

    Full Text Available Exhibition and demonstration are generally used in the promotion and sale-assistance of manufactured products. However, the transportation cost of the real goods from the vender factory to the exposition venue is generally expensive for huge and heavy commodity. With the advancement of computing, graphics, mobile apps, and mobile hardware the 3D visibility technology is getting more and more popular to be adopted in visual-assisted communication such as amusement games. Virtual reality (VR technology has therefore being paid great attention in emulating expensive small and/or huge and heavy equipment. Virtual reality can be characterized as 3D extension with Immersion, Interaction and Imagination. This paper was then be focused on the study of virtual reality in the assistance of CNC machine tool demonstration and exhibition. A commercial CNC machine tool was used in this study to illustrate the effectiveness and usability of using virtual reality for an exhibition. The adopted CNC machine tool is a large and heavy mill-turn machine with the width up to eleven meters and weighted about 35 tons. A head-mounted display (HMD was attached to the developed VR CNC machine tool for the immersion viewing. A user can see around the 3D scene of the large mill-turn machine and the operation of the virtual CNC machine can be actuated by bare hand. Coolant was added to demonstrate more realistic operation while collision detection function was also added to remind the operator. The developed VR demonstration system has been presented in the 2017 Taipei International Machine Tool Show (TIMTOS 2017. This case study has shown that young engineers and/or students are very impressed by the VR-based demonstration while elder persons could not adapt themselves easily to the VR-based scene because of eyesight issues. However, virtual reality has successfully being adopted and integrated with the CNC machine tool in an international show. Another machine tool on

  7. Metal Halide Perovskite Polycrystalline Films Exhibiting Properties of Single Crystals

    NARCIS (Netherlands)

    Brenes, Roberto; Guo, D.; Osherov, Anna; Noel, Nakita K.; Eames, Christopher; Hutter, E.M.; Pathak, Sandeep K.; Niroui, Farnaz; Friend, Richard H.; Islam, M. Saiful; Snaith, Henry J.; Bulović, Vladimir; Savenije, T.J.; Stranks, Samuel D.

    2017-01-01

    Metal halide perovskites are generating enormous excitement for use in solar cells and light-emission applications, but devices still show substantial non-radiative losses. Here, we show that by combining light and atmospheric treatments, we can increase the internal luminescence quantum

  8. Development of constitutive model for composites exhibiting time dependent properties

    International Nuclear Information System (INIS)

    Pupure, L; Joffe, R; Varna, J; Nyström, B

    2013-01-01

    Regenerated cellulose fibres and their composites exhibit highly nonlinear behaviour. The mechanical response of these materials can be successfully described by the model developed by Schapery for time-dependent materials. However, this model requires input parameters that are experimentally determined via large number of time-consuming tests on the studied composite material. If, for example, the volume fraction of fibres is changed we have a different material and new series of experiments on this new material are required. Therefore the ultimate objective of our studies is to develop model which determines the composite behaviour based on behaviour of constituents of the composite. This paper gives an overview of problems and difficulties, associated with development, implementation and verification of such model

  9. Two-dimensional colloidal fluids exhibiting pattern formation.

    Science.gov (United States)

    Chacko, Blesson; Chalmers, Christopher; Archer, Andrew J

    2015-12-28

    Fluids with competing short range attraction and long range repulsive interactions between the particles can exhibit a variety of microphase separated structures. We develop a lattice-gas (generalised Ising) model and analyse the phase diagram using Monte Carlo computer simulations and also with density functional theory (DFT). The DFT predictions for the structures formed are in good agreement with the results from the simulations, which occur in the portion of the phase diagram where the theory predicts the uniform fluid to be linearly unstable. However, the mean-field DFT does not correctly describe the transitions between the different morphologies, which the simulations show to be analogous to micelle formation. We determine how the heat capacity varies as the model parameters are changed. There are peaks in the heat capacity at state points where the morphology changes occur. We also map the lattice model onto a continuum DFT that facilitates a simplification of the stability analysis of the uniform fluid.

  10. In silico characterization of cell-cell interactions using a cellular automata model of cell culture.

    Science.gov (United States)

    Kihara, Takanori; Kashitani, Kosuke; Miyake, Jun

    2017-07-14

    Cell proliferation is a key characteristic of eukaryotic cells. During cell proliferation, cells interact with each other. In this study, we developed a cellular automata model to estimate cell-cell interactions using experimentally obtained images of cultured cells. We used four types of cells; HeLa cells, human osteosarcoma (HOS) cells, rat mesenchymal stem cells (MSCs), and rat smooth muscle A7r5 cells. These cells were cultured and stained daily. The obtained cell images were binarized and clipped into squares containing about 10 4 cells. These cells showed characteristic cell proliferation patterns. The growth curves of these cells were generated from the cell proliferation images and we determined the doubling time of these cells from the growth curves. We developed a simple cellular automata system with an easily accessible graphical user interface. This system has five variable parameters, namely, initial cell number, doubling time, motility, cell-cell adhesion, and cell-cell contact inhibition (of proliferation). Within these parameters, we obtained initial cell numbers and doubling times experimentally. We set the motility at a constant value because the effect of the parameter for our simulation was restricted. Therefore, we simulated cell proliferation behavior with cell-cell adhesion and cell-cell contact inhibition as variables. By comparing growth curves and proliferation cell images, we succeeded in determining the cell-cell interaction properties of each cell. Simulated HeLa and HOS cells exhibited low cell-cell adhesion and weak cell-cell contact inhibition. Simulated MSCs exhibited high cell-cell adhesion and positive cell-cell contact inhibition. Simulated A7r5 cells exhibited low cell-cell adhesion and strong cell-cell contact inhibition. These simulated results correlated with the experimental growth curves and proliferation images. Our simulation approach is an easy method for evaluating the cell-cell interaction properties of cells.

  11. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  12. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics

    Directory of Open Access Journals (Sweden)

    Fikret Emre eKapucu

    2012-06-01

    Full Text Available In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESC, exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI histograms. Moreover, the algorithm calculates interspike interval thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  13. Characteristics of Saccharomyces cerevisiae yeasts exhibiting rough colonies and pseudohyphal morphology with respect to alcoholic fermentation.

    Science.gov (United States)

    Reis, Vanda Renata; Bassi, Ana Paula Guarnieri; da Silva, Jessica Carolina Gomes; Ceccato-Antonini, Sandra Regina

    2013-12-01

    Among the native yeasts found in alcoholic fermentation, rough colonies associated with pseudohyphal morphology belonging to the species Saccharomyces cerevisiae are very common and undesirable during the process. The aim of this work was to perform morphological and physiological characterisations of S. cerevisiae strains that exhibited rough and smooth colonies in an attempt to identify alternatives that could contribute to the management of rough colony yeasts in alcoholic fermentation. Characterisation tests for invasiveness in Agar medium, killer activity, flocculation and fermentative capacity were performed on 22 strains (11 rough and 11 smooth colonies). The effects of acid treatment at different pH values on the growth of two strains ("52"--rough and "PE-02"--smooth) as well as batch fermentation tests with cell recycling and acid treatment of the cells were also evaluated. Invasiveness in YPD Agar medium occurred at low frequency; ten of eleven rough yeasts exhibited flocculation; none of the strains showed killer activity; and the rough strains presented lower and slower fermentative capacities compared to the smooth strains in a 48-h cycle in a batch system with sugar cane juice. The growth of the rough strain was severely affected by the acid treatment at pH values of 1.0 and 1.5; however, the growth of the smooth strain was not affected. The fermentative efficiency in mixed fermentation (smooth and rough strains in the same cell mass proportion) did not differ from the efficiency obtained with the smooth strain alone, most likely because the acid treatment was conducted at pH 1.5 in a batch cell-recycle test. A fermentative efficiency as low as 60% was observed with the rough colony alone.

  14. Adipose tissue-derived microvascular fragments from aged donors exhibit an impaired vascularisation capacity

    Directory of Open Access Journals (Sweden)

    MW Laschke

    2014-10-01

    Full Text Available Adipose tissue-derived microvascular fragments are promising vascularisation units for applications in the field of tissue engineering. Elderly patients are the major future target population of such applications due to an increasing human life expectancy. Therefore, we herein investigated the effect of aging on the fragments’ vascularisation capacity. Microvascular fragments were isolated from epididymal fat pads of adult (8 months and aged (16 months C57BL/6 donor mice. These fragments were seeded onto porous polyurethane scaffolds, which were implanted into dorsal skinfold chambers to study their vascularisation using intravital fluorescence microscopy, histology and immunohistochemistry. Scaffolds seeded with fragments from aged donors exhibited a significantly lower functional microvessel density and intravascular blood flow velocity. This was associated with an impaired vessel maturation, as indicated by vessel wall irregularities, constantly elevated diameters and a lower fraction of CD31/α-smooth muscle actin double positive microvessels in the implants’ border and centre zones. Additional in vitro analyses revealed that microvascular fragments from adult and aged donors do not differ in their stem cell content as well as in their release of angiogenic growth factors, survival and proliferative activity under hypoxic conditions. However, fragments from aged donors exhibit a significantly lower number of matrix metalloproteinase -9-positive perivascular cells. Taken together, these findings demonstrate that aging is a crucial determinant for the vascularisation capacity of isolated microvascular fragments.

  15. High Expression of Antiviral Proteins in Mucosa from Individuals Exhibiting Resistance to Human Immunodeficiency Virus.

    Directory of Open Access Journals (Sweden)

    Sandra Milena Gonzalez

    Full Text Available Several soluble factors have been reported to have the capacity of inhibiting HIV replication at different steps of the virus life cycle, without eliminating infected cells and through enhancement of specific cellular mechanisms. Yet, it is unclear if these antiviral factors play a role in the protection from HIV infection or in the control of viral replication. Here we evaluated two cohorts: i one of 58 HIV-exposed seronegative individuals (HESNs who were compared with 59 healthy controls (HCs, and ii another of 13 HIV-controllers who were compared with 20 HIV-progressors. Peripheral blood, oral and genital mucosa and gut-associated lymphoid tissue (GALT samples were obtained to analyze the mRNA expression of ELAFIN, APOBEC3G, SAMHD1, TRIM5α, RNase 7 and SerpinA1 using real-time PCR.HESNs exhibited higher expression of all antiviral factors in peripheral blood mononuclear cells (PBMCs, oral or genital mucosa when compared with HCs. Furthermore, HIV-controllers exhibited higher levels of SerpinA1 in GALT.These findings suggest that the activity of these factors is compartmentalized and that these proteins have a predominant role depending on the tissue to avoid the infection, reduce the viral load and modulate the susceptibility to HIV infection.

  16. How Can Museum Exhibits Enhance Earthquake and Tsunami Hazard Resiliency?

    Science.gov (United States)

    Olds, S. E.

    2015-12-01

    Creating a natural disaster-ready community requires interoperating scientific, technical, and social systems. In addition to the technical elements that need to be in place, communities and individuals need to be prepared to react when a natural hazard event occurs. Natural hazard awareness and preparedness training and education often takes place through informal learning at science centers and formal k-12 education programs as well as through awareness raising via strategically placed informational tsunami warning signs and placards. Museums and science centers are influential in raising science literacy within a community, however can science centers enhance earthquake and tsunami resiliency by providing hazard science content and preparedness exhibits? Museum docents and informal educators are uniquely situated within the community. They are transmitters and translators of science information to broad audiences. Through interaction with the public, docents are well positioned to be informants of the knowledge beliefs, and feelings of science center visitors. They themselves are life-long learners, both constantly learning from the museum content around them and sharing this content with visitors. They are also members of a community where they live. In-depth interviews with museum informal educators and docents were conducted at a science center in coastal Pacific Northwest. This region has a potential to be struck by a great 9+ Mw earthquake and subsequent tsunami. During the interviews, docents described how they applied learning from natural hazard exhibits at a science visitor center to their daily lives. During the individual interviews, the museum docents described their awareness (knowledge, attitudes, and behaviors) of natural hazards where they live and work, the feelings evoked as they learned about their hazard vulnerability, the extent to which they applied this learning and awareness to their lives, such as creating an evacuation plan, whether

  17. Green light for a permanent exhibition in the Globe

    CERN Multimedia

    2008-01-01

    A donation to the Foundation for the Globe of Science and Innovation by ROLEX S.A. marks the first step towards the planned expansion of the Globe’s infrastructure. The Globe: a CERN emblem.Visible from miles away by day and by night, the Globe, the wooden sphere offered to CERN by the Swiss Confederation in 2004, has become one of the symbols of the Organization. Since being opened to the public in September 2005, the Globe has served as a venue for lectures, exhibitions, press and VIP events and workshops for schoolchildren and as a stage for theatre performances on scientific themes. With a view to turning the Globe into a flagship venue for events for the general public, and for interactions between CERN and its public and private partners, two projects are planned for the near future. CERN is receiving support for these ventures from the Foundation for the Globe. Established at the end of 2007, the Foundation’s mission is to ...

  18. Bonobos and chimpanzees exhibit human-like framing effects

    Science.gov (United States)

    Krupenye, Christopher; Rosati, Alexandra G.; Hare, Brian

    2015-01-01

    Humans exhibit framing effects when making choices, appraising decisions involving losses differently from those involving gains. To directly test for the evolutionary origin of this bias, we examined decision-making in humans' closest living relatives: bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). We presented the largest sample of non-humans to date (n = 40) with a simple task requiring minimal experience. Apes made choices between a ‘framed’ option that provided preferred food, and an alternative option that provided a constant amount of intermediately preferred food. In the gain condition, apes experienced a positive ‘gain’ event in which the framed option was initially presented as one piece of food but sometimes was augmented to two. In the loss condition, apes experienced a negative ‘loss' event in which they initially saw two pieces but sometimes received only one. Both conditions provided equal pay-offs, but apes chose the framed option more often in the positive ‘gain’ frame. Moreover, male apes were more susceptible to framing than were females. These results suggest that some human economic biases are shared through common descent with other apes and highlight the importance of comparative work in understanding the origins of individual differences in human choice. PMID:25672997

  19. Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis

    Science.gov (United States)

    Loos, Julia A.; Dávila, Valeria A.; Rodrígues, Christian R.; Petrigh, Romina; Zoppi, Jorge A.; Crocenzi, Fernando A.; Cumino, Andrea C.

    2017-01-01

    Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy. PMID:28182659

  20. Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.

    Directory of Open Access Journals (Sweden)

    Julia A Loos

    2017-02-01

    Full Text Available Metformin (Met is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy.

  1. Pigeons Exhibit Contextual Cueing to Both Simple and Complex Backgrounds

    Science.gov (United States)

    Wasserman, Edward A.; Teng, Yuejia; Castro, Leyre

    2014-01-01

    Repeated pairings of a particular visual context with a specific location of a target stimulus facilitate target search in humans. We explored an animal model of this contextual cueing effect using a novel Cueing-Miscueing design. Pigeons had to peck a target which could appear in one of four possible locations on four possible color backgrounds or four possible color photographs of real-world scenes. On 80% of the trials, each of the contexts was uniquely paired with one of the target locations; on the other 20% of the trials, each of the contexts was randomly paired with the remaining target locations. Pigeons came to exhibit robust contextual cueing when the context preceded the target by 2 s, with reaction times to the target being shorter on correctly-cued trials than on incorrectly-cued trials. Contextual cueing proved to be more robust with photographic backgrounds than with uniformly colored backgrounds. In addition, during the context-target delay, pigeons predominately pecked toward the location of the upcoming target, suggesting that attentional guidance contributes to contextual cueing. These findings confirm the effectiveness of animal models of contextual cueing and underscore the important part played by associative learning in producing the effect. PMID:24491468

  2. Porcine CD38 exhibits prominent secondary NAD(+) cyclase activity.

    Science.gov (United States)

    Ting, Kai Yiu; Leung, Christina F P; Graeff, Richard M; Lee, Hon Cheung; Hao, Quan; Kotaka, Masayo

    2016-03-01

    Cyclic ADP-ribose (cADPR) mobilizes intracellular Ca(2+) stores and activates Ca(2+) influx to regulate a wide range of physiological processes. It is one of the products produced from the catalysis of NAD(+) by the multifunctional CD38/ADP-ribosyl cyclase superfamily. After elimination of the nicotinamide ring by the enzyme, the reaction intermediate of NAD(+) can either be hydrolyzed to form linear ADPR or cyclized to form cADPR. We have previously shown that human CD38 exhibits a higher preference towards the hydrolysis of NAD(+) to form linear ADPR while Aplysia ADP-ribosyl cyclase prefers cyclizing NAD(+) to form cADPR. In this study, we characterized the enzymatic properties of porcine CD38 and revealed that it has a prominent secondary NAD(+) cyclase activity producing cADPR. We also determined the X-ray crystallographic structures of porcine CD38 and were able to observe conformational flexibility at the base of the active site of the enzyme which allow the NAD(+) reaction intermediate to adopt conformations resulting in both hydrolysis and cyclization forming linear ADPR and cADPR respectively. © 2016 The Protein Society.

  3. Clinical Trichophyton rubrum Strain Exhibiting Primary Resistance to Terbinafine

    Science.gov (United States)

    Mukherjee, Pranab K.; Leidich, Steven D.; Isham, Nancy; Leitner, Ingrid; Ryder, Neil S.; Ghannoum, Mahmoud A.

    2003-01-01

    The in vitro antifungal susceptibilities of six clinical Trichophyton rubrum isolates obtained sequentially from a single onychomycosis patient who failed oral terbinafine therapy (250 mg/day for 24 weeks) were determined by broth microdilution and macrodilution methodologies. Strain relatedness was examined by random amplified polymorphic DNA (RAPD) analyses. Data obtained from both broth micro- and macrodilution assays were in agreement and revealed that the six clinical isolates had greatly reduced susceptibilities to terbinafine. The MICs of terbinafine for these strains were >4 μg/ml, whereas they were terbinafine for all six strains were >128 μg/ml, whereas they were 0.0002 μg/ml for the reference strain. The MIC of terbinafine for the baseline strain (cultured at the initial screening visit and before therapy was started) was already 4,000-fold higher than normal, suggesting that this is a case of primary resistance to terbinafine. The results obtained by the broth macrodilution procedure revealed that the terbinafine MICs and MFCs for sequential isolates apparently increased during the course of therapy. RAPD analyses did not reveal any differences between the isolates. The terbinafine-resistant isolates exhibited normal susceptibilities to clinically available antimycotics including itraconazole, fluconazole, and griseofulvin. However, these isolates were fully cross resistant to several other known squalene epoxidase inhibitors, including naftifine, butenafine, tolnaftate, and tolciclate, suggesting a target-specific mechanism of resistance. This is the first confirmed report of terbinafine resistance in dermatophytes. PMID:12499173

  4. The avian egg exhibits general allometric invariances in mechanical design.

    Science.gov (United States)

    Juang, Jia-Yang; Chen, Pin-Yi; Yang, Da-Chang; Wu, Shang-Ping; Yen, An; Hsieh, Hsin-I

    2017-10-27

    The avian egg exhibits extraordinary diversity in size, shape and color, and has a key role in avian adaptive radiations. Despite extensive work, our understanding of the underlying principles that guide the "design" of the egg as a load-bearing structure remains incomplete, especially over broad taxonomic scales. Here we define a dimensionless number C, a function of egg weight, stiffness and dimensions, to quantify how stiff an egg is with respect to its weight after removing geometry-induced rigidity. We analyze eggs of 463 bird species in 36 orders across five orders of magnitude in body mass, and find that C number is nearly invariant for most species, including tiny hummingbirds and giant elephant birds. This invariance or "design guideline" dictates that evolutionary changes in shell thickness and Young's modulus, both contributing to shell stiffness, are constrained by changes in egg weight. Our analysis illuminates unique reproductive strategies of brood parasites, kiwis, and megapodes, and quantifies the loss of safety margin for contact incubation due to artificial selection and environmental toxins. Our approach provides a mechanistic framework for a better understanding of the mechanical design of the avian egg, and may provide clues to the evolutionary origin of contact incubation of amniote eggs.

  5. Exhibition Session of the exp.at’11 International Conference

    Directory of Open Access Journals (Sweden)

    Alberto Cardoso

    2012-01-01

    Full Text Available Man has been the humanity’s engineer for ages - human knowledge has been continuously built on conceptualization based on constant learning by doing activities. The observation and understanding of concepts and principles in action are the bases of the experimental activity leading to the correlation between reality and theory. Experimental activities are really important, contributing to prepare the future engineers for solving practical problems and for consolidating theoretical understanding and volatile knowledge based on abstract concepts. Therefore, experimental activity has been an essential part of education and training for engineers and engineering scientists. exp.at’11 (the 1st Experiment@ International Conference has been the first event of a new International Conference Experiment@ series devoted to online experimentation, enlarging the world capabilities in this particular area and contributing to collaborative work in emergent technologies, bringing together engineers, researchers and professionals from different areas. In its Exhibition Session, participants demonstrated their systems within developments of educational, medical and industrial applications.

  6. Bonobos and chimpanzees exhibit human-like framing effects.

    Science.gov (United States)

    Krupenye, Christopher; Rosati, Alexandra G; Hare, Brian

    2015-02-01

    Humans exhibit framing effects when making choices, appraising decisions involving losses differently from those involving gains. To directly test for the evolutionary origin of this bias, we examined decision-making in humans' closest living relatives: bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). We presented the largest sample of non-humans to date (n = 40) with a simple task requiring minimal experience. Apes made choices between a 'framed' option that provided preferred food, and an alternative option that provided a constant amount of intermediately preferred food. In the gain condition, apes experienced a positive 'gain' event in which the framed option was initially presented as one piece of food but sometimes was augmented to two. In the loss condition, apes experienced a negative 'loss' event in which they initially saw two pieces but sometimes received only one. Both conditions provided equal pay-offs, but apes chose the framed option more often in the positive 'gain' frame. Moreover, male apes were more susceptible to framing than were females. These results suggest that some human economic biases are shared through common descent with other apes and highlight the importance of comparative work in understanding the origins of individual differences in human choice. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  7. 2005 USSOCOM Chemical, Biological, Radiological Conference and Exhibition

    Science.gov (United States)

    2005-12-08

    communicate with/through building control system ► Output compatible with most building HVAC communication/ control standards (LON, BACNet, etc...curves” indicated sensitivity ranges are expected: ► Bg spores : 1000-3000 cfu/l ► Erwinia cells: 100-1000 cfu/l ► Ovalbumin: 0.1-10 ng/l ► MS2 virus...anthrax, the most lethal form of illness in humans caused by the Bacillus anthracis bacterium Confidential PHARMATHENE, INC. Current Response Mark I

  8. Green Synthesized Silver Nanoparticles Exhibit Reduced Toxicity to Mammalian Cells and Retain Antimicrobial Activity

    Science.gov (United States)

    The interest in silver nanoparticles (AgNPs) and silver nanomaterial stems from their antimicrobial properties. AgNPs are being added to clothing, paint, refrigerators, washing machines and a variety of other commercially available items. Recent in vitro and in vivo studies, howe...

  9. Cold urticaria patients exhibit normal skin levels of functional mast cells and histamine after tolerance induction

    DEFF Research Database (Denmark)

    Kring Tannert, Line; Stahl Skov, Per; Bjerremann Jensen, Louise

    2012-01-01

    Cold urticaria is a skin condition characterized by rapid appearance of itchy wheals and occasionally angioedema in response to cold stimulation. Antihistamines do not sufficiently protect all patients from symptoms, even when used in higher than standard doses. In these patients, desensitization...

  10. 77 FR 4614 - Culturally Significant Objects Imported for Exhibition Determinations: “Children of the Plumed...

    Science.gov (United States)

    2012-01-30

    ... Ancient Mexico,'' imported from abroad for temporary exhibition within the United States, are of cultural... also determine that the exhibition or display of the exhibit objects at the Los Angeles County Museum... exhibition or display of the exhibit at the Dallas Museum of Art, Dallas, TX from on or about July 29, 2012...

  11. Curcuma longa and Curcuma mangga leaves exhibit functional food property.

    Science.gov (United States)

    Liu, Yunbao; Nair, Muraleedharan G

    2012-11-15

    Although leaves of Curcuma mangga and Curcuma longa are used in food preparations, the bioactive components in it are not known. In this study, antioxidant, antiinflammatory and anticancer activities of leave extracts and its isolates were investigated using established bioassay procedures in our laboratory. The leaf extracts of both plants gave similar bioassay and chromatographic profiles. The methanolic and water extracts of C. mangga (CMM and CMW) and C. longa (CLM and CLW), at 100 μg/mL, inhibited lipid peroxidation (LPO) by 78%, 63%, 81% and 43%, cyclooxygenase enzymes COX-1 by 55%, 33%, 43% and 24% and COX-2 by 65%, 55%, 77% and 69%, respectively. At same concentration, CMM, CMW, CLM and CLW showed growth inhibition of human tumour cell lines by 0-46%. Therefore, a bioassay-guided isolation of water and methanolic extracts of C. longa was carried out and afforded nine isolates. At 25 μg/mL, these compounds inhibited LPO by 11-87%, COX-1 and -2 enzymes by 0-35% and 0-82% and growth of human tumour cells by 0-36%, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. 7th IGRSM International Remote Sensing & GIS Conference and Exhibition

    Science.gov (United States)

    Shariff, Abdul Rashid Mohamed

    2014-06-01

    IGRSM This proceedings consists of the peer-reviewed papers from the 7th IGRSM International Conference and Exhibition on Remote Sensing & GIS (IGRSM 2014), which was held on 21-22 April 2014 at Berjaya Times Square Hotel, Kuala Lumpur, Malaysia. The conference, with the theme Geospatial Innovation for Nation Building was aimed at disseminating knowledge, and sharing expertise and experiences in geospatial sciences in all aspects of applications. It also aimed to build linkages between local and international professionals in this field with industries. Highlights of the conference included: Officiation by Y B Datuk Dr Abu Bakar bin Mohamad Diah, Deputy Minister of Minister of Science, Technology & Innovation Keynote presentations by: Associate Professor Dr Francis Harvey, Chair of the Geographic Information Science Commission at the International Geographical Union (IGU) and Director of U-Spatial, University of Minnesota, US: The Next Age of Discovery and a Future in a Post-GIS World. Professor Dr Naoshi Kondo, Bio-Sensing Engineering, University of Kyoto, Japan: Mobile Fruit Grading Machine for Precision Agriculture. Datuk Ir Hj Ahmad Jamalluddin bin Shaaban, Director-General, National Hydraulic Research Institute of Malaysia (NAHRIM), Malaysia: Remote Sensing & GIS in Climate Change Analyses. Oral and poster presentations from 69 speakers, from both Malaysia (35) and abroad (34), covering areas of water resources management, urban sprawl & social mobility, agriculture, land use/cover mapping, infrastructure planning, disaster management, technology trends, environmental monitoring, atmospheric/temperature monitoring, and space applications for the environment. Post-conference workshops on: Space Applications for Environment (SAFE), which was be organised by the Japan Aerospace Exploration Agency (JAXA) Global Positioning System (GPS) Receiver Evaluation Using GPS Simulation, which was be organised by the Science & Technology Research Institute for Defence

  13. Belongings: Oral History, Objects and an Online Exhibition

    Directory of Open Access Journals (Sweden)

    Janis Wilton

    2009-11-01

    Full Text Available The New South Wales Migration Heritage Centre was established in 1998. Since 2003 its physical presence has been located within Sydney’s Powerhouse Museum and it has had the strategic brief to record the memories of ageing migrants before their stories are lost. The Centre is, however, a museum without a collection; a heritage authority without heritage sites; a cultural institution whose main presence is in cyberspace. Among its high profile projects is one entitled Objects through time and another Belongings. Both focus on the ways in which objects can convey aspects of the migration experience. Belongings, the focus of this article, presents the remembered experiences of people who migrated to Australia after World War II, and seeks to highlight significant features of their experiences through asking them to share their memories and to nominate and talk about significant objects. As a project it grew out of movable heritage policy work within state government agencies, and its initiators – John Petersen, Kylie Winkworth and Meredith Walker – were central players in this development. It was also inspired by the National Quilt Register of the Pioneer Women’s Hut at Tumbarumba. With its object-centred approach and accompanying edited interview transcripts, Belongings provides a focus for exploring the messages and emphases that emerge when oral history interviews concerned with migration have the specific brief to ask about material culture and its significance. Belongings also enables an exploration of the layering of those messages that emerges when object captions are located back in the context of the oral history interviews from which they were extracted. As a virtual exhibition, Belongings also provides the opportunity to consider the challenges for museums (virtual and real when they need to condense the richness of migrant oral histories and life stories to captioned objects that can be put on display.

  14. An Interactive Exhibition about Animal Skeletons: Did the Visitors Learn Any Zoology?

    Science.gov (United States)

    Tunnicliffe, Sue Dale; Laterveer-de Beer, Manon

    2002-01-01

    Explores museum visitors' understanding of skeleton exhibits and whether such exhibits increase their understanding of the zoology displayed. The exhibition under study focused on the diversity of vertebrae skeletons which were arranged according to the mode of locomotion. (DDR)

  15. 78 FR 5556 - Culturally Significant Objects Imported for Exhibition Determinations: “Frida & Diego: Passion...

    Science.gov (United States)

    2013-01-25

    ... DEPARTMENT OF STATE [Public Notice 8160] Culturally Significant Objects Imported for Exhibition Determinations: ``Frida & Diego: Passion, Politics and Painting'' SUMMARY: Notice is hereby given of the... exhibition ``Frida & Diego: Passion, Politics and Painting,'' imported from abroad for temporary exhibition...

  16. 76 FR 23642 - Culturally Significant Objects Imported for Exhibition Determinations: “Projects 95: Runa Islam”

    Science.gov (United States)

    2011-04-27

    ... DEPARTMENT OF STATE [Public Notice: 7433] Culturally Significant Objects Imported for Exhibition Determinations: ``Projects 95: Runa Islam'' SUMMARY: Notice is hereby given of the following determinations... the exhibition ``Projects 95: Runa Islam'' imported from abroad for temporary exhibition within the...

  17. 76 FR 29286 - Culturally Significant Objects Imported for Exhibition Determinations: “Pissarro's People”

    Science.gov (United States)

    2011-05-20

    ... DEPARTMENT OF STATE [Public Notice 7462] Culturally Significant Objects Imported for Exhibition Determinations: ``Pissarro's People'' SUMMARY: Notice is hereby given of the following determinations: Pursuant... the exhibition ``Pissarro's People,'' imported from abroad for temporary exhibition within the United...

  18. 78 FR 32000 - Culturally Significant Objects Imported for Exhibition Determinations: “Before and After the...

    Science.gov (United States)

    2013-05-28

    ... Lakes,'' imported from abroad for temporary exhibition within the United States, are of cultural... also determine that the exhibition or display of the exhibit objects at the National Museum of the...

  19. 78 FR 51802 - Culturally Significant Objects Imported for Exhibition Determinations: “Silla: Korea's Golden...

    Science.gov (United States)

    2013-08-21

    ... Golden Kingdom,'' imported from abroad for temporary exhibition within the United States, are of cultural... determine that the exhibition or display of the exhibit objects at The Metropolitan Museum of Art, New York...

  20. 75 FR 38589 - Culturally Significant Objects Imported for Exhibition Determinations: “Venice: Canaletto and His...

    Science.gov (United States)

    2010-07-02

    ... DEPARTMENT OF STATE [Public Notice: 7072] Culturally Significant Objects Imported for Exhibition Determinations: ``Venice: Canaletto and His Rivals'' SUMMARY: Notice is hereby given of the following... exhibition ``Venice: Canaletto and His Rivals,'' imported from abroad for temporary exhibition within the...